EMBO ReportsPub Date : 2025-05-01Epub Date: 2025-04-24DOI: 10.1038/s44319-025-00462-0
Liselotte Højgaard
{"title":"FP10 - the Competitiveness Fund for Europe.","authors":"Liselotte Højgaard","doi":"10.1038/s44319-025-00462-0","DOIUrl":"10.1038/s44319-025-00462-0","url":null,"abstract":"","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2485-2486"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983755","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}
EMBO ReportsPub Date : 2025-05-01Epub Date: 2025-03-20DOI: 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":"<p><p>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 tRNA<sub>CAU</sub>, 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.</p>","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}
EMBO ReportsPub Date : 2025-05-01Epub Date: 2025-04-23DOI: 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
{"title":"Unlocking success : The power of change management in core facilities.","authors":"Saskia Lippens, Katerina Hoskova, Ondrej Hradil, Jutta Steinkoetter, Henri G A M Van Luenen, Geert Van Minnebruggen, Danielle Hoyle","doi":"10.1038/s44319-025-00445-1","DOIUrl":"10.1038/s44319-025-00445-1","url":null,"abstract":"","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":"26 9","pages":"2227-2231"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974777","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}
EMBO ReportsPub Date : 2025-05-01DOI: 10.1038/s44319-025-00465-x
G Paolo Dotto
{"title":"Beyond good and evil : The pursuit of philosophical and scientific truth in a time of moral ambiguity.","authors":"G Paolo Dotto","doi":"10.1038/s44319-025-00465-x","DOIUrl":"10.1038/s44319-025-00465-x","url":null,"abstract":"","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2489-2493"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988092","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}
EMBO ReportsPub Date : 2025-04-01Epub Date: 2025-03-24DOI: 10.1038/s44319-025-00424-6
Sonia Vasconcelos, Ana Marušić
{"title":"Gen AI and research integrity: Where to now? : The integration of Generative AI in the research process challenges well-established definitions of research integrity.","authors":"Sonia Vasconcelos, Ana Marušić","doi":"10.1038/s44319-025-00424-6","DOIUrl":"10.1038/s44319-025-00424-6","url":null,"abstract":"","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1923-1928"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699921","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}
EMBO ReportsPub Date : 2025-04-01Epub Date: 2025-03-07DOI: 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":"<p><p>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.</p>","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}
EMBO ReportsPub Date : 2025-04-01Epub Date: 2025-03-18DOI: 10.1038/s44319-025-00417-5
Alfonso Valencia
{"title":"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.","authors":"Alfonso Valencia","doi":"10.1038/s44319-025-00417-5","DOIUrl":"10.1038/s44319-025-00417-5","url":null,"abstract":"","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1679-1681"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656562","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}
EMBO ReportsPub Date : 2025-04-01Epub Date: 2025-03-03DOI: 10.1038/s44319-025-00407-7
M Emre Kus, Cagatay Sahin, Emre Kilic, Arda Askin, M Mert Ozgur, Gokhan Karahanogullari, Ahmet Aksit, Ryan M O'Connell, H Atakan Ekiz
{"title":"TCGEx: a powerful visual interface for exploring and analyzing cancer gene expression data.","authors":"M Emre Kus, Cagatay Sahin, Emre Kilic, Arda Askin, M Mert Ozgur, Gokhan Karahanogullari, Ahmet Aksit, Ryan M O'Connell, H Atakan Ekiz","doi":"10.1038/s44319-025-00407-7","DOIUrl":"10.1038/s44319-025-00407-7","url":null,"abstract":"<p><p>Analyzing gene expression data from the Cancer Genome Atlas (TCGA) and similar repositories often requires advanced coding skills, creating a barrier for many researchers. To address this challenge, we developed The Cancer Genome Explorer (TCGEx), a user-friendly, web-based platform for conducting sophisticated analyses such as survival modeling, gene set enrichment analysis, unsupervised clustering, and linear regression-based machine learning. TCGEx provides access to preprocessed TCGA data and immune checkpoint inhibition studies while allowing integration of user-uploaded data sets. Using TCGEx, we explore molecular subsets of human melanoma and identify microRNAs associated with intratumoral immunity. These findings are validated with independent clinical trial data on immune checkpoint inhibitors for melanoma and other cancers. In addition, we identify cytokine genes that can be used to predict treatment responses to various immune checkpoint inhibitors prior to treatment. Built on the R/Shiny framework, TCGEx offers customizable features to adapt analyses for diverse research contexts and generate publication-ready visualizations. TCGEx is freely available at https://tcgex.iyte.edu.tr , providing an accessible tool to extract insights from cancer transcriptomics data.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1863-1890"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540592","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":"Sertm2 is a conserved micropeptide that promotes GDNF-mediated motor neuron subtype specification.","authors":"Fang-Yu Hsu, Ya-Ping Yen, Hung-Chi Fan, Mien Chang, Jun-An Chen","doi":"10.1038/s44319-025-00400-0","DOIUrl":"10.1038/s44319-025-00400-0","url":null,"abstract":"<p><p>Small open-reading frame-encoded micropeptides within long noncoding RNAs (lncRNAs) are often overlooked due to their small size and low abundance. However, emerging evidence links these micropeptides to various biological pathways, though their roles in neural development and neurodegeneration remain unclear. Here, we investigate the function of murine micropeptide Sertm2, encoded by the lncRNA A730046J19Rik, during spinal motor neuron (MN) development. Sertm2 is predicted to be a conserved transmembrane protein found in both mouse and human, with subcellular analysis revealing that it is enriched in the cytoplasm and neurites. By generating C terminally Flag-tagged Sertm2 and expressing it from the A730046J19Rik locus, we demonstrate that the Sertm2 micropeptide localizes in spinal MNs in mice. The GDNF signaling-induced Etv4<sup>+</sup> motor pool is impaired in Sertm2 knockout mice, which display motor nerve arborization defects that culminate in impaired motor coordination and muscle weakness. Similarly, human SERTM2 knockout iPSC-derived MNs also display reduced ETV4<sup>+</sup> motor pools, highlighting that Sertm2 is a novel, evolutionarily conserved micropeptide essential for maintaining GDNF-induced MN subtype identity.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2013-2043"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663009","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}
EMBO ReportsPub Date : 2025-04-01Epub Date: 2025-02-27DOI: 10.1038/s44319-025-00392-x
Sara Basse Hansen, Rasmus Kock Flygaard, Magnus Kjaergaard, Poul Nissen
{"title":"Structure of the [Ca]E2P intermediate of Ca<sup>2+</sup>-ATPase 1 from Listeria monocytogenes.","authors":"Sara Basse Hansen, Rasmus Kock Flygaard, Magnus Kjaergaard, Poul Nissen","doi":"10.1038/s44319-025-00392-x","DOIUrl":"10.1038/s44319-025-00392-x","url":null,"abstract":"<p><p>Active transport by P-type Ca<sup>2+</sup>-ATPases maintain internal calcium stores and a low cytosolic calcium concentration. Structural studies of mammalian sarco/endoplasmic reticulum Ca<sup>2+</sup>-ATPases (SERCA) have revealed several steps of the transport cycle, but a calcium-releasing intermediate has remained elusive. Single-molecule FRET studies of the bacterial Ca<sup>2+</sup>-ATPase LMCA1 revealed an intermediate of the transition between so-called [Ca]E1P and E2P states and suggested that calcium release from this intermediate was the essentially irreversible step of transport. Here, we present a 3.5 Å resolution cryo-EM structure for a four-glycine insertion mutant of LMCA1 in a lipid nanodisc obtained under conditions with calcium and ATP and adopting such an intermediate state, denoted [Ca]E2P. The cytosolic domains are positioned in the E2P-like conformation, while the calcium-binding transmembrane (TM) domain adopts a calcium-bound E1P-ADP-like conformation. Missing density for the E292 residue at the calcium site (the equivalent of SERCA1a E309) suggests flexibility and a site poised for calcium release and proton uptake. The structure suggests a mechanism where ADP release and re-organization of the cytoplasmic domains precede calcium release.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1709-1723"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522911","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}