eLife最新文献

{"title":"Integrating past experiences.","authors":"Thomas M W Leir, Matthew P H Gardner","doi":"10.7554/eLife.106291","DOIUrl":"10.7554/eLife.106291","url":null,"abstract":"<p><p>New results help address a longstanding debate regarding which learning strategies allow animals to anticipate negative events based on past associations between sensory stimuli.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729468","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":"Transcriptome profiling of tendon fibroblasts at the onset of embryonic muscle contraction reveals novel force-responsive genes.","authors":"Pavan K Nayak, Arul Subramanian, Thomas F Schilling","doi":"10.7554/eLife.105802","DOIUrl":"https://doi.org/10.7554/eLife.105802","url":null,"abstract":"<p><p>Mechanical forces play a critical role in tendon development and function, influencing cell behavior through mechanotransduction signaling pathways and subsequent extracellular matrix (ECM) remodeling. Here we investigate the molecular mechanisms by which tenocytes in developing zebrafish embryos respond to muscle contraction forces during the onset of swimming and cranial muscle activity. Using genome-wide bulk RNA sequencing of FAC-sorted tenocytes we identify novel tenocyte markers and genes involved in tendon mechanotransduction. Embryonic tendons show dramatic changes in expression of <i>matrix remodeling associated 5b</i> (<i>mxra5b</i>), <i>matrilin1</i> (<i>matn1</i>), and the transcription factor <i>kruppel-like factor 2a</i> (<i>klf2a</i>), as muscles start to contract. Using embryos paralyzed either by loss of muscle contractility or neuromuscular stimulation we confirm that muscle contractile forces influence the spatial and temporal expression patterns of all three genes. Quantification of these gene expression changes across tenocytes at multiple tendon entheses and myotendinous junctions reveals that their responses depend on force intensity, duration and tissue stiffness. These force-dependent feedback mechanisms in tendons, particularly in the ECM, have important implications for improved treatments of tendon injuries and atrophy.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718195","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}

{"title":"Campaigning for science and scientists.","authors":"Adriana Bankston","doi":"10.7554/eLife.106701","DOIUrl":"10.7554/eLife.106701","url":null,"abstract":"<p><p>A Congressional Science & Technology policy fellow outlines some options available for responding to the blatant attacks on science and the scientific workforce in the US.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718190","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":"How to make science more efficient.","authors":"Stuart Buck","doi":"10.7554/eLife.106819","DOIUrl":"10.7554/eLife.106819","url":null,"abstract":"<p><p>DOGE needs to completely rethink its efforts to increase the efficiency of the federal agencies that fund research in the US.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718193","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":"CDK-mediated phosphorylation of PNKP is required for end-processing of single-strand DNA gaps on Okazaki fragments and genome stability.","authors":"Kaima Tsukada, Rikiya Imamura, Tomoko Miyake, Kotaro Saikawa, Mizuki Saito, Naoya Kase, Lingyan Fu, Masamichi Ishiai, Yoshihisa Matsumoto, Mikio Shimada","doi":"10.7554/eLife.99217","DOIUrl":"10.7554/eLife.99217","url":null,"abstract":"<p><p>Polynucleotide kinase phosphatase (PNKP) has enzymatic activities as 3'-phosphatase and 5'-kinase of DNA ends to promote DNA ligation and repair. Here, we show that cyclin-dependent kinases (CDKs) regulate the phosphorylation of threonine 118 (T118) in PNKP. This phosphorylation allows recruitment to the gapped DNA structure found in single-strand DNA (ssDNA) nicks and/or gaps between Okazaki fragments (OFs) during DNA replication. T118A (alanine)-substituted PNKP-expressing cells exhibited an accumulation of ssDNA gaps in S phase and accelerated replication fork progression. Furthermore, PNKP is involved in poly (ADP-ribose) polymerase 1 (PARP1)-dependent replication gap filling as part of a backup pathway in the absence of OFs ligation. Altogether, our data suggest that CDK-mediated PNKP phosphorylation at T118 is important for its recruitment to ssDNA gaps to proceed with OFs ligation and its backup repairs via the gap-filling pathway to maintain genome stability.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729464","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":"Reported transgenerational responses to <i>Pseudomonas aeruginosa</i> in <i>Caenorhabditis elegans</i> are not robust.","authors":"Daniel Patrick Gainey, Andrey V Shubin, Craig P Hunter","doi":"10.7554/eLife.100254","DOIUrl":"10.7554/eLife.100254","url":null,"abstract":"<p><p>We report our attempt to replicate reports of transgenerational epigenetic inheritance in <i>Caenorhabditis elegans</i>. Multiple laboratories report that <i>C. elegans</i> adults and their F1 embryos exposed to the pathogen <i>Pseudomonas aeruginosa</i> show pathogen aversion behavior and increased <i>daf-7/TGFβ</i> reporter gene expression. However, results from one group show persistence of both through the F4 generation. We failed to consistently detect either the avoidance response or elevated <i>daf-7</i> expression beyond the F1 generation. We confirmed that the dsRNA transport proteins SID-1 and SID-2 are required for intergenerational (F1) inheritance of pathogen avoidance, but not for the F1 inheritance of elevated <i>daf-7</i> expression. Reanalysis of RNA seq data provides additional evidence that this intergenerational inherited PA14 response may be mediated by small RNAs. The experimental methods are well-described, the source materials are readily available, including samples from the reporting laboratory, and we explored a variety of environmental conditions likely to account for lab-to-lab variability. None of these adjustments altered our results. We conclude that this example of transgenerational inheritance lacks robustness, confirm that the intergenerational avoidance response, but not the elevated <i>daf-7p::gfp</i> expression in F1 progeny, requires <i>sid-1</i> and <i>sid-2</i>, and identify candidate siRNAs and target genes that may mediate this intergenerational response.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709175","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":"Microphase separation produces interfacial environment within diblock biomolecular condensates.","authors":"Andrew P Latham, Longchen Zhu, Dina A Sharon, Songtao Ye, Adam P Willard, Xin Zhang, Bin Zhang","doi":"10.7554/eLife.90750","DOIUrl":"10.7554/eLife.90750","url":null,"abstract":"<p><p>The phase separation of intrinsically disordered proteins is emerging as an important mechanism for cellular organization. However, efforts to connect protein sequences to the physical properties of condensates, that is, the molecular grammar, are hampered by a lack of effective approaches for probing high-resolution structural details. Using a combination of multiscale simulations and fluorescence lifetime imaging microscopy experiments, we systematically explored a series of systems consisting of diblock elastin-like polypeptides (ELPs). The simulations succeeded in reproducing the variation of condensate stability upon amino acid substitution and revealed different microenvironments within a single condensate, which we verified with environmentally sensitive fluorophores. The interspersion of hydrophilic and hydrophobic residues and a lack of secondary structure formation result in an interfacial environment, which explains both the strong correlation between ELP condensate stability and interfacial hydrophobicity scales, as well as the prevalence of protein-water hydrogen bonds. Our study uncovers new mechanisms for condensate stability and organization that may be broadly applicable.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"12 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709130","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":"The impact on undergraduate students.","authors":"Reenie Tian, Kamna Kalkunte, Esha Pia, Gianna Dunn, Nina Bugg, Mayank Chugh","doi":"10.7554/eLife.106705","DOIUrl":"10.7554/eLife.106705","url":null,"abstract":"<p><p>Anti-science policies, funding cuts, scientific censorship and the US withdrawing from international commitments are worrying members of the ReForm Lab at the College of William & Mary.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709199","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":"Research turns hope into reality.","authors":"Anna C Greene, Casey S Greene","doi":"10.7554/eLife.106706","DOIUrl":"10.7554/eLife.106706","url":null,"abstract":"<p><p>Two scientists describe how an acute myeloid leukemia diagnosis underscores the need for continued federal support for research and access to care.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709195","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":"Transparency of research practices in cardiovascular literature.","authors":"Gabriel O Heckerman, Eileen Tzng, Arely Campos-Melendez, Chisomaga Ekwueme, Adrienne Mueller","doi":"10.7554/eLife.81051","DOIUrl":"https://doi.org/10.7554/eLife.81051","url":null,"abstract":"<p><p><b>Background:</b> Several fields have described low reproducibility of scientific research and poor accessibility in research reporting practices. Although previous reports have investigated accessible reporting practices that lead to reproducible research in other fields, to date, no study has explored the extent of accessible and reproducible research practices in cardiovascular science literature.</p><p><p><b>Methods:</b> To study accessibility and reproducibility in cardiovascular research reporting, we screened 639 randomly selected articles published in 2019 in three top cardiovascular science publications: Circulation, the European Heart Journal, and the Journal of the American College of Cardiology (JACC). Of those 639 articles, 393 were empirical research articles. We screened each paper for accessible and reproducible research practices using a set of accessibility criteria including protocol, materials, data, and analysis script availability, as well as accessibility of the publication itself. We also quantified the consistency of open research practices within and across cardiovascular study types and journal formats.</p><p><p><b>Results:</b> We identified that fewer than 2% of cardiovascular research publications provide sufficient resources (materials, methods, data, and analysis scripts) to fully reproduce their studies. Of the 639 articles screened, 393 were empirical research studies for which reproducibility could be assessed using our protocol, as opposed to commentaries or reviews. After calculating an accessibility score as a measure of the extent to which an article makes its resources available, we also showed that the level of accessibility varies across study types with a score of 0.08 for Case Studies or Case Series and 0.39 for Clinical Trials (p = 5.500E-5) and across journals (0.19 through 0.34, p = 1.230E-2). We further showed that there are significant differences in which study types share which resources.</p><p><p><b>Conclusion:</b> Although the degree to which reproducible reporting practices are present in publications varies significantly across journals and study types, current cardiovascular science reports frequently do not provide sufficient materials, protocols, data, or analysis information to reproduce a study. In the future, having higher standards of accessibility mandated by either journals or funding bodies will help increase the reproducibility of cardiovascular research.</p><p><p><b>Funding:</b> Authors Gabriel Heckerman, Arely Campos-Melendez, and Chisomaga Ekwueme were supported by an NIH R25 grant from the National Heart, Lung and Blood Institute (R25HL147666). Eileen Tzng was supported by an AHA Institutional Training Award fellowship (18UFEL33960207).</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709122","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}