Acta Naturae
Acta Naturae is a new international journal on life sciences based in Moscow, Russia. Our goal is to present scientific work and discovery in molecular biology, biochemistry, biomedical disciplines and biotechnology. These fields represent the most important priorities for the research and engineering development both in Russia and worldwide. Acta Naturae is also a periodical for those who are curious in various aspects of biotechnological business, innovations in pharmaceutical areas, intellectual property protection and social consequences of scientific progress. The journal will publish analytical industrial surveys focused on the development of different spheres of modern life science and technology.
Being a radically new and totally unique publication in Russia, Acta Naturae will be useful to both representatives of fundamental research and experts in applied sciences.
The editorial council and editorial board include prominent scientists from Russia and abroad: Alexander Gabibov, Sergey Kochetkov, Patrick Masson, Alan Friboulet, Alfonso Tramontano, Knud Nierhaus.
The journal is published since April 2009, 4 times a year.
Announcements More Announcements...
![]() Academician Anatoly I. Grigoriev passed away on February 11, 2023Posted: 17.02.2023
The editorial board of the journal Acta Naturae informs with deep regret that on February 11, 2023, the founder of the journal, the permanent chairman of the editorial board, academician Anatoly I. Grigoriev, passed away. |
|
Free Full Open Access to the jornalPosted: 30.10.2019
Journal “Acta Naturae” is now available in open access in PubMed Central and eLIBRARY.RU. |
|
Current Issue
Vol 17, No 2 (2025)
- Year: 2025
- Published: 25.07.2025
- Articles: 12
- URL: https://actanaturae.ru/2075-8251/issue/view/888
Reviews
The Effects of Assisted Reproductive Technologies on De Novo Mutations
Abstract
Recent advances in assisted reproductive technologies (ART) have revolutionized human reproduction, offering hope to millions of couples facing infertility issues. At the same time, concerns persist regarding the potential impact of ART on the genomic integrity of offspring conceived through these techniques. Specifically, questions abound about the effects of these techniques on the incidence of de novo mutations (DNMs), which are genetic alterations that arise spontaneously in the germline or during early embryonic development and are implicated in various human diseases. The extent to which ART directly affects the rate of de novo mutations has been the subject of ongoing debate. This review explores recent studies that have investigated the relationship between ART and DNMs. It underscores the necessity for further research to clarify the clinical implications and long-term consequences of ART.



Generation of TIL-Based Cellular Products for Cancer Immunotherapy: Current Insights and the Challenges
Abstract
Tumor-infiltrating T lymphocytes (TILs) are a population of T cells present in tumor tissue and enriched in tumor antigen-specific clones. TILs participate in the adaptive antitumor immune response, which makes them a promising candidate for cancer immunotherapy. The concept framing this type of therapy involves the extraction of T cells from a patient’s tumor, followed by their in vitro expansion and reinfusion into the same patient in large quantities. This approach enhances the antitumor immune response and allows one to affect cancer cells resistant to other types of treatment. In 2024, the first TIL-based drug was approved for melanoma treatment. The possibility of using TILs for treating other solid tumors is currently being considered, and novel methods aiming to increase the efficiency of generating TIL cultures from tumor tissues in vitro are being developed. However, despite the significant progress achieved in this area, there remain unresolved issues and problems, including the lack of standardized protocols for obtaining, expanding, and cryopreserving TILs, the complexity related to their isolation and the duration of that, as well as insufficient efficiency. Our review focuses on the concept of immunotherapy using TILs, the main stages involved in generating a TIL-based cellular product, associated problems, and further steps in the production of TIL cultures that aim to improve efficiency as relates to production and ensure a wider application of the therapy.



Extracellular Vesicles as a Source of Biomarkers for Cancer Diagnosis
Abstract
Extracellular vesicles (EVs) are secreted by nearly all mammalian cells and play a major role in intercellular communication via the transport of various active biomolecules. In cancer, pathological EVs contribute to tumor progression by participating in metastasis, angiogenesis, and immune evasion. Recent advancements in EV research have revealed their potential as noninvasive biomarkers. This review addresses the latest advancements in EV isolation and characterization techniques, elucidates the molecular mechanisms underlying EV biogenesis, and examines their functional roles in cancer progression. Furthermore, we discuss emerging strategies that leverage EV profiling and molecular composition analysis, in conjunction with liquid biopsy technologies, offering possible breakthroughs in early cancer diagnosis and treatment monitoring. By synthesizing these insights, this review emphasizes the growing significance of EVs as versatile and powerful diagnostic tools in oncology.



Research Articles
Identification of Chalcone Synthase Genes from Garlic (Allium sativum L.) and Their Expression Levels in Response to Stress Factors
Abstract
A plant’s defense response involves the accumulation of flavonoids, whose biosynthetic pathway in garlic Allium sativum L. remains not characterized. In this work, we identified eight AsCHS1–8 genes of chalcone synthases in the A. sativum genome which presumably catalyze the first stage of flavonoid synthesis in garlic plants. These genes were found to be localized on 4 chromosomes: AsCHS2, 6–8 contain 1 to 2 introns, whereas AsCHS1, 3–5 are intronless. The analysis of the organ-specific gene expression profiles revealed significant transcript levels for AsCHS3 and 8. Only AsCHS8 was shown to change its expression level in response to abiotic stressors (salinity, drought, cold) and exogenous phytohormones (abscisic acid, methyl jasmonate). These findings suggest that two out of the eight genes, AsCHS3 and 8, control flavonoid synthesis during garlic development, with AsCHS8 being the most active chalcone synthase gene. The other six genes (AsCHS1, 2, 4–7) may be involved in flavonoid biosynthesis in highly specialized cells/tissues/organs or the developmental stages of the garlic plant. Our results on the identification and characterization of garlic chalcone synthase genes AsCHS1–8 may facilitate further analysis of the mechanisms that regulate stress adaptation in A. sativum and other Allium species.



Возникновение новой инсерционной мутации в онкогене BCR::ABL/p210 при В-клеточном остром лимфобластном лейкозе (B-ОЛЛ) коррелирует с развитием резистентности к нескольким ингибиторам тирозинкиназ
Abstract
У больного с иммунофенотипом, характерным для B-клеточного острого лимфобластного лейкоза (B-ОЛЛ), обнаружили хромосомную транслокацию t(9;22)(q34;q11), или филадельфийскую (Ph) хромосому и менее распространенный вариант химерного онкогена BCR::ABL/p210. При этом в дебюте заболевания с повышенным уровнем бластных клеток (77.6%) и лейкоцитов (48×109/л) каких-либо дополнительных мутаций в гене BCR::ABL, включая точечные мутации, вставки или делеции, выявлено не было. После проведения химиотерапии «Ph+ALL-2012m» с добавлением иматиниба (600 мг) и двух фаз консолидации отмечали развитие полной гематологической ремиссии и глубокого молекулярного ответа. Однако спустя 6 месяцев у пациента развился рецидив (бласты: 15%, BCR::ABL/p210: 105%). Через 3 недели после начала терапии дазатинибом (100 мг) количество бластов уменьшилось до 4.8%, а уровень экспрессии BCR::ABL/p210 снизился до 11.8%. Секвенирование по Сэнгеру позволило идентифицировать два варианта мутаций в гене BCR::ABL, а именно, точечную мутацию F317L и новую вставку из 9 нуклеотидов, ранее не обнаруженную. В последнем случае остаток лизина в позиции 294 был замещен на четыре новых аминокислотных остатка: K294SPSQ. После терапии бозутинибом и инотузумабом наблюдалось исчезновение одного лейкозного клона с мутацией F317L, однако сохранялось присутствие другого клона, несущего вставку из 9 нуклеотидов. Смена курса химиотерапии на понатиниб+блинатумомаб оказалась эффективной. Это привело к исчезновению инсерции. После аллогенной трансплантации гемопоэтических стволовых клеток (алло-ТГСК) от неродственного HLA-совместимого донора наблюдалось развитие полной клинико-гематологической ремиссии и полного молекулярного ответа. Мониторинг минимальной остаточной болезни спустя 6 месяцев после алло-ТГСК показал сохранение ремиссии.



The Drosophila Zinc Finger Protein Aef1 Colocalizes with Enhancers and Is Involved in the Transcriptional Regulation of Numerous Genes
Abstract
In our previous studies, we demonstrated that the Drosophila zinc finger protein Aef1 interacts with the SAGA DUB module. The Aef1 binding sites colocalize with the SAGA histone acetyltransferase complex and the dSWI/SNF chromatin remodeling complex, as well as the origin recognition complex (ORC). Aef1 predominantly localizes with the promoters of active genes (55% of all sites) and can be involved in transcriptional regulation. In this study, we showed that Aef1 binding sites in Drosophila S2 cells, located outside gene promoters, are nucleosome-depleted regions and colocalize with the SAGA, dSWI/SNF, and ORC complexes. Aef1 binding sites colocalize with the CBP protein and the H3K27Ac histone tag, which is considered to be an active enhancer mark. An RNA-Seq experiment was conducted in Drosophila S2 cells, both normal and with RNA interference targeting the Aef1 protein, to study the role played by the Aef1 protein in transcriptional regulation. The Aef1 protein was shown to affect the transcription of 342 genes, more than half of those (178 genes) containing Aef1 at their promoters or enhancers. Hence, we infer that the Aef1 protein is recruited to both promoters and enhancers and is involved, both directly and indirectly, in the regulation of the transcription of the respective genes.



Cis-Regulatory Function of the Pou5f1 Gene Promoter in the Mouse MHC Locus
Abstract
The Pou5f1 gene encodes the Oct4 protein, one of the key transcription factors required for maintaining the pluripotent state of epiblast cells and the viability of germ cells. However, functional genetics provides convincing evidence that Pou5f1 has a broader range of functions in mouse ontogeny, including suppression of atherosclerotic processes. Related studies have primarily focused on the functions of the Oct4 protein, while the regulatory sequences within the Pou5f1 gene have not been considered. In this study, we have developed a genetic model which is based on mouse embryonic stem cells (ESCs) for assessing the roles of the Pou5f1 gene promoter in the transcriptional regulation of neighboring genes within the major histocompatibility complex (MHC) locus. We have demonstrated that deletion of this promoter affects the expression of selected genes within this locus neither in ESCs nor in the trophoblast derivatives of these cells. A notable exception is the Tcf19 gene, which is upregulated upon Pou5f1 promoter deletion and might be associated with the atherosclerosis pathology due to its pro-inflammatory activity. The developed genetic model will pave the way for future studies into the functional contribution of the cis-regulatory association of Pou5f1, Tcf19, and, possibly, other genes with the atherosclerotic phenotype previously reported for mice carrying the Pou5f1 promoter deletion in vascular endothelial and smooth muscle cells.



Classification and Quantification of Unproductive Splicing Events
Abstract
In eukaryotic cells, the nonsense-mediated decay (NMD) pathway degrades mRNAs with premature stop codons. The coupling between NMD and alternative splicing (AS) generates NMD-sensitive transcripts (NMD targets, NMDTs) that play an important role in the gene expression regulation via the unproductive splicing mechanism. Understanding this mechanism requires proper identification of NMDT-generating AS events. Here, we developed NMDj, a tool for the identification, classification and quantification of NMDT-generating AS events which does not rely on the best matching transcript partner principle employed by the existing methods. Instead, NMDj uses a set of characteristic introns that discriminate NMDTs from all protein-coding transcripts. The benchmark on simulated RNA-Seq data demonstrated that NMDj allows to quantify NMDT-generating AS events with better precision compared to other existing methods. NMDj represents a generic method suitable for the accurate classification of arbitrarily complex AS events that generate NMDTs. The NMDj pipeline is available through the repository https://github.com/zavilev/NMDj/.



The Hypomethylating Agent 5-Azacitidine Potentiates the Effect of RAS and Sp1 Inhibitors in Neuroblastoma Cells
Abstract
Neuroblastoma is a malignant solid tumor caused by the transformation of neural crest cells. Neuroblastoma predominantly occurs in children and is associated with a poor prognosis. In this regard, the development of novel approaches to neuroblastoma treatment, including combination therapy, is relevant. DNA hypermethylation of neuroblastoma cells indicates that it is possible to use hypomethylating agents in a combination therapy of the disease. In order to identify effective combinations of antitumor drugs, we analyzed the transcriptomic changes that take place in neuroblastoma SH-SY5Y cells after treatment with the hypomethylating agent 5-azacitidine and then experimentally tested the effectiveness of these combinations. Mithramycin A and lonafarnib were the two drugs that, in combination with 5-azacitidine, appeared to exert a synergistic effect on SH-SY5Y cell death. These drugs inhibit the signaling pathway associated with the transcription factor Sp1 and RAS-MAPK signaling pathway, which are activated by 5-azacitidine. An analysis of the signaling pathways also revealed an activation of the signaling pathways associated with neuroblastoma cell differentiation, as well as apoptosis induction, as confirmed by multiplex and confocal microscopy. Hence, by analyzing the changes in the signaling pathways, the mechanisms of cell death and cell adaptation to hypomethylating agents can be understood, and this can be further used to develop novel therapeutic approaches to neuroblastoma therapy.



Integration of HiMoRNA and RNA-Chrom: Validation of the Functional Role of Long Non-coding RNAs in the Epigenetic Regulation of Human Genes Using RNA-Chromatin Interactome Data
Abstract
Long non-coding RNAs (lncRNAs) play a crucial role in the epigenetic regulation of gene expression by recruiting chromatin-modifying proteins to specific genomic loci. Two databases, previously developed by our groups, HiMoRNA and RNA-Chrom, provide valuable insights into this process. The former contains data on epigenetic modification regions (peaks) correlated with lncRNA expression, while the latter offers genome-wide RNA–chromatin interaction data for tens of thousands of RNAs. This study integrated the two resources to generate experimentally supported, interpretable hypotheses regarding lncRNA-mediated epigenetic gene expression regulation. We adapted the web interfaces of HiMoRNA and RNA-Chrom to enable the retrieval of chromatin contacts for each “lncRNA–epigenetic modification–associated gene” triad from HiMoRNA, either at specific genomic loci or genome-wide via RNA-Chrom. The integration analysis revealed that for the lncRNAs MALAT1, HOXC-AS2, NEAT1, NR2F1-AS1, PVT1, and MEG3, most HiMoRNA peaks are located within 25 kb of their RNA-Chrom contacts. Further investigation confirmed the RNA–chromatin contacts of MIR31HG and PVT1 lncRNAs, with HiMoRNA peaks for H3K27ac and H3K27me3 marks in the loci of the genes GLI2 and LATS2, respectively, which are known to be regulated by these RNAs. Thus, the integration of HiMoRNA and RNA-Chrom offers a powerful platform to elucidate the role of specific lncRNAs in the regulation of histone modifications at both individual loci and genome-wide levels. We expect this integration to help significantly advance the functional annotation of human lncRNAs.



Monomeric α-Synuclein Real-Time Induced Conversion: A New Approach to the Diagnostics of Neurodegenerative Synucleinopathies with Weak RT-QuIC Responses
Abstract
Neurodegenerative disorders classified as synucleinopathies (Parkinson’s disease, dementia with Lewy bodies, and multiple-system atrophy) are characterized by the accumulation of aberrant α-synuclein aggregates in neurons and glial cells. These diseases manifest clinically several years after the initial formation of pathological protein aggregates in the brain, making early and accurate diagnosis challenging. In recent years, a new method, which is based on real-time quaking-induced conversion (RT-QuIC) of α-synuclein, has been developed and validated. This technology holds great promise as a powerful diagnostic tool for the early and precise identification of synucleinopathies, potentially opening new horizons in the study of neurodegenerative diseases. RT-QuIC detects misfolded α-synuclein aggregates in human physiological fluids by introducing an excess of recombinant α-synuclein, which undergoes conformational conversion in an exponential, prion-like manner. The production of high-quality recombinant α-synuclein is a critical step in the effective application of this method, as protein purity significantly affects the sensitivity and specificity of the assay — key factors in its diagnostic utility. Using a three-step chromatographic purification protocol, we produced recombinant monomeric α-synuclein with a purity exceeding 97% from the periplasmic fraction of bacterial cells. While higher purity increases the assay duration, it also reduces the background signal and permits extended incubation times, which are essential for reliably detecting synucleinopathies with weak RT-QuIC responses, such as the cerebellar subtype of multiple-system atrophy. The data presented support the conclusion that optimized components of the RT-QuIC system will enable an accurate diagnosis of neurodegenerative synucleinopathies.



Two Key Substitutions in the Chromophore Environment of mKate2 Produce an Enhanced FusionRed-like Red Fluorescent Protein
Abstract
Red fluorescent proteins (RFPs) are often probes of choice for living tissue microscopy and whole-body imaging. When choosing a specific RFP variant, the priority may be given to the fluorescence brightness, maturation rate, monomericity, excitation/emission wavelengths, and low toxicity, which are rarely combined in an optimal way in a single protein. If additional requirements such as prolonged fluorescence lifetime and/or blinking ability are applied, the available repertoire of probes could dramatically narrow. Since the entire diversity of conventional single-component RFPs belongs to just a few phylogenetic lines (DsRed-, eqFP578- and eqFP611-derived being the major ones), it is not unexpected that their advantageous properties are split between close homologs. In such cases, a systematic mutagenetic analysis focusing on variant-specific amino acid residues can shed light on the origins of the distinctness between related RFPs and may aid in consolidating their strengths in new RFP variants. For instance, the protein FusionRed, despite being efficient in fluorescence labeling thanks to its good monomericity and low cytotoxicity, has undergone considerable loss in fluorescence brightness/lifetime compared to the parental mKate2. In this contribution, we describe a fast-maturing monomeric RFP designed semi-rationally based on the mKate2 and FusionRed templates that outperforms both its parents in terms of molecular brightness, has extended fluorescence lifetime, and displays a spontaneous blinking pattern that is promising for nanoscopy use.


