BMC Biology最新文献

{"title":"Rapid and high-throughput screening of proteolysis targeting chimeras using a dual-reporter system expressing fluorescence protein and luciferase.","authors":"Shuai Meng, Yuan Meng, Xuena Yang, Wenwen Yu, Bole Li, Tianjun Liu, Jie Zhang, Xiubao Ren, Lin Zhang","doi":"10.1186/s12915-025-02153-7","DOIUrl":"10.1186/s12915-025-02153-7","url":null,"abstract":"<p><strong>Background: </strong>Proteolysis targeting chimera (PROTAC), a novel drug discovery strategy, utilizes the ubiquitin-proteasome system to degrade target proteins in cells. While Western blotting, mass spectrometry, and Lumit Immunoassay have been instrumental in determining protein levels, the rapid screening of PROTACs continues to pose challenges, necessitating the development of alternative methodologies.</p><p><strong>Results: </strong>We herein reported an alternative high-throughput method for screening PROTACs using a dual-reporter system expressing a Renilla luciferase (RLUC)-fused target protein and enhanced green fluorescent protein (EGFP). EGFP served as an internal reference and RLUC as an indicated target protein degradation. Rapid measurement of EGFP or RLUC light signals was achieved using a fluorescence/luminescence plate-based reader in the endpoint mode. The feasibility of the screening model was tested using ARV110, a clinical trial-stage PROTAC targeting the androgen receptor (AR). In EGFP/RLUC-tAR-expressing modal cells treated with varying concentrations of ARV110, normalized RLUC luminescence decreased dose-dependently, as confirmed via western blotting detection of AR expression. Then the platform was used to practically screen Sirtuin 2 (SIRT2) degraders from a small group of PROTACs that we built. Normalized RLUC luminescence changes in model cells expressing EGFP/RLUC-SIRT2 reflected the degradation efficiencies of PROTACs. Compounds 128 and 129 exhibited the highest degradation efficacies, leading to dose-dependent degradation of endogenous SIRT2 protein in the MCF-7 cell line and inducing cell growth arrest.</p><p><strong>Conclusions: </strong>The dual-reporter system using both fluorescence and chemiluminescence was successfully constructed. Using this method, we identified effective candidate PROTACs against SIRT2. The dual-reporter system may accelerate drug discovery during PROTAC development.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"51"},"PeriodicalIF":4.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472393","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 ensemble deep learning framework for multi-class LncRNA subcellular localization with innovative encoding strategy.","authors":"Wenxing Hu, Yan Yue, Ruomei Yan, Lixin Guan, Mengshan Li","doi":"10.1186/s12915-025-02148-4","DOIUrl":"10.1186/s12915-025-02148-4","url":null,"abstract":"<p><strong>Background: </strong>Long non-coding RNA (LncRNA) play pivotal roles in various cellular processes, and elucidating their subcellular localization can offer crucial insights into their functional significance. Accurate prediction of lncRNA subcellular localization is of paramount importance. Despite numerous computational methods developed for this purpose, existing approaches still encounter challenges stemming from the complexity of data representation and the difficulty in capturing nucleotide distribution information within sequences.</p><p><strong>Results: </strong>In this study, we propose a novel deep learning-based model, termed MGBLncLoc, which incorporates a unique multi-class encoding technique known as generalized encoding based on the Distribution Density of Multi-Class Nucleotide Groups (MCD-ND). This encoding approach enables more precise reflection of nucleotide distributions, distinguishing between constant and discriminative regions within sequences, thereby enhancing prediction performance. Additionally, our deep learning model integrates advanced neural network modules, including Multi-Dconv Head Transposed Attention, Gated-Dconv Feed-forward Network, Convolutional Neural Network, and Bidirectional Gated Recurrent Unit, to comprehensively exploit sequence features of lncRNA.</p><p><strong>Conclusions: </strong>Comparative analysis against commonly used sequence feature encoding methods and existing prediction models validates the effectiveness of MGBLncLoc, demonstrating superior performance. This research offers novel insights and effective solutions for predicting lncRNA subcellular localization, thereby providing valuable support for related biological investigations.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"47"},"PeriodicalIF":4.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472323","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":"Convergent evolution of noncoding elements associated with short tarsus length in birds.","authors":"Subir B Shakya, Scott V Edwards, Timothy B Sackton","doi":"10.1186/s12915-025-02156-4","DOIUrl":"10.1186/s12915-025-02156-4","url":null,"abstract":"<p><strong>Background: </strong>Convergent evolution is the independent evolution of similar traits in unrelated lineages across the Tree of Life. Various genomic signatures can help identify cases of convergent evolution at the molecular level, including changes in substitution rate in the same genes or gene networks. In this study, utilizing tarsus measurements of ~ 5400 species of birds, we identify independent shifts in tarsus length and use both comparative genomic and population genetic data to identify convergent evolutionary changes among focal clades with shifts to shorter optimal tarsus length.</p><p><strong>Results: </strong>Using a newly generated, comprehensive and broadly accessible set of 932,467 avian conserved non-exonic elements (CNEEs) and a whole-genome alignment of 79 birds, we find strong evidence for convergent acceleration in short-tarsus clades among 14,422 elements. Analysis of 9854 protein-coding genes, however, yielded no evidence of convergent patterns of positive selection. Accelerated elements in short-tarsus clades are concentrated near genes with functions in development, with the strongest enrichment associated with skeletal system development. Analysis of gene networks supports convergent changes in regulation of broadly homologous limb developmental genes and pathways.</p><p><strong>Conclusions: </strong>Our results highlight the important role of regulatory elements undergoing convergent acceleration in convergent skeletal traits and are consistent with previous studies showing the roles of regulatory elements and skeletal phenotypes.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"52"},"PeriodicalIF":4.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472342","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":"Proteomics revealed novel functions and drought tolerance of Arabidopsis thaliana protein kinase ATG1.","authors":"Shan Cheng, Siqi Fan, Chao Yang, Weiming Hu, Fen Liu","doi":"10.1186/s12915-025-02149-3","DOIUrl":"10.1186/s12915-025-02149-3","url":null,"abstract":"<p><p>ATG1 stimulates autophagy biogenesis and serves as a gatekeeper for classical autophagy. To obtain insight into the control of autophagy by ATG1 and determine whether ATG1 has broader processes, we performed a thorough proteomics analysis on the Col-0 wild-type and atg1abct mutant in Arabidopsis thaliana. Proteomic data analysis pointed out that ATG1 has an unidentified function within the inositol trisphosphate and fatty acid metabolism. We also discovered ATG1-dependent autophagy has an emerging connection with ER homeostasis and ABA biosynthesis. Moreover, Gene Ontology terms for abiotic and biotic stress were strongly enriched in differentially abundant proteins, consistent with the reported role of canonical autophagy in these processes. Additional physiological and biochemical analysis revealed that atg1abct exhibited stronger drought resistance under both PEG-simulated drought treatment and natural drought stress. Results from DAB staining also indicated that atg1abct accumulation fewer ROS than Col-0 following drought treatment. As a result, these results illuminate previously unknown functions for ATG1 and offers novel perspectives into the underlying processes of autophagy function.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"48"},"PeriodicalIF":4.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472347","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":"Unraveling the role of satellite DNAs in the evolution of the giant XY sex chromosomes of the flea beetle Omophoita octoguttata (Coleoptera, Chrysomelidae).","authors":"Jhon Alex Dziechciarz Vidal, Deborah Charlesworth, Ricardo Utsunomia, Manuel A Garrido-Ramos, Rodrigo Zeni Dos Santos, Fábio Porto-Foresti, Roberto Ferreira Artoni, Thomas Liehr, Mara Cristina de Almeida, Marcelo de Bello Cioffi","doi":"10.1186/s12915-025-02155-5","DOIUrl":"10.1186/s12915-025-02155-5","url":null,"abstract":"<p><strong>Background: </strong>The flea beetle Omophoita octoguttata (Coleoptera, Chrysomelidae) is a member of a group in which the males completely lack meiotic recombination (male-specific achiasmy) and that have extraordinarily large X and Y chromosomes. We combined genome sequencing, including microdissected Y and X chromosomes, and cytogenetic in situ hybridization studies, to evaluate the potential role of satellite DNAs (satDNAs) in the differentiation of those gigantic sex chromosomes.</p><p><strong>Results: </strong>We report flow cytometry results showing that this species has a very large genome size (estimated to be 4.61 and 5.47 pg, or roughly 4.6 and 5.5 gigabases, for males and females, respectively), higher than the estimates from two other Alticinae species without giant sex chromosomes, suggesting that these sequences have greatly expanded on both the sex chromosomes, and that the Y has not greatly shrunk like the ones of other insects such as Drosophila with male achiasmy. About 68% of this large genome is made up of repetitive DNAs. Satellite DNAs (OocSatDNAs) form ~ 8-9% of their genomes, and we estimate how much of the sex chromosome expansions occurred due to differential amplification of different satellite classes. Analysis of divergence between sequences in the X and Y chromosomes suggests that, during the past roughly 20 mya, different OocSatDNAs amplified independently, leading to different representations. Some are specific to the Y or X chromosome, as expected when males are achiasmate, completely preventing genetic exchanges between the Y and X.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"53"},"PeriodicalIF":4.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472423","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":"Publisher Correction: Accurate RNA velocity estimation based on multibatch network reveals complex lineage in batch scRNA-seq data.","authors":"Zhaoyang Huang, Xinyang Guo, Jie Qin, Lin Gao, Fen Ju, Chenguang Zhao, Liang Yu","doi":"10.1186/s12915-025-02152-8","DOIUrl":"10.1186/s12915-025-02152-8","url":null,"abstract":"","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"46"},"PeriodicalIF":4.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448170","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":"Anemonefish use sialic acid metabolism as Trojan horse to avoid giant sea anemone stinging.","authors":"Natacha Roux, Clément Delannoy, Shin-Yi Yu, Saori Miura, Lilian Carlu, Laurence Besseau, Takahiro Nakagawa, Chihiro Sato, Ken Kitajima, Yann Guerardel, Vincent Laudet","doi":"10.1186/s12915-025-02144-8","DOIUrl":"10.1186/s12915-025-02144-8","url":null,"abstract":"<p><strong>Background: </strong>Anemonefish association with sea anemones is a prime example of mutualistic symbiosis. These fish live inside the sea anemone, benefitting from the protection of its toxic nematocysts, and in return, protect the anemone from its own predators. How anemonefish manage to avoid their host toxic stings remains unclear. One hypothesis suggests that low levels of sialic acids in anemonefish mucus prevent nematocyst discharge.</p><p><strong>Results: </strong>This study verified four predictions: (i) anemonefish mucus has lower sialic acid levels than non-symbiotic damselfish; (ii) this reduction is specific to mucus; (iii) during development, sialic acid levels inversely correlate with protection; (iv) sea anemone mucus has minimal sialic acids.</p><p><strong>Conclusions: </strong>We conclude that anemonefish regulates the level of sialic acids in their mucus to avoid nematocyst discharge. We also highlight several genes implicated in sialic acid removal that could explain the protection mechanisms in place. This mechanism, potentially used by Dascyllus trimaculatus juveniles, suggests a convergent strategy for mutualistic associations with sea anemones.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"39"},"PeriodicalIF":4.4,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424908","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":"Phylogenomics of angiosperms based on mitochondrial genes: insights into deep node relationships.","authors":"Dongliang Lin, Bingyi Shao, Zhiyuan Gao, Jianwu Li, Zhanghai Li, Tingyu Li, Weichang Huang, Xin Zhong, Chao Xu, Mark W Chase, Xiaohua Jin","doi":"10.1186/s12915-025-02135-9","DOIUrl":"10.1186/s12915-025-02135-9","url":null,"abstract":"<p><strong>Background: </strong>Angiosperms are the largest plant group and play an essential role in the biosphere. Phylogenetic relationships of many families and orders remain contentious, and, in an attempt to address these, we performed the most extensive sampling of mitochondrial genes to date.</p><p><strong>Results: </strong>We reconstructed a seed plant phylogenetic framework based on 41 mitochondrial protein-coding sequences (mtCDSs), representing 335 families and 63 orders with 481 angiosperm species. The results for major clades of angiosperms produced moderate to strong support (> 70% bootstrap) for more than 80% of nodes and strong support for most orders. Eight major nodes were supported, including the three paraphyletic ANA orders (Amborellales, Nymphaeales, and Austrobaileyales) and five major core-angiosperm clades. Chloranthales and Ceratophyllales are sister to the eudicots, whereas the monocots are sister to the magnoliids. Although well-supported, relationships within the asterids and rosids were in some cases unresolved or weakly supported, due to the low levels of variability detected in these genes.</p><p><strong>Conclusions: </strong>Our results indicated that mitochondrial genomic data were effective at resolving deep node relationships of angiosperm phylogeny and thus represent an important resource for phylogenetics and evolutionary studies of angiosperm.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"45"},"PeriodicalIF":4.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413477","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":"SpaCcLink: exploring downstream signaling regulations with graph attention network for systematic inference of spatial cell-cell communication.","authors":"Jingtao Liu, Litian Ma, Fen Ju, Chenguang Zhao, Liang Yu","doi":"10.1186/s12915-025-02141-x","DOIUrl":"10.1186/s12915-025-02141-x","url":null,"abstract":"<p><strong>Background: </strong>Cellular communication is vital for the proper functioning of multicellular organisms. A comprehensive analysis of cellular communication demands the consideration not only of the binding between ligands and receptors but also of a series of downstream signal transduction reactions within cells. Thanks to the advancements in spatial transcriptomics technology, we are now able to better decipher the process of cellular communication within the cellular microenvironment. Nevertheless, the majority of existing spatial cell-cell communication algorithms fail to take into account the downstream signals within cells.</p><p><strong>Results: </strong>In this study, we put forward SpaCcLink, a cell-cell communication analysis method that takes into account the downstream influence of individual receptors within cells and systematically investigates the spatial patterns of communication as well as downstream signal networks. Analyses conducted on real datasets derived from humans and mice have demonstrated that SpaCcLink can help in identifying more relevant ligands and receptors, thereby enabling us to systematically decode the downstream genes and signaling pathways that are influenced by cell-cell communication. Comparisons with other methods suggest that SpaCcLink can identify downstream genes that are more closely associated with biological processes and can also discover reliable ligand-receptor relationships.</p><p><strong>Conclusions: </strong>By means of SpaCcLink, a more profound and all-encompassing comprehension of the mechanisms underlying cellular communication can be achieved, which in turn promotes and deepens our understanding of the intricate complexity within organisms.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"44"},"PeriodicalIF":4.4,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405183","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":"Wolbachia enhances the survival of Drosophila infected with fungal pathogens.","authors":"Jessamyn I Perlmutter, Aylar Atadurdyyeva, Margaret E Schedl, Robert L Unckless","doi":"10.1186/s12915-025-02130-0","DOIUrl":"10.1186/s12915-025-02130-0","url":null,"abstract":"<p><strong>Background: </strong>Wolbachia bacteria of arthropods are at the forefront of basic and translational research on multipartite host-symbiont-pathogen interactions. These vertically transmitted microbes are the most widespread endosymbionts on the planet due to factors including host reproductive manipulation and fitness benefits. Importantly, some strains of Wolbachia can inhibit viral pathogenesis within and between arthropod hosts. Mosquitoes carrying the wMel Wolbachia strain of Drosophila melanogaster have a greatly reduced capacity to spread viruses like dengue and Zika to humans. While significant research efforts have focused on viruses, relatively little attention has been given to Wolbachia-fungal interactions despite the ubiquity of fungal entomopathogens in nature.</p><p><strong>Results: </strong>Here, we demonstrate that Wolbachia increase the longevity of their Drosophila melanogaster hosts when challenged with a spectrum of yeast and filamentous fungal pathogens. We find that this pattern can vary based on host genotype, sex, and fungal species. Further, Wolbachia correlates with higher fertility and reduced pathogen titers during initial fungal infection, indicating a significant fitness benefit. Finally, RNA sequencing results show altered expression of many immune and stress response genes in the context of Wolbachia and fungal infection, suggesting host immunity may be involved in the mechanism.</p><p><strong>Conclusions: </strong>This study demonstrates Wolbachia's protective role in diverse fungal pathogen interactions and determines that the phenotype is broad, but with several variables that influence both the presence and strength of the phenotype. It also is a critical step forward to understanding how symbionts can protect their hosts from a variety of pathogens.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"42"},"PeriodicalIF":4.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11817339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397953","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}