Long non-coding RNAs (lncRNAs) are crucial players in the pathogenesis of non-small-cell lung cancer (NSCLC). A competing binding of lncRNAs and mRNAs with microRNAs (miRNAs) is one of the most ...common mechanisms of gene regulation by lncRNAs in NSCLC, which has been extensively researched in the last two decades. However, alternative mechanisms that do not depend on miRNAs have also been reported. Among them, the most intriguing mechanism is mediated by RNA-binding proteins (RBPs) such as IGF2BP1/2/3, YTHDF1, HuR, and FBL, which increase the stability of target mRNAs. IGF2BP2 and YTHDF1 may also be involved in m6A modification of lncRNAs or target mRNAs. Some lncRNAs, such as DLGAP1-AS2, MALAT1, MNX1-AS1, and SNHG12, are involved in several mechanisms depending on the target: lncRNA/miRNA/mRNA interactome and through RBP. The target protein sets selected here were then analyzed using the DAVID database to identify the pathways overrepresented by KEGG, Wikipathways, and the Reactome pathway. Using the STRING website, we assessed interactions between the target proteins and built networks. Our analysis revealed that the JAK-STAT and Hippo signaling pathways, cytokine pathways, the VEGFA-VEGFR2 pathway, mechanisms of cell cycle regulation, and neovascularization are the most relevant to the effect of lncRNA on NSCLC.
The fundamental novelty in the pathogenesis of renal cell carcinoma (RCC) was discovered as a result of the recent identification of the role of long non-coding RNAs (lncRNAs). Here, we discuss ...several mechanisms for the dysregulation of the expression of protein-coding genes initiated by lncRNAs in the most common and aggressive type of kidney cancer-clear cell RCC (ccRCC). A model of competitive endogenous RNA (ceRNA) is considered, in which lncRNA acts on genes through the lncRNA/miRNA/mRNA axis. For the most studied oncogenic lncRNAs, such as HOTAIR, MALAT1, and TUG1, several regulatory axes were identified in ccRCC, demonstrating a number of sites for various miRNAs. Interestingly, the LINC00973/miR-7109/Siglec-15 axis represents a novel agent that can suppress the immune response in patients with ccRCC, serving as a valuable target in addition to the PD1/PD-L1 pathway. Other mechanisms of action of lncRNAs in ccRCC, involving direct binding with proteins, mRNAs, and genes/DNA, are also considered. Our review briefly highlights methods by which various mechanisms of action of lncRNAs were verified. We pay special attention to protein targets and signaling pathways with which lncRNAs are associated in ccRCC. Thus, these new data on the different mechanisms of lncRNA functioning provide a novel basis for understanding the pathogenesis of ccRCC and the identification of new prognostic markers and targets for therapy.
Clear cell renal cell carcinoma (ccRCC) is the third most common urological cancer, and it has the highest mortality rate. The increasing drug resistance of metastatic ccRCC has resulted in the ...search for new biomarkers. Epigenetic regulatory mechanisms, such as genome-wide DNA methylation and inhibition of protein translation by interaction of microRNA (miRNA) with its target messenger RNA (mRNA), are deeply involved in the pathogenesis of human cancers, including ccRCC, and may be used in its diagnosis and prognosis. Here, we review oncogenic and oncosuppressive miRNAs, their putative target genes, and the crucial pathways they are involved in. The contradictory behavior of a number of miRNAs, such as suppressive and anti-metastatic miRNAs with oncogenic potential (for example, miR-99a, miR-106a, miR-125b, miR-144, miR-203, miR-378), is examined. miRNAs that contribute mostly to important pathways and processes in ccRCC, for instance, PI3K/AKT/mTOR, Wnt-β, histone modification, and chromatin remodeling, are discussed in detail. We also separately consider their participation in crucial oncogenic processes, such as hypoxia and angiogenesis, metastasis, and epithelial-mesenchymal transition (EMT). The review also considers the interactions of long non-coding RNAs (lncRNAs) and miRNAs of significance in ccRCC. Recent advances in the understanding of the role of hypermethylated miRNA genes in ccRCC and their usefulness as biomarkers are reviewed based on our own data and those available in the literature. Finally, new data and perspectives concerning the clinical applications of miRNAs in the diagnosis, prognosis, and treatment of ccRCC are discussed.
Diatoms synthesize species-specific exoskeletons inside cells under the control of the cytoskeleton and microtubule center. Previous studies have been conducted with the visualization of the ...microtubule center; however, its composition has not been studied and reliably established. In the present study, several components of MTOC in diatoms, GCP (gamma complex proteins), Aurora A, and centrins have been identified. Analysis of the predicted amino acid sequences of these proteins revealed structural features typical for diatoms. We analyzed the conserved amino acids and the motives necessary for the functioning of proteins. Phylogenetic analysis of GCP showed that all major groups of diatoms are distributed over phylogenetic trees according to their systematic position. This work is a theoretical study; however, it allows drawing some conclusions about the functioning of the studied components and possible ways to regulate them.
Silicon transporters (SIT) are the proteins, which capture silicic acid in the aquatic environment and direct it across the plasmalemma to the cytoplasm of diatoms. Diatoms utilize silicic acid to ...build species-specific ornamented exoskeletons and make a significant contribution to the global silica cycle, estimated at 240 ±40 Tmol a year. Recently SaSIT genes of the freshwater araphid pennate diatom Synedra acus subsp. radians are found to be present in the genome as a cluster of two structural genes (SaSIT-TD and SaSIT-TRI) encoding several concatenated copies of a SIT protein each. These structural genes could potentially be transformed into "mature" SIT proteins by means of posttranslational proteolytic cleavage. In the present study, we discovered three similar structural SuSIT genes in the genome of a closely related freshwater diatom Synedra ulna subsp. danica. Structural gene SuSIT1 is identical to structural gene SuSIT2, and the two are connected by a non-coding nucleotide DNA sequence. All the putative "mature" SITs contain conserved amino acid motifs, which are believed to be important in silicon transport. The data obtained suggest that the predicted "mature" SIT proteins may be the minimal units necessary for the transport of silicon is S. ulna subsp. danica. The comparative analysis of all available multi-SITs has allowed us to detect two conservative motifs YQXDXVYL and DXDID, located between the "mature" proteins. Aspartic acid-rich DXDID motif can, in our opinion, serve as a proteolysis site during the multi-SIT cleavage. The narrow distribution of the distances between CMLD and DXDID motifs can serve as additional evidence to the conservation of their function.
Abstract The article presents a study of the mesonephros ultrastructure of Baikal omul Coregonus migratorius , Baikal whitefish Coregonus baicalensis , and a cross between Baikal whitefish and ...humpback whitefish ( C. baicalensis × Coregonus pidschian ). The mesonephros ultrastructure was studied using electron microscopy methods. The results of the study show that the number of mature granulocytes is a systematic feature and does not depend on the ecology of fish. The quantitative characteristics of blood cells and the ultrastructural features of leukocytes in the mesonephros are associated with the functioning of the nonspecific defence system in fish. Morphological diversity of epithelial cells in nephron tubules is the ancestral characteristic of the modern omul population, associated with geological and climatic events in the history of Lake Baikal. The development of haematopoietic tissue in the mesonephros, the ultrafine structure of ion‐transporting interstitial cells, as well as some ultrastructural features found in the nephron, reflect the adaptive capabilities of the species to live in the ultra‐deep Lake Baikal.
The rapid emergence of evasive SARS-CoV-2 variants is an ongoing challenge for COVID-19 vaccinology. Traditional virus neutralization tests provide detailed datasets of neutralization titers against ...the viral variants. Such datasets are difficult to interpret and do not immediately inform of the sufficiency of the breadth of the antibody response. Some of these issues could be tackled using the antigenic cartography approach. In this study, we created antigenic maps using neutralization titers of sera from donors who received the Sputnik V booster vaccine after primary Sputnik V vaccination and compared them with the antigenic maps based on serum neutralization titers of Comirnaty-boosted donors. A traditional analysis of neutralization titers against the WT (wild-type), Alpha, Beta, Delta, Omicron BA.1, and BA.4/BA.5 variants showed a significant booster humoral response after both homologous (Sputnik V) and heterologous (Comirnaty) revaccinations against all of the studied viral variants. However, despite this, a more in-depth analysis using antigenic cartography revealed that Omicron variants remain antigenically distant from the WT, which is indicative of the formation of insufficient levels of cross-neutralizing antibodies. The implications of these findings may be significant when developing a new vaccine regimen.
A theoretical study of the time-of-flight (TOF) distributions under pulsed laser ablation has been performed. 2D simulations of pulsed evaporation of atoms into vacuum on the base of the direct ...simulation Monte Carlo (DSMC) method have been carried out. It is found that for large evaporating spots (when the spot radius exceeds the initial plume length by a factor of five) the TOF distributions practically do not change with the spot radius variation. Moreover, it is shown that such distributions can be obtained from 1D calculations. Thus, in the frames of 1D approach, the TOF distribution is a function only of the number of the evaporated monolayers, but not of the spot radius. The shape of the TOF distribution is shown to strongly depend on the amount of the evaporated matter. Based on the calculated TOF distributions, dependence of the particle kinetic energy on the number of the evaporated monolayers has been obtained. To verify the theoretical results, experimental data on laser ablation of niobium and mercury have been used, which confirm the obtained dependences. The obtained results allow estimating the irradiated surface temperature from the TOF distributions for monatomic neutral gas.
Antigenic Cartography of SARS-CoV-2 Astakhova, Ekaterina A.; Morozov, Alexey A.; Vavilova, Julia D. ...
Biochemistry (Moscow),
05/2024, Letnik:
89, Številka:
5
Journal Article
Recenzirano
Antigenic cartography is a tool for interpreting and visualizing antigenic differences between virus variants based on virus neutralization data. This approach has been successfully used in the ...selection of influenza vaccine seed strains. With the emergence of SARS-CoV-2 variants escaping vaccine-induced antibody response, adjusting COVID-19 vaccines has become essential. This review provides information on the antigenic differences between SARS-CoV-2 variants revealed by antigenic cartography and explores a potential of antigenic cartography-based methods (e.g., building antibody landscapes and neutralization breadth gain plots) for the quantitative assessment of the breadth of the antibody response. Understanding the antigenic differences of SARS-CoV-2 and the possibilities of the formed humoral immunity aids in the prompt modification of preventative vaccines against COVID-19.
The main problems of remote sensing of the Earth’s surface within the frequency range 1.2–1.6 GHz are discussed. They are related to the resonant quantum properties of the radio wave propagation ...medium in the lower ionosphere. It is shown that, for the passive remote sensing, the main source is incoherent microwave radiation of the D and E ionospheric layers in the decimeter range. For the first time, a theoretically grounded principally new scheme of measurements is suggested. The scheme assumes that the radiation source exists below the satellite orbit and accounts for the fact that two types of radiation (direct and reflected) reach the satellite sensor. The separation of the respective fluxes is a serious problem that should be solved for the correct interpretation of the measurements. The question is raised regarding the correct calibration of measuring equipment, depending on the current state of the ionosphere.
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