Molecular Biology最新文献

{"title":"Sensitivity of Primary Human Glioblastoma Cell Lines to the Mumps Virus Vaccine Strain","authors":"E. Yu. Nikolaeva, Y. R. Zhelayeva, O. Yu. Susova, A. A. Mitrofanov, V. O. Varachev, T. V. Nasedkina, V. V. Zverev, O. A. Svitich, Y. I. Ammour","doi":"10.1134/s0026893324700262","DOIUrl":"https://doi.org/10.1134/s0026893324700262","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>The sensitivity of human glioblastoma cells to virus-mediated oncolysis was investigated on five patient-derived cell lines. Primary glioblastoma cells (Gbl13n, Gbl16n, Gbl17n, Gbl25n, and Gbl27n) were infected with tenfold serial dilutions of the Leningrad-3 strain of the mumps virus, and virus reproduction and cytotoxicity were monitored for 96 −120 h. Immortalized human non-tumor NKE cells were used as controls to determine the virus specificity. Four out of the five glioblastoma cell lines examined were susceptible to mumps virus infection, whereas no virus reproduction was observed in the non-tumor cell line. Moreover, the level of proapoptotic caspase-3 activity was increased in all infected cells 48 h after infection. The kinetics of viral RNA accumulation in the studied glioblastoma cell lines was comparable with the rate of cell death. The data suggest that glioblastoma cell lines were permissive for the mumps virus. Glioblastoma cell lines differed in type I IFN production in response to the mumps virus infection. In addition, it was shown that MV infection was able to induce immunogenic death of glioblastoma cells.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"11 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141941267","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":"Small Non-Coding sRNA53 Modulates the Quorum Sensing System to Enhance Drug Resistance in Escherichia coli Exposed to Heavy Ion and X-ray Irradiation","authors":"S. J. Zhao, X. Y. Pang, Q. W. Zhao, X. Li","doi":"10.1134/s0026893324700420","DOIUrl":"https://doi.org/10.1134/s0026893324700420","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Small non-coding RNAs (sRNAs, also called sncRNAs) known as gene expression regulatory factors are capable of modulating mRNA functions through complementary base pairing. A number of studies has shown that when exposed to radiation, the expression of drug resistance genes increases in some cells. Here, in <i>Escherichia coli</i> subjected to ¹²C⁶⁺ heavy ion beams or X-ray exposure, five sRNAs (sRNA120, sRNA127, sRNA109, sRNA72, sRNA53) with elevated expression were identified by deep sequencing and sRNAscanner prediction. To investigate whether they have a potential role in drug resistance, we engineered strains overexpressing these sRNAs, and assessed their survival rate under sub-lethal antibiotic concentrations. It was noteworthy that under Gentamicin, Norfloxacin, Chloramphenicol and Cfotaxime, the survival rate of ::sRNA53 strain was 1.0667, 1.0251, 1.3797 and 3.9327 times higher, respectively, than for the control and strains overexpressing other sncRNAs. TargetRNA2 software identified <i>lsrA</i> as a likely target gene regulated by sRNA53 based on binding free energy calculations. We analyzed the interaction sites between sRNA53 and <i>lsrA</i> and measured the expression of these molecules in various mutants using RT-qPCR. We also investigated the regulation of Luxs/AI-2 system by the lsr operon and the biofilm formation of mutants. In the ::sRNA53 strain, the log₂FC for sRNA53 and <i>lsrA</i> concurrently escalated by 1.8533 and 1.7367-fold. Additionally, the biofilm formation ability of ::sRNA53, ::<i>lsrA</i>, and ::sRNA53::<i>lsrA</i> (co-expression) strains was increased 5.4542, 3.946, and 7.1758-fold, respectively, compared to wild-type MG1655. Based on these data, we can conclude that sRNA53 plays a critical role in the development of antibiotic resistance in <i>E. coli</i>. Apparently, the action of sRNA53 targets the <i>lsrA</i> gene, which, by modulating the Luxs/AI-2 system, affects the ability to biofilm formation and drug resistance of the bacterium. The study shows that a new sRNA, named sRNA53, is involved in the formation of tolerance to sub-lethal doses of various antibiotics.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"21 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141566972","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":"Zebrafish Xenographs in Oncology and Personalized Medicine","authors":"N. A. Lunina, D. R. Safina, S. V. Kostrov","doi":"10.1134/s0026893324700031","DOIUrl":"https://doi.org/10.1134/s0026893324700031","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>The bony fish <i>Danio rerio</i> (zebrafish) has become one of the important vertebrate model organisms in biomedical cancer research and is used, among other things, for the development of anticancer drugs using xenotransplantation approaches. The <i>ex utero</i> development of zebrafish, optically transparent tissues in the first month of growth, and the immature adaptive immune system during this period greatly facilitate the manipulation of embryos. For highly aggressive cancers where patient survival may be expected to be only a few months, a zebrafish xenograft assay may be the only appropriate method as it requires only four to seven days. Thousands of embryos can be implanted with biopsy tissue from a patient to produce zebrafish xenografts and to use them to screen a large number of drugs and compounds automatically to develop an effective treatment regimen for a specific patient. This review examines the advantages and disadvantages of the zebrafish model in oncology research. The main focus is on the use of zebrafish xenografts to study metastasis and to create avatars in personalized medicine.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"23 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141254417","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":"Study of the Gut Transcriptomic Response in Drosophila melanogaster with Knockdown of Gagr, Domesticated gag Gene of Errantiviruses","authors":"M. L. Nikitina, P. A. Milyaeva, I. V. Kuzmin, L. N. Nefedova","doi":"10.1134/s0026893324700080","DOIUrl":"https://doi.org/10.1134/s0026893324700080","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>As a result of molecular domestication of the <i>gag</i> gene of errantiviruses, the <i>Gagr</i> gene was formed in the genome of <i>Drosophila melanogaster</i>. It has previously been shown that the <i>Gagr</i> gene is transcribed at the highest level in gut tissues relative to other tissues, and its transcription is most effectively induced in females in response to ammonium persulfate added to the nutrient medium. In the present work, the gut transcriptome of females with knockdown of the <i>Gagr</i> gene was studied in all tissues under standard conditions and under stress conditions caused by ammonium persulfate. It was revealed that in females with knockdown of the <i>Gagr</i> gene, the genes of antimicrobial peptides controlled by the Toll and Imd signaling pathways are activated in the gut. Induction of a stress response by ammonium persulfate revealed disruption of the JAK/STAT and JNK/MAPK signaling pathways and an almost complete absence of activation of the ER-stress and UPR-stress pathways in flies with the <i>Gagr</i> gene knockdown. The data obtained confirm the important role of the <i>Gagr</i> gene in maintaining homeostasis and the immune response.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"101 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141254680","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":"Drosophila melanogaster Paip2 Binds ENY2 and Interacts with the TREX-2 Complex in Histone mRNP Particles","authors":"M. M. Kurshakova, A. N. Krasnov, E. N. Nabirochkina, S. G. Georgieva","doi":"10.1134/s0026893324700146","DOIUrl":"https://doi.org/10.1134/s0026893324700146","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>ENY2 is an evolutionarily conserved multifunctional protein and is a member of several complexes that regulate various stages of gene expression. ENY2 is a subunit of the TREX-2 complex, which is necessary for the export of bulk mRNA from the nucleus to the cytoplasm through the nuclear pores in many eukaryotes. The wide range of ENY2 functions suggests that it can also associate with other protein factors or complexes. In a search for proteins that interact with ENY2 of <i>Drosophila melanogaster</i>, a cDNA library was screened in a yeast two-hybrid system. ENY2 was thus found to interact with the RNA-binding protein Paip2. Paip2 directly bound ENY2 in vitro and interacted with ENY2 in vivo at the molecular and genetic levels. Paip2 was capable of association with the ENY2-containing TREX-2 complex. Paip2 was present at the locus of the histone gene cluster. Both Paip2 and ENY2 were detected at histone locus body (HLBs), nuclear structure where coordinated histone mRNA transcription and processing take place. Paip2 and subunits of the TREX-2 complex were shown to associate with histone mRNP particles. A Paip2 knockdown via RNA interference resulted in decreased binding of TREX-2 subunits to histone mRNPs. Thus, Paip2 was identified as a new partner protein of ENY2 within the TREX-2 complex and suggested to participate in TREX-2 binding to histone mRNPs.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"70 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141254087","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":"Participation of Proteins of the CPSF Complex in Polyadenylation of Transcripts Read by RNA Polymerase III from SINEs","authors":"I. G. Ustyantsev, O. R. Borodulina, D. A. Kramerov","doi":"10.1134/s0026893324700122","DOIUrl":"https://doi.org/10.1134/s0026893324700122","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>SINEs are mobile genetic elements of multicellular eukaryotes that arose during evolution from various tRNAs, as well as from 5S rRNA and 7SL RNA. Like the genes of these RNAs, SINEs are transcribed by RNA polymerase III. The transcripts of some mammalian SINEs have the capability of AAUAAA-dependent polyadenylation, which is unique for transcript generated by RNA polymerase III. Despite a certain similarity with canonical polyadenylation of mRNAs (transcripts of RNA polymerase II), these processes apparently differ significantly. The purpose of this work is to evaluate how important for polyadenylation of SINE transcripts are proteins of the CPSF complex formed by mPSF and mCF subcomplexes which direct mRNA polyadenylation. In HeLa cells, siRNA knockdowns of the CPSF components were carried out, after which the cells were transfected with plasmid constructs containing SINEs. A decrease in polyadenylation of the SINE transcripts as a result of the knockdown of the proteins was evaluated by Northern-hybridization. It turned out that the CPSF components, such as Wdr33 and CPSF30, contributed to the polyadenylation of SINE transcriptions, while the knockdown of CPSF100, CPSF73, and symplekin did not reduce the polyadenylation of these transcripts. Wdr33 and CPSF30, along with the CPSF160 and Fip1 previously studied, are components of the subcomplex mPSF responsible for mRNA polyadenylation. Thus, the available data suggest the importance of all mPSF proteins for polyadenylation of SINE transcripts. At the same time, CPSF100, CPSF73, and symplekin, forming the subcomplex mCF, are responsible for the cleavage of pre-mRNA; therefore, their non-participation in the polyadenylation of SINE transcriptions seems quite natural.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"34 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141254363","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":"Synthesis of a Bisbenzoxazole Analogue of Hoechst 33258 as a Potential GC-Selective DNA Ligand","authors":"A. F. Arutuynyan, M. S. Aksenova, A. A. Kostyukov, A. A. Stomakhin, D. N. Kaluzhny, A. L. Zhuze","doi":"10.1134/s0026893324700171","DOIUrl":"https://doi.org/10.1134/s0026893324700171","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Using a computer modeling approach, we proposed a structure for a potential GC-specific DNA ligand, which could form a complex with DNA in the minor groove similar to that formed by Hoechst 33258 at DNA AT-enriched sites. According to this model, MBoz₂A, a bisbenzoxazole ligand, was synthesized. The results of spectrophotometric methods supported the complex formation of the compound under study with DNA differing in the nucleotide composition.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"68 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141254014","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":"Recombinant VLP Vaccines Synthesized in Plant Expression Systems: Current Updates and Prospects","authors":"S. M. Rozov, E. V. Deineko","doi":"10.1134/s0026893324700043","DOIUrl":"https://doi.org/10.1134/s0026893324700043","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>The development and creation of a new generation vaccines based on recombinant proteins that assemble into virus-like particles (VLPs), as well as recombinant proteins in the form of nanoparticles, are promising directions in modern biotechnology. Due to their large size (20–200 nm) and multiplicity of viral antigenic determinants on the surface, VLPs can stimulate strong humoral and cellular immune responses. The main types of VLPs, as well as the features and disadvantages of the main expression systems used for their biosynthesis, are considered in this review. The main focus was on plant expression systems that ensure the biosynthesis of a target recombinant protein from a DNA matrix integrated into the nuclear or chloroplast genomes of a plant (stable expression) or from a matrix for temporary production of the target product (transient expression). Various approaches for increasing the yield of VLP-forming recombinant proteins, including fusion with a transit peptide that directed the protein into the chloroplast, were discussed. The possibility of accumulation of recombinant proteins expressed in plants and intended for creation of VLP-vaccines in another type of nanoparticle, protein bodies, using specific signal sequences was also considered.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"52 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141254260","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":"Development of Biological Microchips on an Aluminum Support with Cells Made of Brush Polymers","authors":"I. Yu. Shishkin, G. F. Shtylev, V. E. Barsky, S. A. Lapa, O. A. Zasedateleva, V. E. Kuznetsova, V. E. Shershov, V. A. Vasiliskov, S. A. Polyakov, A. S. Zasedatelev, A. V. Chudinov","doi":"10.1134/s002689332470016x","DOIUrl":"https://doi.org/10.1134/s002689332470016x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>A method has been developed for manufacturing biological microchips on an aluminum substrate with hydrophilic cells from brush copolymers with the formation of a matrix of cells using photolithography. The surface of aluminum substrates was previously coated with a thin, durable, moderately hydrophobic layer of cross-linked polymer to prevent contact with the aluminum surface of the components used in the analysis of nucleic acids. Aluminum biochip substrates have high thermal conductivity and low heat capacity, which is important for the development of methods for multiplex PCR analysis on a chip. Oligonucleotide probes were covalently immobilized in the cells of the biochip. The preservation of the hybridization activity of the immobilized DNA probes was demonstrated in a hybridization analysis with a synthetic DNA target representing a section of the sequence of the seventh exon of the human <i>ABO</i> gene. The methods developed can be used in the development of a technology for parallel multiple rapid microanalysis of nucleic acids “lab on a chip” for the detection of human somatic and infectious diseases.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"106 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141254360","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":"ArdA Protein Specificity against Type I Restriction–Modification Systems","authors":"A. A. Kudryavtseva, A. V. Vlasov, E. V. Zinovev, D. D. Yanovskaya, A. A. Utkina, S. M. Rastorguev, I. V. Manukhov","doi":"10.1134/s0026893324700158","DOIUrl":"https://doi.org/10.1134/s0026893324700158","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>The ArdA DNA-mimic antirestriction proteins inhibit type I restriction−modification (RMI) systems by binding instead of DNA to RMI. The ArdA specificity to DNA methylation sites recognized by RMI complexes remains poorly understood; i.e., it is unclear whether a particular DNA site is mimicked by ArdA. The <i>ardA</i> genes were cloned from three Gram-positive bacteria: <i>Agrobacterium tumefaciens</i>, <i>Pseudomonas monteilii,</i> and <i>Xanthomonas</i> sp<i>.</i> Antirestriction activities of their products were tested against three <i>Escherichia coli</i> RMI systems differing in DNA recognition/methylation sites. Although similar structures were predicted for the ArdA proteins, the strong specificity to three RMI systems was observed. The results indicate that specific DNA sites may be imitated by DNA mimic ArdA proteins.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"15 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141254258","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}