{"title":"Prp16 enables efficient splicing of introns with diverse exonic consensus elements in the short-intron rich <i>Cryptococcus neoformans</i> transcriptome.","authors":"Manendra Singh Negi, Vishnu Priya Krishnan, Niharika Saraf, Usha Vijayraghavan","doi":"10.1080/15476286.2025.2477844","DOIUrl":"10.1080/15476286.2025.2477844","url":null,"abstract":"<p><p>DEAH box splicing helicase Prp16 in budding yeast governs spliceosomal remodelling from the branching conformation (C complex) to the exon ligation conformation (C* complex). In this study, we examined the genome-wide functions of Prp16 in the short intron-rich genome of the basidiomycete yeast <i>Cryptococcus neoformans</i>. The presence of multiple introns per transcript with intronic features that are more similar to those of higher eukaryotes makes it a promising model for studying spliceosomal splicing. Using a promoter-shutdown conditional Prp16 knockdown strain, we uncovered genome-wide but substrate-specific roles in <i>C. neoformans</i> splicing. The splicing functions of Prp16 are dependent on helicase motifs I and II, which are conserved motifs for helicase activity. A small subset of introns spliced independent of Prp16 activity was investigated to discover that exonic sequences at the 5' splice site (5'SS) and 3' splice site (3'SS) with stronger affinity for U5 loop 1 are a common feature in these introns. Furthermore, short (60-100nts) and ultrashort introns (<60nts) prevalent in the <i>C. neoformans</i> transcriptome were more sensitive to Prp16 knockdown than longer introns, indicating that Prp16 is required for the efficient splicing of short and ultrashort introns. We propose that stronger U5 snRNA-pre-mRNA interactions enable efficient transition of the spliceosome from the first to the second catalytic confirmation in Prp16 knockdown, particularly for short introns and introns with suboptimal features. This study provides insights into fine-tuning spliceosomal helicase function with variations in <i>cis-</i>element features.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-14"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Redox ReportPub Date : 2025-12-01Epub Date: 2025-03-03DOI: 10.1080/13510002.2025.2471738
Paola Mayara Valente Coronel, Denise Caroline Luiz Soares Basilio, Isabelly Teixeira Espinoça, Kamylla Fernanda Souza de Souza, Nathalia Miranda Campos, Rafael Seiji Nakano Ota, Edgar Julian Paredes-Gamero, Danilo Wilhelm Filho, Ana Rita Coimbra Motta-Castro, Renata Trentin Perdomo, Eduardo Benedetti Parisotto
{"title":"Involvement of oxidative stress in post-acute sequelae of COVID-19: clinical implications.","authors":"Paola Mayara Valente Coronel, Denise Caroline Luiz Soares Basilio, Isabelly Teixeira Espinoça, Kamylla Fernanda Souza de Souza, Nathalia Miranda Campos, Rafael Seiji Nakano Ota, Edgar Julian Paredes-Gamero, Danilo Wilhelm Filho, Ana Rita Coimbra Motta-Castro, Renata Trentin Perdomo, Eduardo Benedetti Parisotto","doi":"10.1080/13510002.2025.2471738","DOIUrl":"10.1080/13510002.2025.2471738","url":null,"abstract":"<p><p>Oxidative stress (OS) plays a key role in the pathophysiology of COVID-19 and may be associated with sequelae after severe SARS-CoV-2 infection. This study evaluated OS and inflammation biomarkers in blood from individuals with post-acute sequelae of COVID-19 (PASC). 64 male and female participants were distributed into three groups: healthy individuals (<i>n</i> = 20), acute COVID-19 patients (symptoms for <3 weeks, <i>n</i> = 15), and PASC patients (symptoms for >12 weeks, <i>n</i> = 29). Analyses included inflammatory cytokines, myeloperoxidase (MPO) activity, and OS markers, such as superoxide dismutase (SOD), catalase (CAT), glutathione <i>S</i>-transferase (GST), gamma-glutamyl transferase (GGT), reduced glutathione (GSH), uric acid (UA), thiobarbituric acid reactive substances (TBARS), and protein carbonyls (PC). Individuals with PASC showed increased IL-6 and IL-8. Both COVID-19 groups exhibited decreased SOD and CAT. GST decreased only in the acute group. Elevated GGT and GSH were found in the PASC group. High UA levels were observed in PASC individuals. There were no changes in TBARS values in the PASC group. However, PC concentrations were elevated only in this group. Correlations were identified between inflammatory markers and OS parameters. These findings suggest that individuals with PASC pronounced OS, which potentially exacerbates disease complications. Monitoring OS biomarkers could aid in patient prognosis and management.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2471738"},"PeriodicalIF":5.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Guanosine enhances the bactericidal effect of ceftiofur sodium on <i>Streptococcus suis</i> by activating bacterial metabolism.","authors":"Yue Dong, Xiaona Liu, Shanshan Xiong, Mingyu Cao, Haojie Wu, Long Chen, Mengmeng Zhao, Yadan Zheng, Zhiyun Zhang, Yanyan Liu, Yanhua Li, Qianwei Qu, Chunliu Dong","doi":"10.1080/21505594.2025.2453525","DOIUrl":"10.1080/21505594.2025.2453525","url":null,"abstract":"<p><p>The emergence and rapid development of antibiotic resistance poses a serious threat to global public health. <i>Streptococcus suis</i> (<i>S. suis</i>) is an important zoonotic pathogen, and the development of its antibiotic resistance has made the infections difficult to treat. The combination of non-antibiotic compounds with antibiotics is considered a promising strategy against multidrug-resistant bacteria. However, the mechanism by which metabolites act as antibiotic adjuvant remains unclear. Here, we found that guanosine metabolism was repressed in multidrug-resistant <i>S. suis</i>. Exogenous guanosine promoted the antibacterial effects of ceftiofur sodium (CEF) <i>in vitro</i> and <i>in vivo</i>. Furthermore, we demonstrated that exogenous guanosine promoted the biosynthesis of purine pathway, TCA cycle and bacterial respiration, which make bacteria more sensitive to the killing effect of antibacterial. In addition, the function of the cell membrane is affected by guanosine and the accumulation of antimicrobials in the bacteria increased. Bacterial-oxidative stress and DNA damage induced by guanosine is also one of the mechanisms by which the antibacterial effect is enhanced. These results suggest that guanosine is a promising adjuvant for antibacterial drugs and provide new theoretical basis for the clinical treatment of <i>S. suis</i> infection.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2453525"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
RNA BiologyPub Date : 2025-12-01Epub Date: 2025-05-30DOI: 10.1080/15476286.2025.2512610
Jiyoon Chung, Yerim Lee, Jimin Yoon, Yoosik Kim
{"title":"Deciphering the multifaceted role of double-stranded RNA sensor protein kinase R: pathophysiological function beyond the antiviral response.","authors":"Jiyoon Chung, Yerim Lee, Jimin Yoon, Yoosik Kim","doi":"10.1080/15476286.2025.2512610","DOIUrl":"10.1080/15476286.2025.2512610","url":null,"abstract":"<p><p>Protein kinase R (PKR) is a serine/threonine kinase that recognizes double-stranded RNAs (dsRNAs) to initiate innate immune signalling during viral infection. PKR dimerizes on long dsRNAs and undergoes autophosphorylation. Phosphorylated/Activated PKR then catalyses the phosphorylation of numerous substrates to control global translation, inflammatory response, and cell signalling pathways. While primarily known for its antiviral role, emerging evidence suggests that PKR can play multifaceted roles in uninfected cells by interacting with cellular dsRNAs and protein regulators. The misactivation of PKR in uninfected cells is associated with many degenerative and inflammatory diseases. Even in healthy cells, PKR can affect gene expression by controlling mRNA splicing and gene-specific translation under stress. In addition, PKR can modulate cell cycle progression and promote cellular differentiation in several tissue types. This review explores PKR function in various pathological and physiological contexts in the absence of viral stimuli. By elucidating these diverse functions, we aim to highlight the perspectives in cellular dsRNA research and the therapeutic implications of targeting PKR, stimulating further research into this versatile and essential RNA-dependent kinase.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"22 1","pages":"1-14"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mathematical modelling and optimal control of malaria transmission with antimalarial drug and insecticide resistance.","authors":"Gasper G Mwanga","doi":"10.1080/17513758.2025.2522345","DOIUrl":"https://doi.org/10.1080/17513758.2025.2522345","url":null,"abstract":"<p><p>This study presents a mathematical model to explore malaria transmission dynamics in the presence of antimalarial drug-resistant parasites and insecticide-resistant mosquitoes. The analytical findings demonstrate a stable disease-free equilibrium when the effective reproduction number is below one. For single-strain malaria infections, the endemic equilibrium may exhibit one, two or no solutions. The model is extended to incorporate three time-dependent controls: long-lasting insecticidal nets, antimalarial treatment and mosquito adulticides. Simulation results indicate that interventions excluding drug-resistant parasites and insecticide-resistant mosquitoes are ineffective. The most effective strategies combine insecticides targeting all vectors with treatments for all malaria cases, regardless of resistance. Efficiency analysis suggests implementing all three controls at <math><mo>≥</mo><mn>80</mn><mi>%</mi></math> efficacy for the maximum impact, while assessments of cost-effectiveness highlight the combination of long-lasting insecticidal nets and antimalarial treatment as a practical option in resource-constrained settings. Nonetheless, integrating all three measures is recommended for substantial malaria transmission reduction.</p>","PeriodicalId":48809,"journal":{"name":"Journal of Biological Dynamics","volume":"19 1","pages":"2522345"},"PeriodicalIF":1.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144486737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Modelling and analysis of an epidemic model with awareness caused by deaths due to fear.","authors":"Ling Xue, Junqi Huo, Yuxin Zhang","doi":"10.1080/17513758.2025.2458890","DOIUrl":"10.1080/17513758.2025.2458890","url":null,"abstract":"<p><p>In this paper, we establish a compartmental model in which the transmission rate is associated with the fear of being infected by COVID-19. We provide a detailed analysis of the epidemic model and established results for the existence of a positively invariant set. The expression of the basic reproduction number <math><msub><mi>R</mi><mn>0</mn></msub></math> is characterized. It is shown that the disease-free equilibrium (DFE) is globally asymptotically stable if <math><msub><mi>R</mi><mn>0</mn></msub><mo><</mo><mn>1</mn></math>, and the system exhibits a forward bifurcation if <math><msub><mi>R</mi><mn>0</mn></msub><mo>=</mo><mn>1</mn></math>. When <math><msub><mi>R</mi><mn>0</mn></msub><mo>></mo><mn>1</mn></math>, the system is uniformly persistent, the DFE is unstable and there exists a unique and globally asymptotic stable endemic equilibrium (EE). We fit unknown parameters using the reported data in Canada from September 1 to October 10, 2021, and carry out sensitivity analysis. The quantitative analysis of the model with awareness demonstrates the significance of reducing the transmission rate and enhancing public protective awareness.</p>","PeriodicalId":48809,"journal":{"name":"Journal of Biological Dynamics","volume":"19 1","pages":"2458890"},"PeriodicalIF":1.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Zhang, Feng Lai, Shujing Gao, Yang Liu, Shuixian Yan
{"title":"Dynamical analysis of a stochastic prey-predator model with fear effect and feedback control.","authors":"Yan Zhang, Feng Lai, Shujing Gao, Yang Liu, Shuixian Yan","doi":"10.1080/17513758.2025.2479461","DOIUrl":"10.1080/17513758.2025.2479461","url":null,"abstract":"<p><p>In this work, the intricacies and complexities of dynamical properties are extensively studied for the proposed deterministic and stochastic prey-predator models. The influence of fear effects, prey refuge and feedback control are considered and thorough theoretical research is conducted on the systems. It commences by establishing the global stability and uniqueness of the positive equilibrium of the deterministic model. Then for the stochastic system, the existence, uniqueness and boundedness of a global positive solution are analysed by constructing appropriate Lyapunov functions. Sufficient conditions are established for the extinction and persistence of the stochastic model. It can be observed that both the fear effect and prey refuge have a greatly impact on the dynamics of system. Intermediate values of feedback control intensity may be the most beneficial to species coexistence. It provides new insights into the sustainability of ecosystems.</p>","PeriodicalId":48809,"journal":{"name":"Journal of Biological Dynamics","volume":"19 1","pages":"2479461"},"PeriodicalIF":1.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
RNA BiologyPub Date : 2025-12-01Epub Date: 2025-06-03DOI: 10.1080/15476286.2025.2511318
Tomer Friehmann, Yamama Abu Mohsen, Yehuda Schlesinger, Lucy Ghantous, Lika Gamaev, Chavah Landau Zenilman, Avi Harazi, Eithan Galun, Daniel S Goldenberg
{"title":"The oncogenic microRNA miR-222 promotes human LINE-1 retrotransposition.","authors":"Tomer Friehmann, Yamama Abu Mohsen, Yehuda Schlesinger, Lucy Ghantous, Lika Gamaev, Chavah Landau Zenilman, Avi Harazi, Eithan Galun, Daniel S Goldenberg","doi":"10.1080/15476286.2025.2511318","DOIUrl":"10.1080/15476286.2025.2511318","url":null,"abstract":"<p><p>The Long Interspersed Element-1 (LINE-1) contributes significantly to carcinogenesis and to tumour heterogeneity in many cancer types, including hepatocellular carcinoma (HCC), by its autonomous retrotransposition (RTP) and by its ability to retrotranspose some non-autonomous transposable elements. Previously, multiple proteins and a few microRNAs (miRs) were described as regulators of LINE-1 RTP. Here, we demonstrate that miR-222, which is oncogenic in HCC, promotes LINE-1 RTP in human HCC and some other cell lines <i>in vitro</i>, and that both miR-222-3p and miR-222-5p activate LINE-1 RTP in a cell-type specific manner. We generated miR-222-knockout mutants of the Huh7 and FLC4 hCC cell lines, and performed RNA-seq analysis of Huh7/miR-222-knockout cells and global proteomics analysis of both Huh7 and FLC4 miR-222-knockout mutants. We demonstrate that miR-222 decreases let-7c expression in both Huh7 and FLC4 cells, and that this decrease contributes to promotion of LINE-1 RTP by miR-222 in Huh7 cells.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-15"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell Adhesion & MigrationPub Date : 2025-12-01Epub Date: 2025-06-03DOI: 10.1080/19336918.2025.2514374
Uri Han, Nara Han, Taeck Joong Jeon
{"title":"Nhe1 is required for directional sensing in vegetative <i>Dictyostelium</i> cell migration.","authors":"Uri Han, Nara Han, Taeck Joong Jeon","doi":"10.1080/19336918.2025.2514374","DOIUrl":"10.1080/19336918.2025.2514374","url":null,"abstract":"<p><p>Na+/H+ exchanger 1 (Nhe1) is a crucial regulator of pH homeostasis and the present study demonstrates that Nhe1 is required for directional sensing in vegetative <i>Dictyostelium</i> cell migration. <i>nhe1</i> null cells exhibited severe defects in directional sensing and migration in response to folate gradients and applied electric fields.Specifically, <i>nhe1</i> null cells failed to exhibit proper translocation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) to the cell cortex and showed abnormal intracellular calcium signaling upon folate stimulation. Additionally, cells lacking Nhe1 exhibited a reduced capacity to engulf bacteria and latex beads. In contrast, <i>nhe1</i> null cells in the developed stage displayed a defect in cAMP-directed chemotaxis, but normal translocation kinetics of PIP3 to the cell cortex upon cAMP stimulation.</p>","PeriodicalId":9680,"journal":{"name":"Cell Adhesion & Migration","volume":"19 1","pages":"2514374"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}