eLife最新文献

{"title":"Correction: Binding blockade between TLN1 and integrin β1 represses triple-negative breast cancer.","authors":"Yixiao Zhang, Lisha Sun, Haonan Li, Liping Ai, Qingtian Ma, Xinbo Qiao, Jie Yang, Hao Zhang, Xunyan Ou, Yining Wang, Guanglei Chen, Jinqi Xue, Xudong Zhu, Yu Zhao, Yongliang Yang, Caigang Liu","doi":"10.7554/eLife.107584","DOIUrl":"https://doi.org/10.7554/eLife.107584","url":null,"abstract":"<p><p></p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978694","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":"Characterisation and comparison of semen microbiota and bacterial load in men with infertility, recurrent miscarriage, or proven fertility.","authors":"Shahriar Mowla, Linda Farahani, Tharu Tharakan, Rhianna Davies, Goncalo D S Correia, Yun S Lee, Samit Kundu, Shirin Khanjani, Emad Sindi, Raj Rai, Lesley Regan, Dalia Khalifa, Ralf Henkel, Suks Minhas, Waljit S Dhillo, Jara Ben Nagi, Phillip Bennett, David A MacIntyre, Channa N Jayasena","doi":"10.7554/eLife.96090","DOIUrl":"https://doi.org/10.7554/eLife.96090","url":null,"abstract":"<p><p>Several studies have associated seminal microbiota abnormalities with male infertility but have yielded differing results owing to their limited sizes or depths of analyses. The semen microbiota during recurrent pregnancy loss (RPL) has not been investigated. Comprehensively assessing the seminal microbiota in men with reproductive disorders could elucidate its potential role in clinical management. We used semen analysis, terminal-deoxynucleotidyl-transferase-mediated-deoxyuridine-triphosphate-nick-end-labelling, Comet DNA fragmentation, luminol reactive oxidative species (ROS) chemiluminescence, and metataxonomic profiling of semen microbiota by 16S rRNA amplicon sequencing in this prospective, cross-sectional study to investigate composition and bacterial load of seminal bacterial genera and species, semen parameters, ROS, and sperm DNA fragmentation in men with reproductive disorders and proven fathers. 223 men were enrolled, including healthy men with proven paternity (n=63), the male partners in a couple encountering RPL (n=46), men with male factor infertility (n=58), and the male partners of couples with unexplained infertility (n=56). Rates of high sperm DNA fragmentation, elevated ROS, and oligospermia were more prevalent in the study group compared with control. In all groups, semen microbiota clustered into three major <i>genera</i>-dominant groups (1, <i>Streptococcus</i>; 2, <i>Prevotella</i>; 3, <i>Lactobacillus</i> and <i>Gardnerella</i>); no species clusters were identified. Group 2 had the highest microbial richness (p<0.001), alpha-diversity (p<0.001), and bacterial load (p<0.0001). Overall bacterial composition or load has not been found to associate with semen analysis, ROS, or DNA fragmentation. Whilst global perturbation of the seminal microbiota is not associated with male reproductive disorders, men with unidentified seminal <i>Flavobacterium</i> are more likely to have abnormal seminal analysis. Future studies may elucidate if <i>Flavobacterium</i> reduction has therapeutic potential.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984523","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":"Non-feature-specific elevated responses and feature-specific backward replay in human brain induced by visual sequence exposure.","authors":"Tao He, Xizi Gong, Qian Wang, Xinyi Zhu, Yunzhe Liu, Fang Fang","doi":"10.7554/eLife.101511","DOIUrl":"https://doi.org/10.7554/eLife.101511","url":null,"abstract":"<p><p>The ability of cortical circuits to adapt in response to experience is a fundamental property of the brain. After exposure to a moving dot sequence, flashing a dot as a cue at the starting point of the sequence can elicit successive elevated responses even in the absence of the sequence. These cue-triggered elevated responses have been shown to play a crucial role in predicting future events in dynamic environments. However, temporal sequences we are exposed to typically contain rich feature information. It remains unknown whether the elevated responses are feature-specific and, more crucially, how the brain organizes sequence information after exposure. To address these questions, participants were exposed to a predefined sequence of four motion directions for about 30 min, followed by the presentation of the start or end motion direction of the sequence as a cue. Surprisingly, we found that cue-triggered elevated responses were not specific to any motion direction. Interestingly, motion direction information was spontaneously reactivated, and the motion sequence was backward replayed in a time-compressed manner. These effects were observed even after brief exposure. Notably, no replay events were observed when the second or third motion direction of the sequence served as a cue. Further analyses revealed that activity in the medial temporal lobe (MTL) preceded the ripple power increase in visual cortex at the onset of replay, implying a coordinated relationship between the activities in the MTL and visual cortex. Together, these findings demonstrate that visual sequence exposure induces twofold brain plasticity that may simultaneously serve for different functional purposes. The non-feature-specific elevated responses may facilitate general processing of upcoming stimuli, whereas the feature-specific backward replay may underpin passive learning of visual sequences.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959399","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":"Adolescent alcohol exposure promotes mechanical allodynia and alters synaptic function at inputs from the basolateral amygdala to the prelimbic cortex.","authors":"J Daniel Obray, Erik T Wilkes, Mike Scofield, L Judson Chandler","doi":"10.7554/eLife.101667","DOIUrl":"https://doi.org/10.7554/eLife.101667","url":null,"abstract":"<p><p>Binge drinking is common among adolescents despite mounting evidence linking it to various adverse health outcomes that include heightened pain perception. The prelimbic (PrL) cortex is vulnerable to insult from adolescent alcohol exposure and receives input from the basolateral amygdala (BLA) while sending projections to the ventrolateral periaqueductal gray (vlPAG) - two brain regions implicated in nociception. In this study, adolescent intermittent ethanol (AIE) exposure was carried out in male and female rats using a vapor inhalation procedure. Assessments of mechanical and thermal sensitivity revealed that AIE exposure-induced protracted mechanical allodynia. To investigate synaptic function at BLA inputs onto defined populations of PrL neurons, retrobeads and viral labeling were combined with optogenetics and slice electrophysiology. Recordings from retrobead labeled cells in the PrL revealed AIE reduced BLA-driven feedforward inhibition of neurons projecting from the PrL to the vlPAG, resulting in augmented excitation/inhibition (E/I) balance and increased intrinsic excitability. Consistent with this finding, recordings from virally tagged PrL parvalbumin interneurons (PVINs) demonstrated that AIE exposure reduced both E/I balance at BLA inputs onto PVINs and PVIN intrinsic excitability. These findings provide compelling evidence that AIE alters synaptic function and intrinsic excitability within a prefrontal nociceptive circuit.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987419","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":"HERV activation segregates ME/CFS from fibromyalgia while defining a novel nosologic entity.","authors":"Karen Giménez-Orenga, Eva Martín-Martínez, Lubov Nathanson, Elisa Oltra","doi":"10.7554/eLife.104441","DOIUrl":"https://doi.org/10.7554/eLife.104441","url":null,"abstract":"<p><p>Research of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM), two acquired chronic illnesses affecting mainly females, has failed to ascertain their frequent co-appearance and etiology. Despite prior detection of human endogenous retrovirus (HERV) activation in these diseases, the potential biomarker value of HERV expression profiles for their diagnosis, and the relationship of HERV expression profiles with patient immune systems and symptoms had remained unexplored. By using HERV-V3 high-density microarrays (including over 350k HERV elements and more than 1500 immune-related genes) to interrogate the transcriptomes of peripheral blood mononuclear cells from female patients diagnosed with ME/CFS, FM, or both, and matched healthy controls (<i>n</i> = 43), this study fills this gap of knowledge. Hierarchical clustering of HERV expression profiles strikingly allowed perfect participant assignment into four distinct groups: ME/CFS, FM, co-diagnosed, or healthy, pointing at a potent biomarker value of HERV expression profiles to differentiate between these hard-to-diagnose chronic syndromes. Differentially expressed HERV-immune-gene modules revealed unique profiles for each of the four study groups and highlighting decreased γδ T cells, and increased plasma and resting CD4 memory T cells, correlating with patient symptom severity in ME/CFS. Moreover, activation of HERV sequences coincided with enrichment of binding sequences targeted by transcription factors which recruit SETDB1 and TRIM28, two known epigenetic silencers of HERV, in ME/CFS, offering a mechanistic explanation for the findings. Unexpectedly, HERV expression profiles appeared minimally affected in co-diagnosed patients denoting a new nosological entity with low epigenetic impact, a seemingly relevant aspect for the diagnosis and treatment of this prevalent group of patients.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964511","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":"Linking O-GlcNAc and intron retention.","authors":"John A Hanover","doi":"10.7554/eLife.107226","DOIUrl":"https://doi.org/10.7554/eLife.107226","url":null,"abstract":"<p><p>An elegant screening strategy unveils a molecular actor that connects widespread changes in mRNA processing with a nutrient-sensing protein modification.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998053","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":"VGLL2 and TEAD1 fusion proteins identified in human sarcoma drive YAP/TAZ-independent tumorigenesis by engaging EP300.","authors":"Susu Guo, Xiaodi Hu, Jennifer L Cotton, Lifang Ma, Qi Li, Jiangtao Cui, Yongjie Wang, Ritesh P Thakare, Zhipeng Tao, Y Tony Ip, Xu Wu, Jiayi Wang, Junhao Mao","doi":"10.7554/eLife.98386","DOIUrl":"https://doi.org/10.7554/eLife.98386","url":null,"abstract":"<p><p>Studies on Hippo pathway regulation of tumorigenesis largely center on YAP and TAZ, the transcriptional co-regulators of TEADs. Here, we present an oncogenic mechanism involving VGLL and TEAD fusions that is Hippo pathway-related but YAP/TAZ-independent. We characterize two recurrent fusions, <i>VGLL2-NCOA2</i> and <i>TEAD1-NCOA2</i>, recently identified in human spindle cell rhabdomyosarcoma. We demonstrate that in contrast to VGLL2 and TEAD1 the fusion proteins are potent activators of TEAD-dependent transcription, and the function of these fusion proteins does not require YAP/TAZ. Furthermore, we identify that VGLL2 and TEAD1 fusions engage specific epigenetic regulation by recruiting histone acetyltransferase EP300 to control TEAD-mediated transcriptional and epigenetic landscapes. We show that small-molecule EP300 inhibition can suppress fusion protein-induced oncogenic transformation both in vitro and in vivo in mouse models. Overall, our study reveals a molecular basis for VGLL involvement in cancer and provides a framework for targeting tumors carrying <i>VGLL</i>, <i>TEAD</i>, or <i>NCOA</i> translocations.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978999","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":"MARK2 regulates Golgi apparatus reorientation by phosphorylation of CAMSAP2 in directional cell migratio.","authors":"Peipei Xu, Rui Zhang, Zhengrong Zhou, Honglin Xu, Yuejia Li, Mengge Yang, Ruifan Lin, Yingchun Wang, Xiahe Huang, Qi Xie, Wenxiang Meng","doi":"10.7554/eLife.105977","DOIUrl":"https://doi.org/10.7554/eLife.105977","url":null,"abstract":"<p><p>The reorientation of the Golgi apparatus is crucial for cell migration and is regulated by multipolarity signals. A number of non-centrosomal microtubules anchor at the surface of the Golgi apparatus and play a vital role in the Golgi reorientation, but how the Golgi are regulated by polarity signals remains unclear. Calmodulin-regulated spectrin-associated protein 2 (CAMSAP2) is a protein that anchors microtubules to the Golgi, a cellular organelle. Our research indicates that CAMSAP2 is dynamically localized at the Golgi during its reorientation processing. Further research shows that CAMSAP2 is potentially regulated by a polarity signaling molecule called MARK2, which interacts with CAMSAP2. We used mass spectrometry to find that MARK2 phosphorylates CAMSAP2 at serine-835, which affects its interaction with the Golgi-associated protein USO1 but not with CG-NAP or CLASPs. This interaction is critical for anchoring microtubules to the Golgi during cell migration, altering microtubule polarity distribution, and aiding Golgi reorientation. Our study reveals an important signaling pathway in Golgi reorientation during cell migration, which can provide insights for research in cancer cell migration, immune response, and targeted drug development.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984131","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":"SIRT2-mediated ACSS2 K271 deacetylation suppresses lipogenesis under nutrient stress.","authors":"Rezwana Karim, Wendi Teng, Cameron D Behram, Hening Lin","doi":"10.7554/eLife.97019","DOIUrl":"https://doi.org/10.7554/eLife.97019","url":null,"abstract":"<p><p>De novo lipogenesis is associated with the development of human diseases such as cancer, diabetes, and obesity. At the core of lipogenesis lies acetyl coenzyme A (CoA), a metabolite that plays a crucial role in fatty acid synthesis. One of the pathways contributing to the production of cytosolic acetyl-CoA is mediated by acetyl-CoA synthetase 2 (ACSS2). Here, we reveal that when cells encounter nutrient stress, particularly a deficiency in amino acids, Sirtuin 2 (SIRT2) catalyzes the deacetylation of ACSS2 at the lysine residue K271. This results in K271 ubiquitination and subsequently proteasomal degradation of ACSS2. Substitution of K271 leads to decreased ubiquitination of ACSS2, increased ACSS2 protein level, and thus increased lipogenesis. Our study uncovers a mechanism that cells employ to efficiently manage lipogenesis during periods of nutrient stress.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968398","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":"Quantifying feral pig interactions to inform disease transmission networks.","authors":"Tatiana Proboste, Abigail Turnlund, Andrew Bengsen, Matthew Gentle, Cameron Wilson, Lana Harriott, Richard A Fuller, Darren Marshall, Ricardo J Soares-Magalhaes","doi":"10.7554/eLife.102643","DOIUrl":"https://doi.org/10.7554/eLife.102643","url":null,"abstract":"<p><p>Feral pigs threaten biodiversity in 54 countries and cause an estimated $120 billion in damages annually in the USA. They endanger over 600 native species and have driven 14 to extinction. Additionally, they pose a significant zoonotic disease risk, carrying pathogens such as Brucella, leptospirosis, and Japanese encephalitis. Understanding and controlling disease spread relies on models of social dynamics, but these vary widely across regions, limiting the transferability of findings from the USA and Europe to other locations like Australia. This study addresses this gap by analysing the social interactions of 146 GPS-tracked feral pigs in Australia using a proximity-based social network approach. Findings reveal that females exhibit stronger group cohesion, while males act as key connectors between groups. Contact rates are high within groups, facilitating rapid intra-group disease spread, whereas inter-group transmission is slower. Seasonal variations further impact dynamics, with increased contact in summer. These insights suggest that targeting adult males in control programs could help limit disease outbreaks. Given the rising economic and public health concerns associated with animal diseases, the study highlights the need for localized strategies based on feral pig social behaviour to enhance global control efforts.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982673","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}