BMC Biology最新文献

{"title":"Associations between immunosenescence and domain-specific cognition in the Health and Retirement Study Harmonized Cognitive Assessment Protocol.","authors":"Grace A Noppert, Rebecca C Stebbins, Kelvin Pengyuan Zhang, Lindsay Kobayashi, Kenneth M Langa, Bonnie Levin, Chihua Li, Allison E Aiello","doi":"10.1186/s12915-026-02679-4","DOIUrl":"10.1186/s12915-026-02679-4","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease and related dementias (ADRD) pose a critical challenge for the aging U.S. population, yet many biological pathways remain unclear. Recent work has focused on whether peripheral immunosenescence contributes to cognitive aging. Using the Health and Retirement Study (HRS), we examined associations between peripheral immunosenescence and domain-specific cognitive function.</p><p><strong>Results: </strong>Immune function was associated with general and domain-specific cognition, with variation by sex and immune marker. The CD4 + EMRA:Naïve T Cell Ratio, CD4 + Naïve:CD8 + EMRA Ratio, and CMV IgG showed the most consistent associations, particularly with general and executive function. A one-SD increase in CMV IgG was associated with 0.06 SD lower executive function (95% CI: -0.07, -0.05), persisting after adjustment for confounders.</p><p><strong>Conclusions: </strong>Associations with peripheral immune markers suggest a potential role for peripheral immunosenescence in cognitive aging. The immune system may be an early contributor to cognitive vulnerability, underscoring the need to integrate immune aging into ADRD research.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An endogenous viral element of Aedes albopictus is translated and limits cognate virus.","authors":"Laila Gasmi, Claudia Alfaro, Claudio Casali, Marco Biggiogera, Mariangela Bonizzoni","doi":"10.1186/s12915-026-02668-7","DOIUrl":"10.1186/s12915-026-02668-7","url":null,"abstract":"<p><strong>Background: </strong>The genomes of Aedes spp. mosquitoes host hundreds of non-retroviral endogenous viral elements (nrEVEs). The majority of nrEVEs are confined in piRNA clusters and produce P-element-induced wimpy testis-interacting RNAs (piRNAs), which were shown to be antiviral. Whether this is a universal mechanism or some nrEVEs have been exapted for antiviral functions as transcribed RNA or translated proteins remains unknown.</p><p><strong>Results: </strong>We identified 20 nrEVEs located outside piRNA clusters and encompassing complete viral open reading frame in the genome of the Asian tiger mosquito Aedes albopictus. By integrating in vivo and in vitro experimental approaches using Aag2 cells, we provide evidence suggesting that one nrEVE, designated Flavi24, is translated in adult mosquitoes and contributes to controlling cognate viral infection.</p><p><strong>Conclusion: </strong>Our results expand the functions of Ae. albopictus nrEVEs suggesting they can regulate host-virus interactions through various mechanisms.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental sex determination in the cyst nematode Globodera pallida defaults to male development.","authors":"Arno S Schaveling, Stefan J S van de Ruitenbeek, Geert Smant, Mark G Sterken","doi":"10.1186/s12915-026-02671-y","DOIUrl":"10.1186/s12915-026-02671-y","url":null,"abstract":"<p><strong>Background: </strong>Environmental sex determination (ESD) enables organisms to adjust their sexual fate in response to external cues. Fluctuating sex ratios have long suggested the presence of ESD in populations of plant-parasitic nematodes.</p><p><strong>Results: </strong>We show that in the potato cyst nematode Globodera pallida sex is regulated by nutritional cues. By manipulating sucrose availability to the host plant, we could steer the sex determination of G. pallida. Whereas high-sucrose medium promotes female development, low-sucrose medium promotes male development. Transcriptome analyses on the early stages of parasitism reveal that female development requires extensive transcriptional activation and post-transcriptional regulation. We identify Gp-lin-29, a transcription factor homologous to lin-29 in Caenorhabditis elegans, as a potential regulator of ESD. Small RNA sequencing uncovered the male-biased expression of Gp-let-7, a putative repressor of Gp-lin-29, and the female-biased expression of four miRNAs, including Gp-miR-100, located at the same genomic locus as Gp-let-7. Target prediction and enrichment analyses suggest that these female-biased miRNAs may actively suppress male developmental programs.</p><p><strong>Conclusions: </strong>Together, our findings support a model in which G. pallida juveniles follow a default male developmental trajectory unless redirected by favourable environmental cues to become female. This study provides mechanistic insight into ESD in cyst nematodes and positions G. pallida as a tractable system for exploring epigenetic regulation of developmental plasticity.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experimental evidence for behavioural cooling as a response to virus infection in an ectothermic vertebrate.","authors":"Dávid Herczeg, Veronika Bókony, Gábor Herczeg, Dóra Holly, Andrea Kásler, János Ujszegi, Tibor Papp, Attila Hettyey","doi":"10.1186/s12915-026-02669-6","DOIUrl":"10.1186/s12915-026-02669-6","url":null,"abstract":"<p><strong>Background: </strong>Behavioural plasticity may contribute to the ability of wild animals to survive disease outbreaks. In absence of endogen heat control, ectothermic animals adjust their body temperature behaviourally. While many studies reported behavioural fever, its opposite, behavioural cooling-when infected animals lower their body temperature by using cool microenvironments-remains poorly documented.</p><p><strong>Results: </strong>Here, we report the first experimental evidence of behavioural cooling in an ectothermic vertebrate as a response to pathogenic infection. We investigated thermoregulatory responses in tadpoles of the agile frog Rana dalmatina, a cool-adapted amphibian, following experimental infection with a ranavirus that can replicate well at high temperatures. Tadpoles were placed either in thermal gradients or homogeneously cool environments for 5 days post-exposure. In thermal gradients, all tadpoles reduced their preferred temperatures over time, but this decrease was steeper in infected tadpoles, and individuals with higher infection intensities preferred cooler temperatures. Infected tadpoles decreased the range of their preferred body temperatures over time, while a similar trend was not detectable in non-infected tadpoles. Infection prevalence was similar between the two thermal environments, yet infection intensities were significantly higher in the thermal gradient.</p><p><strong>Conclusions: </strong>These results suggest fine-tuned thermoregulation by infected tadpoles to balance out the benefits of behavioural cooling for fighting a pathogen versus the immune-suppressive and developmental costs of low temperatures.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 damage at an early developmental stage affects neurodevelopment in sterlet (Acipenser ruthenus).","authors":"Abhipsha Dey, Małgorzata Rzepkowska, Magdalena Fajkowska, Roman Franěk, Christoph Steinbach, Martin Pšenička, Radek Šindelka, Martin Flajšhans, Ievgeniia Gazo","doi":"10.1186/s12915-026-02667-8","DOIUrl":"10.1186/s12915-026-02667-8","url":null,"abstract":"<p><strong>Background: </strong>Exposure to DNA damaging agents during fish embryogenesis can induce malformations and developmental disorders. However, there is scarcity of knowledge on dynamics of embryonic DNA repair and its effect on organogenesis. To address this knowledge gap, we exposed sterlet (Acipenser ruthenus) embryos to DNA-alkylating agent, methyl methanesulfonate (MMS), during blastulation (from 2 to 24 h post-fertilization (hpf)) and observed the effects at hatching (8 days post-fertilization (dpf)) and post-hatching stage (10 dpf).</p><p><strong>Results: </strong>In contrast to control, DNA alkylation damage in treated embryos significantly persisted up to 3 dpf but was resolved by 8 dpf. These observations coincided with a significant increase in expression of key base excision repair (BER) genes (apex1, ogg1, polβ, xrcc1, lig3) and 1.5-fold increase in APE1 protein levels by hatching. These findings suggest that sterlet embryos activate functional BER pathway in response to DNA alkylation. Despite successful DNA repair, embryos exhibited disrupted retinal layers differentiation and reduced expression of tyrosine hydroxylase (TH) at 10 dpf.</p><p><strong>Conclusions: </strong>Collectively, our results suggest that DNA alkylation can interfere with organogenesis, potentially through misregulation of DNA repair proteins during critical developmental windows. We speculate that DNA alkylation can affect expression of genes critical for early brain and eye development indicating an organ-specific DNA damage response. Notably, this study emphasizes that future studies should address the link between activation of BER pathway and developmental abnormalities when sterlet embryos are genotoxically challenged.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The landscape of human genomic diversity.","authors":"Segun Fatumo, Wibhu Kutanan, Jordan I King","doi":"10.1186/s12915-026-02664-x","DOIUrl":"10.1186/s12915-026-02664-x","url":null,"abstract":"","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"24 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AGCECDA: attention-guided heterogeneous graph collaborative embedding for circRNA-drug sensitivity association prediction.","authors":"Chao Cao, Mengli Li, Maozu Guo, Chunyu Wang, Quan Zou, Mengting Niu","doi":"10.1186/s12915-026-02656-x","DOIUrl":"10.1186/s12915-026-02656-x","url":null,"abstract":"<p><strong>Background: </strong>Circular RNAs (circRNAs) are an emerging class of non-coding RNAs with covalently closed loop structures and have been increasingly recognized for their regulatory roles in disease progression and drug response. Accurately identifying circRNA-drug sensitivity associations is therefore essential for understanding therapeutic mechanisms and advancing precision medicine. However, most existing computational methods fail to effectively integrate semantic and structural information and overlook cross-modal feature co-optimization, thereby limiting their predictive performance.</p><p><strong>Results: </strong>To address these limitations, we develop an end-to-end graph representation learning framework for circRNA-drug sensitivity prediction by jointly modeling homogeneous similarity structures and heterogeneous interaction relationships. The framework integrates fused similarity graphs, semantic feature encoding with pre-norm residual attention, and structural representation learning via graph convolutional networks with Top-K sparse adjacency. In addition, a large-scale heterogeneous graph and a cross-modal collaborative feature mining module are employed to jointly optimize multi-source representations. Experimental results from 5-fold and 10-fold cross-validation, independent test evaluations, ablation study, and case study demonstrate that the proposed framework consistently achieves superior performance compared with state-of-the-art methods.</p><p><strong>Conclusions: </strong>The proposed framework provides a robust and effective computational strategy for circRNA-drug sensitivity prediction and offers a valuable tool for uncovering potential therapeutic associations, thereby facilitating future research in drug response analysis and precision medicine.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 decoy receptor antagonizes interferon mediated antiviral responses in teleost fish.","authors":"Yanjie Shi, Kangyong Chen, Hui Yan, Teng Xie, Wenji Huang, Zhao Jia, Gaoliang Yuan, Yanwei Zhang, Junya Wang, Jun Zou","doi":"10.1186/s12915-026-02663-y","DOIUrl":"10.1186/s12915-026-02663-y","url":null,"abstract":"<p><strong>Background: </strong>Negative regulation of interferon (IFN) responses is crucial for preventing IFN-induced cellular damage and restoring immune homeostasis after viral clearance. However, whether such regulation occurs at the receptor level has not been explored in lower vertebrates.</p><p><strong>Results: </strong>Here we characterized a decoy receptor (CRFB15) in zebrafish, belonging to the cytokine receptor family B, that functions as a decoy receptor to antagonize IFN-mediated signaling. CRFB15 was shown to be upregulated upon viral infection. It bound to IFN ligands and suppressed STAT1 phosphorylation and downstream antiviral effector gene expression, ultimately promoting viral replication. It also interacted with IFN receptors, including CRFB1, CRFB2, and CRFB5, selectively promoting degradation of CRFB2 and CRFB5 and attenuating IFN-induced antiviral response. Furthermore, crfb15^-/- zebrafish exhibited enhanced resistance to viral infection, confirming its role as a negative regulator of IFN signaling.</p><p><strong>Conclusions: </strong>This study establishes CRFB15 as a key negative regulator of teleost type I IFN signaling. Upon viral infection, CRFB15 is upregulated and suppresses IFN signaling through two distinct pathways: by functioning as a decoy receptor that competitively binds type I IFNs and their functional receptors, and/or by promoting the degradation of the key receptor subunits CRFB2 and CRFB5.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the association between platinum resistance and HPV status in cervical cancer using organoid models.","authors":"Bin Zhang, Yao Lin, Suyao Xie, Xiaohong Zhu, Xinping Zhang, Lingyu Hu, Min Qiu, Hongkai Lee, Chongyang Shen, Mingliang You, Huayang Xing","doi":"10.1186/s12915-026-02665-w","DOIUrl":"10.1186/s12915-026-02665-w","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer remains a leading cause of cancer-related mortality in women, with high-risk HPV types (16, 18, 31, 33, 45, 52, and 58) playing a key role in its development. Platinum-based chemotherapy is standard for recurrent or metastatic cervical cancer, but platinum resistance remains a major challenge. The link between HPV infection and platinum resistance is not well understood. Tumor organoids offer a physiologically relevant model for investigating drug resistance mechanisms in cervical cancer.</p><p><strong>Results: </strong>We successfully established 37 cervical cancer organoids (CCOs), with 27 expanded for characterization and drug sensitivity testing. CCOs recapitulated the biomarker expression patterns and genomic features of their corresponding tissues. Drug sensitivity assays revealed increased cisplatin/carboplatin resistance in the non-HPV16 high-risk HPV CCOs subgroup, compared to HPV-negative CCOs. Single-cell RNA sequencing identified diverse cellular populations within CCOs, with platinum-resistant CCOs showing enhanced DNA repair, activation of the PI3K/AKT pathway, and suppressed apoptotic signaling. We also found that the PI3K/AKT inhibitor BYL719 enhanced the response to cisplatin and carboplatin in non-HPV16 high-risk HPV CCOs but not in HPV-negative CCOs.</p><p><strong>Conclusions: </strong>Cervical cancer organoids faithfully replicate the histopathological and genomic characteristics of their parental tumors, demonstrating their potential as preclinical models for studying cancer progression and drug resistance. Our findings suggest that the non-HPV16 high-risk HPV infections may contribute to increased platinum resistance through enhanced DNA repair mechanisms, increased PI3K/AKT activation and suppressed apoptosis, providing new insights for personalized cervical cancer treatment. The PI3K/AKT inhibitor BYL719 may serve as a potential therapeutic adjunct to enhance platinum efficacy in those patients with platinum-resistant cervical cancer.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of the RAD-51 isoform A redirects DNA repair and preserves genome stability in FANCD2-deficient Caenorhabditis elegans.","authors":"Alessandra Masullo, Marcello Germoglio, Rosanna Mattossovich, Claudia Esposito, Anna Valenti, Adele Adamo","doi":"10.1186/s12915-026-02652-1","DOIUrl":"10.1186/s12915-026-02652-1","url":null,"abstract":"<p><strong>Background: </strong>Fanconi anemia is a rare genomic instability syndrome associated with congenital abnormalities and cancer predisposition. These alterations are mainly due to deficiencies in DNA repair mechanisms. The Fanconi anemia pathway is evolutionarily conserved, allowing functional studies in model organisms like Caenorhabditis elegans, where it promotes and executes error-free homologous-recombination over the mutagenic non-homologous-end-joining pathway; fcd-2 (FANCD2 ortholog) plays a key role in this regulation to preserve genome stability. In this study, we report that the choice of DNA repair pathway for resolving double-strand breaks is influenced by absence of the RAD-51 long isoform, a key component of the Fanconi anemia pathway that plays a central role in homologous strand exchange during recombination.</p><p><strong>Results: </strong>In C. elegans, which is predicted to encode three RAD-51 isoforms, we find that loss of RAD-51 isoform A enhances homologous recombination efficiency. Additionally, RAD-51 isoform A depletion decreases developmental and meiotic defects in fcd-2 mutants as well as reduces chromosome aggregation in fcd-2-deficient germ cells.</p><p><strong>Conclusions: </strong>Together, these findings reveal a novel role for RAD-51 C. elegans, suggesting that the pattern of RAD-51 isoform expression modulates the balance between homologous recombination and non-homologous-end-joining, thereby preserving genome stability.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148300992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}