eLife最新文献

{"title":"Wide transition-state ensemble as key component for enzyme catalysis.","authors":"Gabriel E Jara, Francesco Pontiggia, Renee Otten, Roman V Agafonov, Marcelo A Martí, Dorothee Kern","doi":"10.7554/eLife.93099","DOIUrl":"10.7554/eLife.93099","url":null,"abstract":"<p><p>Transition-state (TS) theory has provided the theoretical framework to explain the enormous rate accelerations of chemical reactions by enzymes. Given that proteins display large ensembles of conformations, unique TSs would pose a huge entropic bottleneck for enzyme catalysis. To shed light on this question, we studied the nature of the enzymatic TS for the phosphoryl-transfer step in adenylate kinase by quantum-mechanics/molecular-mechanics calculations. We find a structurally wide set of energetically equivalent configurations that lie along the reaction coordinate and hence a broad transition-state ensemble (TSE). A conformationally delocalized ensemble, including asymmetric TSs, is rooted in the macroscopic nature of the enzyme. The computational results are buttressed by enzyme kinetics experiments that confirm the decrease of the entropy of activation predicted from such wide TSE. TSEs as a key for efficient enzyme catalysis further boosts a unifying concept for protein folding and conformational transitions underlying protein function.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"12 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440247","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":"Mechanisms of PP2A-Ankle2 dependent nuclear reassembly after mitosis.","authors":"Jingjing Li, Xinyue Wang, Laia Jordana, Éric Bonneil, Victoria Ginestet, Momina Ahmed, Mohammed Bourouh, Cristina Mirela Pascariu, T Martin Schmeing, Pierre Thibault, Vincent Archambault","doi":"10.7554/eLife.104233","DOIUrl":"10.7554/eLife.104233","url":null,"abstract":"<p><p>In animals, mitosis involves the breakdown of the nucleus. The reassembly of a nucleus after mitosis requires the reformation of the nuclear envelope around a single mass of chromosomes. This process requires Ankle2 (also known as LEM4 in humans) which interacts with PP2A and promotes the function of the Barrier-to-Autointegration Factor (BAF). Upon dephosphorylation, BAF dimers cross-bridge chromosomes and bind lamins and transmembrane proteins of the reassembling nuclear envelope. How Ankle2 functions in mitosis is incompletely understood. Using a combination of approaches in <i>Drosophila</i>, along with structural modeling, we provide several lines of evidence that suggest that Ankle2 is a regulatory subunit of PP2A, explaining how it promotes BAF dephosphorylation. In addition, we discovered that Ankle2 interacts with the endoplasmic reticulum protein Vap33, which is required for Ankle2 localization at the reassembling nuclear envelope during telophase. We identified the interaction sites of PP2A and Vap33 on Ankle2. Through genetic rescue experiments, we show that the Ankle2/PP2A interaction is essential for the function of Ankle2 in nuclear reassembly and that the Ankle2/Vap33 interaction also promotes this process. Our study sheds light on the molecular mechanisms of post-mitotic nuclear reassembly and suggests that the endoplasmic reticulum is not merely a source of membranes in the process, but also provides localized enzymatic activity.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440221","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":"Development and assessment of a sustainable PhD internship program supporting diverse biomedical career outcomes.","authors":"Patrick Brandt, Dawayne Whittington, Kimberley D Wood, Christopher Holmquist, Ana T Nogueira, Christiann H Gaines, Patrick Brennwald, Rebekah L Layton","doi":"10.7554/eLife.91011","DOIUrl":"10.7554/eLife.91011","url":null,"abstract":"<p><p>A doctoral-level internship program was developed at the University of North Carolina at Chapel Hill with the intent to create customizable experiential learning opportunities for biomedical trainees to support career exploration, preparation, and transition into their postgraduate professional roles. We report the outcomes of this program over a 5-year period. During that 5-year period, 123 internships took place at over 70 partner sites, representing at least 20 academic, for-profit, and non-profit career paths in the life sciences. A major goal of the program was to enhance trainees' skill development and expertise in careers of interest. The benefits of the internship program for interns, host/employer, and supervisor/principal investigator were assessed using a mixed-methods approach, including surveys with closed- and open-ended responses as well as focus group interviews. Balancing stakeholder interests is key to creating a sustainable program with widespread support; hence, the level of support from internship hosts and faculty members were the key metrics analyzed throughout. We hypothesized that once a successful internship program was implemented, faculty culture might shift to be more accepting of internships; indeed, the data quantifying faculty attitudes support this. Furthermore, host motivation and performance expectations of interns were compared with results achieved, and this data revealed both expected and surprising benefits to hosts. Data suggests a myriad of benefits for each stakeholder group, and themes are cataloged and discussed. Program outcomes, evaluation data, policies, resources, and best practices developed through the implementation of this program are shared to provide resources that facilitate the creation of similar internship programs at other institutions. Program development was initially spurred by National Institutes of Health pilot funding, thereafter, successfully transitioning from a grant-supported model, to an institutionally supported funding model to achieve long-term programmatic sustainability.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"12 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440246","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":"Maintenance of cell wall remodeling and vesicle production are connected in <i>Mycobacterium tuberculosis</i>.","authors":"Vivian C Salgueiro-Toledo, Jorge Bertol, Claude Gutierrez, Jose L Serrano-Mestre, Noelia Ferrer-Luzon, Lucia Vázquez-Iniesta, Ainhoa Palacios, Laia Pasquina-Lemonche, Akbar Espaillat, Laura Lerma, Brian Weinrick, Jose L Lavin, Felix Elortza, Mikel Azkargorta, Alicia Prieto, Pilar Buendía-Nacarino, Jose L Luque-García, Olivier Neyrolles, Felipe Cava, Jamie K Hobbs, Joaquín Sanz, Rafael Prados-Rosales","doi":"10.7554/eLife.94982","DOIUrl":"10.7554/eLife.94982","url":null,"abstract":"<p><p>Pathogenic and nonpathogenic mycobacteria secrete extracellular vesicles (EVs) under various conditions. EVs produced by <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) have raised significant interest for their potential in cell communication, nutrient acquisition, and immune evasion. However, the relevance of vesicle secretion during tuberculosis infection remains unknown due to the limited understanding of mycobacterial vesicle biogenesis. We have previously shown that a transposon mutant in the LCP-related gene <i>virR</i> (<i>virR^mut</i>) manifested a strong attenuated phenotype during experimental macrophage and murine infections, concomitant to enhanced vesicle release. In this study, we aimed to understand the role of VirR in the vesicle production process in <i>Mtb</i>. We employ genetic, transcriptional, proteomics, ultrastructural, and biochemical methods to investigate the underlying processes explaining the enhanced vesiculogenesis phenomenon observed in the <i>virR^mut</i>. Our results establish that VirR is critical to sustain proper cell permeability via regulation of cell envelope remodeling possibly through the interaction with similar cell envelope proteins, which control the link between peptidoglycan and arabinogalactan. These findings advance our understanding of mycobacterial extracellular vesicle biogenesis and suggest that these set of proteins could be attractive targets for therapeutic intervention.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440184","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":"De novo identification of universal cell mechanics gene signatures.","authors":"Marta Urbanska, Yan Ge, Maria Winzi, Shada Abuhattum, Syed Shafat Ali, Maik Herbig, Martin Kräter, Nicole Toepfner, Joanne Durgan, Oliver Florey, Martina Dori, Federico Calegari, Fidel-Nicolás Lolo, Miguel Ángel Del Pozo, Anna Taubenberger, Carlo Vittorio Cannistraci, Jochen Guck","doi":"10.7554/eLife.87930","DOIUrl":"10.7554/eLife.87930","url":null,"abstract":"<p><p>Cell mechanical properties determine many physiological functions, such as cell fate specification, migration, or circulation through vasculature. Identifying factors that govern the mechanical properties is therefore a subject of great interest. Here, we present a mechanomics approach for establishing links between single-cell mechanical phenotype changes and the genes involved in driving them. We combine mechanical characterization of cells across a variety of mouse and human systems with machine learning-based discriminative network analysis of associated transcriptomic profiles to infer a conserved network module of five genes with putative roles in cell mechanics regulation. We validate in silico that the identified gene markers are universal, trustworthy, and specific to the mechanical phenotype across the studied mouse and human systems, and demonstrate experimentally that a selected target, <i>CAV1</i>, changes the mechanical phenotype of cells accordingly when silenced or overexpressed. Our data-driven approach paves the way toward engineering cell mechanical properties on demand to explore their impact on physiological and pathological cell functions.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"12 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440229","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":"Mapping kinase domain resistance mechanisms for the MET receptor tyrosine kinase via deep mutational scanning.","authors":"Gabriella O Estevam, Edmond Linossi, Jingyou Rao, Christian B Macdonald, Ashraya Ravikumar, Karson M Chrispens, John A Capra, Willow Coyote-Maestas, Harold Pimentel, Eric A Collisson, Natalia Jura, James S Fraser","doi":"10.7554/eLife.101882","DOIUrl":"10.7554/eLife.101882","url":null,"abstract":"<p><p>Mutations in the kinase and juxtamembrane domains of the MET Receptor Tyrosine Kinase are responsible for oncogenesis in various cancers and can drive resistance to MET-directed treatments. Determining the most effective inhibitor for each mutational profile is a major challenge for MET-driven cancer treatment in precision medicine. Here, we used a deep mutational scan (DMS) of ~5764 MET kinase domain variants to profile the growth of each mutation against a panel of 11 inhibitors that are reported to target the MET kinase domain. We validate previously identified resistance mutations, pinpoint common resistance sites across type I, type II, and type I ½ inhibitors, unveil unique resistance and sensitizing mutations for each inhibitor, and verify non-cross-resistant sensitivities for type I and type II inhibitor pairs. We augment a protein language model with biophysical and chemical features to improve the predictive performance for inhibitor-treated datasets. Together, our study demonstrates a pooled experimental pipeline for identifying resistance mutations, provides a reference dictionary for mutations that are sensitized to specific therapies, and offers insights for future drug development.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440185","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":"Identification of nonsense-mediated decay inhibitors that alter the tumor immune landscape.","authors":"Ashley L Cook, Surojit Sur, Laura Dobbyn, Evangeline Watson, Joshua D Cohen, Blair Ptak, Bum Seok Lee, Suman Paul, Emily Hsiue, Maria Popoli, Bert Vogelstein, Nickolas Papadopoulos, Chetan Bettegowda, Kathy Gabrielson, Shibin Zhou, Kenneth W Kinzler, Nicolas Wyhs","doi":"10.7554/eLife.95952","DOIUrl":"10.7554/eLife.95952","url":null,"abstract":"<p><p>Despite exciting developments in cancer immunotherapy, its broad application is limited by the paucity of targetable antigens on the tumor cell surface. As an intrinsic cellular pathway, nonsense-mediated decay (NMD) conceals neoantigens through the destruction of the RNA products from genes harboring truncating mutations. We developed and conducted a high-throughput screen, based on the ratiometric analysis of transcripts, to identify critical mediators of NMD in human cells. This screen implicated disruption of kinase SMG1's phosphorylation of UPF1 as a potential disruptor of NMD. This led us to design a novel SMG1 inhibitor, KVS0001, that elevates the expression of transcripts and proteins resulting from human and murine truncating mutations in vitro and murine cells in vivo. Most importantly, KVS0001 concomitantly increased the presentation of immune-targetable human leukocyte antigens (HLA) class I-associated peptides from NMD-downregulated proteins on the surface of human cancer cells. KVS0001 provides new opportunities for studying NMD and the diseases in which NMD plays a role, including cancer and inherited diseases.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440259","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":"Protection afforded by post-infection SARS-CoV-2 vaccine doses: A cohort study in Shanghai.","authors":"Bo Zheng, Bronner P Gonçalves, Pengfei Deng, Weibing Wang, Jie Tian, Xueyao Liang, Ye Yao, Caoyi Xue","doi":"10.7554/eLife.94990","DOIUrl":"10.7554/eLife.94990","url":null,"abstract":"<p><strong>Background: </strong>In many settings, a large fraction of the population has both been vaccinated against and infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hence, quantifying the protection provided by post-infection vaccination has become critical for policy. We aimed to estimate the protective effect against SARS-CoV-2 reinfection of an additional vaccine dose after an initial Omicron variant infection.</p><p><strong>Methods: </strong>We report a retrospective, population-based cohort study performed in Shanghai, China, using electronic databases with information on SARS-CoV-2 infections and vaccination history. We compared reinfection incidence by post-infection vaccination status in individuals initially infected during the April-May 2022 Omicron variant surge in Shanghai and who had been vaccinated before that period. Cox models were fit to estimate adjusted hazard ratios (aHRs).</p><p><strong>Results: </strong>275,896 individuals were diagnosed with real-time polymerase chain reaction-confirmed SARS-CoV-2 infection in April-May 2022; 199,312/275,896 were included in analyses on the effect of a post-infection vaccine dose. Post-infection vaccination provided protection against reinfection (aHR 0.82; 95% confidence interval 0.79-0.85). For patients who had received one, two, or three vaccine doses before their first infection, hazard ratios for the post-infection vaccination effect were 0.84 (0.76-0.93), 0.87 (0.83-0.90), and 0.96 (0.74-1.23), respectively. Post-infection vaccination within 30 and 90 days before the second Omicron wave provided different degrees of protection (in aHR): 0.51 (0.44-0.58) and 0.67 (0.61-0.74), respectively. Moreover, for all vaccine types, but to different extents, a post-infection dose given to individuals who were fully vaccinated before first infection was protective.</p><p><strong>Conclusions: </strong>In previously vaccinated and infected individuals, an additional vaccine dose provided protection against Omicron variant reinfection. These observations will inform future policy decisions on COVID-19 vaccination in China and other countries.</p><p><strong>Funding: </strong>This study was funded the Key Discipline Program of Pudong New Area Health System (PWZxk2022-25), the Development and Application of Intelligent Epidemic Surveillance and AI Analysis System (21002411400), the Shanghai Public Health System Construction (GWVI-11.2-XD08), the Shanghai Health Commission Key Disciplines (GWVI-11.1-02), the Shanghai Health Commission Clinical Research Program (20214Y0020), the Shanghai Natural Science Foundation (22ZR1414600), and the Shanghai Young Health Talents Program (2022YQ076).</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440224","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":"Statistical learning beyond words in human neonates.","authors":"Ana Fló, Lucas Benjamin, Marie Palu, Ghislaine Dehaene-Lambertz","doi":"10.7554/eLife.101802","DOIUrl":"10.7554/eLife.101802","url":null,"abstract":"<p><p>Interest in statistical learning in developmental studies stems from the observation that 8-month-olds were able to extract words from a monotone speech stream solely using the transition probabilities (TP) between syllables (Saffran et al., 1996). A simple mechanism was thus part of the human infant's toolbox for discovering regularities in language. Since this seminal study, observations on statistical learning capabilities have multiplied across domains and species, challenging the hypothesis of a dedicated mechanism for language acquisition. Here, we leverage the two dimensions conveyed by speech -speaker identity and phonemes- to examine (1) whether neonates can compute TPs on one dimension despite irrelevant variation on the other and (2) whether the linguistic dimension enjoys an advantage over the voice dimension. In two experiments, we exposed neonates to artificial speech streams constructed by concatenating syllables while recording EEG. The sequence had a statistical structure based either on the phonetic content, while the voices varied randomly (Experiment 1) or on voices with random phonetic content (Experiment 2). After familiarisation, neonates heard isolated duplets adhering, or not, to the structure they were familiarised with. In both experiments, we observed neural entrainment at the frequency of the regularity and distinct Event-Related Potentials (ERP) to correct and incorrect duplets, highlighting the universality of statistical learning mechanisms and suggesting it operates on virtually any dimension the input is factorised. However, only linguistic duplets elicited a specific ERP component, potentially an N400 precursor, suggesting a lexical stage triggered by phonetic regularities already at birth. These results show that, from birth, multiple input regularities can be processed in parallel and feed different higher-order networks.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440226","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":"Behavioural pharmacology predicts disrupted signalling pathways and candidate therapeutics from zebrafish mutants of Alzheimer's disease risk genes.","authors":"François Kroll, Joshua Donnelly, Güliz Gürel Özcan, Eirinn Mackay, Jason Rihel","doi":"10.7554/eLife.96839","DOIUrl":"10.7554/eLife.96839","url":null,"abstract":"<p><p>By exposing genes associated with disease, genomic studies provide hundreds of starting points that should lead to druggable processes. However, our ability to systematically translate these genomic findings into biological pathways remains limited. Here, we combine rapid loss-of-function mutagenesis of Alzheimer's risk genes and behavioural pharmacology in zebrafish to predict disrupted processes and candidate therapeutics. FramebyFrame, our expanded package for the analysis of larval behaviours, revealed that decreased night-time sleep was common to F0 knockouts of all four late-onset Alzheimer's risk genes tested. We developed an online tool, ZOLTAR, which compares any behavioural fingerprint to a library of fingerprints from larvae treated with 3677 compounds. ZOLTAR successfully predicted that <i>sorl1</i> mutants have disrupted serotonin signalling and identified betamethasone as a drug which normalises the excessive day-time sleep of <i>presenilin-2</i> knockout larvae with minimal side effects. Predictive behavioural pharmacology offers a general framework to rapidly link disease-associated genes to druggable pathways.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440257","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}