Acta Naturae最新文献

{"title":"RNAcontacts, a pipeline for predicting contacts from RNA proximity ligation assays","authors":"Sergey Margasyuk, Mariia Vlasenok, Guo Li, Changchang Cao, Dmitri Pervouchine","doi":"10.1101/2022.10.06.511089","DOIUrl":"https://doi.org/10.1101/2022.10.06.511089","url":null,"abstract":"Background High-throughput RNA proximity ligation assays are molecular methods that simultaneously analyze spatial proximity of many RNAs in living cells. Their principle is based on cross-linking, fragmentation, and consequent religation of RNAs followed by high-throughput sequencing. The generated fragments have two distinct types of splits, one resulting from pre-mRNA splicing, and the other resulting from ligating spatially close RNA strands. Findings Here, we present RNAcontacts, a universal pipeline for detecting RNA-RNA contacts in high-throughput RNA proximity ligation assays. It circumvents the inherent problem of mapping sequences with two distinct split types using a two-pass alignment, in which splice junctions are inferred from a control RNA-seq experiment on the first pass and then provided to the aligner on the second pass as bona fide introns. This approach allows for a more sensitive detection of RNA contacts and has higher specificity with respect to splice junctions that are present in the biological sample in comparison to previously developed methods. RNAcontacts extracts contacts, clusters their ligation points, computes the read support, and generates tracks for the visualization through the UCSC Genome Browser. It is implemented in a reproducible and scalable workflow management system Snakemake that allows fast and uniform processing of multiple datasets. Conclusions RNAcontacts represents a generic pipeline for the detection of RNA contacts that can be used with any proximity ligation method as long as one of the interacting partners is RNA. RNAcontacts is available via github at https://github.com/smargasyuk/RNAcontacts/","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2022-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62353118","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":"Sciences participatives sur l’île de la Réunion : quand le Busard de Maillard Circus maillardi J. Verreaux, 1862 fédère bénévoles et professionnels","authors":"Thibaut Couturier, D. Chiron, Pierrick Ferret, N. Laurent, T. Cornulier, A. Villers, A. Besnard, M. Salamolard, François-Xavier Couzi, S. Augiron","doi":"10.5852/naturae2022a15","DOIUrl":"https://doi.org/10.5852/naturae2022a15","url":null,"abstract":"Les programmes en sciences participatives dans le domaine de l’écologie se sont amplement développés depuis les années 2000 en France. La diversité de compétences des participants à de tels programmes peut toutefois constituer un frein dans la conception de protocoles complexes. Le programme FEDER pour la conservation du Busard de Maillard Circus maillardi J. Verreaux, 1862 sur l’île de la Réunion avait pour ambition de répondre à plusieurs questions scientifiques, dont certaines nécessitaient l’utilisation de méthodologies avancées, notamment pour corriger les problèmes de biais de détection. Nous avons alors conçu un protocole en plusieurs étapes à destination de bénévoles, de professionnels et d’étudiants aux compétences en ornithologie variées. Parmi 150 personnes initialement inscrites à ce programme, 103 ont effectivement collecté des données en mai et juin 2017 sur 330 « postes d’observation » déployés sur toute l’île. Elles avaient été préalablement formées en salle puis sur le terrain afin d’homogénéiser leurs compétences en ornithologie et de s’assurer auprès d’elles de la bonne compréhension des objectifs et du protocole de collecte de données. À l’issue de l’opération de collecte des données sur le terrain, un questionnaire a été soumis aux observateurs afin de recueillir leurs impressions sur les aspects positifs de la démarche et les difficultés rencontrées. 71 participants y ont répondu. Nous détaillons ici les différentes étapes qui ont permis de concevoir puis de déployer ce protocole et nous analysons ses forces et faiblesses, en termes de constitution et de fidélisation d’un réseau de participants. Cette analyse est à l’usage des concepteurs d’autres programmes de sciences participatives. Nous insistons en particulier sur le rôle de l’animation pour garantir le succès d’un tel programme.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2022-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88559712","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":"The Fallout of Catastrophic Technogenic Emissions of Toxic Gases Can Negatively Affect Covid-19 Clinical Course.","authors":"G Succi,&nbsp;W Pedrycz,&nbsp;A P Bogachuk,&nbsp;A G Tormasov,&nbsp;A A Belogurov,&nbsp;A Spallone","doi":"10.32607/actanaturae.11754","DOIUrl":"10.32607/actanaturae.11754","url":null,"abstract":"<p><p>The coronavirus D-19 (Covid-19) pandemic has shaken almost every country in the world: as we stand, 6,3 million deaths from the infection have already been recorded, 167,000 and 380,000 of which are in Italy and the Russian Federation, respectively. In the first wave of the pandemic, Italy suffered an abnormally high death toll. A detailed analysis of available epidemiological data suggests that that rate was shockingly high in the Northern regions and in Lombardy, in particular, whilst in the southern region the situation was less dire. This inexplicably high mortality rate in conditions of a very well-developed health care system such as the one in Lombardy - recognized as one of the best in Italy - certainly cries for a convincing explanation. In 1976, the small city of Seveso, Lombardy, experienced a release of dioxin into the atmosphere after a massive technogenic accident. The immediate effects of the industrial disaster did not become apparent until a surge in the number of tumors in the affected population in the subsequent years. In this paper, we endeavor to prove our hypothesis that the release of dioxin was a negative cofactor that contributed to a worsening of the clinical course of COVID-19 in Lombardy.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10277326","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 Low-Molecular-Weight BDNF Mimetic, Dipeptide GSB-214, Prevents Memory Impairment in Rat Models of Alzheimer's Disease.","authors":"P Yu Povarnina, A A Volkova, O N Vorontsova, A A Kamensky, T A Gudasheva, S B Seredenin","doi":"10.32607/actanaturae.11755","DOIUrl":"10.32607/actanaturae.11755","url":null,"abstract":"<p><p>Brain-derived neurotrophic factor (BDNF) is known to be involved in the pathogenesis of Alzheimer's disease (AD). However, the pharmacological use of full-length neurotrophin is limited, because of its macromolecular protein nature. A dimeric dipeptide mimetic of the BDNF loop 1, bis-(N-monosuccinyl-L-methionyl-L-serine) heptamethylene diamide (GSB-214), was designed at the Zakusov Research Institute of Pharmacology. GSB-214 activates TrkB, PI3K/AKT, and PLC-γ1 in vitro. GSB-214 exhibited a neuroprotective activity during middle cerebral artery occlusion in rats when administered intraperitoneally (i.p.) at a dose of 0.1 mg/kg and improved memory in the novel object recognition test (0.1 and 1.0 mg/kg, i.p.). In the present study, we investigated the effects of GSB-214 on memory in the scopolamine- and steptozotocin-induced AD models, with reference to activation of TrkB receptors. AD was modeled in rats using a chronic i.p. scopolamine injection or a single streptozotocin injection into the cerebral ventricles. GSB-214 was administered within 10 days after the exposure to scopolamine at doses of 0.05, 0.1, and 1 mg/kg (i.p.) or within 14 days after the exposure to streptozotocin at a dose of 0.1 mg/kg (i.p.). The effect of the dipeptide was evaluated in the novel object recognition test; K252A, a selective inhibitor of tyrosine kinase receptors, was used to reveal a dependence between the mnemotropic action and Trk receptors. GSB-214 at doses of 0.05 and 0.1 mg/kg statistically significantly prevented scopolamine-induced long-term memory impairment, while not affecting short-term memory. In the streptozotocin-induced model, GSB-214 completely eliminated the impairment of short-term memory. No mnemotropic effect of GSB-214 was registered when Trk receptors were inhibited by K252A.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10269688","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":"DNA Methylation: Genomewide Distribution, Regulatory Mechanism and Therapy Target.","authors":"D S Kaplun,&nbsp;D N Kaluzhny,&nbsp;E B Prokhortchouk,&nbsp;S V Zhenilo","doi":"10.32607/actanaturae.11822","DOIUrl":"10.32607/actanaturae.11822","url":null,"abstract":"<p><p>DNA methylation is the most important epigenetic modification involved in the regulation of transcription, imprinting, establishment of X-inactivation, and the formation of a chromatin structure. DNA methylation in the genome is often associated with transcriptional repression and the formation of closed heterochromatin. However, the results of genome-wide studies of the DNA methylation pattern and transcriptional activity of genes have nudged us toward reconsidering this paradigm, since the promoters of many genes remain active despite their methylation. The differences in the DNA methylation distribution in normal and pathological conditions allow us to consider methylation as a diagnostic marker or a therapy target. In this regard, the need to investigate the factors affecting DNA methylation and those involved in its interpretation becomes pressing. Recently, a large number of protein factors have been uncovered, whose ability to bind to DNA depends on their methylation. Many of these proteins act not only as transcriptional activators or repressors, but also affect the level of DNA methylation. These factors are considered potential therapeutic targets for the treatment of diseases resulting from either a change in DNA methylation or a change in the interpretation of its methylation level. In addition to protein factors, a secondary DNA structure can also affect its methylation and can be considered as a therapy target. In this review, the latest research into the DNA methylation landscape in the genome has been summarized to discuss why some DNA regions avoid methylation and what factors can affect its level or interpretation and, therefore, can be considered a therapy target.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10269687","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":"Comprehensive Analysis of Stromal and Serum Markers in Gastric Cancer.","authors":"O V Kovaleva,&nbsp;P A Podlesnaya,&nbsp;V L Chang,&nbsp;N A Ognerubov,&nbsp;A N Gratchev,&nbsp;N A Kozlov,&nbsp;I S Stilidi,&nbsp;N E Kushlinskii","doi":"10.32607/actanaturae.11753","DOIUrl":"10.32607/actanaturae.11753","url":null,"abstract":"<p><p>A comprehensive analysis of the cell phenotype of the inflammatory infiltrate of the tumor stroma represents a promising area of molecular oncology. The study of not only soluble forms of various immunoregulatory molecules, but also their membrane-bound forms is also considered highly relevant. We performed a comprehensive analysis of tissue and circulating forms of the PD-1 and PD-L1 proteins, as well as macrophage and B-cell markers in the tumor stroma of gastric cancer, to assess their clinical and prognostic significance. The tumor and blood plasma samples from 63 gastric cancer patients were studied using ELISA and immunohistochemistry. Malignant gastric tumors were shown to be strongly infiltrated by B-cells, and their number was comparable to that of macrophages. For PU.1 expression, an association with tumor size was observed; i.e., larger tumors were characterized by fewer PU.1+ infiltrating cells (p = 0.005). No clinical significance was found for CD20 and CD163, but their numbers were higher at earlier stages of the disease and in the absence of metastases. It was also demonstrated that the PD-L1 content in tumor cells was not associated with the clinical and morphological characteristics of GC. At the same time, PD-L1 expression in tumor stromal cells was associated with the presence of distant metastases. The analysis of the prognostic significance of all the markers studied demonstrated that CD163 was statistically significantly associated with a poor prognosis for the disease (p = 0.019). In addition, PD-L1 expression in tumor cells tended to indicate a favorable prognosis (p = 0.122). The results obtained in this work indicate that the study of soluble and tissue markers of tumor stroma is promising in prognosticating the course of GC. The search for combinations of markers seems to be highly promising, with their comprehensive analysis capable of helping personalize advanced antitumor therapy.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9187720","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":"About the Biodiversity of the Air Microbiome.","authors":"N B Naumova,&nbsp;M R Kabilov","doi":"10.32607/actanaturae.11671","DOIUrl":"10.32607/actanaturae.11671","url":null,"abstract":"<p><p>This brief review focuses on the properties of bioaerosols, presenting some recent results of metagenomic studies of the air microbiome performed using next-generation sequencing. The taxonomic composition and structure of the bioaerosol microbiome may display diurnal and seasonal dynamics and be dependent on meteorological events such as dust storms, showers, fogs, etc., as well as air pollution. The Proteobacteria and Ascomycota members are common dominants in bioaerosols in different troposphere layers. The microbiological composition of the lower troposphere air affects the composition and diversity of the indoor bioaerosol microbiome, and information about the latter is very important, especially during exacerbated epidemiological situations. Few studies focusing on the bioaerosol microbiome of the air above Russia urge intensification of such research.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10642847","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":"Comparison of the Effectiveness of Transepidemal and Intradermal Immunization of Mice with the Vacinia Virus.","authors":"S N Shchelkunov, A A Sergeev, K A Titova, S A Pyankov, E V Starostina, M B Borgoyakova, L A Kisakova, D N Kisakov, L I Karpenko, S N Yakubitskiy","doi":"10.32607/actanaturae.11857","DOIUrl":"10.32607/actanaturae.11857","url":null,"abstract":"<p><p>The spread of the monkeypox virus infection among humans in many countries outside of Africa, which started in 2022, is now drawing the attention of the medical and scientific communities to the fact that immunization against this infection is sorely needed. According to current guidelines, immunization of people with the first-generation smallpox vaccine based on the vaccinia virus (VACV) LIVP strain, which is licensed in Russia, should be performed via transepidermal inoculation (skin scarification, s.s.). However, the long past experience of using this vaccination technique suggests that it does not ensure virus inoculation into patients' skin with enough reliability. The procedure of intradermal (i.d.) injection of a vaccine can be an alternative to s.s. inoculation. The effectiveness of i.d. vaccination can depend on the virus injection site on the body. Therefore, the aim of this study was to compare the development of the humoral and cellular immune responses in BALB/c mice immunized with the LIVP VACV strain, which was administered either by s.s. inoculation or i.d. injection into the same tail region of the animal. A virus dose of 105 pfu was used in both cases. ELISA of serum samples revealed no significant difference in the dynamics and level of production of VACV-specific IgM and IgG after i.d. or s.s. vaccination. A ELISpot analysis of splenocytes from the vaccinated mice showed that i.d. administration of VACV LIVP to mice induces a significantly greater T-cell immune response compared to s.s. inoculation. In order to assess the protective potency, on day 45 post immunization, mice were intranasally infected with lethal doses of either the cowpox virus (CPXV) or the ectromelia virus (ECTV), which is evolutionarily distant from the VACV and CPXV. Both vaccination techniques ensured complete protection of mice against infection with the CPXV. However, when mice were infected with a highly virulent strain of ECTV, 50% survived in the i.d. immunized group, whereas only 17% survived in the s.s. immunized group. It appears, therefore, that i.d. injection of the VACV can elicit a more potent protective immunity against orthopoxviruses compared to the conventional s.s. technique.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10277319","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":"Bulky Adducts in Clustered DNA Lesions: Causes of Resistance to the NER System.","authors":"N V Naumenko, I O Petruseva, O I Lavrik","doi":"10.32607/actanaturae.11741","DOIUrl":"10.32607/actanaturae.11741","url":null,"abstract":"<p><p>The nucleotide excision repair (NER) system removes a wide range of bulky DNA lesions that cause significant distortions of the regular double helix structure. These lesions, mainly bulky covalent DNA adducts, are induced by ultraviolet and ionizing radiation or the interaction between exogenous/endogenous chemically active substances and nitrogenous DNA bases. As the number of DNA lesions increases, e.g., due to intensive chemotherapy and combination therapy of various diseases or DNA repair impairment, clustered lesions containing bulky adducts may occur. Clustered lesions are two or more lesions located within one or two turns of the DNA helix. Despite the fact that repair of single DNA lesions by the NER system in eukaryotic cells has been studied quite thoroughly, the repair mechanism of these lesions in clusters remains obscure. Identification of the structural features of the DNA regions containing irreparable clustered lesions is of considerable interest, in particular due to a relationship between the efficiency of some antitumor drugs and the activity of cellular repair systems. In this review, we analyzed data on the induction of clustered lesions containing bulky adducts, the potential biological significance of these lesions, and methods for quantification of DNA lesions and considered the causes for the inhibition of NER-catalyzed excision of clustered bulky lesions.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9187722","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":"Flow-Seq Method: Features and Application in Bacterial Translation Studies.","authors":"E S Komarova, O A Dontsova, D V Pyshnyi, M R Kabilov, P V Sergiev","doi":"10.32607/actanaturae.11820","DOIUrl":"10.32607/actanaturae.11820","url":null,"abstract":"<p><p>The Flow-seq method is based on using reporter construct libraries, where a certain element regulating the gene expression of fluorescent reporter proteins is represented in many thousands of variants. Reporter construct libraries are introduced into cells, sorted according to their fluorescence level, and then subjected to next-generation sequencing. Therefore, it turns out to be possible to identify patterns that determine the expression efficiency, based on tens and hundreds of thousands of reporter constructs in one experiment. This method has become common in evaluating the efficiency of protein synthesis simultaneously by multiple mRNA variants. However, its potential is not confined to this area. In the presented review, a comparative analysis of the Flow-seq method and other alternative approaches used for translation efficiency evaluation of mRNA was carried out; the features of its application and the results obtained by Flow-seq were also considered.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9187719","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}