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Brief but not bland. 简短但不乏味。
IF 6.2 1区 生物学
EMBO Reports Pub Date : 2025-09-01 Epub Date: 2025-09-08 DOI: 10.1038/s44319-025-00570-x
Howy Jacobs
{"title":"Brief but not bland.","authors":"Howy Jacobs","doi":"10.1038/s44319-025-00570-x","DOIUrl":"10.1038/s44319-025-00570-x","url":null,"abstract":"","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4391-4392"},"PeriodicalIF":6.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029124","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
How stupid has science been? 科学有多愚蠢?
IF 6.2 1区 生物学
EMBO Reports Pub Date : 2025-09-01 Epub Date: 2025-08-26 DOI: 10.1038/s44319-025-00562-x
Arthur Caplan
{"title":"How stupid has science been?","authors":"Arthur Caplan","doi":"10.1038/s44319-025-00562-x","DOIUrl":"10.1038/s44319-025-00562-x","url":null,"abstract":"","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4395-4396"},"PeriodicalIF":6.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947048","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
The E3 ubiquitin ligase adaptor KLHL8 targets ZAR1 to regulate maternal mRNA degradation in oocytes. E3泛素连接酶接头KLHL8靶向ZAR1调节母细胞mRNA降解。
IF 6.2 1区 生物学
EMBO Reports Pub Date : 2025-09-01 Epub Date: 2025-07-28 DOI: 10.1038/s44319-025-00537-y
Huizhen Fan, Ruyi Liu, Ran Yu, Biaobang Chen, Qiaoli Li, Jian Mu, Weijie Wang, Tianyu Wu, Lin He, Lei Wang, Qing Sang, Zhihua Zhang
{"title":"The E3 ubiquitin ligase adaptor KLHL8 targets ZAR1 to regulate maternal mRNA degradation in oocytes.","authors":"Huizhen Fan, Ruyi Liu, Ran Yu, Biaobang Chen, Qiaoli Li, Jian Mu, Weijie Wang, Tianyu Wu, Lin He, Lei Wang, Qing Sang, Zhihua Zhang","doi":"10.1038/s44319-025-00537-y","DOIUrl":"10.1038/s44319-025-00537-y","url":null,"abstract":"<p><p>Maternal protein homeostasis and timely degradation of maternal mRNAs are essential for meiotic cell-cycle progression and subsequent embryonic development, but the mechanisms of maternal protein degradation are poorly understood. Here, we show that KLHL8, a substrate adaptor of Cullin-RING E3 ubiquitin ligases, is highly expressed in mouse oocytes and co-localizes with mitochondria. Oocyte-specific deletion of Klhl8 causes oocyte maturation defects and female infertility. ZAR1, an RNA binding protein that is required for mitochondria-associated ribonucleoprotein domain (MARDO) dissolution, is specifically recognized and degraded by KLHL8-mediated ubiquitination. In Klhl8-deficient oocytes, ZAR1 accumulation causes abnormal MARDO and mitochondria clustering, correlating with impaired maternal mRNA decay. Supplementation with exogenous Klhl8 mRNA rescues the degradation of ZAR1 and the dissolution of the MARDO in Klhl8<sup>oo-/-</sup> oocytes. Taken together, our study shows that KLHL8 mediates the ubiquitination and degradation of ZAR1, thus regulating maternal mRNA clearance during oocyte maturation. These findings provide new insights into the roles of the ubiquitin proteasome system during oocyte maturation and establish an interaction network between ubiquitination modification, RNA binding proteins, and maternal mRNA.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4364-4387"},"PeriodicalIF":6.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728785","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
Hyperactive PLCG1 induces cell-autonomous and bystander T cell activation and drug resistance. 过度活跃的PLCG1诱导细胞自主和旁观者T细胞活化和耐药。
IF 6.2 1区 生物学
EMBO Reports Pub Date : 2025-09-01 Epub Date: 2025-08-12 DOI: 10.1038/s44319-025-00546-x
Longhui Zeng, Xinyan Zhang, Yiwei Xiong, Kazuki Sato, Nicole Hajicek, Yasunori Kogure, Keisuke Kataoka, Seishi Ogawa, John Sondek, Xiaolei Su
{"title":"Hyperactive PLCG1 induces cell-autonomous and bystander T cell activation and drug resistance.","authors":"Longhui Zeng, Xinyan Zhang, Yiwei Xiong, Kazuki Sato, Nicole Hajicek, Yasunori Kogure, Keisuke Kataoka, Seishi Ogawa, John Sondek, Xiaolei Su","doi":"10.1038/s44319-025-00546-x","DOIUrl":"10.1038/s44319-025-00546-x","url":null,"abstract":"<p><p>Phospholipase C gamma 1 (PLCG1) has been identified as the most frequently mutated gene in adult T-cell leukemia/lymphoma, suggesting a critical function of PLCG1 in driving T cell activation. However, it remains unclear how these mutations regulate T cell physiology and pathology. Here, we investigate three common leukemia/lymphoma-associated mutations (R48W, S345F, and D1165H). We discover that these mutations induce hyperactive T cell signaling and cause pro-survival phenotypes. PLCG1 mutants enhance LAT condensation, calcium influx, and ERK activation. They also promote T cell proliferation, upregulate cell adhesion molecules, induce cell aggregation, and confer resistance to Vorinostat, an FDA-approved drug for cutaneous T-cell lymphoma. The resistance depends on ERK signaling and can be reversed with an ERK inhibitor. Interestingly, PLCG1 mutants also induce bystander drug resistance in nearby cells expressing wild-type PLCG1. Mechanistically, alpha smooth muscle actin, which is specifically induced by PLCG1 mutants, directly binds PLCG1 to promote its activation. These results demonstrate that hyperactive PLCG1 promotes T cell survival and drug resistance by inducing non-canonical signaling.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4563-4586"},"PeriodicalIF":6.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834511","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
Dysfunctional mitochondria in ageing T cells: a perspective on mitochondrial quality control mechanisms. 老化T细胞中功能失调的线粒体:线粒体质量控制机制的观点。
IF 6.2 1区 生物学
EMBO Reports Pub Date : 2025-09-01 Epub Date: 2025-08-29 DOI: 10.1038/s44319-025-00536-z
Lin Luo, Ana Victoria Lechuga-Vieco, Clara Sattentau, Mariana Borsa, Anna Katharina Simon
{"title":"Dysfunctional mitochondria in ageing T cells: a perspective on mitochondrial quality control mechanisms.","authors":"Lin Luo, Ana Victoria Lechuga-Vieco, Clara Sattentau, Mariana Borsa, Anna Katharina Simon","doi":"10.1038/s44319-025-00536-z","DOIUrl":"10.1038/s44319-025-00536-z","url":null,"abstract":"<p><p>Dysfunctional mitochondria are a hallmark of T cell ageing and contribute to organismal ageing. This arises from the accumulation of reactive oxygen species (ROS), impaired mitochondrial dynamics, and inefficient removal of dysfunctional mitochondria. Both cell-intrinsic and cell-extrinsic mechanisms for removing mitochondria and their byproducts have been identified in T cells. In this review, we explore how T cells manage mitochondrial damage through changes in mitochondrial metabolism, mitophagy, asymmetric mitochondrial inheritance, and mitochondrial transfer, highlighting the impact of these mechanisms on T cell ageing and overall organismal ageing. We also discuss current therapeutic strategies aimed at removing dysfunctional mitochondria and their byproducts and propose potential new therapeutic targets that may reverse immune ageing or organismal ageing.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4402-4418"},"PeriodicalIF":6.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947046","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
Astrocyte diversity and subtypes: aligning transcriptomics with multimodal perspectives. 星形胶质细胞多样性和亚型:与多模态视角对齐转录组学。
IF 6.2 1区 生物学
EMBO Reports Pub Date : 2025-09-01 Epub Date: 2025-08-01 DOI: 10.1038/s44319-025-00529-y
Maroussia Hennes, Maria L Richter, Judith Fischer-Sternjak, Magdalena Götz
{"title":"Astrocyte diversity and subtypes: aligning transcriptomics with multimodal perspectives.","authors":"Maroussia Hennes, Maria L Richter, Judith Fischer-Sternjak, Magdalena Götz","doi":"10.1038/s44319-025-00529-y","DOIUrl":"10.1038/s44319-025-00529-y","url":null,"abstract":"<p><p>Astrocytes are considered a diverse cell population, carrying out many functions essential for supporting neuronal activity. The surge of sc/snRNA-sequencing data greatly expands our understanding of heterogeneous astrocyte gene expression, but also leads to confusion about the multitude of described astrocyte subtypes and substates in the mammalian brain. Here we discuss and review the definition of distinct subtypes and the evidence for this amongst astrocytes. Determining whether an astrocyte subtype represents a stable identity or a dynamic substate requires generalization of findings across datasets, incorporation of validation, and ideally, functional analyses. How to best achieve this is the focus of this review, including considerations about the different transcriptomic approaches. We further discuss the alignment of astrocyte subtype transcriptomes with other hallmarks, such as their position. These considerations are embedded in an overview of the current astrocyte heterogeneity knowledge as a basis for subtype definitions using different analysis techniques. Following technical and biological considerations of transcriptome analyses, we advocate for multimodal alignment to identify stable astrocyte subtypes.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4203-4218"},"PeriodicalIF":6.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764778","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
DNA methylation at retrotransposons protects the germline by preventing NRF1-mediated activation. 逆转录转座子上的DNA甲基化通过阻止nrf1介导的激活来保护种系。
IF 6.2 1区 生物学
EMBO Reports Pub Date : 2025-09-01 Epub Date: 2025-08-04 DOI: 10.1038/s44319-025-00526-1
Jessica Leismann, Styliani-Eirini Kanta, Ishita Amar, Anna Szczepińska, Monika Mielnicka, Giuseppe Petrosino, Anke Busch, Marion Scheibe, Pengxiang Wang, Yuan Wang, Falk Butter, Matthieu Boulard, Joan Barau
{"title":"DNA methylation at retrotransposons protects the germline by preventing NRF1-mediated activation.","authors":"Jessica Leismann, Styliani-Eirini Kanta, Ishita Amar, Anna Szczepińska, Monika Mielnicka, Giuseppe Petrosino, Anke Busch, Marion Scheibe, Pengxiang Wang, Yuan Wang, Falk Butter, Matthieu Boulard, Joan Barau","doi":"10.1038/s44319-025-00526-1","DOIUrl":"10.1038/s44319-025-00526-1","url":null,"abstract":"<p><p>Silencing evolutionary young retrotransposons by cytosine DNA methylation is essential for spermatogenesis, as failure to methylate their promoters leads to reactivation, meiotic failure, and infertility. How retrotransposons reactivate in the absence of DNA methylation is poorly understood. We show that upon defective DNA methylation, distinct retrotransposon families display unique expression patterns and chromatin landscapes during mouse spermatogenesis. We find that their reactivation in meiotic spermatocytes correlates with the loss of bivalent H3K4me3-H3K27me3 chromatin marks. Through proteomics and chromatin profiling, we identify NRF1 as a DNA methylation-sensitive transcription factor that transactivates unmethylated retrotransposons. Conditional germline knockout of Nrf1 in the absence of DNA methylation rescues the silencing of the most mutagenic retrotransposon in mice, namely Intracisternal A-particle or IAP. Our findings reveal that chromatin modifications together with a DNA methylation-sensitive transcription factor regulate retrotransposon expression in the absence of DNA methylation in spermatogenesis, revealing a mechanism by which retrotransposons proliferate in the germline after evading DNA methylation-based silencing.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4312-4339"},"PeriodicalIF":6.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783826","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
Shared worlds, shared minds : Strategies to develop physically and socially embedded AI. 共享的世界,共享的思想:开发物理和社会嵌入式人工智能的策略。
IF 6.2 1区 生物学
EMBO Reports Pub Date : 2025-09-01 Epub Date: 2025-08-20 DOI: 10.1038/s44319-025-00549-8
Giovanni Pezzulo, Thomas Parr, Karl J Friston
{"title":"Shared worlds, shared minds : Strategies to develop physically and socially embedded AI.","authors":"Giovanni Pezzulo, Thomas Parr, Karl J Friston","doi":"10.1038/s44319-025-00549-8","DOIUrl":"10.1038/s44319-025-00549-8","url":null,"abstract":"","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4197-4202"},"PeriodicalIF":6.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947023","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
Peri-mitochondrial actin filaments inhibit Parkin assembly by disrupting ER-mitochondria contacts. 线粒体周围肌动蛋白丝通过破坏er -线粒体接触抑制Parkin组装。
IF 6.2 1区 生物学
EMBO Reports Pub Date : 2025-08-29 DOI: 10.1038/s44319-025-00561-y
Tak Shun Fung, Amrapali Ghosh, Maite R Zavala, Zuzana Nichtova, Dhavalkumar Shukal, Marco Tigano, Gyorgy Csordas, Henry N Higgs, Rajarshi Chakrabarti
{"title":"Peri-mitochondrial actin filaments inhibit Parkin assembly by disrupting ER-mitochondria contacts.","authors":"Tak Shun Fung, Amrapali Ghosh, Maite R Zavala, Zuzana Nichtova, Dhavalkumar Shukal, Marco Tigano, Gyorgy Csordas, Henry N Higgs, Rajarshi Chakrabarti","doi":"10.1038/s44319-025-00561-y","DOIUrl":"https://doi.org/10.1038/s44319-025-00561-y","url":null,"abstract":"<p><p>Mitochondrial damage represents a dramatic change in cellular homeostasis, necessitating metabolic adaptation and clearance of the damaged organelle. One rapid response to mitochondrial damage is peri-mitochondrial actin polymerization within 2 min, which we term ADA (Acute Damage-induced Actin). ADA is vital for a metabolic shift from oxidative phosphorylation to glycolysis upon mitochondrial dysfunction. In the current study, we investigated the effect of ADA on Pink1/Parkin mediated mitochondrial quality control. We show that inhibition of proteins involved in the ADA pathway significantly accelerates Parkin recruitment onto depolarized mitochondria. Addressing the mechanism by which ADA resists Parkin recruitment onto depolarized mitochondria, we found that ADA disrupts ER-mitochondria contacts in an Arp2/3 complex-dependent manner. Interestingly, overexpression of ER-mitochondria tethers overrides the effect of ADA, allowing rapid recruitment of not only Parkin but also LC3 after mitochondrial depolarization. During chronic mitochondrial dysfunction, Parkin and LC3 recruitment are completely blocked, which is reversed rapidly by inhibiting ADA. Taken together we show that ADA acts as a protective mechanism, delaying mitophagy following acute damage, and blocking mitophagy during chronic mitochondrial damage.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947014","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}
引用次数: 0
Direct visualization of HIV-1 core nuclear import and its interplay with the nuclear pore. 直接可视化HIV-1核心核输入及其与核孔的相互作用。
IF 6.2 1区 生物学
EMBO Reports Pub Date : 2025-08-29 DOI: 10.1038/s44319-025-00567-6
Zhen Hou, Stanley Fronik, Yao Shen, Long Chen, Christopher Thompson, Sarah Neumann, Peijun Zhang
{"title":"Direct visualization of HIV-1 core nuclear import and its interplay with the nuclear pore.","authors":"Zhen Hou, Stanley Fronik, Yao Shen, Long Chen, Christopher Thompson, Sarah Neumann, Peijun Zhang","doi":"10.1038/s44319-025-00567-6","DOIUrl":"https://doi.org/10.1038/s44319-025-00567-6","url":null,"abstract":"<p><p>Direct visualization of HIV-1 nuclear import through the nuclear pore complex (NPC) presents a technical challenge due to the rarity of this process. To enable systematic investigation, we developed a robust in situ system that mimics HIV-1 nuclear import in a near-native context using isolated HIV-1 virus like particles (VLP) cores and permeabilized CD4 + T lymphocyte (CEM) cells. This approach supports docking and translocation of abundant viral cores through nuclear pores into the nucleus. For high-resolution visualization, we implemented an integrated correlative approach to guide cryo-focused ion beam (cryo-FIB) milling and cryo-electron tomography (cryo-ET) imaging, enabling precise targeting and structural characterization of individual nuclear import events. Using this workflow, we visualized 510 HIV-1 VLP cores at distinct stages of nuclear import, capturing key snapshots of the full progression of nuclear import. Subsequent statistical and structural analyses allow classification of core morphologies and identification of translocation-associated remodeling in nuclear pores. This work provides a methodological foundation for dissecting HIV-1 and potentially other viruses nuclear import processes and post-entry events in a controlled and quantitative manner.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947021","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}
引用次数: 0
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