EMBO Reports最新文献_第10页

Syndecans and glycosaminoglycans influence B-cell development and activation. Syndecans和糖胺聚糖影响b细胞的发育和活化。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-03-28 DOI: 10.1038/s44319-025-00432-6

Craig I McKenzie, Alexandra R Dvorscek, Zhoujie Ding, Marcus J Robinson, Kristy O'Donnell, Catherine Pitt, Daniel T Ferguson, Jesse Mulder, Marco J Herold, David M Tarlinton, Isaak Quast

{"title":"Syndecans and glycosaminoglycans influence B-cell development and activation.","authors":"Craig I McKenzie, Alexandra R Dvorscek, Zhoujie Ding, Marcus J Robinson, Kristy O'Donnell, Catherine Pitt, Daniel T Ferguson, Jesse Mulder, Marco J Herold, David M Tarlinton, Isaak Quast","doi":"10.1038/s44319-025-00432-6","DOIUrl":"10.1038/s44319-025-00432-6","url":null,"abstract":"Syndecans (SDCs) are glycosaminoglycan-containing cell surface proteins with diverse functions in the immune system with SDC1 (CD138) and SDC4 expressed in B-lineage cells. Here, we show that stem cells lacking either molecule generate fewer B-cell progenitors but give rise to mature B cells in vivo. Deletion of the plasma cell \"marker\" CD138 has no effect on homeostatic or antigen-induced plasma cell formation. Naive B cells express high SDC4 and encounter with cognate antigen results in transient CD138 upregulation and SDC4 loss, both further modulated by IL-4, IL-21, and CD40 ligation. SDC4 is downregulated on germinal center B cells and absent on most memory B cells. Glycosaminoglycans such as those attached to SDCs, and heparin, a commonly used therapeutic, regulate survival and activation of naive B cells by limiting responsiveness to cognate antigen. Conversely, ablation of SDC4 results in increased baseline and antigen-induced B-cell activation. Collectively, our data reveal B-cell activation- and subset-dependent SDC expression and show that SDC4 and GAGs can limit antigen-induced activation to promote B-cell survival and expansion.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2435-2458"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742655","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}

引用次数: 0

Espin enhances confined cell migration by promoting filopodia formation and contributes to cancer metastasis. Espin通过促进丝状足形成和促进癌症转移来增强受限细胞的迁移。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-04-04 DOI: 10.1038/s44319-025-00437-1

Yan Wang, Peng Shi, Geyao Liu, Wei Chen, Ya-Jun Wang, Yiping Hu, Ao Yang, Tonghua Wei, Yu-Chen Chen, Ling Liang, Zheng Liu, Yan-Jun Liu, Congying Wu

{"title":"Espin enhances confined cell migration by promoting filopodia formation and contributes to cancer metastasis.","authors":"Yan Wang, Peng Shi, Geyao Liu, Wei Chen, Ya-Jun Wang, Yiping Hu, Ao Yang, Tonghua Wei, Yu-Chen Chen, Ling Liang, Zheng Liu, Yan-Jun Liu, Congying Wu","doi":"10.1038/s44319-025-00437-1","DOIUrl":"10.1038/s44319-025-00437-1","url":null,"abstract":"Genes regulating the finger-like cellular protrusions-filopodia have long been implicated in cancer metastasis. However, depleting the flat lamellipodia but retaining filopodia drastically hampers cell migration on spread surface, obscuring the role of filopodia in cell motility. It has been noticed recently that cells under confinement may employ distinct migratory machineries. However, the regulating factors have mainly been focused on cell blebbing, nuclear deformation and cell rear contractility, without much emphasis on cell protrusions and even less on filopodia. Here, by micropore-based screening, we identified espin as an active regulator for confined migration and that its overexpression was associated with metastasis. In comparison to fascin, espin showed stronger actin bundling in vitro and induced shorter and thicker filopodia in cells. Combining the imaging-compatible microchannels and DNA-based tension probes, we uncovered that espin overexpression induced excessive filopodia at the leading edge and along the sides, exerting force for confined migration. Our results demonstrate an important role for filopodia and the regulating protein-espin in confined cell migration and shed new light on cytoskeletal mechanisms underlying metastasis.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2574-2596"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788028","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}

引用次数: 0

Group A Streptococcal asparagine metabolism regulates bacterial virulence. A组链球菌天冬酰胺代谢调节细菌毒力。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-04-14 DOI: 10.1038/s44319-025-00447-z

Abhinay Sharma, Aparna Anand, Miriam Ravins, Xiaolan Zhang, Nicola Horstmann, Samuel A Shelburne, Kevin S McIver, Emanuel Hanski

{"title":"Group A Streptococcal asparagine metabolism regulates bacterial virulence.","authors":"Abhinay Sharma, Aparna Anand, Miriam Ravins, Xiaolan Zhang, Nicola Horstmann, Samuel A Shelburne, Kevin S McIver, Emanuel Hanski","doi":"10.1038/s44319-025-00447-z","DOIUrl":"10.1038/s44319-025-00447-z","url":null,"abstract":"Group A Streptococcus (GAS) causes various human diseases linked to virulome expression predominantly regulated by the two-component system (TCS), CovR/S. Here, we demonstrate that asparagine (Asn) presence in a minimal chemically defined medium increases virulence gene expression in a CovR-dependent fashion. It also decreases the transcription of asparagine synthetase (AsnA), the ABC transporter responsible for Asn uptake (GlnPQ), and that of the hemolysin toxins responsible for scavenging Asn from the host. Metabolomics data show that Asn availability increases intracellular ADP/ATP ratio, which enhances phosphatase activity in structurally related CovS sensors and is probably responsible for the Asn-mediated decrease in CovR phosphorylation. Mutants deficient in AsnA, GlnPQ, asparaginase, (AsnB) activities are attenuated in a mouse model of human GAS invasive soft tissue infection. The similarity between the mechanisms of Asn-mediated regulation of GAS virulence and tumor growth suggests that, as in cancer, components maintaining Asn homeostasis could be targeted for anti-GAS treatments.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2767-2791"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974615","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}

引用次数: 0

FP10 - the Competitiveness Fund for Europe. FP10 -欧洲竞争力基金。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-04-24 DOI: 10.1038/s44319-025-00462-0

Liselotte Højgaard

引用次数: 0

tRNA lysidinylation is essential for the minimal translation system in the Plasmodium falciparum apicoplast. tRNA溶苷基化对于恶性疟原虫顶质体的最小翻译系统至关重要。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-03-20 DOI: 10.1038/s44319-025-00420-w

Rubayet Elahi, Sean T Prigge

{"title":"tRNA lysidinylation is essential for the minimal translation system in the Plasmodium falciparum apicoplast.","authors":"Rubayet Elahi, Sean T Prigge","doi":"10.1038/s44319-025-00420-w","DOIUrl":"10.1038/s44319-025-00420-w","url":null,"abstract":"For decades, researchers have sought to define minimal translation systems to uncover fundamental principles of life and advance biotechnology. tRNAs, essential components of this machinery, decode mRNA codons into amino acids. The apicoplast of malaria parasites contains 25 tRNA isotypes in its organellar genome-the lowest number found in known translation systems. Efficient translation in such minimal systems depends heavily on post-transcriptional tRNA modifications. One such modification, lysidine at the wobble position (C34) of tRNACAU, distinguishes between methionine (AUG) and isoleucine (AUA) codons. tRNA isoleucine lysidine synthetase (TilS) produces lysidine, which is nearly ubiquitous in bacteria and essential for cellular viability. Here, we report a TilS ortholog (PfTilS) targeted to the apicoplast of Plasmodium falciparum. We demonstrate that PfTilS activity is essential for parasite survival and apicoplast function, likely due to its role in protein translation. This study is the first to characterize TilS in an endosymbiotic organelle, contributing to research on eukaryotic organelles and minimal translational systems. Moreover, the absence of lysidine in humans highlights a potential target for antimalarial strategies.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2300-2322"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669293","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}

引用次数: 0

Unlocking success : The power of change management in core facilities. 解锁成功：核心设施变革管理的力量。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-04-23 DOI: 10.1038/s44319-025-00445-1

Saskia Lippens, Katerina Hoskova, Ondrej Hradil, Jutta Steinkoetter, Henri G A M Van Luenen, Geert Van Minnebruggen, Danielle Hoyle

引用次数: 0

Beyond good and evil : The pursuit of philosophical and scientific truth in a time of moral ambiguity. 超越善恶：道德模糊时代对哲学和科学真理的追求。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 DOI: 10.1038/s44319-025-00465-x

G Paolo Dotto

引用次数: 0

Gen AI and research integrity: Where to now? : The integration of Generative AI in the research process challenges well-established definitions of research integrity. 新一代人工智能与研究诚信：何去何从？生成式人工智能在研究过程中的整合挑战了研究完整性的既定定义。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-03-24 DOI: 10.1038/s44319-025-00424-6

Sonia Vasconcelos, Ana Marušić

引用次数: 0

Modulating tumor immunity using advanced microbiome therapeutics producing an indole metabolite. 利用产生吲哚代谢物的先进微生物组疗法调节肿瘤免疫。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-03-07 DOI: 10.1038/s44319-025-00386-9

Troels Holger Vaaben, Ditte Olsen Lützhøft, Andreas Koulouktsis, Ida Melisa Dawoodi, Camilla Stavnsbjerg, Lasse Kvich, Ismail Gögenur, Ruben Vazquez-Uribe, Morten Otto Alexander Sommer

{"title":"Modulating tumor immunity using advanced microbiome therapeutics producing an indole metabolite.","authors":"Troels Holger Vaaben, Ditte Olsen Lützhøft, Andreas Koulouktsis, Ida Melisa Dawoodi, Camilla Stavnsbjerg, Lasse Kvich, Ismail Gögenur, Ruben Vazquez-Uribe, Morten Otto Alexander Sommer","doi":"10.1038/s44319-025-00386-9","DOIUrl":"10.1038/s44319-025-00386-9","url":null,"abstract":"The gut microbiome has emerged as a key player in modulating immune responses against cancer, suggesting that microbial interventions can enhance treatment outcomes. Indole metabolites produced by probiotic bacteria activate the aryl hydrocarbon receptor (AhR), a transcription factor important for immune cell regulation. Cancer patients with high plasma concentrations of these metabolites have shown improved survival. Building on these findings, we have engineered Escherichia coli Nissle 1917 to produce the AhR agonist indole-3-acetic acid. Delivery of indole-3-acetic acid by tumor-colonizing bacteria changes the tumor microenvironment in a murine model, significantly increasing levels of CXCL9 and IFN-γ and elevating tumor-infiltrating T-cell abundance and activation. Treatment with our engineered strain inhibits tumor growth, improves survival in syngeneic tumor models, and leads to long-lasting immunity in a tumor rechallenge experiment. Further investigation indicates that this immune modulation is driven by the direct activation of AhR by indole-3-acetic acid, leading to differential cytokine expression and a shift in immune cell composition within the tumor. This study highlights the importance of microbial metabolites in immune modulation and supports exploring microbiome-based therapies in oncology.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1688-1708"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585193","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}

引用次数: 0

Decentralized databases in biomedical research: lessons from recent events : The recent shutdown of critical health databases by the US CDC is a wake-up call for the research community about the vulnerability of centralised databases. 生物医学研究中的分散式数据库：从近期事件中吸取的教训.........：美国疾病控制与预防中心最近关闭了重要的健康数据库，这为研究界敲响了警钟，使他们认识到集中式数据库的脆弱性。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-03-18 DOI: 10.1038/s44319-025-00417-5

Alfonso Valencia

引用次数: 0