BMC Biology最新文献

{"title":"TRAM-LAG1-CLN8 domain-containing protein TMEM56 regulates cell migration by changing intracellular ceramide levels.","authors":"Benjamin Dorschner, Ralf Wiedemuth, Cornelia Richter, Marc Gentzel, Tobias Lindau, Gunes Ozhan, Gilbert Weidinger, Sebastian Brenner, Sebastian Thieme","doi":"10.1186/s12915-026-02614-7","DOIUrl":"https://doi.org/10.1186/s12915-026-02614-7","url":null,"abstract":"<p><strong>Background: </strong>Cell migration is a fundamental biological process essential for embryonic development and hematopoiesis. In a shRNA screen, we identified the TRAM-LAG1-CLN8 domain-containing transmembrane protein TMEM56 as a previously uncharacterized regulator of stromal cell-derived factor 1 (SDF-1)-mediated cell migration. This study investigates the molecular mechanisms underlying TMEM56 function.</p><p><strong>Results: </strong>TMEM56 is expressed in both murine embryonic and adult tissues, with enrichment in hematopoietic stem and erythroid progenitor cells. Lipidomic analysis reveals that TMEM56 modulates ceramide metabolism, particularly affecting levels of hexosylated ceramides. Co-immunoprecipitation assays indicate that TMEM56 physically interacts with ceramide synthase 2 (CerS2), suggesting a role in lipid signaling pathways.</p><p><strong>Conclusion: </strong>Our findings identify TMEM56 as a key regulator of cell migration, linking lipid metabolism with hematopoietic and developmental processes. These results provide novel insights into the molecular mechanisms governing migration.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"24 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834001","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 sponge homolog of BRMS1 reveals ancient origin of metastasis-suppressing functions.","authors":"Antea Talajić, Kristina Dominko, Bastien Proust, Nikolina Škrobot Vidaček, Matija Harcet, Helena Ćetković","doi":"10.1186/s12915-026-02616-5","DOIUrl":"https://doi.org/10.1186/s12915-026-02616-5","url":null,"abstract":"<p><strong>Background: </strong>Early-branching metazoans, such as sponges (Porifera), can provide valuable insight into the emergence of complex gene regulatory systems and cancer-related mechanisms in early metazoan evolution. BRMS1 (breast cancer metastasis suppressor 1) is a component of the Sin3-HDAC complex involved in chromatin remodeling and transcriptional regulation. In humans, BRMS1 inhibits cancer metastasis by modulating signaling pathways that control cell migration, adhesion, and proliferation. Despite its biomedical importance, the evolutionary origin and basic functions of BRMS1 remain largely unexplored.</p><p><strong>Results: </strong>We identified and characterized a BRMS1 homolog from the cave sponge Eunapius subterraneus and compared it with human BRMS1 and BRMS1-like paralogs. Phylogenetic analyses revealed that BRMS1 and BRMS1-like arose from a duplication of an ancestral BRMS1 gene during early vertebrate evolution. Structural modeling showed that sponge BRMS1 shares high similarity with human BRMS1. Co-immunoprecipitation assays demonstrated that sponge BRMS1 physically associates with human BRMS1 in mammalian cells. In both sponge and human cells, sponge BRMS1 localized predominantly to the nucleus, similar to human BRMS1 and BRMS1-like. Functional assays in human breast cancer cells revealed that sponge BRMS1 suppresses proliferation, colony formation, and migration to a degree comparable to its human homologs.</p><p><strong>Conclusions: </strong>Our findings demonstrate that the key structural features, subcellular localization, and biological functions of BRMS1 are conserved between sponges and humans. The ability of a sponge BRMS1 homolog to integrate into human protein complexes and suppress cancer cell migration and proliferation suggests that fundamental BRMS1 activities arose early in metazoan evolution, independent of anatomical and functional complexity.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The direct cost of amphibian metamorphosis: insights from body weight loss in facultative paedomorphs.","authors":"Mathieu Denoël, Anthony G E Mathiron, Sarah Baouch, Jean-Paul Lena","doi":"10.1186/s12915-026-02608-5","DOIUrl":"10.1186/s12915-026-02608-5","url":null,"abstract":"<p><strong>Background: </strong>Metamorphosis is a key event in the life history of many organisms, including amphibians, because it can involve abrupt changes in morphology and habitat. However, metamorphosis can also be bypassed by paedomorphic processes that allow reproduction at the larval stage. The evolution of these alternative developmental processes depends on the payoffs of life in larval and adult environments, as well as the cost of transition. Previous studies on the cost of metamorphosis have focused on the larval stage, which is still subject to the achievement of a minimal size threshold as well as growth to adulthood. Therefore, facultatively paedomorphic species could be valuable models for testing the direct costs of metamorphosis. This is because facultative paedomorphs are sexually dimorphic adults that are capable of metamorphosis.</p><p><strong>Results: </strong>By modelling weight loss using an experimental, longitudinal design that manipulated the ecological drivers of metamorphosis in a facultatively paedomorphic amphibian, the palmate newt (Lissotriton helveticus), we found that metamorphosis imposes costs in terms of body weight, whereas temperature has a smaller effect. In contrast, newts that do not metamorphose did not lose weight. The costs were sex-related with females at a disadvantage during metamorphosis. Furthermore, the decrease in food consumption associated with metamorphosis resulted in a loss of body weight.</p><p><strong>Conclusions: </strong>Overall, these results emphasise the importance of considering direct costs when studying the evolutionary ecology of metamorphosis. They also show that polymorphic species are suitable models for investigating the drivers of metamorphosis and its loss in micro- and macroevolution.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"24 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811373","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":"Saccade-synchronized alpha rhythms predict strength of memory trace of stimulus orientation.","authors":"Chiara Terzo, David C Burr, Xin-Yu Xie, Maria Concetta Morrone","doi":"10.1186/s12915-026-02609-4","DOIUrl":"https://doi.org/10.1186/s12915-026-02609-4","url":null,"abstract":"<p><strong>Background: </strong>Saccadic eye movements allow us to sample the world sequentially, but pose challenges to the visual system, which must integrate information across successive fixations. The mechanisms subserving the integration may share properties with \"serial dependence,\" the assimilative bias caused by previous sensory experience on current perception.</p><p><strong>Results: </strong>We investigated serial dependence during saccadic eye movements by measuring ERP responses from participants during visually driven saccadic eye movements while they viewed a brief Gabor patch, presented at various orientations (± 35°, ± 45°, or ± 55°), and then reproduced its orientation. Our findings demonstrate that both alpha and beta oscillations are synchronized by the saccades. Importantly, we found that the strength of alpha oscillations correlates (negatively) with the magnitude of serial dependence, particular in the right parietal cortex, while that of beta oscillations does not.</p><p><strong>Conclusions: </strong>These results provide evidence that pre-saccadic alpha oscillations contain information to be carried across saccades, probably fundamental for integration of visual information across saccades, and trans-saccadic perceptual stability.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma membrane invaginations and their diverse cellular functions.","authors":"Hongxian Zhu, Carina Lyons, Andrew M Sydor, Donald W Hilgemann, John H Brumell","doi":"10.1186/s12915-026-02615-6","DOIUrl":"https://doi.org/10.1186/s12915-026-02615-6","url":null,"abstract":"<p><p>The plasma membrane (PM), a dynamic boundary between a cell and its environment, has a complex inner architecture that includes diverse subcellular structures. Among these, PM invaginations (membrane infolds) exhibit varied morphologies and functions. This review explores the structural diversity and physiological roles of PM invaginations, emphasizing their importance in regulating cellular processes in complex organisms. We describe their presence and significance in diverse cell types and organisms. Understanding these specialized structures offers deeper insight into cellular organization and function, highlighting their indispensable role in sustaining biological activity.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of neuronal oscillations in memory driven visual processing.","authors":"Yeganeh Shaverdi, Seyed Kamaledin Setarehdan, Stefan Treue, Moein Esghaei","doi":"10.1186/s12915-026-02605-8","DOIUrl":"https://doi.org/10.1186/s12915-026-02605-8","url":null,"abstract":"<p><strong>Background: </strong>Successful working memory of previous locations is critical for optimal navigation of the environment in primates. However, it remains unclear how successful working memory influences the statistics of sensory-motor probing (e.g., whisking, sniffing, saccading). This study addresses this gap by investigating the coupling between saccadic eye movements and neural oscillations in the frontal eye field.</p><p><strong>Results: </strong>We demonstrate that the influence of working memory on saccadic behaviors involves a distinct coupling to beta rhythms. Analyzing local field potentials (LFPs) and saccadic patterns in rhesus monkeys performing a visual foraging task, we find that prior memory of visual targets is followed by a significant reduction of the synchronization of saccades with beta oscillations. This reduction suggests that working memory refines saccadic strategies by dynamically modulating neural synchronization, thereby optimizing visual search efficiency.</p><p><strong>Conclusions: </strong>Our findings elucidate a fundamental mechanism through which memory may affect sensory-motor integration, highlighting the pivotal role of neural oscillatory adjustments in enhancing the cognitive processes that govern strategic eye movements and perception.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Embedding multilayer RNA networks for lncRNA-miRNA interaction prediction via LMI-MHGAT.","authors":"Jing Chen, Peimeng Zhen, Zhengxuan Liu, Yongtian Wang, Jiajie Peng, Yifu Xiao, Tao Wang","doi":"10.1186/s12915-026-02600-z","DOIUrl":"https://doi.org/10.1186/s12915-026-02600-z","url":null,"abstract":"<p><strong>Background: </strong>The identification of lncRNA-miRNA interactions (LMIs) is crucial for deciphering post-transcriptional regulatory networks and their roles in development and disease. While computational methods have been developed to predict LMIs, existing approaches are often limited by an inability to effectively integrate multimodal biological data and to handle the severe class imbalance inherent to biological networks.</p><p><strong>Results: </strong>To overcome these limitations, we present LMI-MHGAT, a novel deep learning framework for LMI prediction based on a Multilayer Heterogeneous Graph Attention network. Our model integrates diverse data-including RNA sequences, expression profiles, and known molecular interactions-into a unified graph representation. A key innovation is the use of a graph attention mechanism that dynamically learns to weight information from different relational layers, enabling the model to learn robust embeddings for lncRNAs and miRNAs. LMI-MHGAT significantly outperforms 14 existing methods on human LMI data, demonstrating exceptional robustness under severe class imbalance (positive-to-negative ratio 1:60). The model generalizes effectively, achieving state-of-the-art performance on rat and plant datasets. Case studies confirm its ability to recover disease-associated regulatory axes and predict novel, biologically plausible interactions.</p><p><strong>Conclusions: </strong>LMI-MHGAT provides a more powerful and robust framework for LMI prediction by simultaneously addressing key limitations in data utilization and integration. The tool is freely accessible at https://github.com/Zhenpm/LMI-MHGAT.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell phenotype-associated subpopulation identification via transfer foundation model and statistical ensemble learning.","authors":"Yuming Zhao, Xiaonan Pan, Zeyu Luo, Qiaoming Liu","doi":"10.1186/s12915-026-02613-8","DOIUrl":"https://doi.org/10.1186/s12915-026-02613-8","url":null,"abstract":"<p><strong>Background: </strong>Single-cell RNA sequencing (scRNA-seq) enables the characterization of cell types, states, and lineages within heterogeneous tissues, thereby providing unprecedented opportunities to dissect cellular heterogeneity. However, single-cell data alone cannot directly establish cell-phenotype relationships, which pose major challenges in linking cellular heterogeneity to complex traits and disease outcomes.</p><p><strong>Results: </strong>Here, we introduce scPASI, which integrates single-cell and bulk-level information to uncover phenotype-associated cell subpopulations. scPASI combines a pre-trained foundation model (PFM) with a residual variational autoencoder (Res-VAE) to extract feature embeddings of cells and samples. Cell clusters are calculated using the Leiden algorithm, after which phenotype associations are inferred based on regression coefficients derived from LASSO and sparse group LASSO (SGL) models. This design enables scPASI to stratify cells into four subpopulations with different levels of phenotype association: strongly positive (SP), weakly positive (WP), strongly negative (SN), and weakly negative (WN) groups. Furthermore, scPASI characterizes phenotype-relevant genes within subpopulations and provides insights into the relationship between cellular heterogeneity and bulk phenotypes. Extensive evaluations across diverse datasets show that scPASI outperforms existing methods and generalizes well across multiple phenotype settings, including tumor status, genetic mutations, and clinical prognosis. Biological analyses demonstrate that signature genes derived from the identified subpopulations can distinguish tumor cells, genetic alterations, and survival outcomes.</p><p><strong>Conclusions: </strong>By bridging single-cell transcriptomics with phenotype information, scPASI can uncover biologically meaningful cell-phenotype associations underlying tumor biology, enabling the identification of disease-relevant subpopulations and providing a framework for potential therapeutic targeting.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HNRM: hyperedge neighborhood-based representation for predicting N6-methyladenosine-related regulatory pathways.","authors":"Dongdong Jiang, Yan Li, Liang Yu","doi":"10.1186/s12915-026-02612-9","DOIUrl":"https://doi.org/10.1186/s12915-026-02612-9","url":null,"abstract":"<p><strong>Background: </strong>N6-methyladenosine (m6A), the most predominant post-transcriptional RNA modification, regulates splicing, translation, and decay processes. Its dysregulation is implicated in cancers, metabolic disorders, and neurological diseases. Despite accumulating evidence highlighting m6A as a key player in human pathologies, no previous computational framework has investigated the high-order associations among m6A sites, diseases, and drugs within a unified model.</p><p><strong>Results: </strong>Here, we introduce HNRM, a data-driven approach designed to model hyperedges across these entities. We frame this problem as a high-order link-prediction task on a hypergraph. We employ a hypergraph neural network based on hyperedge neighborhoods to learn embedding representations of both hyperedges and nodes.</p><p><strong>Conclusions: </strong>The performance of HNRM is evaluated on a newly collected and processed m6A dataset, as well as on five additional datasets from other domains, demonstrating its superior effectiveness. Ablation studies and Gene Ontology enrichment analysis further validate its capability in identifying potential associations.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytochrome P450 inhibition impedes the insecticide pyrethroid effects on insects through Nav channels regulation.","authors":"Beata Niklas, Eléonore Moreau, Caroline Deshayes, Jakub Rydzewski, Milena Jankowska, Jacek Kęsy, Ademir J Martins, Pie Müller, Vincent Corbel, Wiesław Nowak, Bruno Lapied","doi":"10.1186/s12915-026-02611-w","DOIUrl":"https://doi.org/10.1186/s12915-026-02611-w","url":null,"abstract":"<p><strong>Background: </strong>Insecticides in various formulations are indispensable for agricultural pest control and the prevention of vector-borne diseases. Piperonyl butoxide (PBO) is a synergist widely used to enhance the effectiveness of insecticides, notably pyrethroids, by inhibiting the detoxifying cytochrome P450 enzymes, thus reducing the capacity of insects to metabolize and resist insecticides. Recent studies have revealed an unexpectedly weak enhancement of pyrethroid efficacy by PBO, which may have serious implications for insect control. The underlying mechanism of this effect remains unclear.</p><p><strong>Results: </strong>Here, we demonstrate that the PBO-induced inhibition of cytochrome P450 impedes the effect of deltamethrin by mainly affecting its interaction with the inactivated state of voltage-gated sodium channels (Nav). We describe a new octopamine-dependent regulatory mechanism involving Gαs, PKA, DARPP-32, and PP1-2A, which affect the cytochrome P450 conformation, thus limiting the effect of PBO and modulating the Nav gating. As a result, deltamethrin cannot reach its final binding site in the fenestration to exert its full effect. We confirmed in vivo that the octopamine level is elevated in insects under the treatment with a chemical stressor, which decreases the deltamethrin efficacy.</p><p><strong>Conclusions: </strong>Our findings reveal a novel adaptive mechanism that increases insect survival by reducing insecticide efficacy, underscoring the need to develop more effective formulations and technologies for pest and vector control.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}