[{"_id":"14502","date_published":"2023-11-21T00:00:00Z","abstract":[{"text":"A precise quantitative description of the ultrastructural characteristics underlying biological mechanisms is often key to their understanding. This is particularly true for dynamic extra- and intracellular filamentous assemblies, playing a role in cell motility, cell integrity, cytokinesis, tissue formation and maintenance. For example, genetic manipulation or modulation of actin regulatory proteins frequently manifests in changes of the morphology, dynamics, and ultrastructural architecture of actin filament-rich cell peripheral structures, such as lamellipodia or filopodia. However, the observed ultrastructural effects often remain subtle and require sufficiently large datasets for appropriate quantitative analysis. The acquisition of such large datasets has been enabled by recent advances in high-throughput cryo-electron tomography (cryo-ET) methods. This also necessitates the development of complementary approaches to maximize the extraction of relevant biological information. We have developed a computational toolbox for the semi-automatic quantification of segmented and vectorized fila- mentous networks from pre-processed cryo-electron tomograms, facilitating the analysis and cross-comparison of multiple experimental conditions. GUI-based components simplify the processing of data and allow users to obtain a large number of ultrastructural parameters describing filamentous assemblies. We demonstrate the feasibility of this workflow by analyzing cryo-ET data of untreated and chemically perturbed branched actin filament networks and that of parallel actin filament arrays. In principle, the computational toolbox presented here is applicable for data analysis comprising any type of filaments in regular (i.e. parallel) or random arrangement. We show that it can ease the identification of key differences between experimental groups and facilitate the in-depth analysis of ultrastructural data in a time-efficient manner.","lang":"eng"}],"date_created":"2023-11-08T19:40:54Z","file":[{"file_name":"Computational_Toolbox_v1.2.zip","file_size":347641117,"creator":"fschur","checksum":"a8b9adeb53a4109dea4d5e39fa1acccf","date_updated":"2023-11-08T20:23:07Z","access_level":"open_access","content_type":"application/zip","file_id":"14503","relation":"main_file","date_created":"2023-11-08T20:23:07Z","success":1},{"checksum":"14db2addbfca61a085ba301ed6f2900b","date_updated":"2023-11-21T08:20:23Z","access_level":"open_access","file_name":"Readme.txt","creator":"dernst","file_size":1522,"date_created":"2023-11-21T08:20:23Z","success":1,"content_type":"text/plain","relation":"main_file","file_id":"14586"}],"month":"11","oa":1,"publisher":"Institute of Science and Technology Austria","license":"https://choosealicense.com/licenses/agpl-3.0/","status":"public","tmp":{"short":"GNU AGPLv3  ","name":"GNU Affero General Public License v3.0","legal_code_url":"https://www.gnu.org/licenses/agpl-3.0.html"},"file_date_updated":"2023-11-21T08:20:23Z","department":[{"_id":"FlSc"}],"title":"Computational toolbox for ultrastructural quantitative analysis of filament networks in cryo-ET data","citation":{"mla":"Dimchev, Georgi A., et al. <i>Computational Toolbox for Ultrastructural Quantitative Analysis of Filament Networks in Cryo-ET Data</i>. Institute of Science and Technology Austria, 2023, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:14502\">10.15479/AT:ISTA:14502</a>.","chicago":"Dimchev, Georgi A, Behnam Amiri, Florian Fäßler, Martin Falcke, and Florian KM Schur. “Computational Toolbox for Ultrastructural Quantitative Analysis of Filament Networks in Cryo-ET Data.” Institute of Science and Technology Austria, 2023. <a href=\"https://doi.org/10.15479/AT:ISTA:14502\">https://doi.org/10.15479/AT:ISTA:14502</a>.","ista":"Dimchev GA, Amiri B, Fäßler F, Falcke M, Schur FK. 2023. Computational toolbox for ultrastructural quantitative analysis of filament networks in cryo-ET data, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:14502\">10.15479/AT:ISTA:14502</a>.","ieee":"G. A. Dimchev, B. Amiri, F. Fäßler, M. Falcke, and F. K. Schur, “Computational toolbox for ultrastructural quantitative analysis of filament networks in cryo-ET data.” Institute of Science and Technology Austria, 2023.","ama":"Dimchev GA, Amiri B, Fäßler F, Falcke M, Schur FK. Computational toolbox for ultrastructural quantitative analysis of filament networks in cryo-ET data. 2023. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:14502\">10.15479/AT:ISTA:14502</a>","apa":"Dimchev, G. A., Amiri, B., Fäßler, F., Falcke, M., &#38; Schur, F. K. (2023). Computational toolbox for ultrastructural quantitative analysis of filament networks in cryo-ET data. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:14502\">https://doi.org/10.15479/AT:ISTA:14502</a>","short":"G.A. Dimchev, B. Amiri, F. Fäßler, M. Falcke, F.K. Schur, (2023)."},"has_accepted_license":"1","year":"2023","type":"software","author":[{"id":"38C393BE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8370-6161","last_name":"Dimchev","first_name":"Georgi A","full_name":"Dimchev, Georgi A"},{"last_name":"Amiri","full_name":"Amiri, Behnam","first_name":"Behnam"},{"id":"404F5528-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7149-769X","last_name":"Fäßler","first_name":"Florian","full_name":"Fäßler, Florian"},{"last_name":"Falcke","full_name":"Falcke, Martin","first_name":"Martin"},{"first_name":"Florian KM","full_name":"Schur, Florian KM","last_name":"Schur","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4790-8078"}],"day":"21","related_material":{"record":[{"status":"public","relation":"used_for_analysis_in","id":"10290"}]},"project":[{"name":"Structure and isoform diversity of the Arp2/3 complex","grant_number":"P33367","_id":"9B954C5C-BA93-11EA-9121-9846C619BF3A"}],"ddc":["570"],"doi":"10.15479/AT:ISTA:14502","date_updated":"2023-11-21T08:36:02Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","keyword":["cryo-electron tomography","actin cytoskeleton","toolbox"]},{"issue":"9","article_processing_charge":"Yes","file":[{"date_created":"2019-11-26T22:30:43Z","file_id":"7129","relation":"main_file","content_type":"application/pdf","checksum":"c5d855d07263bfec718673385d0ea2d7","access_level":"open_access","date_updated":"2020-07-14T12:47:50Z","file_size":4650750,"creator":"rcubero","file_name":"torrini_cellreports_2019.pdf"}],"_id":"7128","date_published":"2019-05-28T00:00:00Z","abstract":[{"text":"Loss of functional cardiomyocytes is a major determinant of heart failure after myocardial infarction. Previous high throughput screening studies have identified a few microRNAs (miRNAs) that can induce cardiomyocyte proliferation and stimulate cardiac regeneration in mice. Here, we show that all of the most effective of these miRNAs activate nuclear localization of the master transcriptional cofactor Yes-associated protein (YAP) and induce expression of YAP-responsive genes. In particular, miR-199a-3p directly targets two mRNAs coding for proteins impinging on the Hippo pathway, the upstream YAP inhibitory kinase TAOK1, and the E3 ubiquitin ligase β-TrCP, which leads to YAP degradation. Several of the pro-proliferative miRNAs (including miR-199a-3p) also inhibit filamentous actin depolymerization by targeting Cofilin2, a process that by itself activates YAP nuclear translocation. Thus, activation of YAP and modulation of the actin cytoskeleton are major components of the pro-proliferative action of miR-199a-3p and other miRNAs that induce cardiomyocyte proliferation.","lang":"eng"}],"publication_status":"published","oa":1,"file_date_updated":"2020-07-14T12:47:50Z","volume":27,"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)"},"article_type":"original","oa_version":"Published Version","has_accepted_license":"1","year":"2019","date_updated":"2021-01-12T08:11:56Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","external_id":{"pmid":["31141697"]},"publication_identifier":{"issn":["2211-1247"]},"page":"2759-2771.e5","extern":"1","month":"05","date_created":"2019-11-26T22:30:07Z","publisher":"Elsevier","quality_controlled":"1","publication":"Cell Reports","status":"public","intvolume":"        27","citation":{"short":"C. Torrini, R.J. Cubero, E. Dirkx, L. Braga, H. Ali, G. Prosdocimo, M.I. Gutierrez, C. Collesi, D. Licastro, L. Zentilin, M. Mano, S. Zacchigna, M. Vendruscolo, M. Marsili, A. Samal, M. Giacca, Cell Reports 27 (2019) 2759–2771.e5.","apa":"Torrini, C., Cubero, R. J., Dirkx, E., Braga, L., Ali, H., Prosdocimo, G., … Giacca, M. (2019). Common regulatory pathways mediate activity of microRNAs inducing cardiomyocyte proliferation. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2019.05.005\">https://doi.org/10.1016/j.celrep.2019.05.005</a>","ama":"Torrini C, Cubero RJ, Dirkx E, et al. Common regulatory pathways mediate activity of microRNAs inducing cardiomyocyte proliferation. <i>Cell Reports</i>. 2019;27(9):2759-2771.e5. doi:<a href=\"https://doi.org/10.1016/j.celrep.2019.05.005\">10.1016/j.celrep.2019.05.005</a>","ieee":"C. Torrini <i>et al.</i>, “Common regulatory pathways mediate activity of microRNAs inducing cardiomyocyte proliferation,” <i>Cell Reports</i>, vol. 27, no. 9. Elsevier, p. 2759–2771.e5, 2019.","ista":"Torrini C, Cubero RJ, Dirkx E, Braga L, Ali H, Prosdocimo G, Gutierrez MI, Collesi C, Licastro D, Zentilin L, Mano M, Zacchigna S, Vendruscolo M, Marsili M, Samal A, Giacca M. 2019. Common regulatory pathways mediate activity of microRNAs inducing cardiomyocyte proliferation. Cell Reports. 27(9), 2759–2771.e5.","chicago":"Torrini, Consuelo, Ryan J Cubero, Ellen Dirkx, Luca Braga, Hashim Ali, Giulia Prosdocimo, Maria Ines Gutierrez, et al. “Common Regulatory Pathways Mediate Activity of MicroRNAs Inducing Cardiomyocyte Proliferation.” <i>Cell Reports</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.celrep.2019.05.005\">https://doi.org/10.1016/j.celrep.2019.05.005</a>.","mla":"Torrini, Consuelo, et al. “Common Regulatory Pathways Mediate Activity of MicroRNAs Inducing Cardiomyocyte Proliferation.” <i>Cell Reports</i>, vol. 27, no. 9, Elsevier, 2019, p. 2759–2771.e5, doi:<a href=\"https://doi.org/10.1016/j.celrep.2019.05.005\">10.1016/j.celrep.2019.05.005</a>."},"title":"Common regulatory pathways mediate activity of microRNAs inducing cardiomyocyte proliferation","day":"28","author":[{"full_name":"Torrini, Consuelo","first_name":"Consuelo","last_name":"Torrini"},{"orcid":"0000-0003-0002-1867","id":"850B2E12-9CD4-11E9-837F-E719E6697425","last_name":"Cubero","first_name":"Ryan J","full_name":"Cubero, Ryan J"},{"first_name":"Ellen","full_name":"Dirkx, Ellen","last_name":"Dirkx"},{"last_name":"Braga","first_name":"Luca","full_name":"Braga, Luca"},{"last_name":"Ali","first_name":"Hashim","full_name":"Ali, Hashim"},{"last_name":"Prosdocimo","full_name":"Prosdocimo, Giulia","first_name":"Giulia"},{"first_name":"Maria Ines","full_name":"Gutierrez, Maria Ines","last_name":"Gutierrez"},{"full_name":"Collesi, Chiara","first_name":"Chiara","last_name":"Collesi"},{"full_name":"Licastro, Danilo","first_name":"Danilo","last_name":"Licastro"},{"last_name":"Zentilin","full_name":"Zentilin, Lorena","first_name":"Lorena"},{"first_name":"Miguel","full_name":"Mano, Miguel","last_name":"Mano"},{"last_name":"Zacchigna","first_name":"Serena","full_name":"Zacchigna, Serena"},{"last_name":"Vendruscolo","full_name":"Vendruscolo, Michele","first_name":"Michele"},{"full_name":"Marsili, Matteo","first_name":"Matteo","last_name":"Marsili"},{"first_name":"Areejit","full_name":"Samal, Areejit","last_name":"Samal"},{"full_name":"Giacca, Mauro","first_name":"Mauro","last_name":"Giacca"}],"type":"journal_article","pmid":1,"language":[{"iso":"eng"}],"keyword":["cardiomyocyte","cell cycle","Cofilin2","cytoskeleton","Hippo","microRNA","regeneration","YAP"],"ddc":["576"],"doi":"10.1016/j.celrep.2019.05.005"}]