eLife最新文献

{"title":"Natural variation in salt-induced changes in root:shoot ratio reveals SR3G as a negative regulator of root suberization and salt resilience in <i>Arabidopsis</i>.","authors":"Maryam Rahmati Ishka, Hayley Sussman, Yunfei Hu, Mashael Daghash Alqahtani, Eric Craft, Ronell Sicat, Minmin Wang, Li'ang Yu, Rachid Ait-Haddou, Bo Li, Georgia Drakakaki, Andrew D L Nelson, Miguel Pineros, Arthur Korte, Łukasz Jaremko, Christa Testerink, Mark Tester, Magdalena M Julkowska","doi":"10.7554/eLife.98896","DOIUrl":"10.7554/eLife.98896","url":null,"abstract":"<p><p>Soil salinity is one of the major threats to agricultural productivity worldwide. Salt stress exposure alters root and shoots growth rates, thereby affecting overall plant performance. While past studies have extensively documented the effect of salt stress on root elongation and shoot development separately, here we take an innovative approach by examining the coordination of root and shoot growth under salt stress conditions. Utilizing a newly developed tool for quantifying the root:shoot ratio in agar-grown <i>Arabidopsis</i> seedlings, we found that salt stress results in a loss of coordination between root and shoot growth rates. We identify a specific gene cluster encoding domain-of-unknown-function 247 (DUF247), and characterize one of these genes as <u>S</u>alt <u>R</u>oot:shoot <u>R</u>atio <u>R</u>egulator <u>G</u>ene (SR3G). Further analysis elucidates the role of SR3G as a negative regulator of salt stress tolerance, revealing its function in regulating shoot growth, root suberization, and sodium accumulation. We further characterize that <i>SR3G</i> expression is modulated by <i>WRKY75</i> transcription factor, known as a positive regulator of salt stress tolerance. Finally, we show that the salt stress sensitivity of <i>wrky75</i> mutant is completely diminished when it is combined with <i>sr3g</i> mutation. Together, our results demonstrate that utilizing root:shoot ratio as an architectural feature leads to the discovery of a new stress resilience gene. The study's innovative approach and findings not only contribute to our understanding of plant stress tolerance mechanisms but also open new avenues for genetic and agronomic strategies to enhance crop environmental resilience.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735837","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":"Deciphering the preeclampsia-specific immune microenvironment and the role of pro-inflammatory macrophages at the maternal-fetal interface.","authors":"Haiyi Fei, Xiaowen Lu, Zhan Shi, Xiu Liu, Cuiyu Yang, Xiaohong Zhu, Yuhan Lin, Ziqun Jiang, Jianmin Wang, Dong Huang, Liu Liu, Songying Zhang, Lingling Jiang","doi":"10.7554/eLife.100002","DOIUrl":"10.7554/eLife.100002","url":null,"abstract":"<p><p>Preeclampsia (PE), a major cause of maternal and perinatal mortality with highly heterogeneous causes and symptoms, is usually complicated by gestational diabetes mellitus (GDM). However, a comprehensive understanding of the immune microenvironment in the placenta of PE and the differences between PE and GDM is still lacking. In this study, cytometry by time of flight indicated that the frequencies of memory-like Th17 cells (CD45RA^-CCR7⁺IL-17A⁺CD4⁺), memory-like CD8⁺ T cells (CD38⁺CXCR3^-CCR7⁺Helios^-CD127^-CD8⁺) and pro-inflam Macs (CD206^-CD163^-CD38^midCD107a^lowCD86^midHLA-DR^midCD14⁺) were increased, while the frequencies of anti-inflam Macs (CD206⁺CD163^-CD86^midCD33⁺HLA-DR⁺CD14⁺) and granulocyte myeloid-derived suppressor cells (gMDSCs, CD11b⁺CD15^hiHLA-DR^low) were decreased in the placenta of PE compared with that of normal pregnancy (NP), but not in that of GDM or GDM&PE. The pro-inflam Macs were positively correlated with memory-like Th17 cells and memory-like CD8⁺ T cells but negatively correlated with gMDSCs. Single-cell RNA sequencing revealed that transferring the F4/80⁺CD206^- pro-inflam Macs with a Folr2⁺Ccl7⁺Ccl8⁺C1qa⁺C1qb⁺C1qc⁺ phenotype from the uterus of PE mice to normal pregnant mice induced the production of memory-like IL-17a⁺Rora⁺Il1r1⁺TNF⁺Cxcr6⁺S100a4⁺CD44⁺ Th17 cells via IGF1-IGF1R, which contributed to the development and recurrence of PE. Pro-inflam Macs also induced the production of memory-like CD8⁺ T cells but inhibited the production of Ly6g⁺S100a8⁺S100a9⁺Retnlg⁺Wfdc21⁺ gMDSCs at the maternal-fetal interface, leading to PE-like symptoms in mice. In conclusion, this study revealed the PE-specific immune cell network, which was regulated by pro-inflam Macs, providing new ideas about the pathogenesis of PE.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729451","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":"Electrophysiology and morphology of human cortical supragranular pyramidal cells in a wide age range.","authors":"Pál Barzó, Ildikó Szöts, Martin Tóth, Éva Adrienn Csajbók, Gábor Molnár, Gábor Tamás","doi":"10.7554/eLife.100390","DOIUrl":"10.7554/eLife.100390","url":null,"abstract":"<p><p>The basic excitatory neurons of the cerebral cortex, the pyramidal cells, are the most important signal integrators for the local circuit. They have quite characteristic morphological and electrophysiological properties that are known to be largely constant with age in the young and adult cortex. However, the brain undergoes several dynamic changes throughout life, such as in the phases of early development and cognitive decline in the aging brain. We set out to search for intrinsic cellular changes in supragranular pyramidal cells across a broad age range: from birth to 85 y of age and we found differences in several biophysical properties between defined age groups. During the first year of life, subthreshold and suprathreshold electrophysiological properties changed in a way that shows that pyramidal cells become less excitable with maturation, but also become temporarily more precise. According to our findings, the morphological features of the three-dimensional reconstructions from different life stages showed consistent morphological properties and systematic dendritic spine analysis of an infantile and an old pyramidal cell showed clear significant differences in the distribution of spine shapes. Overall, the changes that occur during development and aging may have lasting effects on the properties of pyramidal cells in the cerebral cortex. Understanding these changes is important to unravel the complex mechanisms underlying brain development, cognition, and age-related neurodegenerative diseases.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729459","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":"Functionally important residues from graph analysis of coevolved dynamic couplings.","authors":"Manming Xu, Sarath Chandra Dantu, James A Garnett, Robert A Bonomo, Alessandro Pandini, Shozeb Haider","doi":"10.7554/eLife.105005","DOIUrl":"10.7554/eLife.105005","url":null,"abstract":"<p><p>The relationship between protein dynamics and function is essential for understanding biological processes and developing effective therapeutics. Functional sites within proteins are critical for activities such as substrate binding, catalysis, and structural changes. Existing computational methods for the predictions of functional residues are trained on sequence, structural, and experimental data, but they do not explicitly model the influence of evolution on protein dynamics. This overlooked contribution is essential as it is known that evolution can fine-tune protein dynamics through compensatory mutations either to improve the proteins' performance or diversify its function while maintaining the same structural scaffold. To model this critical contribution, we introduce DyNoPy, a computational method that combines residue coevolution analysis with molecular dynamics simulations, revealing hidden correlations between functional sites. DyNoPy constructs a graph model of residue-residue interactions, identifies communities of key residue groups, and annotates critical sites based on their roles. By leveraging the concept of coevolved dynamical couplings-residue pairs with critical dynamical interactions that have been preserved during evolution-DyNoPy offers a powerful method for predicting and analysing protein evolution and dynamics. We demonstrate the effectiveness of DyNoPy on SHV-1 and PDC-3, chromosomally encoded β-lactamases linked to antibiotic resistance, highlighting its potential to inform drug design and address pressing healthcare challenges.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735852","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":"Compositional editing of extracellular matrices by CRISPR/Cas9 engineering of human mesenchymal stem cell lines.","authors":"Sujeethkumar Prithiviraj, Alejandro Garcia Garcia, Karin Linderfalk, Bai Yiguang, Sonia Ferveur, Ludvig Nilsén Falck, Agatheeswaran Subramaniam, Sofie Mohlin, David Hidalgo Gil, Steven J Dupard, Dimitra Zacharaki, Deepak Bushan Raina, Paul E Bourgine","doi":"10.7554/eLife.96941","DOIUrl":"10.7554/eLife.96941","url":null,"abstract":"<p><p>Tissue engineering strategies predominantly rely on the production of living substitutes, whereby implanted cells actively participate in the regenerative process. Beyond cost and delayed graft availability, the patient-specific performance of engineered tissues poses serious concerns on their clinical translation ability. A more exciting paradigm consists in exploiting cell-laid, engineered extracellular matrices (eECMs), which can be used as off-the-shelf materials. Here, the regenerative capacity solely relies on the preservation of the eECM structure and embedded signals to instruct an endogenous repair. We recently described the possibility to exploit custom human stem cell lines for eECM manufacturing. In addition to the conferred standardization, the availability of such cell lines opened avenues for the design of tailored eECMs by applying dedicated genetic tools. In this study, we demonstrated the exploitation of CRISPR/Cas9 as a high precision system for editing the composition and function of eECMs. Human mesenchymal stromal/stem cell (hMSC) lines were modified to knock out vascular endothelial growth factor (VEGF) and Runt-related transcription factor 2 (RUNX2) and assessed for their capacity to generate osteoinductive cartilage matrices. We report the successful editing of hMSCs, subsequently leading to targeted VEGF and RUNX2-knockout cartilage eECMs. Despite the absence of VEGF, eECMs retained full capacity to instruct ectopic endochondral ossification. Conversely, RUNX2-edited eECMs exhibited impaired hypertrophy, reduced ectopic ossification, and superior cartilage repair in a rat osteochondral defect. In summary, our approach can be harnessed to identify the necessary eECM factors driving endogenous repair. Our work paves the road toward the compositional eECMs editing and their exploitation in broad regenerative contexts.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729449","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":"Deficiency in DNAH12 causes male infertility by impairing DNAH1 and DNALI1 recruitment in humans and mice.","authors":"Menglei Yang, Hafiz Muhammad Jafar Hussain, Manan Khan, Zubair Muhammad, Jianteng Zhou, Ao Ma, Xiongheng Huang, Jingwei Ye, Min Chen, Aoran Zhi, Tao Liu, Ranjha Khan, Ali Asim, Wasim Shah, Aurang Zeb, Nisar Ahmad, Huan Zhang, Bo Xu, Hui Ma, Qinghua Shi, Baolu Shi","doi":"10.7554/eLife.100350","DOIUrl":"10.7554/eLife.100350","url":null,"abstract":"<p><p>Asthenoteratozoospermia, a prevalent cause of male infertility, lacks a well-defined etiology. DNAH12 is a special dynein featured by the absence of a microtubule-binding domain, however, its functions in spermatogenesis remain largely unknown. Through comprehensive genetic analyses involving whole-exome sequencing and subsequent Sanger sequencing on infertile patients and fertile controls from six distinct families, we unveiled six biallelic mutations in <i>DNAH12</i> that co-segregate recessively with male infertility in the studied families. Transmission electron microscopy (TEM) revealed pronounced axonemal abnormalities, including inner dynein arms (IDAs) impairment and central pair (CP) loss in sperm flagella of the patients. Mouse models (<i>Dnah12</i>^-/- and <i>Dnah12^mut/mut</i>) were generated and recapitulated the reproductive defects in the patients. Noteworthy, DNAH12 deficiency did not show effects on cilium organization and function. Mechanistically, DNAH12 was confirmed to interact with two other IDA components DNALI1 and DNAH1, while disruption of DNAH12 leads to failed recruitment of DNALI1 and DNAH1 to IDAs and compromised sperm development. Furthermore, DNAH12 also interacts with radial spoke head proteins RSPH1, RSPH9, and DNAJB13 to regulate CP stability. Moreover, the infertility of <i>Dnah12</i>^-/- mice could be overcome by intracytoplasmic sperm injection (ICSI) treatment. Collectively, DNAH12 plays a crucial role in the proper organization of axoneme in sperm flagella, but not cilia, by recruiting DNAH1 and DNALI1 in both humans and mice. These findings expand our comprehension of dynein component assembly in flagella and cilia and provide a valuable marker for genetic counseling and diagnosis of asthenoteratozoospermia in clinical practice.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718161","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":"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}