Acta Naturae最新文献

{"title":"Effect of the ati Gene Deletion on the Pathogenicity and Immunogenicity of the Vaccinia Virus.","authors":"S N Yakubitskiy,&nbsp;A A Sergeev,&nbsp;K A Titova,&nbsp;I S Shulgina,&nbsp;E V Starostina,&nbsp;M B Borgoyakova,&nbsp;L I Karpenko,&nbsp;S N Shchelkunov","doi":"10.32607/actanaturae.17872","DOIUrl":"https://doi.org/10.32607/actanaturae.17872","url":null,"abstract":"<p><p>Among the nonvirion proteins of the vaccinia virus (VACV), a 94-kDa long protein is most abundantly present; the protein is a truncated form of the 150-kDa A-type inclusion (ATI) protein of the cowpox virus encoded by the <i>ati</i> gene. This VACV protein does not form intracellular ATIs, being as it is a major immunogen upon infection/immunization of humans or animals with the VACV. Antibodies specific to this protein are not virus-neutralizing. The present study focused on the effect of the production of this nonstructural major immunogenic VACV protein on the manifestation of pathogenicity and immunogenicity of the virus in the BALB/c mouse model of infection. In order to introduce a targeted deletion into the VACV LIVP genome, the recombinant integration/deletion plasmid pΔati was constructed and further used to generate the recombinant virus LIVPΔati. The pathogenicity of the VACV LIVP and LIVPΔati strains was studied in 3-week-old mice. The mice were intranasally infected with the viruses at a dose of 107 pfu; 50% of the animals infected with the parent LIVP strain died, while infection with the LIVPΔati strain led to the death of only 20% of the mice. Intradermal vaccination of mice aged 6- weeks with the LIVPΔati virus statistically significantly increased the production of VACV-specific IgG, compared to that after intradermal vaccination with VACV LIVP. Meanwhile, no differences were noted in the cell-mediated immune response to the vaccination of mice with VACV LIVP or LIVPΔati, which was assessed by ELISpot according to the number of splenocytes producing IFN-γ in response to stimulation with virus-specific peptides. Intranasal infection of mice with lethal doses of the cowpox virus or the ectromelia virus on day 60 post-immunization with the studied VACV variants demonstrated that the mutant LIVPΔati elicits a stronger protective response compared to the parent LIVP.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71419621","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":null,"pages":null},"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":"Suivis de biodiversité par la reconnaissance automatique des espèces sur photographies : perspectives et défis","authors":"Hélène LE BORGNE, Christophe BOUGET","doi":"10.5852/naturae2023a6","DOIUrl":"https://doi.org/10.5852/naturae2023a6","url":null,"abstract":"La reconnaissance d’espèces basée sur des données d’images analysées par l’intelligence artificielle est de plus en plus populaire dans les suivis de biodiversité, pour faire face aux limites des méthodes plus traditionnelles et à l’émergence de considérations déontologiques préconisant le développement de pièges non destructifs (i.e. non létaux, « no kill »). Cette augmentation dans l’utilisation de nouvelles technologies peut largement s’expliquer par un besoin de gain en temps et en précision. Ce type de méthodologie est particulièrement intéressant pour les personnes qui n’ont pas l’expertise nécessaire pour distinguer de nombreuses espèces telles que les Insectes. De plus, les données photographiques sont moins susceptibles de créer un biais observateur que l’observation directe, car elles sont réutilisables et vérifiables. Dans ce document nous allons voir comment les données peuvent être acquises en milieu terrestre (i.e. méthodologies et outils de capture) et la manière dont les images sont ensuite traitées pour la classification des espèces (i.e. gestion des données et analyses). En particulier, nous avons considéré la possibilité d’automatiser les grands volumes de données collectées à l’aide de techniques d’apprentissage automatique et d’apprentissage profond afin de réaliser l’identification des espèces. Cette étude présente également les avantages et les limites de l’utilisation de ces outils pour l’identification automatique des espèces dans un contexte de suivi de biodiversité en milieu terrestre.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135045630","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":"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}

{"title":"CRISPR/Cas9 Essential Gene Editing in Drosophila.","authors":"I S Osadchiy, S O Kamalyan, K Y Tumashova, P G Georgiev, O G Maksimenko","doi":"10.32607/actanaturae.11874","DOIUrl":"10.32607/actanaturae.11874","url":null,"abstract":"<p><p>Since the addition of the CRISPR/Cas9 technology to the genetic engineering toolbox, the problems of low efficiency and off-target effects hamper its widespread use in all fields of life sciences. Furthermore, essential gene knockout usually results in failure and it is often not obvious whether the gene of interest is an essential one. Here, we report on a new strategy to improve the CRISPR/Cas9 genome editing, which is based on the idea that editing efficiency is tightly linked to how essential the gene to be modified is. The more essential the gene, the less the efficiency of the editing and the larger the number of off-targets, due to the survivorship bias. Considering this, we generated deletions of three essential genes in <i>Drosophila</i>: <i>trf2, top2,</i> and <i>mep-1</i>, using fly strains with previous target gene overexpression (\"pre-rescued\" genetic background).</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10395781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9939456","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":"The Unique Genome of the Virus and Alternative Strategies for its Realization.","authors":"O P Zhirnov","doi":"10.32607/actanaturae.11904","DOIUrl":"10.32607/actanaturae.11904","url":null,"abstract":"<p><p>Dedicated to the 130th anniversary of Dmitry Ivanovsky's discovery of the virus kingdom as a new form of biological life. The genome of some RNA-containing viruses comprises ambipolar genes that are arranged in stacks (one above the other) encoding proteins in opposite directions. Ambipolar genes provide a new approach for developing viral diversity when virions possessing an identical genome may differ in its expression scheme (strategy) and have distinct types of progeny virions varying in the genomic RNA polarity and the composition of proteins expressed by positive- or negative-sense genes, the so-called ambipolar virions. So far, this pathway of viral genome expression remains hypothetical and hidden from us, like the dark side of the Moon, and deserves a detailed study.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10395775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9939458","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":"EGFR Suppression Inhibits the Sphere Formation of MCF7 Cells Overexpressing EGFR.","authors":"D D Novak,&nbsp;O S Troitskaya,&nbsp;A A Nushtaeva,&nbsp;M V Zhilnikova,&nbsp;V A Richter,&nbsp;M I Meschaninova,&nbsp;O A Koval","doi":"10.32607/actanaturae.17857","DOIUrl":"10.32607/actanaturae.17857","url":null,"abstract":"<p><p>The epidermal growth factor receptor (EGFR) is an oncogenic tyrosine kinase that is involved in tumor initiation and progression, making EGFR inhibitors and monoclonal antibodies to this receptor essential for anti-tumor therapy. We have previously shown that EGFR transgene expression in the human breast adenocarcinoma cell line MCF7 (MCF7-EGFR) stimulates the 3D spheroid-like growth. The primary focus of our present work was to investigate whether EGFR inhibition could affect the assembly of spheroids or lead to the destruction of pre-existing spheroids. We compared the effects of anti-EGFR siRNA, the anti-EGFR monoclonal antibody cetuximab, and the tyrosine kinase inhibitor AG1478 on dissociated and spheroid MCF7-EGFR cells. MCF7-EGFR cells were found to have a 2.5-fold higher sensitivity towards the cytotoxic effects of cetuximab and AG1478 compared with the parental MCF7 cell line. The suppression of EGFR mRNA with siRNA was found to reduce the sphere formation, whereas treating the pre-existing spheroids had no such effect. Treatment of dissociated spheroids with cetuximab and AG1478 was also found to inhibit the MCF7-EGFR sphere formation. We suggest that EGFR expression is important, at least, during the spheroid formation stage. The transition of a MCF7wt adherent cell culture to MCF7-EGFR spheroids was accompanied by a considerable increase in N-cadherin adhesion proteins. The level of N-cadherin decreased when MCF7-EGFR cells were treated with siRNA and cetuximab. Thus, we have demonstrated that N-cadherin is involved in the EGFR-dependent formation of MCF7-EGFR spheroids. Accordingly, MCF7-EGFR spheroids can be considered a suitable model for studying aggressive hormone-positive breast tumors.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10395776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10314626","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":"Search for Inhibitors of Mycobacterium tuberculosis Transketolase in a Series of Sulfo-Substituted Compounds.","authors":"I V Gushchina,&nbsp;D K Nilov,&nbsp;T A Shcherbakova,&nbsp;S M Baldin,&nbsp;V K Švedas","doi":"10.32607/actanaturae.15709","DOIUrl":"10.32607/actanaturae.15709","url":null,"abstract":"<p><p>As a result of the computer screening of a library of sulfo-substituted compounds, molecules capable of binding to the active site of transketolase from <i>Mycobacterium tuberculosis</i> were identified. An experimental verification of the inhibitory activity of the most promising compound, STK045765, against a highly purified recombinant enzyme preparation was carried out. It was shown that the STK045765 molecule competes for the binding site of the pyrophosphate group of the thiamine diphosphate cofactor and, at a micromolar concentrations, is able to suppress the activity of mycobacterial transketolase. The discovered furansulfonate scaffold may serve as the basis for the creation of anti-tuberculosis drugs.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10395774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9929763","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}