FEBS Open Bio最新文献_第10页

Refinement of amino-acid conformation vs. difference density maps in time-resolved serial femtosecond crystallography data analysis. 时间分辨序列飞秒晶体学数据分析中氨基酸构象与差密度图的改进。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-06-05 DOI: 10.1002/2211-5463.70250

Meng Iao Fong, Yuhei Hosokawa, Lars Oliver Essen, Manuel Maestre-Reyna

引用次数: 0

Hyperosmotic stress-induced redistribution of pre-mRNA cleavage factor I subunits is associated with shifts in alternative polyadenylation. 高渗应激诱导的前mrna切割因子I亚基的重新分配与选择性聚腺苷化的转移有关。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-06-04 DOI: 10.1002/2211-5463.70278

Hitomi Soumiya, Masatake Osawa, Hidefumi Fukumitsu

{"title":"Hyperosmotic stress-induced redistribution of pre-mRNA cleavage factor I subunits is associated with shifts in alternative polyadenylation.","authors":"Hitomi Soumiya, Masatake Osawa, Hidefumi Fukumitsu","doi":"10.1002/2211-5463.70278","DOIUrl":"10.1002/2211-5463.70278","url":null,"abstract":"Alternative polyadenylation (APA) is an important mechanism of cellular stress response mediated in part by the cleavage factor Im (CFIm) complex. However, the spatiotemporal dynamics and regulatory activity of the mammalian CFIm complex during stress remain poorly understood. In this study, we determined the effect of moderate hyperosmotic stress on CFIm localization and APA profiles in HEK293 cells. Using a dual-normalization strategy that included 18S rRNA- and a CDS-based ratiometric qPCR, we identified a significant shift toward proximal polyadenylation sites (PAS) in the established CFIm targets, NUDT21 (encoding CFIm25) and DICER1. Notably, these APA dynamics displayed distinct kinetic profiles influenced by the metabolic environment: While the NUDT21 L-3'UTR/CDS ratio recovered to baseline by Day 4, DICER1 exhibited a serum-dependent response, showing a progressive decline under low-serum conditions but recovering under high-serum conditions. Crucially, these alterations were absent in non-target multi-PAS genes such as GOLGA2 and preceded any substantial reduction in total mRNA abundance, suggesting these effects represent a targeted regulatory event rather than a nonspecific byproduct of transcriptional decline. Mechanistically, hyperosmotic stress triggers a transient, coordinated redistribution of CFIm25 and CFIm68 from the nucleus to the cytoplasm, while total cellular protein concentrations remain stable. We propose that this spatial shift creates a 'stoichiometric bottleneck' within the nuclear CFIm pool, effectively limiting the processing of distal PAS. This 'stoichiometric stress response' offers a robust mechanistic framework linking subnuclear protein reorganization to the rapid reprogramming of the 3'UTR landscape, providing new insights into how cells modulate gene expression potential during osmotic adaptation.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148162507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular characterization of covRS mutations in M1_UK Streptococcus pyogenes. M1UK化脓性链球菌covRS突变的分子特征

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-06-04 DOI: 10.1002/2211-5463.70275

Jarrad Pritchard, Emma-Jayne Proctor, Jiawa Wang, Nikolas P Johnston, Andrew Hayes, Georgia McCorkell, Haibo Yu, Jai Tree, Mark R Davies, Mark J Walker, Ronald Sluyter, Stephan Brouwer, Martina L Sanderson-Smith

{"title":"Molecular characterization of covRS mutations in M1UK Streptococcus pyogenes.","authors":"Jarrad Pritchard, Emma-Jayne Proctor, Jiawa Wang, Nikolas P Johnston, Andrew Hayes, Georgia McCorkell, Haibo Yu, Jai Tree, Mark R Davies, Mark J Walker, Ronald Sluyter, Stephan Brouwer, Martina L Sanderson-Smith","doi":"10.1002/2211-5463.70275","DOIUrl":"10.1002/2211-5463.70275","url":null,"abstract":"Increasingly invasive Streptococcus pyogenes disease has been linked to the emergence of the M1UK lineage. Here, we used a murine infection model to investigate the ability of M1UK to accumulate mutations in the covRS operon which regulates up to 15% of the genome, including multiple virulence factors. Assessing an M1UK isolate carrying an Ala111Val nonsynonymous mutation showed that in vitro, M1UK CovRAla111Val was characterized by decreased SpeB expression, increased streptolysin O and hyaluronic acid capsule expression, and resistance to neutrophil killing. While Ala111Val represents a minor biochemical change, we show that CovRAla111Val prevents phosphorylation-dependent dimerization. Specifically, molecular dynamics simulations suggest CovRAla111Val destabilizes the interface between CovR monomers that facilitate dimerization, likely inhibiting CovR dimer-mediated transcriptional repression and promoting altered virulence factor expression. Ultimately, this work underscores the need for ongoing epidemiological surveillance to monitor the emergence of such mutations within the already hypervirulent M1UK lineage.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148162443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Time-restricted feeding prior to Mycobacterium tuberculosis infection reduces tissue CD4+ T cells with limited impact on bacterial clearance. 结核分枝杆菌感染前的限时喂养减少了组织CD4+ T细胞，但对细菌清除的影响有限。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-06-04 DOI: 10.1002/2211-5463.70263

Ashish Gupta, Nidhi Yadav, Subhasmita Das, R Rajendra Kumar Reddy, Nupur Sharma, Amol Ratnakar Suryawanshi, Jaswinder Singh Maras, Ranjan Kumar Nanda

{"title":"Time-restricted feeding prior to Mycobacterium tuberculosis infection reduces tissue CD4+ T cells with limited impact on bacterial clearance.","authors":"Ashish Gupta, Nidhi Yadav, Subhasmita Das, R Rajendra Kumar Reddy, Nupur Sharma, Amol Ratnakar Suryawanshi, Jaswinder Singh Maras, Ranjan Kumar Nanda","doi":"10.1002/2211-5463.70263","DOIUrl":"10.1002/2211-5463.70263","url":null,"abstract":"The effects of time-restricted feeding (TRF) on immune responses during bacterial infection are not well-studied. Here, we subjected mice (6-8 weeks, male) to 8 h of TRF for 30 days and then infected them with a low dose of Mycobacterium tuberculosis (Mtb) H37Rv. During the first 15 days, TRF improved glucose tolerance with marginal weight loss. However, global serum and liver metabolomics alongside liver proteomics indicated that TRF perturbed fatty acid biosynthesis and degradation, steroid hormone biosynthesis, and tyrosine metabolism. Together, these results indicate that TRF potentially affected the distribution and functionality of host immune cells. TRF mice had similar mycobacterial burdens in lungs and spleen at 21 days postinfection but had significantly lower CD3+ T cells in bone marrow and CD4+ T cells in both bone marrow and lungs. Ultimately, we show that TRF induced changes in amino acid and lipid metabolism persist during Mtb infection.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluating the involvement of autolysosomes in the nuclear translocation of fluorescent proteins. 评价自溶酶体在荧光蛋白核易位中的作用。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-06-03 DOI: 10.1002/2211-5463.70279

Keiichi Ikeda

{"title":"Evaluating the involvement of autolysosomes in the nuclear translocation of fluorescent proteins.","authors":"Keiichi Ikeda","doi":"10.1002/2211-5463.70279","DOIUrl":"10.1002/2211-5463.70279","url":null,"abstract":"During the construction of control mCherry-labelled HeLa cells, we unexpectedly observed red fluorescence in cell nuclei and therefore investigated the mechanisms underlying the transport of fluorescent proteins (FPs) into the nuclei. We confirmed that mCherry and mCherry/EGFP tandem FPs were translocated into the nucleus and found that FPs are taken up by autophagosomes and translocated into the nucleus after entering lysosomes. However, pharmacological inhibition of autophagosome-lysosome fusion and syntaxin 17 knockdown decreased the nuclear translocation of mCherry in HeLa cells, but not in HepG2 cells, indicating that autophagy may also be involved in the nuclear translocation of FPs. Electron microscopy revealed that autolysosomes fused with the nuclear envelope and continued into the nucleus in HeLa cells but not in HepG2 cells, indicating that autophagy is involved in the nuclear translocation of FPs in HeLa cells. In addition, immunotransmission electron microscopy revealed that FPs can be transported directly into the nucleus through the nuclear pore complex. Our results suggest that autophagy is involved in the intracellular degradation and nuclear translocalisation of FPs.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148149055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Loss of AMBRA1 activates MAPK and angiogenesis signaling pathways in melanoma cells. AMBRA1的缺失激活了黑色素瘤细胞中MAPK和血管生成信号通路。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-06-02 DOI: 10.1002/2211-5463.70281

Milad Ibrahim, Marco Corazzari, Iman Osman, Jane Armstrong, Noel Carter

引用次数: 0

Tumor-stromal crosstalk and macrophage enrichment are associated with chemotherapy response in bladder cancer 肿瘤间质串扰和巨噬细胞富集与膀胱癌化疗反应相关。

IF 2.3 4区生物学

FEBS Open Bio Pub Date : 2026-06-01 Epub Date: 2025-12-12 DOI: 10.1002/2211-5463.70179

Sophie Leypold, Janik Riese, Lancelot Seillier, Mark Kühnel, Julia Pannhausen, Charlotte O. J. Fröhlich, Christian Martin, Peter Boor, Matthias Saar, Danny D. Jonigk, Nadine T. Gaisa, Michael Rose

{"title":"Tumor-stromal crosstalk and macrophage enrichment are associated with chemotherapy response in bladder cancer","authors":"Sophie Leypold, Janik Riese, Lancelot Seillier, Mark Kühnel, Julia Pannhausen, Charlotte O. J. Fröhlich, Christian Martin, Peter Boor, Matthias Saar, Danny D. Jonigk, Nadine T. Gaisa, Michael Rose","doi":"10.1002/2211-5463.70179","DOIUrl":"10.1002/2211-5463.70179","url":null,"abstract":"Gemcitabine/Cisplatin (Gem/Cis) chemotherapy is a standard treatment for muscle-invasive bladder cancer (MIBC) but yields suboptimal response rates. The contribution of tumor-stromal crosstalk and macrophage recruitment to chemoresistance remains poorly understood. This study investigated these mechanisms using a functional ex vivo bladder cancer tissue slice model combined with n = 64 spatial transcriptomics. Spatial analysis revealed transcriptomic changes involving the immunomodulating gene SPP1 that has been also recently presented as a putative predictive biomarker for neoadjuvant chemotherapy in bladder cancer. Moreover, Non-Responders exhibited upregulation of chemokines including CXCL1 and CXCL8 and enrichment of immunoregulatory M2 macrophages in tumor regions, suggesting active macrophage recruitment from the stroma. On the contrary, Responders showed upregulation of complement components, proinflammatory macrophage subsets and signals associated with cytotoxic lymphocyte recruitment. Tissue slices corresponding cell cultures confirmed overexpression of immunomodulating markers including checkpoints PD-L1 and PD-L2 in Non-Responder cancer cells upon Gem/Cis treatment. Using TCGA bladder cancer data, the transcriptomic gene set was further validated revealing a prognostic signature associated with patients' outcome. These findings uncover a novel mechanism of chemotherapy resistance in bladder cancer driven by tumor–stromal interactions and macrophage recruitment and suggest that targeting macrophage infiltration may improve chemotherapy response in bladder cancer.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 6","pages":"1197-1212"},"PeriodicalIF":2.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.70179","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

dUTPase is essential in zebrafish development and possesses several single-nucleotide variants with pronounced structural and functional consequences dUTPase在斑马鱼的发育中是必不可少的，并且具有几个单核苷酸变体，具有明显的结构和功能后果。

IF 2.3 4区生物学

FEBS Open Bio Pub Date : 2026-06-01 Epub Date: 2025-12-16 DOI: 10.1002/2211-5463.70176

Viktória Perey-Simon, Angéla Békesi, Latifa Kazzazy, Jázmin Mihály, Máté Varga, Beáta G. Vértessy, Kinga Nyíri

{"title":"dUTPase is essential in zebrafish development and possesses several single-nucleotide variants with pronounced structural and functional consequences","authors":"Viktória Perey-Simon, Angéla Békesi, Latifa Kazzazy, Jázmin Mihály, Máté Varga, Beáta G. Vértessy, Kinga Nyíri","doi":"10.1002/2211-5463.70176","DOIUrl":"10.1002/2211-5463.70176","url":null,"abstract":"Genome stability and faithful DNA replication are essential for cell viability. Numerous interlinked pathways in DNA damage recognition, repair and maintenance of physiologically competent nucleotide pools contribute to providing a solid framework to uphold DNA integrity. The enzyme family of dUTPases is involved in balancing the appropriate nucleotide pools by removing dUTP from the cellular milieu and providing dUMP for thymidylate de novo biosynthesis. In the present study, we show that dUTPase is essential for normal development in zebrafish. We also found that the fish dut gene from different genomes contains several single-nucleotide variations (SNPs). This observation prompted structural and functional investigations of the SNP variants at the protein level. Results indicated that none of the mutation sites of the variants are within the active site. Still, one of the variants showed drastically lower protein stability and catalytic efficiency as compared to the other two dUTPase variants, underlining the importance of detailed characterization of SNPs even at sites distant from the active site. In conclusion, we demonstrate the importance of dUTPase function in zebrafish development and unveil the role of several point mutations on protein structure and function.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 6","pages":"1087-1101"},"PeriodicalIF":2.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.70176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multi-omics and low-input proteomics profiling reveals dynamic regulation driving pluripotency initiation in early mouse embryos 多组学和低输入蛋白质组学分析揭示了驱动早期小鼠胚胎多能性起始的动态调控。

IF 2.3 4区生物学

FEBS Open Bio Pub Date : 2026-06-01 Epub Date: 2026-01-03 DOI: 10.1002/2211-5463.70184

Wanqiong Li, Xi Xiao, Lingbin Qi, Chanyi Li, Sirui Song, Jiaying Qin, Zhigang Xue, Jinfeng Xue, Huaifang Li

{"title":"Multi-omics and low-input proteomics profiling reveals dynamic regulation driving pluripotency initiation in early mouse embryos","authors":"Wanqiong Li, Xi Xiao, Lingbin Qi, Chanyi Li, Sirui Song, Jiaying Qin, Zhigang Xue, Jinfeng Xue, Huaifang Li","doi":"10.1002/2211-5463.70184","DOIUrl":"10.1002/2211-5463.70184","url":null,"abstract":"Pre-implantation of a mouse embryo is a process of transitioning from totipotency to pluripotency. However, the regulatory mechanisms underlining this transition remain poorly understood. We combined single-cell transcriptomic analysis, epigenetic profiling, low-input proteomics and functional validation experiments with the aim of gaining insight into the dynamic regulatory networks underlying the transition from the eight-cell to the 16-cell stage of mouse development. Transcriptomic analysis and H3K4me3 modification profiling, combined with functional half of the blastomeres biopsy, revealed that eight-cell mouse embryos retained residual totipotency-related molecular features and developmental potential. Furthermore, we identified dynamic cytoskeletal remodeling, regulated in part by the ubiquitin-proteasome system, as a prominent molecular event during the transition from the eight-cell to the 16-cell stage. Collectively, our findings highlight the eight-cell stage as a critical developmental window characterized by gradual restriction of developmental potential, and also underscore cytoskeletal remodeling as a key molecular process coinciding with the onset of pluripotency. These results provide insight into the biological processes underlying totipotent features and how these are progressively attenuated during early mouse embryogenesis.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 6","pages":"1102-1114"},"PeriodicalIF":2.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.70184","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alcohol-induced altered glycans in human tracheal epithelial cells promote bacterial adhesion 酒精诱导的人气管上皮细胞聚糖改变可促进细菌粘附。

IF 2.3 4区生物学

FEBS Open Bio Pub Date : 2026-06-01 Epub Date: 2025-12-21 DOI: 10.1002/2211-5463.70188

Pi-Wan Cheng, Souvik Datta, Derrick R. Samuelson

{"title":"Alcohol-induced altered glycans in human tracheal epithelial cells promote bacterial adhesion","authors":"Pi-Wan Cheng, Souvik Datta, Derrick R. Samuelson","doi":"10.1002/2211-5463.70188","DOIUrl":"10.1002/2211-5463.70188","url":null,"abstract":"Heavy alcohol drinking is known to increase the risk of bacterial pneumonia. However, the link between alcohol levels and risk of infection remains underexplored. Recently, we found that alcohol induced α2-6sialo mucin O-glycans in human tracheobronchial epithelial cells, which mediated the killing of U937 macrophages. By extending this study, we focus here on whether altered glycans induced by alcohol in human airway epithelial cells can promote adhesion of Klebsiella pneumoniae (Kp) and Streptococcus pneumoniae (Sp). We have found that exposure of human tracheal epithelial cells to alcohol also induces high mannose N-glycans terminated with α3mannose and increases adhesion of Kp, which is inhibited by αmethylmannoside or aldehyde dehydrogenase 2 activator 1. Further, the α2-6sialo mucin O-glycans induced by alcohol in human tracheal epithelial cells also enhance the adhesion of Sp, which is inhibited by ovine submaxillary mucin or aldehyde dehydrogenase 2 activator 1. We conclude that alcohol induces altered glycans in human airway epithelial cells, which increase the risk of bacterial pneumonia by compromising immune function and promoting the adhesion of Kp and Sp.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 6","pages":"1142-1149"},"PeriodicalIF":2.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.70188","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0