[{"publication_status":"published","year":"2026","has_accepted_license":"1","date_published":"2026-01-05T00:00:00Z","title":"Geometry-driven asymmetric cell divisions pattern cell cycles and zygotic genome activation in the zebrafish embryo","author":[{"first_name":"Nikhil","orcid":"0000-0002-6425-5788","last_name":"Mishra","id":"C4D70E82-1081-11EA-B3ED-9A4C3DDC885E","full_name":"Mishra, Nikhil"},{"full_name":"Li, Yuting I","id":"ee7a5ca8-8b71-11ed-b662-b3341c05b7eb","last_name":"Li","first_name":"Yuting I"},{"first_name":"Edouard B","orcid":"0000-0001-6005-1561","last_name":"Hannezo","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","full_name":"Hannezo, Edouard B"},{"orcid":"0000-0002-0912-4566","first_name":"Carl-Philipp J","last_name":"Heisenberg","full_name":"Heisenberg, Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87"}],"_id":"21015","publisher":"Springer Nature","article_processing_charge":"Yes (via OA deal)","external_id":{"oaworkid":["W7118187193"]},"quality_controlled":"1","oaworkid":1,"license":"https://creativecommons.org/licenses/by/4.0/","acknowledgement":"We thank N. Petridou (EMBL) for sharing results before publication. N.M. was supported by funding from the European Union’s Horizon 2020 programme under the Marie Skłodowska-Curie COFUND Actions ISTplus grant agreement number 754411. Y.I.L. acknowledges funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement number 101034413. The research was supported by funding to C.-P.H. from the NOMIS Foundation, Project ID 1.844. We would like to thank past and present members of the Heisenberg and Hannezo groups for discussions, particularly S. Shamipour, V. Doddihal, M. Jovic, N. Hino, F. N. Arslan, R. Kobylinska and C. Camelo for feedback on the draft manuscript. This research was supported by the Scientific Service Units (SSU) of Institute of Science and Technology Austria through resources provided by the Aquatics Facility, Imaging & Optics Facility (IOF), Scientific Computing (SciComp) facility and Lab Support Facility (LSF). Open access funding provided by Institute of Science and Technology (IST Austria).","language":[{"iso":"eng"}],"status":"public","intvolume":"        22","abstract":[{"lang":"eng","text":"Early embryo geometry is one of the most invariant species-specific traits, yet its role in ensuring developmental reproducibility and robustness remains underexplored. Here we show that in zebrafish, the geometry of the fertilized egg—specifically its curvature and volume—serves as a critical initial condition triggering a cascade of events that influence development. The embryo geometry guides patterned asymmetric cell divisions in the blastoderm, generating radial gradients of cell volume and nucleocytoplasmic ratio. These gradients generate mitotic phase waves, with the nucleocytoplasmic ratio determining individual cell cycle periods independently of other cells. We demonstrate that reducing cell autonomy reshapes these waves, emphasizing the instructive role of geometry-derived volume patterns in setting the intrinsic period of the cell cycle oscillator. In addition to organizing cell cycles, early embryo geometry spatially patterns zygotic genome activation at the midblastula transition, a key step in establishing embryonic autonomy. Disrupting the embryo shape alters the zygotic genome activation pattern and causes ectopic germ layer specification, underscoring the developmental significance of geometry. Together, our findings reveal a symmetry-breaking function of early embryo geometry in coordinating cell cycle and transcriptional patterning."}],"publication":"Nature Physics","volume":22,"date_updated":"2026-04-28T12:55:30Z","date_created":"2026-01-20T10:12:19Z","doi":"10.1038/s41567-025-03122-1","month":"01","corr_author":"1","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","ddc":["570"],"oa_version":"Published Version","related_material":{"link":[{"description":"News on ISTA website","relation":"research_data","url":"https://ista.ac.at/en/news/geometry-shapes-life/"}]},"project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships"},{"grant_number":"101034413","call_identifier":"H2020","_id":"fc2ed2f7-9c52-11eb-aca3-c01059dda49c","name":"IST-BRIDGE: International postdoctoral program"},{"_id":"917c023a-16d5-11f0-9cad-eb5cafc52090","name":"Cytoplasmic self-organization into cell-like compartments as a common guiding principle in early animal development"}],"page":"139-150","department":[{"_id":"EdHa"},{"_id":"CaHe"}],"ec_funded":1,"type":"journal_article","scopus_import":"1","oa":1,"OA_place":"publisher","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"citation":{"chicago":"Mishra, Nikhil, Yuting I Li, Edouard B Hannezo, and Carl-Philipp J Heisenberg. “Geometry-Driven Asymmetric Cell Divisions Pattern Cell Cycles and Zygotic Genome Activation in the Zebrafish Embryo.” <i>Nature Physics</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41567-025-03122-1\">https://doi.org/10.1038/s41567-025-03122-1</a>.","ista":"Mishra N, Li YI, Hannezo EB, Heisenberg C-PJ. 2026. Geometry-driven asymmetric cell divisions pattern cell cycles and zygotic genome activation in the zebrafish embryo. Nature Physics. 22, 139–150.","short":"N. Mishra, Y.I. Li, E.B. Hannezo, C.-P.J. Heisenberg, Nature Physics 22 (2026) 139–150.","apa":"Mishra, N., Li, Y. I., Hannezo, E. B., &#38; Heisenberg, C.-P. J. (2026). Geometry-driven asymmetric cell divisions pattern cell cycles and zygotic genome activation in the zebrafish embryo. <i>Nature Physics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41567-025-03122-1\">https://doi.org/10.1038/s41567-025-03122-1</a>","ieee":"N. Mishra, Y. I. Li, E. B. Hannezo, and C.-P. J. Heisenberg, “Geometry-driven asymmetric cell divisions pattern cell cycles and zygotic genome activation in the zebrafish embryo,” <i>Nature Physics</i>, vol. 22. Springer Nature, pp. 139–150, 2026.","mla":"Mishra, Nikhil, et al. “Geometry-Driven Asymmetric Cell Divisions Pattern Cell Cycles and Zygotic Genome Activation in the Zebrafish Embryo.” <i>Nature Physics</i>, vol. 22, Springer Nature, 2026, pp. 139–50, doi:<a href=\"https://doi.org/10.1038/s41567-025-03122-1\">10.1038/s41567-025-03122-1</a>.","ama":"Mishra N, Li YI, Hannezo EB, Heisenberg C-PJ. Geometry-driven asymmetric cell divisions pattern cell cycles and zygotic genome activation in the zebrafish embryo. <i>Nature Physics</i>. 2026;22:139-150. doi:<a href=\"https://doi.org/10.1038/s41567-025-03122-1\">10.1038/s41567-025-03122-1</a>"},"fulldoi":"https://doi.org/10.1038/s41567-025-03122-1","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"ScienComp"},{"_id":"LifeSc"}],"publication_identifier":{"issnl":[" 1745-2473"],"eissn":["1745-2481"],"issn":["1745-2473"]},"file":[{"success":1,"access_level":"open_access","date_created":"2026-01-21T08:21:11Z","relation":"main_file","date_updated":"2026-01-21T08:21:11Z","file_name":"2026_NaturePhysics_Mishra.pdf","file_size":7335694,"file_id":"21026","checksum":"0ab7ac2fbcb61a364dba57152db64ed7","content_type":"application/pdf","creator":"dernst"}],"file_date_updated":"2026-01-21T08:21:11Z","OA_type":"hybrid","article_type":"original","PlanS_conform":"1","day":"05"},{"_id":"21291","article_processing_charge":"No","publication":"bioRxiv","abstract":[{"text":"The complexity and specificity of movement in vertebrates is driven by a rich diversity of spinal motor and interneuron cell types. During development, eleven spinal cord progenitor domains generate an equivalent number of cardinal neuron types. How progenitor domains, individual progenitors, and post-mitotic diversity relate is still unknown. We performed high-resolution, single-progenitor cell lineage tracing in the embryonic mouse spinal cord using mosaic analysis with double markers (MADM). Our quantitative study of lineage progression revealed that spinal cord progenitors undergo highly variable numbers of proliferative, neurogenic, and gliogenic cell divisions. The nascent clonally-related neurons migrate radially over large distances, span the dorsoventral axis, and even cross the midline, demonstrating striking bilaterality. Molecular and morphometric analysis indicate high levels of progenitor multipotency, with an individual progenitor capable of producing several molecularly and morphologically distinct neuron types, as well as astrocytes. These findings redefine spinal cord development as a process in which lineage variability — rather than rigid progenitor identity — drives the generation of cellular diversity.","lang":"eng"}],"status":"public","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","language":[{"iso":"eng"}],"acknowledgement":"We would like to thank Elizabeth Marin, Anna Kicheva, Igor Adameyko, and James Briscoe as\r\nwell as members of the Sweeney and Hippemeyer labs and SFB consortium for comments on\r\nthe manuscript. We are also grateful for the technical support of the Preclinical and Imaging and\r\nOptics Facilities support teams (ISTA). In addition, we thank our funding sources for providing\r\nthe resources to do these experiments: Horizon Europe ERC Starting Grant Number 101041551\r\n(M.S.; L.B.S.); Special Research Program (SFB) of the Austrian Science Fund (FWF)\r\nNeuroStem Modulation Project numbers F7814-B (S.A.G.; M.S.; G.S.; and L.B.S.) and F7805\r\n(G.C. and S.H.). S.A.G is supported by a Boehringer Ingelheim Fonds PhD Fellowship, F.D.S.N.\r\nby an Institute of Science and Technology Austria (ISTA) GROW fellowship, and G.C. by an\r\nISTA Plus postdoctoral fellowship from the European Commission. S.H./L.B.S. and G.C. were\r\nadditionally supported by institutional funds from the ISTA and the University of Exeter,\r\nrespectively. ","publication_status":"submitted","has_accepted_license":"1","year":"2026","author":[{"full_name":"Gobeil, Sophie A","id":"2f3e9efb-eb24-11ec-86b2-88efb11d59fa","last_name":"Gobeil","first_name":"Sophie A"},{"full_name":"Da Silveira Neto, Francisco","id":"8cfb7412-10a7-11f1-add1-82b44e6418f2","first_name":"Francisco","last_name":"Da Silveira Neto"},{"first_name":"Giulia","last_name":"Silvestrelli","id":"12632ae8-799e-11ef-94a2-e5a3b5ef49e9","full_name":"Silvestrelli, Giulia"},{"full_name":"Smits, Matthijs Geert","id":"7a231d52-e216-11ee-a0bb-8acd55f8f1f0","first_name":"Matthijs Geert","last_name":"Smits"},{"last_name":"Streicher","first_name":"Carmen","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-8457-2572","first_name":"Giselle T","last_name":"Cheung","full_name":"Cheung, Giselle T","id":"471195F6-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","first_name":"Simon","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-9242-5601","first_name":"Lora Beatrice Jaeger","last_name":"Sweeney","id":"56BE8254-C4F0-11E9-8E45-0B23E6697425","full_name":"Sweeney, Lora Beatrice Jaeger"}],"title":"Lineage origin of spinal cord cell type diversity","date_published":"2026-02-16T00:00:00Z","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"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"},"fulldoi":"https://doi.org/10.64898/2026.02.12.705305","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"}],"citation":{"ista":"Gobeil SA, Da Silveira Neto F, Silvestrelli G, Smits MG, Streicher C, Cheung GT, Hippenmeyer S, Sweeney LB. Lineage origin of spinal cord cell type diversity. bioRxiv, <a href=\"https://doi.org/10.64898/2026.02.12.705305\">10.64898/2026.02.12.705305</a>.","chicago":"Gobeil, Sophie A, Francisco Da Silveira Neto, Giulia Silvestrelli, Matthijs Geert Smits, Carmen Streicher, Giselle T Cheung, Simon Hippenmeyer, and Lora B. Sweeney. “Lineage Origin of Spinal Cord Cell Type Diversity.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.64898/2026.02.12.705305\">https://doi.org/10.64898/2026.02.12.705305</a>.","short":"S.A. Gobeil, F. Da Silveira Neto, G. Silvestrelli, M.G. Smits, C. Streicher, G.T. Cheung, S. Hippenmeyer, L.B. Sweeney, BioRxiv (n.d.).","ama":"Gobeil SA, Da Silveira Neto F, Silvestrelli G, et al. Lineage origin of spinal cord cell type diversity. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.64898/2026.02.12.705305\">10.64898/2026.02.12.705305</a>","mla":"Gobeil, Sophie A., et al. “Lineage Origin of Spinal Cord Cell Type Diversity.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.64898/2026.02.12.705305\">10.64898/2026.02.12.705305</a>.","ieee":"S. A. Gobeil <i>et al.</i>, “Lineage origin of spinal cord cell type diversity,” <i>bioRxiv</i>. .","apa":"Gobeil, S. A., Da Silveira Neto, F., Silvestrelli, G., Smits, M. G., Streicher, C., Cheung, G. T., … Sweeney, L. B. (n.d.). Lineage origin of spinal cord cell type diversity. <i>bioRxiv</i>. <a href=\"https://doi.org/10.64898/2026.02.12.705305\">https://doi.org/10.64898/2026.02.12.705305</a>"},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.64898/2026.02.12.705305"}],"oa":1,"OA_place":"repository","OA_type":"green","day":"16","month":"02","oa_version":"Preprint","ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","corr_author":"1","date_created":"2026-02-17T11:36:20Z","doi":"10.64898/2026.02.12.705305","date_updated":"2026-04-14T08:16:55Z","department":[{"_id":"SiHi"},{"_id":"LoSw"}],"type":"preprint","project":[{"grant_number":"101041551","_id":"ebb66355-77a9-11ec-83b8-b8ac210a4dae","name":"Development and Evolution of Tetrapod Motor Circuits"},{"name":"Stem Cell Modulation in Neural Development and Regeneration/ P14-Swim-to-limb transition: cell type to connection diversity","grant_number":"F7814","_id":"8da85f50-16d5-11f0-9cad-eab8b0ff6c9e"},{"name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression","grant_number":"F7805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E"}]},{"fulldoi":"https://doi.org/10.1016/j.jid.2026.03.026","citation":{"ama":"Klein K, Johnson L, Rîca R, et al. Langerhans cell–targeted mRNA delivery: A strategy for dose-sparing and enhanced antitumor immunity. <i>Journal of Investigative Dermatology</i>. doi:<a href=\"https://doi.org/10.1016/j.jid.2026.03.026\">10.1016/j.jid.2026.03.026</a>","ieee":"K. Klein <i>et al.</i>, “Langerhans cell–targeted mRNA delivery: A strategy for dose-sparing and enhanced antitumor immunity,” <i>Journal of Investigative Dermatology</i>. Elsevier.","apa":"Klein, K., Johnson, L., Rîca, R., Sarcevic, M., Carta, G., Seiser, S., … Sparber, F. (n.d.). Langerhans cell–targeted mRNA delivery: A strategy for dose-sparing and enhanced antitumor immunity. <i>Journal of Investigative Dermatology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.jid.2026.03.026\">https://doi.org/10.1016/j.jid.2026.03.026</a>","mla":"Klein, Klara, et al. “Langerhans Cell–Targeted MRNA Delivery: A Strategy for Dose-Sparing and Enhanced Antitumor Immunity.” <i>Journal of Investigative Dermatology</i>, Elsevier, doi:<a href=\"https://doi.org/10.1016/j.jid.2026.03.026\">10.1016/j.jid.2026.03.026</a>.","ista":"Klein K, Johnson L, Rîca R, Sarcevic M, Carta G, Seiser S, Elbe-Bürger A, Langer F, Rahhal N, Rademacher C, Wawrzinek R, Quattrone F, Sparber F. Langerhans cell–targeted mRNA delivery: A strategy for dose-sparing and enhanced antitumor immunity. Journal of Investigative Dermatology.","chicago":"Klein, Klara, Litty Johnson, Ramona Rîca, Mirza Sarcevic, Gabriele Carta, Saskia Seiser, Adelheid Elbe-Bürger, et al. “Langerhans Cell–Targeted MRNA Delivery: A Strategy for Dose-Sparing and Enhanced Antitumor Immunity.” <i>Journal of Investigative Dermatology</i>. Elsevier, n.d. <a href=\"https://doi.org/10.1016/j.jid.2026.03.026\">https://doi.org/10.1016/j.jid.2026.03.026</a>.","short":"K. Klein, L. Johnson, R. Rîca, M. Sarcevic, G. Carta, S. Seiser, A. Elbe-Bürger, F. Langer, N. Rahhal, C. Rademacher, R. Wawrzinek, F. Quattrone, F. Sparber, Journal of Investigative Dermatology (n.d.)."},"acknowledged_ssus":[{"_id":"PreCl"}],"publication_identifier":{"issn":["0022-202X"],"eissn":["1523-1747"]},"scopus_import":"1","oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2025.06.25.661517"}],"OA_place":"repository","OA_type":"green","article_type":"original","day":"07","month":"04","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Preprint","doi":"10.1016/j.jid.2026.03.026","date_updated":"2026-05-11T06:07:32Z","date_created":"2026-05-10T22:02:16Z","department":[{"_id":"PreCl"}],"type":"journal_article","_id":"21848","publisher":"Elsevier","article_processing_charge":"No","publication":"Journal of Investigative Dermatology","status":"public","language":[{"iso":"eng"}],"acknowledgement":"We thank Mareike Rentzsch for her intellectual contributions during the course of our discussions. We thank Michael Schunn from the Preclinical Facility of the Institute of Science and Technology Austria for his continuous technical support. Guarantor of the work is FS. This project was supported by “Seedfinancing” (P2282679) of the Austrian Federal Ministry of Digital and Economic Affairs and the Ministry of Climate Action and Energy, handled by the Austrian Wirtschaftsservice, as well as by...","abstract":[{"lang":"eng","text":"Despite the success of mRNA therapeutics, challenges remain in optimizing immune responses and minimizing side effects. Cell-specific antigen delivery may help reduce required doses and improve vaccine efficacy. In this study, we report on a targeted delivery system for mRNA to a specific subset of skin-resident antigen-presenting cells: Langerhans cells. By functionalizing lipid nanoparticles with a langerin-specific glycomimetic ligand, we achieve selective mRNA delivery to both murine and human primary Langerhans cells with minimal off-target uptake, at the same time resulting in significantly increased mRNA translation. This targeted mRNA delivery not only enhances antigen presentation and T-cell responses but also enables dose-sparing and superior antitumor immunity compared with conventional immunization in a B16-OVA tumor model. Importantly, our platform’s high compatibility with various lipid nanoparticle formulations offers a flexible and precise tool for skin-directed mRNA delivery."}],"publication_status":"inpress","year":"2026","title":"Langerhans cell–targeted mRNA delivery: A strategy for dose-sparing and enhanced antitumor immunity","author":[{"first_name":"Klara","last_name":"Klein","full_name":"Klein, Klara"},{"full_name":"Johnson, Litty","last_name":"Johnson","first_name":"Litty"},{"full_name":"Rîca, Ramona","last_name":"Rîca","first_name":"Ramona"},{"full_name":"Sarcevic, Mirza","last_name":"Sarcevic","first_name":"Mirza"},{"full_name":"Carta, Gabriele","first_name":"Gabriele","last_name":"Carta"},{"first_name":"Saskia","last_name":"Seiser","full_name":"Seiser, Saskia"},{"full_name":"Elbe-Bürger, Adelheid","first_name":"Adelheid","last_name":"Elbe-Bürger"},{"id":"3C1BE782-F248-11E8-B48F-1D18A9856A87","full_name":"Langer, Freyja","first_name":"Freyja","last_name":"Langer"},{"first_name":"Nowras","last_name":"Rahhal","full_name":"Rahhal, Nowras"},{"full_name":"Rademacher, Christoph","last_name":"Rademacher","first_name":"Christoph"},{"first_name":"Robert","last_name":"Wawrzinek","full_name":"Wawrzinek, Robert"},{"full_name":"Quattrone, Federica","first_name":"Federica","last_name":"Quattrone"},{"full_name":"Sparber, Florian","last_name":"Sparber","first_name":"Florian"}],"date_published":"2026-04-07T00:00:00Z"},{"abstract":[{"lang":"eng","text":"The generation of faithful cell-type diversity and correct projection neuron numbers is essential for cerebral cortex development. Corticogenesis is however susceptible to genetic interference of critical signaling pathways, including mutations in Mtor/Rptor that lead to microcephaly. How the loss of Rptor/mTORC1 function affects cortical developmental programs, at single cell level, is still unknown. Here, we utilized Mosaic Analysis with Double Markers (MADM) technology to probe Rptor gene function upon sparse single cell- or global tissue-wide ablation. We found that tissue-wide effects drive the etiology of cortical microcephaly upon loss of Rptor, rather than deficits in projection neuron genesis. Conversely, Rptor function is cell-autonomously required for postnatal projection neuron survival in a highly cell-type-specific manner. Collectively, our results suggest that the fine balance of precise cell-type-specific cell-autonomous Rptor/mTORC1 function in concert with non-cell-autonomous tissue-wide effects is essential for the development of a properly-sized cerebral cortex with accurate projection neuron diversity."}],"license":"https://creativecommons.org/licenses/by-nc/4.0/","language":[{"iso":"eng"}],"status":"public","acknowledgement":"We thank A. Heger (IST Austria Preclinical Facility), A. Sommer (VBCF GmbH, NGS Unit), and A.\r\nNicolas (IST Austria Lab Support Facility / Mass Spectrometry Facility) for technical support; K. Ferencak,\r\nI. Aykara, P. Hirschfeld, E. Fisher, S. Laukoter, L. Andersen for initial experiments and/or assistance; and\r\nall members of the Hippenmeyer lab for discussion. This research was supported by the Scientific Service\r\nUnits (SSU) of IST Austria through resources provided by the Imaging and Optics- (IOF), Lab Support-\r\n(LSF) and Preclinical Facilities (PCF). R.B. received support from FWF Meitner-Programm (M 2416). This\r\nwork was also supported by IST Austria institutional funds; the People Programme (Marie Curie Actions)\r\nof the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement\r\nNo 618444 to S.H., and the European Research Council (ERC) under the European Union’s Horizon 2020\r\nresearch and innovation programme (grant agreement No 725780 LinPro) to S.H.","publication":"bioRxiv","article_processing_charge":"No","_id":"21962","date_published":"2026-05-05T00:00:00Z","author":[{"full_name":"Villalba Requena, Ana","id":"68cb85a0-39f7-11eb-9559-9aaab4f6a247","last_name":"Villalba Requena","orcid":"0000-0002-5615-5277","first_name":"Ana"},{"last_name":"Beattie","first_name":"Robert J","orcid":"0000-0002-8483-8753","full_name":"Beattie, Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","orcid":"0000-0002-7462-0048","last_name":"Pauler"},{"id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen","last_name":"Streicher","first_name":"Carmen"},{"first_name":"Osvaldo","orcid":"0000-0001-6618-6889","last_name":"Miranda","full_name":"Miranda, Osvaldo","id":"862A3C56-A8BF-11E9-B4FA-D9E3E5697425"},{"first_name":"Thomas","last_name":"Krausgruber","full_name":"Krausgruber, Thomas"},{"last_name":"Senekowitsch","first_name":"Martin","full_name":"Senekowitsch, Martin"},{"full_name":"Farlik, Matthias","first_name":"Matthias","last_name":"Farlik"},{"last_name":"Bock","first_name":"Christoph","full_name":"Bock, Christoph"},{"first_name":"Thomas","last_name":"Rülicke","full_name":"Rülicke, Thomas"},{"full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer"}],"title":"Mtor/Rptor function globally prevents cortical microcephaly and cell-autonomously promotes postnatal neuron survival in cell type specific manner","has_accepted_license":"1","year":"2026","publication_status":"submitted","day":"05","OA_type":"green","OA_place":"repository","main_file_link":[{"url":"https://doi.org/10.64898/2026.05.01.722172","open_access":"1"}],"oa":1,"fulldoi":"https://doi.org/10.64898/2026.05.01.722172","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"MassSpec"},{"_id":"Bio"}],"citation":{"ista":"Villalba Requena A, Beattie RJ, Pauler F, Streicher C, Miranda O, Krausgruber T, Senekowitsch M, Farlik M, Bock C, Rülicke T, Hippenmeyer S. Mtor/Rptor function globally prevents cortical microcephaly and cell-autonomously promotes postnatal neuron survival in cell type specific manner. bioRxiv, <a href=\"https://doi.org/10.64898/2026.05.01.722172\">10.64898/2026.05.01.722172</a>.","chicago":"Villalba Requena, Ana, Robert J Beattie, Florian Pauler, Carmen Streicher, Osvaldo Miranda, Thomas Krausgruber, Martin Senekowitsch, et al. “Mtor/Rptor Function Globally Prevents Cortical Microcephaly and Cell-Autonomously Promotes Postnatal Neuron Survival in Cell Type Specific Manner.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.64898/2026.05.01.722172\">https://doi.org/10.64898/2026.05.01.722172</a>.","short":"A. Villalba Requena, R.J. Beattie, F. Pauler, C. Streicher, O. Miranda, T. Krausgruber, M. Senekowitsch, M. Farlik, C. Bock, T. Rülicke, S. Hippenmeyer, BioRxiv (n.d.).","ama":"Villalba Requena A, Beattie RJ, Pauler F, et al. Mtor/Rptor function globally prevents cortical microcephaly and cell-autonomously promotes postnatal neuron survival in cell type specific manner. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.64898/2026.05.01.722172\">10.64898/2026.05.01.722172</a>","mla":"Villalba Requena, Ana, et al. “Mtor/Rptor Function Globally Prevents Cortical Microcephaly and Cell-Autonomously Promotes Postnatal Neuron Survival in Cell Type Specific Manner.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.64898/2026.05.01.722172\">10.64898/2026.05.01.722172</a>.","ieee":"A. Villalba Requena <i>et al.</i>, “Mtor/Rptor function globally prevents cortical microcephaly and cell-autonomously promotes postnatal neuron survival in cell type specific manner,” <i>bioRxiv</i>. .","apa":"Villalba Requena, A., Beattie, R. J., Pauler, F., Streicher, C., Miranda, O., Krausgruber, T., … Hippenmeyer, S. (n.d.). Mtor/Rptor function globally prevents cortical microcephaly and cell-autonomously promotes postnatal neuron survival in cell type specific manner. <i>bioRxiv</i>. <a href=\"https://doi.org/10.64898/2026.05.01.722172\">https://doi.org/10.64898/2026.05.01.722172</a>"},"tmp":{"short":"CC BY-NC (4.0)","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png"},"project":[{"grant_number":"M02416","call_identifier":"FWF","_id":"264E56E2-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms Regulating Gliogenesis in the Neocortex"},{"name":"Molecular Mechanisms of Cerebral Cortex Development","grant_number":"618444","call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425"},{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"725780"}],"type":"preprint","ec_funded":1,"department":[{"_id":"SiHi"}],"date_updated":"2026-06-16T08:45:25Z","date_created":"2026-06-09T08:08:18Z","doi":"10.64898/2026.05.01.722172","ddc":["570"],"oa_version":"Preprint","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"05"},{"_id":"21963","article_processing_charge":"No","abstract":[{"lang":"eng","text":"The cerebral cortex consists of immense numbers of neuronal and glial cell-types derived from radial glial progenitor (RGP) cells. How RGPs generate appropriate quantities of distinct cortical cell-types to safeguard a brain of correct size, is not well understood. However, genetic aberration in human, including mutations in PTEN, lead to cortical malformation such as macrocephaly, albeit with unknown etiology. Here we utilized Mosaic Analysis with Double Markers (MADM)-based clonal analysis and single cell phenotyping to decipher the role of Pten in neurogenic and gliogenic RGP lineage progression during cortical ontogeny. While neurogenic RGP lineage progression and projection neuron production was moderately altered in the absence of Pten, cortical astrocyte production was drastically increased. Through genetic epistasis experiments we show that the loss of Pten uncouples astrocyte generation from essential growth factor signaling hubs, funneling into MAPK. Collectively, our results suggest that Pten regulates RGP lineage progression with distinct sequential functions in cortical projection neurogenesis and astrocyte production to ensure the emergence of a correctly-sized cerebral cortex."}],"language":[{"iso":"eng"}],"status":"public","acknowledgement":"We thank Kay-Uwe Wagner (Wayne State University) for generously sharing Jak1/2–flox mouse lines; A.\r\nSommer (VBCF GmbH, NGS Unit) for technical support; N. Kim, V. Mick, S. Schnabl, S. Gobeil, and L.\r\nAndersen for technical assistance; all members of the Hippenmeyer lab for discussion and B. Novitch for\r\ncomments on earlier versions of the manuscript. This research was supported by the Scientific Service Units\r\n(SSU) of IST Austria through resources provided by the Imaging and Optics Facility (IOF), Lab Support-\r\n(LSF) and Preclinical Facilities (PCF). O.A.M received support from the Austrian Academy of Sciences\r\nÖAW (DOC 186584), and N.A. from FWF Elise Richter Program (Grant V1041T). This work was also\r\nsupported by IST Austria institutional funds; FWF SFB F78 (Neuro Stem Modulation) to S.H., and the\r\nEuropean Research Council (ERC) under the European Union’s Horizon 2020 research and innovation\r\nprogramme (grant agreement No 725780 LinPro) to S.H.","publication":"bioRxiv","publication_status":"submitted","has_accepted_license":"1","year":"2026","date_published":"2026-05-05T00:00:00Z","author":[{"orcid":"0000-0001-6618-6889","first_name":"Osvaldo","last_name":"Miranda","id":"862A3C56-A8BF-11E9-B4FA-D9E3E5697425","full_name":"Miranda, Osvaldo"},{"last_name":"Contreras","first_name":"Ximena","id":"475990FE-F248-11E8-B48F-1D18A9856A87","full_name":"Contreras, Ximena"},{"id":"48EA0138-F248-11E8-B48F-1D18A9856A87","full_name":"Pauler, Florian","last_name":"Pauler","orcid":"0000-0002-7462-0048","first_name":"Florian"},{"full_name":"Davaatseren, Amarbayasgalan","id":"70ADC922-B424-11E9-99E3-BA18E6697425","first_name":"Amarbayasgalan","last_name":"Davaatseren"},{"last_name":"Amberg","first_name":"Nicole","orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87"},{"id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen","first_name":"Carmen","last_name":"Streicher"},{"id":"68cb85a0-39f7-11eb-9559-9aaab4f6a247","full_name":"Villalba Requena, Ana","orcid":"0000-0002-5615-5277","first_name":"Ana","last_name":"Villalba Requena"},{"first_name":"Anna-Magdalena","last_name":"Heger","id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87","full_name":"Heger, Anna-Magdalena"},{"first_name":"Corentine","last_name":"Marie","full_name":"Marie, Corentine"},{"full_name":"Hassan, Bassem A.","last_name":"Hassan","first_name":"Bassem A."},{"first_name":"Thomas","last_name":"Rülicke","full_name":"Rülicke, Thomas"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","first_name":"Simon"}],"title":"Pten orchestrates neurogenic radial glia lineage progression and tunes neocortical astrocyte production","main_file_link":[{"open_access":"1","url":"https://doi.org/10.64898/2026.05.01.722191"}],"oa":1,"OA_place":"repository","tmp":{"short":"CC BY-NC (4.0)","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png"},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"fulldoi":"https://doi.org/10.64898/2026.05.01.722191","citation":{"ieee":"O. Miranda <i>et al.</i>, “Pten orchestrates neurogenic radial glia lineage progression and tunes neocortical astrocyte production,” <i>bioRxiv</i>. .","mla":"Miranda, Osvaldo, et al. “Pten Orchestrates Neurogenic Radial Glia Lineage Progression and Tunes Neocortical Astrocyte Production.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.64898/2026.05.01.722191\">10.64898/2026.05.01.722191</a>.","apa":"Miranda, O., Contreras, X., Pauler, F., Davaatseren, A., Amberg, N., Streicher, C., … Hippenmeyer, S. (n.d.). Pten orchestrates neurogenic radial glia lineage progression and tunes neocortical astrocyte production. <i>bioRxiv</i>. <a href=\"https://doi.org/10.64898/2026.05.01.722191\">https://doi.org/10.64898/2026.05.01.722191</a>","ama":"Miranda O, Contreras X, Pauler F, et al. Pten orchestrates neurogenic radial glia lineage progression and tunes neocortical astrocyte production. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.64898/2026.05.01.722191\">10.64898/2026.05.01.722191</a>","chicago":"Miranda, Osvaldo, Ximena Contreras, Florian Pauler, Amarbayasgalan Davaatseren, Nicole Amberg, Carmen Streicher, Ana Villalba Requena, et al. “Pten Orchestrates Neurogenic Radial Glia Lineage Progression and Tunes Neocortical Astrocyte Production.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.64898/2026.05.01.722191\">https://doi.org/10.64898/2026.05.01.722191</a>.","ista":"Miranda O, Contreras X, Pauler F, Davaatseren A, Amberg N, Streicher C, Villalba Requena A, Heger A-M, Marie C, Hassan BA, Rülicke T, Hippenmeyer S. Pten orchestrates neurogenic radial glia lineage progression and tunes neocortical astrocyte production. bioRxiv, <a href=\"https://doi.org/10.64898/2026.05.01.722191\">10.64898/2026.05.01.722191</a>.","short":"O. Miranda, X. Contreras, F. Pauler, A. Davaatseren, N. Amberg, C. Streicher, A. Villalba Requena, A.-M. Heger, C. Marie, B.A. Hassan, T. Rülicke, S. Hippenmeyer, BioRxiv (n.d.)."},"OA_type":"green","day":"05","date_created":"2026-06-09T08:08:53Z","doi":"10.64898/2026.05.01.722191","date_updated":"2026-06-16T08:57:20Z","month":"05","oa_version":"Preprint","ddc":["570"],"corr_author":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","project":[{"_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","grant_number":"F7805","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression"},{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"725780"}],"ec_funded":1,"department":[{"_id":"SiHi"},{"_id":"PreCl"},{"_id":"GradSch"}],"type":"preprint"},{"month":"06","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","corr_author":"1","oa_version":"Published Version","ddc":["570"],"date_updated":"2026-07-01T06:47:49Z","doi":"10.1038/s41467-026-71914-x","date_created":"2026-06-30T13:05:52Z","department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"ec_funded":1,"supplementarymaterial":"yes","type":"journal_article","pmid":1,"related_material":{"record":[{"id":"21442","status":"public","relation":"research_data"}]},"project":[{"grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"grant_number":"101199096","_id":"e62b56fe-ab3c-11f0-94c7-d181dd352b3b","name":"Synaptic mechanisms of engram storage and retrieval in CA3 hippocampal microcircuits"},{"call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships"},{"name":"Synaptic computations of the hippocampal CA3 circuitry","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","call_identifier":"H2020","grant_number":"101026635"},{"_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","grant_number":"P36232","name":"Mechanisms of GABA release in hippocampal circuits"},{"_id":"8d9195e9-16d5-11f0-9cad-d075be887a1e","grant_number":"PAT 4178023","name":"Synaptic networks of human brain"},{"_id":"26366136-B435-11E9-9278-68D0E5697425","name":"Reglas de Conectividad funcional en el hipocampo"}],"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"DOAJ_listed":"1","fulldoi":"https://doi.org/10.1038/s41467-026-71914-x","citation":{"chicago":"Vargas Barroso, Victor M, Jake Watson, Andrea C Navas Olivé, Alois Schlögl, and Peter M Jonas. “Developmental Emergence of Sparse and Structured Synaptic Connectivity in the Hippocampal CA3 Memory Circuit.” <i>Nature Communications</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41467-026-71914-x\">https://doi.org/10.1038/s41467-026-71914-x</a>.","ista":"Vargas Barroso VM, Watson J, Navas Olivé AC, Schlögl A, Jonas PM. 2026. Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit. Nature Communications. 17, 5540.","short":"V.M. Vargas Barroso, J. Watson, A.C. Navas Olivé, A. Schlögl, P.M. Jonas, Nature Communications 17 (2026).","mla":"Vargas Barroso, Victor M., et al. “Developmental Emergence of Sparse and Structured Synaptic Connectivity in the Hippocampal CA3 Memory Circuit.” <i>Nature Communications</i>, vol. 17, 5540, Springer Nature, 2026, doi:<a href=\"https://doi.org/10.1038/s41467-026-71914-x\">10.1038/s41467-026-71914-x</a>.","apa":"Vargas Barroso, V. M., Watson, J., Navas Olivé, A. C., Schlögl, A., &#38; Jonas, P. M. (2026). Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-026-71914-x\">https://doi.org/10.1038/s41467-026-71914-x</a>","ieee":"V. M. Vargas Barroso, J. Watson, A. C. Navas Olivé, A. Schlögl, and P. M. Jonas, “Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit,” <i>Nature Communications</i>, vol. 17. Springer Nature, 2026.","ama":"Vargas Barroso VM, Watson J, Navas Olivé AC, Schlögl A, Jonas PM. Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit. <i>Nature Communications</i>. 2026;17. doi:<a href=\"https://doi.org/10.1038/s41467-026-71914-x\">10.1038/s41467-026-71914-x</a>"},"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"M-Shop"},{"_id":"ScienComp"}],"publication_identifier":{"eissn":["2041-1723"]},"scopus_import":"1","oa":1,"OA_place":"publisher","PlanS_conform":"1","OA_type":"gold","article_type":"original","day":"23","file":[{"checksum":"d0b0093493926985b4c268662ff4d556","creator":"dernst","content_type":"application/pdf","date_created":"2026-07-01T06:46:06Z","relation":"main_file","date_updated":"2026-07-01T06:46:06Z","file_id":"22231","file_size":18304997,"file_name":"2026_NatureComm_VargasBarroso.pdf","access_level":"open_access","success":1}],"file_date_updated":"2026-07-01T06:46:06Z","publication_status":"published","year":"2026","has_accepted_license":"1","title":"Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit","author":[{"id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87","full_name":"Vargas Barroso, Victor M","first_name":"Victor M","last_name":"Vargas Barroso"},{"last_name":"Watson","first_name":"Jake","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"last_name":"Navas Olivé","first_name":"Andrea C","orcid":"0000-0002-9280-8597","id":"739d26c9-52e8-11ee-8d72-f14d3893b4ce","full_name":"Navas Olivé, Andrea C"},{"full_name":"Schlögl, Alois","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","last_name":"Schlögl","orcid":"0000-0002-5621-8100","first_name":"Alois"},{"first_name":"Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"researchdata_availability":"yes","date_published":"2026-06-23T00:00:00Z","external_id":{"pmid":["42014695"]},"article_number":"5540","quality_controlled":"1","das_tickbox":"1","_id":"22229","publisher":"Springer Nature","article_processing_charge":"Yes","dataavailabilitystatement":"Source data are provided with this paper. Additional original data are available from the corresponding author upon request. Code is available from https://doi.org/10.15479/AT-ISTA-21442 under the link https://research-explorer.ista.ac.at/download/21442/21443/ca3simu-vargas2026v1.tar.gz","publication":"Nature Communications","volume":17,"intvolume":"        17","acknowledgement":"We thank Jose Guzman, Simon Hippenmeyer, and Tim Vogels for critically reading the manuscript, Jozsef Csicsvari for useful discussions, Florian Marr for technical assistance, and Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA: the preclinical facility (PCF) provided housing and breeding of the animals, the imaging and optics facility (IOF) offered technical training and state of the art equipment, the Miba machine shop contributed to the construction and maintenance of multicellular recording setups, and the scientific computing unit helped with the large-scale simulations. The project received funding from the European Union’s Horizon 2020 research and innovation programme (ERC Advanced Grants No 692692 GIANTSYN and 101199096 CA3-SYNGRAM to P.J.; Marie Skłodowska-Curie Grant 754411 to V.V.B.; Marie Skłodowska-Curie Grant 101026635 to J.F.W.), the Fond zur Förderung der Wissenschaftlichen Forschung (P 36232-B, PAT4178023, and 10.55776/CoE16 to P.J.), and the Nomis Foundation (fellowship to A.N.-O.). V.V.B. received funding from a CONACyT fellowship (289638).","language":[{"iso":"eng"}],"status":"public","abstract":[{"lang":"eng","text":"Hippocampal CA3 pyramidal neurons (PNs) form the largest autoassociative network in the mammalian brain. Whether CA3–CA3 recurrent connectivity is genetically preconfigured or environmentally shaped during ongoing memory storage is currently unknown. To address this question, we performed multicellular patch-clamp-based circuit mapping of up to eight CA3 PNs in the mouse hippocampus at multiple postnatal time points (P7–8, P18–25, and P45–50). Here, we show that the hippocampal CA3 network undergoes a developmental transformation from local, dense, and random connectivity to a distributed, sparse, and structured configuration. Thus, sparse and structured connectivity may emerge via experience-dependent mechanisms. In parallel, the strength of single synapses is downregulated; single synaptic events are sufficient to trigger postsynaptic spiking early in development, whereas spatial summation of several inputs is required at later time points. Biologically inspired models of memory storage by Hebbian synaptic plasticity and retrieval via pattern completion suggest that developmental changes improve specific aspects of memory storage and retrieval. Our results imply a developmental transformation of the neuronal code and the memory functions in the hippocampal CA3 network.</jats:p>"}]},{"fulldoi":"https://doi.org/10.1038/s41467-026-75416-8","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"EM-Fac"},{"_id":"ScienComp"},{"_id":"PreCl"}],"publication_identifier":{"eissn":["2041-1723"]},"citation":{"chicago":"Hlavata, Annamaria, Benjamin Neuditschko, Ulla Schellhaas, Clemens Plaschka, Franz Herzog, and Carrie Bernecky. “Structure of Cytoplasmic RNA Polymerase II.” <i>Nature Communications</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41467-026-75416-8\">https://doi.org/10.1038/s41467-026-75416-8</a>.","ista":"Hlavata A, Neuditschko B, Schellhaas U, Plaschka C, Herzog F, Bernecky C. 2026. Structure of cytoplasmic RNA polymerase II. Nature Communications.","short":"A. Hlavata, B. Neuditschko, U. Schellhaas, C. Plaschka, F. Herzog, C. Bernecky, Nature Communications (2026).","apa":"Hlavata, A., Neuditschko, B., Schellhaas, U., Plaschka, C., Herzog, F., &#38; Bernecky, C. (2026). Structure of cytoplasmic RNA polymerase II. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-026-75416-8\">https://doi.org/10.1038/s41467-026-75416-8</a>","mla":"Hlavata, Annamaria, et al. “Structure of Cytoplasmic RNA Polymerase II.” <i>Nature Communications</i>, Springer Nature, 2026, doi:<a href=\"https://doi.org/10.1038/s41467-026-75416-8\">10.1038/s41467-026-75416-8</a>.","ieee":"A. Hlavata, B. Neuditschko, U. Schellhaas, C. Plaschka, F. Herzog, and C. Bernecky, “Structure of cytoplasmic RNA polymerase II,” <i>Nature Communications</i>. Springer Nature, 2026.","ama":"Hlavata A, Neuditschko B, Schellhaas U, Plaschka C, Herzog F, Bernecky C. Structure of cytoplasmic RNA polymerase II. <i>Nature Communications</i>. 2026. doi:<a href=\"https://doi.org/10.1038/s41467-026-75416-8\">10.1038/s41467-026-75416-8</a>"},"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"DOAJ_listed":"1","OA_place":"publisher","main_file_link":[{"url":"https://doi.org/10.1038/s41467-026-75416-8","open_access":"1"}],"oa":1,"scopus_import":"1","day":"13","PlanS_conform":"1","article_type":"original","OA_type":"gold","ddc":["570"],"oa_version":"Published Version","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","corr_author":"1","month":"07","doi":"10.1038/s41467-026-75416-8","date_created":"2026-07-14T07:27:59Z","date_updated":"2026-07-16T11:29:31Z","supplementarymaterial":"yes","type":"journal_article","department":[{"_id":"CaBe"}],"biorxivid":1,"quality_controlled":"1","das_tickbox":"1","external_id":{"biorxivid":["10.64898/2025.12.10.692585"]},"publisher":"Springer Nature","article_processing_charge":"Yes","dataavailabilitystatement":"The\r\nc ryo EM maps generated in this study were deposited to the EM Data Bank under the\r\naccession codes: EMD 55583 [https://www.ebi.ac.uk/pdbe/entry/emdb/EMD 55583\r\n(Pol II Gdown1 RPAP2 composite map), EMD 55578\r\n[https://www.ebi.ac.uk/pdbe/entry/emdb/EMD 55578 Pol II Gdown1 RPAP2 Pol II core\r\nmap EMD 55579 [https://www.ebi.ac.uk/pdbe/entry/emdb/EMD 55579 Pol II\r\nGdown1 RPAP2 Pol II stalk map EMD 55580\r\n[https://www.ebi.ac.uk/pdbe/entry/emdb/EMD 55580 Pol II Gdown1 RPAP2 RPAP2\r\nmap EMD 55581 [https://www.ebi.ac.uk/pdbe/entry/emdb/EMD 55 581 Pol II\r\nGdown1 RPAP2 Gdown1 N terminus map EMD 55582\r\n[https://www.ebi.ac.uk/pdbe/entry/emdb/EMD 55582 Pol II Gdown1 RPAP2 Gdown1\r\nC terminus map and EMD 55585 [https://www.ebi.ac.uk/pdbe/entry/emdb/EMD\r\n55585 RPAP2 GPN1 GPN3 map Model coordi nates were deposited to the PDBe under\r\nthe accession codes: 9T5H [http://doi.org/10.2210/pdb 9T5H / (Pol II Gdown1\r\nRPAP2 complex structure) and 9T5J [http://doi.org/10.2210/pdb 9T5H / (GPN1\r\nGPN3 RPAP2 structure). Immunoprecipitation mass spectrometry and crosslinking mass\r\nspectrometry proteomics data have been deposited to the ProteomeXchange Consortium\r\nvia the PRIDE partner repository with the dataset identifiers PXD071638\r\n[http://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD 071638 and\r\nP XD070852\r\n[http://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD 070852\r\nAlphaFold3 structure predictions have been deposited to the Zenodo repository\r\nhttps://doi.org/10.5281/zenodo.20687910 P reviously published model coordinates\r\nwere utilized and are available at the PDB under the accession codes 8QEP\r\n[http://doi.org/10.2210/pdb 8QEP / 9BZ 0 [http://doi.org/10.2210/pdb 9BZ 0 /\r\nand 7B7U [http://doi.org/10.2210/pdb 7B7U / Source Data are provided with this\r\npaper.","_id":"22333","publication":"Nature Communications","abstract":[{"lang":"eng","text":"RNA polymerase II (Pol II) must be assembled in the cytoplasm before it enters the nucleus, where it transcribes protein-coding genes. Although transcription by Pol II is intensively studied, how this central multi-subunit enzyme is made and the role of dedicated assembly factors remains unclear. Here, we report the integrative structural analysis of a native human Pol II from the cytoplasm captured near the end of biogenesis. The complex contains Gdown1 and three biogenesis factors – RPAP2 and the critical small GTPases GPN1 and GPN3. Cryo-EM analysis of the complex reveals how Gdown1 and RPAP2 associate with Pol II and prevent the premature association of transcription factors. Further biochemical and cryo-EM analysis reveals how RPAP2 tethers GPN1–GPN3 to the complex and how the assembly of the RPAP2–GPN1–GPN3 complex is controlled by GTP hydrolysis. The combined results uncover a network of interactions that chaperone cytoplasmic Pol II to prevent aberrant interactions, reveal a molecular switch regulating biogenesis factor association, and suggest a general mechanism for the action of GPN-loop GTPase family of enzymes."}],"acknowledgement":"We thank A. Salmazo for assistance with Pol II purification. We thank staff at the Vienna BioCenter Core Facilities (VBCF) Proteomics facility for immunoprecipitation-mass spectrometry analysis, and J.A. Stopp for assistance with IP-MS data visualization. This research was further supported by the Scientific Service Units (SSUs) of ISTA through resources provided by the Lab Support Facility (LSF), Electron Microscopy Facility (EMF), Scientific Computing (SciComp), and the Preclinical Facility (PCF). F.H. was funded by the Endowed Professorship of the Lower Austria Research Funding Agency (GFF NÖ) and by the Austrian Research Promotion Agency (FFG) through the COIN Establishment Grant n.o. 45624401.","status":"public","language":[{"iso":"eng"}],"has_accepted_license":"1","year":"2026","publication_status":"epub_ahead","researchdata_availability":"yes","title":"Structure of cytoplasmic RNA polymerase II","author":[{"first_name":"Annamaria","last_name":"Hlavata","id":"36062FEC-F248-11E8-B48F-1D18A9856A87","full_name":"Hlavata, Annamaria"},{"first_name":"Benjamin","last_name":"Neuditschko","full_name":"Neuditschko, Benjamin"},{"first_name":"Ulla","last_name":"Schellhaas","full_name":"Schellhaas, Ulla"},{"first_name":"Clemens","last_name":"Plaschka","full_name":"Plaschka, Clemens"},{"full_name":"Herzog, Franz","first_name":"Franz","last_name":"Herzog"},{"full_name":"Bernecky, Carrie A","id":"2CB9DFE2-F248-11E8-B48F-1D18A9856A87","last_name":"Bernecky","first_name":"Carrie A","orcid":"0000-0003-0893-7036"}],"date_published":"2026-07-13T00:00:00Z"},{"oa":1,"OA_place":"repository","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"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"},"fulldoi":"https://doi.org/10.15479/AT-ISTA-22704","acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"PreCl"}],"citation":{"chicago":"Le Monnier, Elodie, and Cihan Önal. “Asymmetrical Modulation of Fear Expression via GABAB Receptors in the Mouse Medial Habenula.” Institute of Science and Technology Austria, 2026. <a href=\"https://doi.org/10.15479/AT-ISTA-22704\">https://doi.org/10.15479/AT-ISTA-22704</a>.","ista":"Le Monnier E, Önal C. 2026. Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT-ISTA-22704\">10.15479/AT-ISTA-22704</a>.","short":"E. Le Monnier, C. Önal, (2026).","ieee":"E. Le Monnier and C. Önal, “Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula.” Institute of Science and Technology Austria, 2026.","mla":"Le Monnier, Elodie, and Cihan Önal. <i>Asymmetrical Modulation of Fear Expression via GABAB Receptors in the Mouse Medial Habenula</i>. Institute of Science and Technology Austria, 2026, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-22704\">10.15479/AT-ISTA-22704</a>.","apa":"Le Monnier, E., &#38; Önal, C. (2026). Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-22704\">https://doi.org/10.15479/AT-ISTA-22704</a>","ama":"Le Monnier E, Önal C. Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula. 2026. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-22704\">10.15479/AT-ISTA-22704</a>"},"file":[{"checksum":"7742bb211a43bb87c2b5ce7bda3068ae","creator":"elemonni","content_type":"application/x-zip-compressed","date_created":"2026-08-13T12:07:53Z","relation":"main_file","date_updated":"2026-08-13T12:07:53Z","file_id":"22705","file_name":"Behavior.zip","file_size":162086,"access_level":"open_access","success":1},{"relation":"main_file","date_created":"2026-08-13T12:07:57Z","date_updated":"2026-08-13T12:07:57Z","file_name":"image_analysis.zip","file_size":6643,"file_id":"22706","checksum":"a162eb6103a770d94536374e02934fcf","content_type":"application/x-zip-compressed","creator":"elemonni","success":1,"access_level":"open_access"},{"date_created":"2026-08-13T12:07:59Z","date_updated":"2026-08-13T12:07:59Z","relation":"main_file","file_id":"22707","file_size":1193016,"file_name":"Recordings.zip","checksum":"608aaf395bba5fd9cf62d8c8940d63aa","creator":"elemonni","content_type":"application/x-zip-compressed","success":1,"access_level":"open_access"},{"success":1,"access_level":"open_access","date_created":"2026-08-13T13:06:29Z","relation":"main_file","date_updated":"2026-08-13T13:06:29Z","file_id":"22708","file_size":246,"file_name":"README.txt","checksum":"2389ebd71238bd7de03d20504a8cf962","creator":"elemonni","content_type":"text/plain"}],"doi_confirm":"1","file_date_updated":"2026-08-13T13:06:29Z","day":"13","date_created":"2026-08-13T12:20:08Z","date_updated":"2026-08-13T13:30:37Z","doi":"10.15479/AT-ISTA-22704","month":"08","oa_version":"None","user_id":"68b8ca59-c5b3-11ee-8790-cd641c68093d","corr_author":"1","project":[{"grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"International IST Doctoral Program"},{"name":"New regime of presynaptic release regulation","_id":"92503f6e-16d5-11f0-9cad-8c571927f3b7","grant_number":"PAT 5720324"}],"ec_funded":1,"department":[{"_id":"RySh"}],"type":"research_data","_id":"22704","publisher":"Institute of Science and Technology Austria","article_processing_charge":"No","abstract":[{"lang":"eng","text":"The medial habenula (MHb) is implicated in regulating emotional responses to aversive events. Studies in zebrafish have identified a remarkable morphological left–right asymmetry in the dorsal habenula (zebrafish equivalent of mammalian MHb)-interpeduncular nucleus (IPN) pathway and its asymmetrical roles in behavior. However, there is little evidence for structural or functional lateralization in the mammalian MHb-IPN pathway. Here, we investigated the synaptic properties of left- and right-MHb afferents to the IPN and their roles in the expression of conditioned fear in mice. We found that each IPN neuron receives inputs from both left and right MHb, but the left MHb-originating synapses exhibit lower release probability and higher γ-aminobutyric acid type B receptor (GABABR)-mediated potentiation compared to the right MHb-originating synapses. Interestingly, these asymmetrical properties persist in the inversus visceral mutant mice with normal internal organ laterality (situs solitus), but nearly disappear in those with reversed internal organ laterality (situs inversus). Behaviorally, chemogenetic inhibition of cholinergic neurons and conditional deletion of GABABR in the left, but not the right, MHb significantly attenuated cue-dependent fear recall. Our results demonstrate functional asymmetry of the MHb under partial influence of the nodal flow in mice, revealing a predominant role of GABABR-mediated signaling in the left MHb-IPN pathway in modulating fear memories. These findings suggest that lateralized MHb pathways could represent a fundamental principle in the neural regulation of emotion across species but that they develop differently in zebrafish and mice.\r\n"}],"status":"public","has_accepted_license":"1","year":"2026","date_published":"2026-08-13T00:00:00Z","title":"Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula","author":[{"id":"3B59276A-F248-11E8-B48F-1D18A9856A87","full_name":"Le Monnier, Elodie","last_name":"Le Monnier","first_name":"Elodie"},{"first_name":"Cihan","last_name":"Önal","full_name":"Önal, Cihan"}]},{"_id":"22735","article_processing_charge":"No","publisher":"Institute of Science and Technology Austria","degree_awarded":"PhD","alternative_title":["ISTA Thesis"],"das_tickbox":"0","acknowledgement":"This project was supported by the following funding agencies: ERC under the European\r\nUnion's Horizon 2020 research and innovation program (ERC Advanced Grants No 692692\r\n“GIANTSYN” and 101199096 “CA3-SYNGRAM” to P.J.), the Fonds zur Förderung der\r\nwissenschaftlichen Forschung (P 36232-B, stand-alone grant, PAT 4178023, principal\r\ninvestigator project, and 10.55776/CoE 16 “GABA neurons” to P.J.), and the European Union’s\r\nHorizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant\r\nagreement (No 101034413, to K.L.).","status":"public","language":[{"iso":"eng"}],"publication_status":"published","year":"2026","has_accepted_license":"1","date_published":"2026-08-25T00:00:00Z","title":"Calibrating the teacher synapse: Mechanisms and functional significance of presynaptic inhibition at hippocampal mossy fiber synapses","author":[{"full_name":"Lin, Peipeng","id":"7E3060D0-A92C-11E9-A326-26C8E5697425","last_name":"Lin","first_name":"Peipeng"}],"researchdata_availability":"upon request","OA_place":"publisher","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"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"},"citation":{"ista":"Lin P. 2026. Calibrating the teacher synapse: Mechanisms and functional significance of presynaptic inhibition at hippocampal mossy fiber synapses. Institute of Science and Technology Austria.","chicago":"Lin, Peipeng. “Calibrating the Teacher Synapse: Mechanisms and Functional Significance of Presynaptic Inhibition at Hippocampal Mossy Fiber Synapses.” Institute of Science and Technology Austria, 2026. <a href=\"https://doi.org/10.15479/AT-ISTA-22735\">https://doi.org/10.15479/AT-ISTA-22735</a>.","short":"P. Lin, Calibrating the Teacher Synapse: Mechanisms and Functional Significance of Presynaptic Inhibition at Hippocampal Mossy Fiber Synapses, Institute of Science and Technology Austria, 2026.","ama":"Lin P. Calibrating the teacher synapse: Mechanisms and functional significance of presynaptic inhibition at hippocampal mossy fiber synapses. 2026. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-22735\">10.15479/AT-ISTA-22735</a>","apa":"Lin, P. (2026). <i>Calibrating the teacher synapse: Mechanisms and functional significance of presynaptic inhibition at hippocampal mossy fiber synapses</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-22735\">https://doi.org/10.15479/AT-ISTA-22735</a>","mla":"Lin, Peipeng. <i>Calibrating the Teacher Synapse: Mechanisms and Functional Significance of Presynaptic Inhibition at Hippocampal Mossy Fiber Synapses</i>. Institute of Science and Technology Austria, 2026, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-22735\">10.15479/AT-ISTA-22735</a>.","ieee":"P. Lin, “Calibrating the teacher synapse: Mechanisms and functional significance of presynaptic inhibition at hippocampal mossy fiber synapses,” Institute of Science and Technology Austria, 2026."},"fulldoi":"https://doi.org/10.15479/AT-ISTA-22735","supervisor":[{"last_name":"Jonas","first_name":"Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M"}],"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"PreCl"},{"_id":"Bio"}],"publication_identifier":{"isbn":["978-3-99078-088-6"],"issn":["2663-337X"]},"file":[{"checksum":"13cc7ead72aad90a134f310b531c73cd","content_type":"application/pdf","creator":"plin","date_created":"2026-08-26T10:09:48Z","relation":"main_file","date_updated":"2026-08-26T10:09:48Z","file_size":6376229,"embargo":"2027-09-01","file_name":"2026_Lin_Peipeng_Thesis.pdf","file_id":"22765","access_level":"closed","embargo_to":"open_access"},{"access_level":"closed","creator":"plin","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","checksum":"8c9c1445a7df284377be1a8c9dadd7c5","file_id":"22766","file_name":"2026_Lin_Peipeng_Thesis.docx","file_size":17681883,"date_updated":"2026-08-26T10:09:53Z","date_created":"2026-08-26T10:09:53Z","relation":"source_file"}],"doi_confirm":"1","file_date_updated":"2026-08-26T10:09:53Z","day":"25","date_created":"2026-08-18T15:23:41Z","date_updated":"2026-08-31T11:11:55Z","doi":"10.15479/AT-ISTA-22735","month":"08","corr_author":"1","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","oa_version":"Published Version","ddc":["571","573"],"project":[{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"_id":"e62b56fe-ab3c-11f0-94c7-d181dd352b3b","grant_number":"101199096","name":"Synaptic mechanisms of engram storage and retrieval in CA3 hippocampal microcircuits"},{"_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","grant_number":"P36232","name":"Mechanisms of GABA release in hippocampal circuits"},{"name":"Synaptic networks of human brain","_id":"8d9195e9-16d5-11f0-9cad-d075be887a1e","grant_number":"PAT 4178023"},{"call_identifier":"H2020","_id":"fc2ed2f7-9c52-11eb-aca3-c01059dda49c","grant_number":"101034413","name":"IST-BRIDGE: International postdoctoral program"}],"page":"88","department":[{"_id":"GradSch"},{"_id":"PeJo"}],"ec_funded":1,"type":"dissertation","supplementarymaterial":"yes"},{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","corr_author":"1","ddc":["570"],"oa_version":"Published Version","month":"08","date_updated":"2026-09-09T07:11:02Z","date_created":"2026-08-23T22:01:47Z","doi":"10.1038/s41586-026-10916-7","type":"journal_article","supplementarymaterial":"yes","department":[{"_id":"SiHi"}],"ec_funded":1,"project":[{"grant_number":"F7805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression"},{"_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"}],"pmid":1,"citation":{"short":"M.A. Stouffer, O. Miranda, F. Pauler, F. Pipicelli, C. Streicher, G.T. Cheung, S. Hippenmeyer, Nature (2026).","ista":"Stouffer MA, Miranda O, Pauler F, Pipicelli F, Streicher C, Cheung GT, Hippenmeyer S. 2026. Temporal uncoupling of radial glia lineage progression in cortical organoids. Nature.","chicago":"Stouffer, Melissa A, Osvaldo Miranda, Florian Pauler, Fabrizia Pipicelli, Carmen Streicher, Giselle T Cheung, and Simon Hippenmeyer. “Temporal Uncoupling of Radial Glia Lineage Progression in Cortical Organoids.” <i>Nature</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41586-026-10916-7\">https://doi.org/10.1038/s41586-026-10916-7</a>.","ama":"Stouffer MA, Miranda O, Pauler F, et al. Temporal uncoupling of radial glia lineage progression in cortical organoids. <i>Nature</i>. 2026. doi:<a href=\"https://doi.org/10.1038/s41586-026-10916-7\">10.1038/s41586-026-10916-7</a>","ieee":"M. A. Stouffer <i>et al.</i>, “Temporal uncoupling of radial glia lineage progression in cortical organoids,” <i>Nature</i>. Springer Nature, 2026.","apa":"Stouffer, M. A., Miranda, O., Pauler, F., Pipicelli, F., Streicher, C., Cheung, G. T., &#38; Hippenmeyer, S. (2026). Temporal uncoupling of radial glia lineage progression in cortical organoids. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-026-10916-7\">https://doi.org/10.1038/s41586-026-10916-7</a>","mla":"Stouffer, Melissa A., et al. “Temporal Uncoupling of Radial Glia Lineage Progression in Cortical Organoids.” <i>Nature</i>, Springer Nature, 2026, doi:<a href=\"https://doi.org/10.1038/s41586-026-10916-7\">10.1038/s41586-026-10916-7</a>."},"fulldoi":"https://doi.org/10.1038/s41586-026-10916-7","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"OA_place":"publisher","scopus_import":"1","oa":1,"day":"12","PlanS_conform":"1","OA_type":"hybrid","article_type":"original","file_date_updated":"2026-09-07T13:24:10Z","file":[{"relation":"main_file","date_updated":"2026-09-07T13:24:10Z","date_created":"2026-09-07T13:24:10Z","file_id":"22844","file_size":48513068,"file_name":"2026_Nature_Stouffer.pdf","checksum":"11383e28fc430b28d2666f73833e8b56","creator":"dernst","content_type":"application/pdf","success":1,"access_level":"open_access"}],"year":"2026","has_accepted_license":"1","publication_status":"epub_ahead","researchdata_availability":"yes","title":"Temporal uncoupling of radial glia lineage progression in cortical organoids","author":[{"id":"4C9372C4-F248-11E8-B48F-1D18A9856A87","full_name":"Stouffer, Melissa A","last_name":"Stouffer","first_name":"Melissa A"},{"first_name":"Osvaldo","orcid":"0000-0001-6618-6889","last_name":"Miranda","id":"862A3C56-A8BF-11E9-B4FA-D9E3E5697425","full_name":"Miranda, Osvaldo"},{"id":"48EA0138-F248-11E8-B48F-1D18A9856A87","full_name":"Pauler, Florian","last_name":"Pauler","first_name":"Florian","orcid":"0000-0002-7462-0048"},{"last_name":"Pipicelli","first_name":"Fabrizia","id":"649134fd-d012-11ed-8f82-db1e5050f9ba","full_name":"Pipicelli, Fabrizia"},{"last_name":"Streicher","first_name":"Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen"},{"id":"471195F6-F248-11E8-B48F-1D18A9856A87","full_name":"Cheung, Giselle T","orcid":"0000-0001-8457-2572","first_name":"Giselle T","last_name":"Cheung"},{"last_name":"Hippenmeyer","first_name":"Simon","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"date_published":"2026-08-12T00:00:00Z","quality_controlled":"1","das_tickbox":"1","external_id":{"pmid":["42587153"]},"dataavailabilitystatement":"All data generated and analysed in this study are included in the paper, source data and/or Supplementary Tables 2 and 3. Raw sequencing data have been deposited with Gene Expression Omnibus (GEO) accession number GSE327470. Source data are provided with this paper. All scripts used to prepare data and figures for this manuscript are accessible on GitHub at https://github.com/fpauler/Temporal-Uncoupling-of-Radial-Glia-Lineage-Progression-in-Cortical-Organoid.","publisher":"Springer Nature","article_processing_charge":"Yes (via OA deal)","_id":"22753","publication":"Nature","acknowledgement":"We thank M. L. de Guevara, S. Jayaram and A. Heger for technical assistance with mESC derivation; M. Goudarzi for assistance with organoid imaging; M. Leeb and F. Freeman for advice in culturing mESCs and organoids; S. Gobeil and L. Sweeney for reagents and advice for organoid clearing; A. Heger for mouse colony management; J. Hauser for technical assistance; the Stanford Brain Organogenesis Workshop; and all members of the Hippenmeyer laboratory for discussion and/or comments on the manuscript. This study was supported by the Scientific Service Units (SSU) of the Institute of Science and Technology, Austria through resources provided by the Imaging and Optics Facility (IOF), Laboratory Support Facility (LSF) and Preclinical Facility (PCF). M.S. received funding from the European Commission (IST plus postdoctoral fellowship). This work was supported by ISTA institutional funds to S.H., FWF SFB F78 Neuro Stem Modulation to S.H., and by the European Research Council (ERC) under the European Union’s Horizon 2020 Research And Innovation Program (grant agreement 725780 LinPro) to S.H. Open access funding provided by Institute of Science and Technology (IST Austria).","language":[{"iso":"eng"}],"status":"public","abstract":[{"text":"Radial glial progenitors (RGPs) produce all excitatory neurons in the developing cerebral cortex. Mosaic analysis with double markers (MADM)-based lineage tracing in vivo has revealed a quantitative framework of RGP lineage progression1. Here we established MADM technology2,3 in mouse embryonic stem cells to probe RGP lineage progression in a self-organizing cortical organoid system. We found that RGPs exhibit a high level of plasticity in proliferative potential in organoids rather than strict temporally stereotyped lineage progression as observed in vivo. RGPs in organoids showed increased lineage restriction, diminishing cell-type diversity in clones of cortical projection neurons, despite uniform single-cell transcriptional signatures of RGPs and a unitary lineage trajectory. Thus, critical non-cell-autonomous cues that are absent in self-organizing systems and/or the genuine stem cell niche are essential for faithful temporal control of RGP lineage progression and the generation of clonal cortical cell-type diversity.","lang":"eng"}]},{"_id":"18697","publisher":"Institute of Science and Technology Austria","article_processing_charge":"No","contributor":[{"id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","contributor_type":"researcher","last_name":"Tavakoli","orcid":"0000-0002-7667-6854","first_name":"Mojtaba"},{"last_name":"Lyudchik","first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","contributor_type":"researcher"},{"first_name":"Michal","last_name":"Januszewski","contributor_type":"researcher"},{"id":"7e146587-8972-11ed-ae7b-d7a32ea86a81","contributor_type":"researcher","last_name":"Vistunou","first_name":"Vitali"},{"first_name":"Nathalie","last_name":"Agudelo Duenas","contributor_type":"researcher","id":"40E7F008-F248-11E8-B48F-1D18A9856A87"},{"id":"937696FA-C996-11E9-8C7C-CF13E6697425","contributor_type":"researcher","last_name":"Vorlaufer","first_name":"Jakob"},{"contributor_type":"researcher","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","first_name":"Christoph M","last_name":"Sommer"},{"contributor_type":"researcher","id":"382077BA-F248-11E8-B48F-1D18A9856A87","first_name":"Caroline","last_name":"Kreuzinger"},{"last_name":"Oliveira","first_name":"Bárbara","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","contributor_type":"researcher"},{"last_name":"Cenameri","first_name":"Alban","contributor_type":"researcher"},{"contributor_type":"researcher","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino"},{"last_name":"Jain","first_name":"Viren","contributor_type":"researcher"},{"first_name":"Johann G","orcid":"0000-0001-8559-3973","last_name":"Danzl","contributor_type":"researcher","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"}],"status":"public","license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","abstract":[{"lang":"eng","text":"The information-processing capability of the brain’s cellular network depends on the physical wiring pattern between neurons and their molecular and functional characteristics. Mapping neurons and resolving their individual synaptic connections can be achieved by volumetric imaging at nanoscale resolution with dense cellular labelling. Light microscopy is uniquely positioned to visualize specific molecules but dense, synapse-level circuit reconstruction by light microscopy has been out of reach due to limitations in resolution, contrast, and volumetric imaging capability. Here we developed light-microscopy based connectomics (LICONN). We integrated specifically engineered hydrogel embedding and expansion with comprehensive deep-learning based segmentation and analysis of connectivity, thus directly incorporating molecular information in synapse-level brain tissue reconstructions. LICONN will allow synapse-level brain tissue phenotyping in biological experiments in a readily adoptable manner."}],"year":"2025","has_accepted_license":"1","date_published":"2025-03-03T00:00:00Z","author":[{"orcid":"0000-0001-8559-3973","first_name":"Johann G","last_name":"Danzl","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Julia","last_name":"Lyudchik","full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"id":"382077BA-F248-11E8-B48F-1D18A9856A87","full_name":"Kreuzinger, Caroline","last_name":"Kreuzinger","first_name":"Caroline"}],"title":"Light-microscopy based connectomic reconstruction of mammalian brain tissue","oa":1,"OA_place":"repository","tmp":{"short":"CC BY-NC-SA (4.0)","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","image":"/images/cc_by_nc_sa.png"},"fulldoi":"https://doi.org/10.15479/AT:ISTA:18697","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"ScienComp"},{"_id":"PreCl"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"citation":{"chicago":"Danzl, Johann G, Julia Lyudchik, and Caroline Kreuzinger. “Light-Microscopy Based Connectomic Reconstruction of Mammalian Brain Tissue.” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT:ISTA:18697\">https://doi.org/10.15479/AT:ISTA:18697</a>.","ista":"Danzl JG, Lyudchik J, Kreuzinger C. 2025. Light-microscopy based connectomic reconstruction of mammalian brain tissue, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:18697\">10.15479/AT:ISTA:18697</a>.","short":"J.G. Danzl, J. Lyudchik, C. Kreuzinger, (2025).","apa":"Danzl, J. G., Lyudchik, J., &#38; Kreuzinger, C. (2025). Light-microscopy based connectomic reconstruction of mammalian brain tissue. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:18697\">https://doi.org/10.15479/AT:ISTA:18697</a>","mla":"Danzl, Johann G., et al. <i>Light-Microscopy Based Connectomic Reconstruction of Mammalian Brain Tissue</i>. Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:18697\">10.15479/AT:ISTA:18697</a>.","ieee":"J. G. Danzl, J. Lyudchik, and C. Kreuzinger, “Light-microscopy based connectomic reconstruction of mammalian brain tissue.” Institute of Science and Technology Austria, 2025.","ama":"Danzl JG, Lyudchik J, Kreuzinger C. Light-microscopy based connectomic reconstruction of mammalian brain tissue. 2025. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:18697\">10.15479/AT:ISTA:18697</a>"},"file":[{"checksum":"d2c3efcd354f967290f91ff34dfb3cc1","creator":"jdanzl","content_type":"text/rtf","date_created":"2025-02-28T16:50:39Z","date_updated":"2025-02-28T16:50:39Z","relation":"main_file","file_id":"19275","file_name":"Readme_Data_Tavakoli_et_al_2025.rtf","file_size":1922,"access_level":"open_access","success":1},{"access_level":"open_access","success":1,"content_type":"image/tiff","creator":"ckreuzin","checksum":"b20cfb9b7030375f94d4b9bc5ce5cee9","file_name":"Fig1b (1).tif","file_size":69884200,"file_id":"19089","date_created":"2025-02-27T08:16:37Z","relation":"main_file","date_updated":"2025-02-27T08:16:37Z"},{"access_level":"open_access","success":1,"content_type":"image/tiff","creator":"ckreuzin","checksum":"2059d95e6f289cc10c970c30cd5c09a0","file_size":4511994,"file_name":"Fig1b (2).tif","file_id":"19090","date_created":"2025-02-27T08:16:36Z","relation":"main_file","date_updated":"2025-02-27T08:16:36Z"},{"success":1,"access_level":"open_access","date_created":"2025-02-27T08:16:36Z","relation":"main_file","date_updated":"2025-02-27T08:16:36Z","file_id":"19091","file_name":"Fig1b (3).tif","file_size":636956,"checksum":"a259143bb581b998e9411f90403951a3","creator":"ckreuzin","content_type":"image/tiff"},{"file_name":"Fig1b (4).tif","file_size":76830,"file_id":"19092","date_updated":"2025-02-27T08:16:37Z","date_created":"2025-02-27T08:16:37Z","relation":"main_file","content_type":"image/tiff","creator":"ckreuzin","checksum":"e4f07b9a7a40ceac70d1c02efdaac8c0","success":1,"access_level":"open_access"},{"checksum":"99a9790285bea3ef600c1590e41c32ec","content_type":"image/tiff","creator":"ckreuzin","date_created":"2025-02-27T08:16:37Z","date_updated":"2025-02-27T08:16:37Z","relation":"main_file","file_size":226548,"file_name":"Fig1c (1).tif","file_id":"19093","access_level":"open_access","success":1},{"access_level":"open_access","success":1,"creator":"ckreuzin","content_type":"image/tiff","checksum":"4e90c8724de5a3ae7537eb5bb2ef0480","file_id":"19094","file_name":"Fig1c (2).tif","file_size":219676,"date_updated":"2025-02-27T08:16:37Z","relation":"main_file","date_created":"2025-02-27T08:16:37Z"},{"success":1,"access_level":"open_access","file_name":"Fig1c (3).tif","file_size":219676,"file_id":"19095","date_updated":"2025-02-27T08:16:37Z","date_created":"2025-02-27T08:16:37Z","relation":"main_file","content_type":"image/tiff","creator":"ckreuzin","checksum":"218d009d9f15c77954ada71c507da531"},{"success":1,"access_level":"open_access","date_created":"2025-02-27T08:16:37Z","relation":"main_file","date_updated":"2025-02-27T08:16:37Z","file_id":"19096","file_size":3824598,"file_name":"Fig1c (4).tif","checksum":"cb58d865959cbdffae61f47e1d41d53e","creator":"ckreuzin","content_type":"image/tiff"},{"success":1,"access_level":"open_access","file_name":"Fig 2a_b_c_d_e_f.rtf","file_size":1510,"file_id":"19097","relation":"main_file","date_updated":"2025-02-27T12:26:54Z","date_created":"2025-02-27T12:26:54Z","content_type":"text/rtf","creator":"ckreuzin","checksum":"0b8c790576fe30307050675103eafe93"},{"access_level":"open_access","success":1,"content_type":"image/tiff","creator":"ckreuzin","checksum":"c9c1a66ed113c4bb74c8b2f65c5edcbb","file_name":"Fig3f.tif","file_size":83049,"file_id":"19098","date_updated":"2025-02-27T12:27:25Z","date_created":"2025-02-27T12:27:25Z","relation":"main_file"},{"success":1,"access_level":"open_access","relation":"main_file","date_created":"2025-02-27T12:27:43Z","date_updated":"2025-02-27T12:27:43Z","file_size":640644,"file_name":"Fig5l (1).tif","file_id":"19099","checksum":"4a822dffdca45d97d4a9b5b89aaec0f9","content_type":"image/tiff","creator":"ckreuzin"},{"content_type":"image/tiff","creator":"ckreuzin","checksum":"af130e9951a9716f40b11a5e67183fe7","file_name":"Fig5l (2).tif","file_size":640644,"file_id":"19100","relation":"main_file","date_updated":"2025-02-27T12:27:43Z","date_created":"2025-02-27T12:27:43Z","access_level":"open_access","success":1},{"success":1,"access_level":"open_access","file_id":"19101","file_size":503452,"file_name":"ExD2 (1).tif","date_updated":"2025-02-27T12:27:55Z","relation":"main_file","date_created":"2025-02-27T12:27:55Z","creator":"ckreuzin","content_type":"image/tiff","checksum":"cdc8829aa194593c9daf1cdaf79d9c9b"},{"access_level":"open_access","success":1,"checksum":"66808762dad2c15d0fce0dc892ce2cf0","content_type":"image/tiff","creator":"ckreuzin","relation":"main_file","date_created":"2025-02-27T12:27:55Z","date_updated":"2025-02-27T12:27:55Z","file_name":"ExD2 (2).tif","file_size":503452,"file_id":"19102"},{"relation":"main_file","date_updated":"2025-02-27T12:27:56Z","date_created":"2025-02-27T12:27:56Z","file_size":497260,"file_name":"ExD2 (3).tif","file_id":"19103","checksum":"c7e29bf95022538a9e63149413ab2691","content_type":"image/tiff","creator":"ckreuzin","success":1,"access_level":"open_access"},{"success":1,"access_level":"open_access","file_name":"EXD2 overview.tif","file_size":2240788643,"file_id":"19104","date_created":"2025-02-27T12:28:58Z","relation":"main_file","date_updated":"2025-02-27T12:28:58Z","content_type":"image/tiff","creator":"ckreuzin","checksum":"7da1e01b4a5ec0c598b95bcf1b1746e1"},{"success":1,"access_level":"open_access","file_name":"ExD3_a (1).tif","file_size":635780,"file_id":"19105","relation":"main_file","date_updated":"2025-02-27T12:28:06Z","date_created":"2025-02-27T12:28:06Z","content_type":"image/tiff","creator":"ckreuzin","checksum":"b87093567e71c5e27007bde717017f02"},{"access_level":"open_access","success":1,"creator":"ckreuzin","content_type":"image/tiff","checksum":"ccbfca6f0943887c202d635e1988e15c","file_id":"19106","file_name":"ExD3_a (2).tif","file_size":635780,"date_updated":"2025-02-27T12:28:06Z","relation":"main_file","date_created":"2025-02-27T12:28:06Z"},{"access_level":"open_access","success":1,"checksum":"a601cd6153f3dd3900496bd3715780dc","content_type":"image/tiff","creator":"ckreuzin","date_updated":"2025-02-27T12:28:06Z","date_created":"2025-02-27T12:28:06Z","relation":"main_file","file_size":8850309,"file_name":"ExD3_a overview.tif","file_id":"19107"},{"relation":"main_file","date_created":"2025-02-27T12:28:06Z","date_updated":"2025-02-27T12:28:06Z","file_id":"19108","file_size":888645,"file_name":"ExD3_b (1).tif","checksum":"82fe82494388f2b514e5eab08cf42567","creator":"ckreuzin","content_type":"image/tiff","success":1,"access_level":"open_access"},{"creator":"ckreuzin","content_type":"image/tiff","checksum":"6f0b4bc3cc46f9f139776b5baf608d40","file_id":"19109","file_size":888645,"file_name":"ExD3_b (2).tif","date_updated":"2025-02-27T12:28:06Z","relation":"main_file","date_created":"2025-02-27T12:28:06Z","access_level":"open_access","success":1},{"creator":"ckreuzin","content_type":"image/tiff","checksum":"f6d984add5f2bdf4bf0c5a8d52c3dbdd","file_id":"19110","file_size":25170991,"file_name":"ExD3_b overview.tif","date_created":"2025-02-27T12:28:08Z","date_updated":"2025-02-27T12:28:08Z","relation":"main_file","access_level":"open_access","success":1},{"access_level":"open_access","success":1,"checksum":"c508a203601d322039716d74799df4fd","creator":"ckreuzin","content_type":"image/tiff","relation":"main_file","date_created":"2025-02-27T12:28:16Z","date_updated":"2025-02-27T12:28:16Z","file_id":"19111","file_name":"ExD5_a (1).tif","file_size":748126},{"content_type":"image/tiff","creator":"ckreuzin","checksum":"195a02aa816058454d6fb9347834aef8","file_name":"ExD5_a (2).tif","file_size":167518,"file_id":"19112","date_updated":"2025-02-27T12:28:17Z","relation":"main_file","date_created":"2025-02-27T12:28:17Z","access_level":"open_access","success":1},{"success":1,"access_level":"open_access","file_id":"19113","file_name":"ExD5_a (3).tif","file_size":167518,"date_created":"2025-02-27T12:28:17Z","date_updated":"2025-02-27T12:28:17Z","relation":"main_file","creator":"ckreuzin","content_type":"image/tiff","checksum":"1eb28e43902974d7f424e803e99c0234"},{"file_name":"ExD5_a (4).tif","file_size":25169039,"file_id":"19114","date_created":"2025-02-27T12:28:18Z","relation":"main_file","date_updated":"2025-02-27T12:28:18Z","content_type":"image/tiff","creator":"ckreuzin","checksum":"e450c88cac136a11af8c52e4966dcb15","success":1,"access_level":"open_access"},{"file_size":748126,"file_name":"ExD5_a (5).tif","file_id":"19115","date_created":"2025-02-27T12:28:18Z","relation":"main_file","date_updated":"2025-02-27T12:28:18Z","content_type":"image/tiff","creator":"ckreuzin","checksum":"839a53eb45926407639ccdf07a326f73","success":1,"access_level":"open_access"},{"content_type":"image/tiff","creator":"ckreuzin","checksum":"080703b3ee6001af8805d079f0ef101d","file_size":5959861,"file_name":"ExD5_b (1).tif","file_id":"19116","relation":"main_file","date_created":"2025-02-27T12:28:18Z","date_updated":"2025-02-27T12:28:18Z","access_level":"open_access","success":1},{"file_name":"ExD5_b (2).tif","file_size":603445,"file_id":"19128","relation":"main_file","date_created":"2025-02-27T12:30:13Z","date_updated":"2025-02-27T12:30:13Z","content_type":"image/tiff","creator":"ckreuzin","checksum":"a51cca7fd7283491f09ead98bac06be8","success":1,"access_level":"open_access"},{"checksum":"417d4c6c4cbf4580d1b0f252ad0d1b53","content_type":"image/tiff","creator":"ckreuzin","relation":"main_file","date_created":"2025-02-27T12:28:19Z","date_updated":"2025-02-27T12:28:19Z","file_size":603445,"file_name":"ExD5_b (3).tif","file_id":"19117","access_level":"open_access","success":1},{"checksum":"a7cfb8c48d9696f7be2068d7e5b97ec0","creator":"ckreuzin","content_type":"image/tiff","date_updated":"2025-02-27T12:28:19Z","relation":"main_file","date_created":"2025-02-27T12:28:19Z","file_id":"19118","file_name":"ExD5_c (1).tif","file_size":480392,"access_level":"open_access","success":1},{"date_updated":"2025-02-27T12:28:20Z","date_created":"2025-02-27T12:28:20Z","relation":"main_file","file_id":"19119","file_name":"ExD5_c (2).tif","file_size":5947784,"checksum":"4e61066979d7002bd1d5e295a0031fa6","creator":"ckreuzin","content_type":"image/tiff","success":1,"access_level":"open_access"},{"access_level":"open_access","success":1,"creator":"ckreuzin","content_type":"image/tiff","checksum":"2c1e59c738e9ca2cf6d474a522746bd0","file_id":"19120","file_size":480392,"file_name":"ExD5_c (3).tif","date_updated":"2025-02-27T12:28:20Z","date_created":"2025-02-27T12:28:20Z","relation":"main_file"},{"content_type":"image/tiff","creator":"ckreuzin","checksum":"86ff0d32c6004ba817c0fb8581853f70","file_size":25170872,"file_name":"ExD6_C (1).tif","file_id":"19121","date_created":"2025-02-27T12:28:34Z","relation":"main_file","date_updated":"2025-02-27T12:28:34Z","access_level":"open_access","success":1},{"relation":"main_file","date_created":"2025-02-27T12:28:34Z","date_updated":"2025-02-27T12:28:34Z","file_id":"19122","file_size":595434,"file_name":"ExD6_C (2).tif","checksum":"ba8c3fd2cb84bea6d0ff4b7346a1f617","creator":"ckreuzin","content_type":"image/tiff","success":1,"access_level":"open_access"},{"file_id":"19123","file_size":595434,"file_name":"ExD6_C (3).tif","relation":"main_file","date_created":"2025-02-27T12:28:34Z","date_updated":"2025-02-27T12:28:34Z","creator":"ckreuzin","content_type":"image/tiff","checksum":"6c235a6fc961ca5fec8e6ad90cca585b","success":1,"access_level":"open_access"},{"success":1,"access_level":"open_access","relation":"main_file","date_created":"2025-02-27T12:28:34Z","date_updated":"2025-02-27T12:28:34Z","file_name":"ExD6_HT (1).tif","file_size":12589048,"file_id":"19124","checksum":"aae7959ad3571773a60c93d8fb239f0e","content_type":"image/tiff","creator":"ckreuzin"},{"file_size":12589516,"file_name":"ExD6_HT (2).tif","file_id":"19125","date_created":"2025-02-27T12:28:35Z","relation":"main_file","date_updated":"2025-02-27T12:28:35Z","content_type":"image/tiff","creator":"ckreuzin","checksum":"91d134716e3162c7a1a399729ed43b84","success":1,"access_level":"open_access"},{"access_level":"open_access","success":1,"content_type":"image/tiff","creator":"ckreuzin","checksum":"154e29281e9640da6a86d55a191a7684","file_name":"ExD6_PA (1).tif","file_size":12595178,"file_id":"19126","date_created":"2025-02-27T12:28:36Z","date_updated":"2025-02-27T12:28:36Z","relation":"main_file"},{"content_type":"image/tiff","creator":"ckreuzin","checksum":"86f22b9fd2e5b231451f6f98c9345acb","file_size":12595070,"file_name":"ExD6_PA (2).tif","file_id":"19127","date_created":"2025-02-27T12:28:36Z","relation":"main_file","date_updated":"2025-02-27T12:28:36Z","access_level":"open_access","success":1},{"file_name":"ExD7 (1).tif","file_size":210228181,"file_id":"19129","date_updated":"2025-02-27T12:30:55Z","date_created":"2025-02-27T12:30:55Z","relation":"main_file","content_type":"image/tiff","creator":"ckreuzin","checksum":"c5d8929322f3123dd03d77a51b9dc32d","success":1,"access_level":"open_access"},{"success":1,"access_level":"open_access","date_created":"2025-02-27T12:30:51Z","relation":"main_file","date_updated":"2025-02-27T12:30:51Z","file_size":8439640,"file_name":"ExD7 (2).tif","file_id":"19130","checksum":"12cfa75bba1c486f8127d28c114ec4bf","content_type":"image/tiff","creator":"ckreuzin"},{"file_name":"ExD7 (3).tif","file_size":8439640,"file_id":"19131","relation":"main_file","date_updated":"2025-02-27T12:30:51Z","date_created":"2025-02-27T12:30:51Z","content_type":"image/tiff","creator":"ckreuzin","checksum":"9b4b4fde987f0585ccb2ba43ccf64ae0","success":1,"access_level":"open_access"},{"access_level":"open_access","success":1,"checksum":"3430b0e859cb2840078e63acca6dc5a7","content_type":"image/tiff","creator":"ckreuzin","date_created":"2025-02-27T12:31:02Z","relation":"main_file","date_updated":"2025-02-27T12:31:02Z","file_name":"ExD8 (1).tif","file_size":12583305,"file_id":"19132"},{"success":1,"access_level":"open_access","date_created":"2025-02-27T12:31:02Z","date_updated":"2025-02-27T12:31:02Z","relation":"main_file","file_size":12583304,"file_name":"ExD8 (2).tif","file_id":"19133","checksum":"8eb083751ef494d0a982110702a4e076","content_type":"image/tiff","creator":"ckreuzin"},{"success":1,"access_level":"open_access","file_size":12583296,"file_name":"ExD8 (3).tif","file_id":"19134","date_created":"2025-02-27T12:31:03Z","date_updated":"2025-02-27T12:31:03Z","relation":"main_file","content_type":"image/tiff","creator":"ckreuzin","checksum":"9a016467f871c78cefc7c13cd71b8a23"},{"access_level":"open_access","success":1,"checksum":"719785390d3e417325673f218a03c2ae","content_type":"image/tiff","creator":"ckreuzin","date_updated":"2025-02-27T12:31:03Z","relation":"main_file","date_created":"2025-02-27T12:31:03Z","file_name":"ExD8 (4).tif","file_size":12583307,"file_id":"19135"},{"success":1,"access_level":"open_access","file_id":"19136","file_size":12583307,"file_name":"ExD8 (5).tif","date_updated":"2025-02-27T12:31:03Z","relation":"main_file","date_created":"2025-02-27T12:31:03Z","creator":"ckreuzin","content_type":"image/tiff","checksum":"65a0aee4b5c8cd3f76189e4397bd6544"},{"file_id":"19137","file_size":12583286,"file_name":"ExD8 (6).tif","date_created":"2025-02-27T12:31:03Z","relation":"main_file","date_updated":"2025-02-27T12:31:03Z","creator":"ckreuzin","content_type":"image/tiff","checksum":"667753716b7148878a0b512ddc2074b4","success":1,"access_level":"open_access"},{"file_name":"ExD8 (7).tif","file_size":12583305,"file_id":"19138","relation":"main_file","date_created":"2025-02-27T12:31:03Z","date_updated":"2025-02-27T12:31:03Z","content_type":"image/tiff","creator":"ckreuzin","checksum":"61eb5fc89cbacc3bb027919139b3a4ab","success":1,"access_level":"open_access"},{"creator":"ckreuzin","content_type":"image/tiff","checksum":"eed374ceb917f66b0e9cf4ee3aed0eba","file_id":"19139","file_size":12583264,"file_name":"ExD8 (8).tif","relation":"main_file","date_created":"2025-02-27T12:31:03Z","date_updated":"2025-02-27T12:31:03Z","access_level":"open_access","success":1},{"relation":"main_file","date_created":"2025-02-27T12:31:04Z","date_updated":"2025-02-27T12:31:04Z","file_size":12583305,"file_name":"ExD8 (9).tif","file_id":"19140","checksum":"51d3c92bffe30a6ee417a42d24c42449","content_type":"image/tiff","creator":"ckreuzin","success":1,"access_level":"open_access"},{"success":1,"access_level":"open_access","relation":"main_file","date_updated":"2025-02-27T12:32:26Z","date_created":"2025-02-27T12:32:26Z","file_size":2637707980,"file_name":"ExD9_a.tif","file_id":"19141","checksum":"a451c488fca7772e55d534e65f739a5d","content_type":"image/tiff","creator":"ckreuzin"},{"access_level":"open_access","success":1,"checksum":"2b671ae3857517cc2493d95435eb5017","content_type":"image/tiff","creator":"ckreuzin","relation":"main_file","date_updated":"2025-02-27T12:31:12Z","date_created":"2025-02-27T12:31:12Z","file_size":5931874,"file_name":"ExD9_b (1).tif","file_id":"19142"},{"file_size":5574502,"file_name":"ExD9_b (2).png","file_id":"19143","date_created":"2025-02-27T12:31:13Z","date_updated":"2025-02-27T12:31:13Z","relation":"main_file","content_type":"image/png","creator":"ckreuzin","checksum":"5b0a6d2fbd3a4790e42d64ddf082ac44","success":1,"access_level":"open_access"},{"access_level":"open_access","success":1,"content_type":"image/tiff","creator":"ckreuzin","checksum":"93b1ca9fe6689f972466ca7021333a2b","file_size":936816,"file_name":"ExD9_c (1).tif","file_id":"19144","relation":"main_file","date_created":"2025-02-27T12:31:13Z","date_updated":"2025-02-27T12:31:13Z"},{"date_created":"2025-02-27T12:31:14Z","relation":"main_file","date_updated":"2025-02-27T12:31:14Z","file_size":9971050,"file_name":"ExD9_c (2).tif","file_id":"19145","checksum":"087a6e5cd69ed279f4135e5acbcf0243","content_type":"image/tiff","creator":"ckreuzin","success":1,"access_level":"open_access"},{"success":1,"access_level":"open_access","date_updated":"2025-02-27T12:31:14Z","date_created":"2025-02-27T12:31:14Z","relation":"main_file","file_size":12589300,"file_name":"ExD9_c (3).tif","file_id":"19146","checksum":"055512e172d8c0b3f552ecdcf62d8913","content_type":"image/tiff","creator":"ckreuzin"},{"success":1,"access_level":"open_access","file_size":12587348,"file_name":"ExD10_a (1).tif","file_id":"19155","date_created":"2025-02-27T12:35:44Z","date_updated":"2025-02-27T12:35:44Z","relation":"main_file","content_type":"image/tiff","creator":"ckreuzin","checksum":"0c49d7bae8d7ce058d9339d2acb5108a"},{"access_level":"open_access","success":1,"creator":"ckreuzin","content_type":"image/tiff","checksum":"108d47b78fd5af3a751319b8a0f336c5","file_id":"19147","file_size":12587344,"file_name":"ExD10_a (2).tif","relation":"main_file","date_created":"2025-02-27T12:32:38Z","date_updated":"2025-02-27T12:32:38Z"},{"access_level":"open_access","success":1,"content_type":"image/tiff","creator":"ckreuzin","checksum":"dab543a769dd05cfbd66c8bc5877decf","file_name":"ExD10_a (3).tif","file_size":622780,"file_id":"19148","date_updated":"2025-02-27T12:32:39Z","date_created":"2025-02-27T12:32:39Z","relation":"main_file"},{"access_level":"open_access","success":1,"creator":"ckreuzin","content_type":"image/tiff","checksum":"31feb7fcc156ba1f62c9c18c7adee1bd","file_id":"19149","file_size":424064,"file_name":"ExD10_a (4).tif","relation":"main_file","date_updated":"2025-02-27T12:32:39Z","date_created":"2025-02-27T12:32:39Z"},{"access_level":"open_access","success":1,"checksum":"069fa6237648dee9080bc779ae8bb7ab","creator":"ckreuzin","content_type":"image/png","relation":"main_file","date_updated":"2025-02-27T12:32:39Z","date_created":"2025-02-27T12:32:39Z","file_id":"19150","file_size":695657,"file_name":"ExD10_c.png"},{"success":1,"access_level":"open_access","file_name":"ExD10_d (1).png","file_size":2510928,"file_id":"19151","date_updated":"2025-02-27T12:32:39Z","date_created":"2025-02-27T12:32:39Z","relation":"main_file","content_type":"image/png","creator":"ckreuzin","checksum":"774a892849e024ee079e14d456908529"},{"checksum":"4f6f50fb534e7419189b82fc2b2359e8","content_type":"image/png","creator":"ckreuzin","relation":"main_file","date_created":"2025-02-27T12:32:39Z","date_updated":"2025-02-27T12:32:39Z","file_name":"ExD10_d (2).png","file_size":975236,"file_id":"19152","access_level":"open_access","success":1},{"access_level":"open_access","success":1,"content_type":"image/png","creator":"ckreuzin","checksum":"03ae30c2aa151892778e1d5be85c5722","file_size":714346,"file_name":"ExD10_e.png","file_id":"19153","date_created":"2025-02-27T12:32:40Z","relation":"main_file","date_updated":"2025-02-27T12:32:40Z"},{"relation":"main_file","date_created":"2025-02-27T12:32:45Z","date_updated":"2025-02-27T12:32:45Z","file_id":"19154","file_size":239750348,"file_name":"ExD10_h.tif","checksum":"a973fcca17ee02a0377a3494cafb66e9","creator":"ckreuzin","content_type":"image/tiff","success":1,"access_level":"open_access"},{"access_level":"open_access","success":1,"checksum":"270a780148d7bde70bcaabeeb8188559","content_type":"image/tiff","creator":"ckreuzin","date_created":"2025-02-27T12:36:23Z","date_updated":"2025-02-27T12:36:23Z","relation":"main_file","file_size":1096875,"file_name":"SF2 (1).tif","file_id":"19156"},{"checksum":"f095b4b71c027734f10d91dad1a90911","content_type":"image/tiff","creator":"ckreuzin","relation":"main_file","date_updated":"2025-02-27T12:36:24Z","date_created":"2025-02-27T12:36:24Z","file_name":"SF2 (2).tif","file_size":12588982,"file_id":"19157","access_level":"open_access","success":1},{"file_id":"19158","file_size":1096897,"file_name":"SF2 (3).tif","relation":"main_file","date_created":"2025-02-27T12:36:24Z","date_updated":"2025-02-27T12:36:24Z","creator":"ckreuzin","content_type":"image/tiff","checksum":"3d635b68a0790297d8e1c854924a0e4b","success":1,"access_level":"open_access"},{"success":1,"access_level":"open_access","date_updated":"2025-02-27T12:36:24Z","relation":"main_file","date_created":"2025-02-27T12:36:24Z","file_id":"19159","file_size":12583306,"file_name":"SF2 (4).tif","checksum":"233f4c55114dbf4fff623775ac7629ed","creator":"ckreuzin","content_type":"image/tiff"},{"date_created":"2025-02-27T12:36:24Z","relation":"main_file","date_updated":"2025-02-27T12:36:24Z","file_name":"SF2 (5).tif","file_size":1091221,"file_id":"19160","checksum":"a86fc86d60b7a43f60ed204eac15ae9e","content_type":"image/tiff","creator":"ckreuzin","success":1,"access_level":"open_access"},{"success":1,"access_level":"open_access","file_name":"SF2 (6).tif","file_size":12588974,"file_id":"19161","date_updated":"2025-02-27T12:36:24Z","relation":"main_file","date_created":"2025-02-27T12:36:24Z","content_type":"image/tiff","creator":"ckreuzin","checksum":"732a94d766c59c5bc55bfb572c24b672"},{"success":1,"access_level":"open_access","relation":"main_file","date_created":"2025-02-27T12:36:24Z","date_updated":"2025-02-27T12:36:24Z","file_id":"19162","file_size":1096889,"file_name":"SF2 (7).tif","checksum":"2a566be2ea4c9fa81d078832bce4c230","creator":"ckreuzin","content_type":"image/tiff"},{"relation":"main_file","date_updated":"2025-02-27T12:36:25Z","date_created":"2025-02-27T12:36:25Z","file_name":"SF2 (8).tif","file_size":12588960,"file_id":"19163","checksum":"f262512298c9c8ca3d9e00dcd3a86b44","content_type":"image/tiff","creator":"ckreuzin","success":1,"access_level":"open_access"},{"content_type":"image/tiff","creator":"ckreuzin","checksum":"40ce5647c948013a5f5442fdc7ac0ad2","file_size":12589182,"file_name":"SF3 (1).tif","file_id":"19164","date_created":"2025-02-27T12:36:36Z","relation":"main_file","date_updated":"2025-02-27T12:36:36Z","access_level":"open_access","success":1},{"access_level":"open_access","success":1,"creator":"ckreuzin","content_type":"image/tiff","checksum":"54f91d6ba3eb8e32779705e2eff261d3","file_id":"19165","file_name":"SF3 (2).tif","file_size":12589224,"date_created":"2025-02-27T12:36:36Z","date_updated":"2025-02-27T12:36:36Z","relation":"main_file"},{"success":1,"access_level":"open_access","file_id":"19166","file_size":12589178,"file_name":"SF3 (3).tif","date_created":"2025-02-27T12:36:36Z","date_updated":"2025-02-27T12:36:36Z","relation":"main_file","creator":"ckreuzin","content_type":"image/tiff","checksum":"ce8aa0f3bb62f1f29d138707cb6ced3c"},{"date_updated":"2025-02-27T12:36:40Z","date_created":"2025-02-27T12:36:40Z","relation":"main_file","file_size":12589180,"file_name":"SF3 (4).tif","file_id":"19167","checksum":"00169473fb4fe3d28b38755a4757bc62","content_type":"image/tiff","creator":"ckreuzin","success":1,"access_level":"open_access"},{"file_name":"SF3 (5).tif","file_size":12589270,"file_id":"19168","date_updated":"2025-02-27T12:36:40Z","relation":"main_file","date_created":"2025-02-27T12:36:40Z","content_type":"image/tiff","creator":"ckreuzin","checksum":"2e3304c513266b6d88fdcdd950e5b1c7","success":1,"access_level":"open_access"},{"checksum":"19ca076e8bc48758af33f689d5b3fece","content_type":"image/tiff","creator":"ckreuzin","relation":"main_file","date_updated":"2025-02-27T12:36:45Z","date_created":"2025-02-27T12:36:45Z","file_size":12583264,"file_name":"SF3 (6).tif","file_id":"19169","access_level":"open_access","success":1},{"checksum":"f1257eb05a38cb93c07deb98ac6bacdb","content_type":"image/tiff","creator":"ckreuzin","date_updated":"2025-02-27T12:36:45Z","date_created":"2025-02-27T12:36:45Z","relation":"main_file","file_name":"SF3 (7).tif","file_size":12589292,"file_id":"19170","access_level":"open_access","success":1},{"date_updated":"2025-02-27T12:36:49Z","date_created":"2025-02-27T12:36:49Z","relation":"main_file","file_name":"SF3 (8).tif","file_size":12589318,"file_id":"19171","checksum":"ba6747859b2c7564b1c6fd826ed1d16e","content_type":"image/tiff","creator":"ckreuzin","success":1,"access_level":"open_access"},{"file_name":"SF3 (9).tif","file_size":12589530,"file_id":"19172","date_updated":"2025-02-27T12:36:49Z","relation":"main_file","date_created":"2025-02-27T12:36:49Z","content_type":"image/tiff","creator":"ckreuzin","checksum":"b7b9a7cb86b74ed201b3e7f2ace5699c","success":1,"access_level":"open_access"},{"success":1,"access_level":"open_access","file_id":"19173","file_name":"SF3 (10).tif","file_size":12589334,"date_updated":"2025-02-27T12:37:09Z","relation":"main_file","date_created":"2025-02-27T12:37:09Z","creator":"ckreuzin","content_type":"image/tiff","checksum":"ebd6ecf4e7054de8661df83045e0a24c"},{"file_id":"19174","file_size":12589540,"file_name":"SF3 (11).tif","date_updated":"2025-02-27T12:36:54Z","relation":"main_file","date_created":"2025-02-27T12:36:54Z","creator":"ckreuzin","content_type":"image/tiff","checksum":"0269d65803ad587ae5d12d67df645f8b","success":1,"access_level":"open_access"},{"access_level":"open_access","success":1,"creator":"ckreuzin","content_type":"image/tiff","checksum":"cd43ef86a3853e1b18da109f50d4d8ac","file_id":"19175","file_name":"SF3 (12).tif","file_size":12589296,"date_created":"2025-02-27T12:36:58Z","relation":"main_file","date_updated":"2025-02-27T12:36:58Z"},{"access_level":"open_access","success":1,"creator":"ckreuzin","content_type":"image/tiff","checksum":"77509629a7d63427fe188cd893174c50","file_id":"19176","file_size":12589300,"file_name":"SF3 (13).tif","date_created":"2025-02-27T12:36:58Z","date_updated":"2025-02-27T12:36:58Z","relation":"main_file"},{"date_updated":"2025-02-27T12:36:59Z","relation":"main_file","date_created":"2025-02-27T12:36:59Z","file_id":"19177","file_name":"SF3 (14).tif","file_size":12589228,"checksum":"5b2a4870ada42b714a8d0cb3b0a22897","creator":"ckreuzin","content_type":"image/tiff","success":1,"access_level":"open_access"},{"access_level":"open_access","success":1,"creator":"ckreuzin","content_type":"image/tiff","checksum":"d45667253f1fc955141b92e71c3ec0f1","file_id":"19178","file_name":"SF3 (15).tif","file_size":12589230,"date_updated":"2025-02-27T12:36:59Z","date_created":"2025-02-27T12:36:59Z","relation":"main_file"},{"access_level":"open_access","success":1,"checksum":"82e507681c2a8ee6a5fb5ebcbcb2eda1","content_type":"image/tiff","creator":"ckreuzin","date_created":"2025-02-27T12:37:34Z","date_updated":"2025-02-27T12:37:34Z","relation":"main_file","file_name":"SF4_d (1).tif","file_size":12595602,"file_id":"19179"},{"success":1,"access_level":"open_access","file_id":"19180","file_size":12583305,"file_name":"SF4_d (2).tif","relation":"main_file","date_updated":"2025-02-27T12:37:34Z","date_created":"2025-02-27T12:37:34Z","creator":"ckreuzin","content_type":"image/tiff","checksum":"edda9a389955107a15c762df2c1bc80b"},{"relation":"main_file","date_updated":"2025-02-27T12:37:34Z","date_created":"2025-02-27T12:37:34Z","file_name":"SF4_d (3).tif","file_size":12595602,"file_id":"19181","checksum":"2455e23b33bab231ab3b94bb31ffff8b","content_type":"image/tiff","creator":"ckreuzin","success":1,"access_level":"open_access"},{"success":1,"access_level":"open_access","file_size":12583305,"file_name":"SF4_d (4).tif","file_id":"19182","date_updated":"2025-02-27T12:37:34Z","date_created":"2025-02-27T12:37:34Z","relation":"main_file","content_type":"image/tiff","creator":"ckreuzin","checksum":"5970d5fe32278b3c0fdb2345d22ede22"},{"access_level":"open_access","success":1,"creator":"ckreuzin","content_type":"image/tiff","checksum":"8b19af3b6dafb364e437373beb2c8249","file_id":"19183","file_size":12583293,"file_name":"SF4_d (5).tif","relation":"main_file","date_created":"2025-02-27T12:37:35Z","date_updated":"2025-02-27T12:37:35Z"},{"success":1,"access_level":"open_access","date_created":"2025-02-27T12:37:35Z","relation":"main_file","date_updated":"2025-02-27T12:37:35Z","file_id":"19184","file_name":"SF4_d (6).tif","file_size":12595630,"checksum":"5948ca9e8cd4431d301829f185648e98","creator":"ckreuzin","content_type":"image/tiff"},{"checksum":"89f4b99ea59b28132380b573ac6872b7","creator":"ckreuzin","content_type":"image/tiff","relation":"main_file","date_updated":"2025-02-27T12:37:35Z","date_created":"2025-02-27T12:37:35Z","file_id":"19185","file_name":"SF4_d (7).tif","file_size":12595652,"access_level":"open_access","success":1},{"access_level":"open_access","success":1,"creator":"ckreuzin","content_type":"image/tiff","checksum":"37fb13a610da23d59fc8eba640417844","file_id":"19186","file_size":12595554,"file_name":"SF4_d (8).tif","relation":"main_file","date_created":"2025-02-27T12:37:35Z","date_updated":"2025-02-27T12:37:35Z"},{"file_size":12589366,"file_name":"SF5 (1).tif","file_id":"19187","date_updated":"2025-02-27T12:37:50Z","relation":"main_file","date_created":"2025-02-27T12:37:50Z","content_type":"image/tiff","creator":"ckreuzin","checksum":"59355dcf56e7caca0c7ab5896d6eee19","success":1,"access_level":"open_access"},{"creator":"ckreuzin","content_type":"image/tiff","checksum":"02b045794b183ca0f1a3fb7746742b11","file_id":"19188","file_size":12587012,"file_name":"SF5 (2).tif","relation":"main_file","date_updated":"2025-02-27T12:37:50Z","date_created":"2025-02-27T12:37:50Z","access_level":"open_access","success":1},{"success":1,"access_level":"open_access","date_updated":"2025-02-27T12:37:56Z","relation":"main_file","date_created":"2025-02-27T12:37:56Z","file_name":"SF5 (3).tif","file_size":12589322,"file_id":"19189","checksum":"e5dddad8cdca618c0cb7aa5f1b1d6f4a","content_type":"image/tiff","creator":"ckreuzin"},{"access_level":"open_access","success":1,"content_type":"image/tiff","creator":"ckreuzin","checksum":"51a51d33c07f18777279c36498694048","file_name":"SF5 (4).tif","file_size":12589322,"file_id":"19190","date_updated":"2025-02-27T12:37:56Z","relation":"main_file","date_created":"2025-02-27T12:37:56Z"},{"success":1,"access_level":"open_access","file_size":12589322,"file_name":"SF5 (5).tif","file_id":"19191","date_created":"2025-02-27T12:38:03Z","relation":"main_file","date_updated":"2025-02-27T12:38:03Z","content_type":"image/tiff","creator":"ckreuzin","checksum":"f923ceac728d5ccfdfbb828615f13cbc"},{"file_name":"SF5 (6).tif","file_size":12589020,"file_id":"19192","relation":"main_file","date_updated":"2025-02-27T12:38:03Z","date_created":"2025-02-27T12:38:03Z","content_type":"image/tiff","creator":"ckreuzin","checksum":"15ab0e44297bf05ad0b033a00377bc9f","success":1,"access_level":"open_access"},{"success":1,"access_level":"open_access","relation":"main_file","date_updated":"2025-02-27T12:38:11Z","date_created":"2025-02-27T12:38:11Z","file_id":"19193","file_size":12589020,"file_name":"SF5 (7).tif","checksum":"f79330486ce56e11e1e1e44e7425e40e","creator":"ckreuzin","content_type":"image/tiff"},{"success":1,"access_level":"open_access","file_id":"19194","file_name":"SF5 (8).tif","file_size":12589372,"relation":"main_file","date_created":"2025-02-27T12:38:11Z","date_updated":"2025-02-27T12:38:11Z","creator":"ckreuzin","content_type":"image/tiff","checksum":"970e48a64b8414590606074355b67857"},{"success":1,"access_level":"open_access","file_id":"19195","file_name":"SF5 (9).tif","file_size":12589372,"date_created":"2025-02-27T12:38:18Z","date_updated":"2025-02-27T12:38:18Z","relation":"main_file","creator":"ckreuzin","content_type":"image/tiff","checksum":"d1f671671c23159ad33d1d5ea33f84e4"},{"success":1,"access_level":"open_access","date_updated":"2025-02-27T12:38:18Z","date_created":"2025-02-27T12:38:18Z","relation":"main_file","file_id":"19196","file_size":12589366,"file_name":"SF5 (10).tif","checksum":"3e7f08d4e4c72fc5455fc5a8cb11a9eb","creator":"ckreuzin","content_type":"image/tiff"},{"file_size":1415036,"file_name":"SF6_a.tif","file_id":"19197","date_created":"2025-02-27T12:38:27Z","relation":"main_file","date_updated":"2025-02-27T12:38:27Z","content_type":"image/tiff","creator":"ckreuzin","checksum":"0fa65d9519b84ca6cac7767928f47620","success":1,"access_level":"open_access"},{"success":1,"access_level":"open_access","file_id":"19198","file_name":"SF6_b.png","file_size":14771950,"relation":"main_file","date_updated":"2025-02-27T12:38:28Z","date_created":"2025-02-27T12:38:28Z","creator":"ckreuzin","content_type":"image/png","checksum":"41250d19f197453bc558d72a39523e40"},{"date_created":"2025-02-27T12:38:28Z","relation":"main_file","date_updated":"2025-02-27T12:38:28Z","file_id":"19199","file_name":"SF6_c.png","file_size":29541400,"checksum":"7ad4f1a30c7953aea60e4b5830eb00c1","creator":"ckreuzin","content_type":"image/png","success":1,"access_level":"open_access"},{"access_level":"open_access","success":1,"content_type":"image/tiff","creator":"ckreuzin","checksum":"a542e3ae50144025482e5fa6727594d6","file_size":12583284,"file_name":"SF7_a (1).tif","file_id":"19200","date_updated":"2025-02-27T12:40:48Z","date_created":"2025-02-27T12:40:48Z","relation":"main_file"},{"content_type":"image/tiff","creator":"ckreuzin","checksum":"f6ed6317a6d4586d5f456ca8b423f357","file_size":971691,"file_name":"SF7_a (2).tif","file_id":"19201","date_created":"2025-02-27T12:40:47Z","date_updated":"2025-02-27T12:40:47Z","relation":"main_file","access_level":"open_access","success":1},{"success":1,"access_level":"open_access","file_id":"19202","file_size":971691,"file_name":"SF7_a (3).tif","date_updated":"2025-02-27T12:40:47Z","relation":"main_file","date_created":"2025-02-27T12:40:47Z","creator":"ckreuzin","content_type":"image/tiff","checksum":"da6aef7d3b8434c7ea7e7118377cd6cb"},{"checksum":"0fdaca32872449bdd4773f25fedce0c2","creator":"ckreuzin","content_type":"image/tiff","date_created":"2025-02-27T12:40:48Z","date_updated":"2025-02-27T12:40:48Z","relation":"main_file","file_id":"19203","file_size":12583284,"file_name":"SF7_a (4).tif","access_level":"open_access","success":1},{"access_level":"open_access","success":1,"checksum":"593636fa0c65b77d9909abce3bae27e6","creator":"ckreuzin","content_type":"image/tiff","date_created":"2025-02-27T12:40:48Z","date_updated":"2025-02-27T12:40:48Z","relation":"main_file","file_id":"19204","file_size":971689,"file_name":"SF7_b (1).tif"},{"success":1,"access_level":"open_access","date_created":"2025-02-27T12:40:48Z","date_updated":"2025-02-27T12:40:48Z","relation":"main_file","file_name":"SF7_b (2).tif","file_size":971689,"file_id":"19205","checksum":"008754d1e50a7f17c04ea57f3065b889","content_type":"image/tiff","creator":"ckreuzin"},{"file_size":12583282,"file_name":"SF7_b (3).tif","file_id":"19206","date_updated":"2025-02-27T12:40:48Z","date_created":"2025-02-27T12:40:48Z","relation":"main_file","content_type":"image/tiff","creator":"ckreuzin","checksum":"33c60d97c526f9f8f585b91255f0c9fb","success":1,"access_level":"open_access"},{"success":1,"access_level":"open_access","date_updated":"2025-02-27T12:40:48Z","date_created":"2025-02-27T12:40:48Z","relation":"main_file","file_id":"19207","file_size":12583282,"file_name":"SF7_b (4).tif","checksum":"cdb164e16c7e9b8e81baff00570e1beb","creator":"ckreuzin","content_type":"image/tiff"},{"success":1,"access_level":"open_access","date_created":"2025-02-27T12:40:48Z","relation":"main_file","date_updated":"2025-02-27T12:40:48Z","file_size":971719,"file_name":"SF7_c (1).tif","file_id":"19208","checksum":"b406c3f975b6ee62e4a69c36a8659395","content_type":"image/tiff","creator":"ckreuzin"},{"file_name":"SF7_c (2).tif","file_size":12583312,"file_id":"19209","relation":"main_file","date_updated":"2025-02-27T12:40:49Z","date_created":"2025-02-27T12:40:49Z","content_type":"image/tiff","creator":"ckreuzin","checksum":"baaf68d9c42824d2152ce347903a9e52","success":1,"access_level":"open_access"},{"content_type":"image/tiff","creator":"ckreuzin","checksum":"a54fa646e45ead1eca8de2cb828b6efa","file_name":"SF7_c (3).tif","file_size":971719,"file_id":"19210","date_created":"2025-02-27T12:40:48Z","relation":"main_file","date_updated":"2025-02-27T12:40:48Z","access_level":"open_access","success":1},{"file_name":"SF7_c (4).tif","file_size":12583312,"file_id":"19211","relation":"main_file","date_updated":"2025-02-27T12:40:49Z","date_created":"2025-02-27T12:40:49Z","content_type":"image/tiff","creator":"ckreuzin","checksum":"f35b92e63a88d7dcb29399205f509058","success":1,"access_level":"open_access"},{"file_size":971721,"file_name":"SF7_d (1).tif","file_id":"19212","date_created":"2025-02-27T12:40:49Z","date_updated":"2025-02-27T12:40:49Z","relation":"main_file","content_type":"image/tiff","creator":"ckreuzin","checksum":"f625e76556a9274e95962cc03b69c6ce","success":1,"access_level":"open_access"},{"success":1,"access_level":"open_access","file_id":"19213","file_name":"SF7_d (2).tif","file_size":12583313,"relation":"main_file","date_created":"2025-02-27T12:40:49Z","date_updated":"2025-02-27T12:40:49Z","creator":"ckreuzin","content_type":"image/tiff","checksum":"dd38206d764413f1969dea862d0a775e"},{"success":1,"access_level":"open_access","date_created":"2025-02-27T12:40:49Z","date_updated":"2025-02-27T12:40:49Z","relation":"main_file","file_id":"19214","file_size":971721,"file_name":"SF7_d (3).tif","checksum":"891705e5dd2bcc4b761f9fe1e01fe5eb","creator":"ckreuzin","content_type":"image/tiff"},{"success":1,"access_level":"open_access","file_id":"19215","file_size":12583313,"file_name":"SF7_d (4).tif","relation":"main_file","date_updated":"2025-02-27T12:40:49Z","date_created":"2025-02-27T12:40:49Z","creator":"ckreuzin","content_type":"image/tiff","checksum":"c0ad4758bfe9b10df96545c76ac70ae6"},{"access_level":"open_access","success":1,"creator":"ckreuzin","content_type":"image/tiff","checksum":"f28181e59bdee004afab0d2526918892","file_id":"19216","file_name":"SF8 (1).tif","file_size":12594788,"date_created":"2025-02-27T12:45:44Z","date_updated":"2025-02-27T12:45:44Z","relation":"main_file"},{"date_created":"2025-02-27T12:45:44Z","date_updated":"2025-02-27T12:45:44Z","relation":"main_file","file_name":"SF8 (2).tif","file_size":12594804,"file_id":"19217","checksum":"45ac190192a5067be7c21a5fd2155a16","content_type":"image/tiff","creator":"ckreuzin","success":1,"access_level":"open_access"},{"file_name":"SF8 (3).tif","file_size":12594768,"file_id":"19218","relation":"main_file","date_created":"2025-02-27T12:45:44Z","date_updated":"2025-02-27T12:45:44Z","content_type":"image/tiff","creator":"ckreuzin","checksum":"df5a2f23c83ee70d29def18624700228","success":1,"access_level":"open_access"},{"success":1,"access_level":"open_access","relation":"main_file","date_created":"2025-02-27T12:45:44Z","date_updated":"2025-02-27T12:45:44Z","file_id":"19219","file_size":12594796,"file_name":"SF8 (4).tif","checksum":"4d7fe6b7d73527449cbadc99c6438c73","creator":"ckreuzin","content_type":"image/tiff"},{"file_id":"19220","file_size":12594808,"file_name":"SF8 (5).tif","date_updated":"2025-02-27T12:45:44Z","relation":"main_file","date_created":"2025-02-27T12:45:44Z","creator":"ckreuzin","content_type":"image/tiff","checksum":"96c36e0b7c0a58163a67d8bbbab93b3f","success":1,"access_level":"open_access"},{"creator":"ckreuzin","content_type":"image/tiff","checksum":"68f6de9a8e37adf6c826cb0da6bb9761","file_id":"19221","file_size":12594788,"file_name":"SF8 (6).tif","date_updated":"2025-02-27T12:45:45Z","relation":"main_file","date_created":"2025-02-27T12:45:45Z","access_level":"open_access","success":1},{"checksum":"3ded92c972cf4693929ba34af17cc05f","content_type":"image/tiff","creator":"ckreuzin","date_created":"2025-02-27T12:45:45Z","date_updated":"2025-02-27T12:45:45Z","relation":"main_file","file_name":"SF8 (7).tif","file_size":12594790,"file_id":"19222","access_level":"open_access","success":1},{"access_level":"open_access","success":1,"checksum":"b5273316902e3568be63bbced5a6bad1","creator":"ckreuzin","content_type":"image/tiff","date_updated":"2025-02-27T12:45:45Z","relation":"main_file","date_created":"2025-02-27T12:45:45Z","file_id":"19223","file_name":"SF8 (8).tif","file_size":12594782},{"checksum":"8af6262e2f9652d25fa029981ade9de9","content_type":"image/tiff","creator":"ckreuzin","date_updated":"2025-02-27T12:45:45Z","date_created":"2025-02-27T12:45:45Z","relation":"main_file","file_size":12594778,"file_name":"SF8 (9).tif","file_id":"19224","access_level":"open_access","success":1},{"content_type":"image/tiff","creator":"ckreuzin","checksum":"d643c481d2eccd5f67fb2d27223068bf","file_name":"SF8 (10).tif","file_size":12594782,"file_id":"19225","date_updated":"2025-02-27T12:45:45Z","date_created":"2025-02-27T12:45:45Z","relation":"main_file","access_level":"open_access","success":1},{"file_id":"19226","file_size":12594790,"file_name":"SF8 (11).tif","date_updated":"2025-02-27T12:45:45Z","relation":"main_file","date_created":"2025-02-27T12:45:45Z","creator":"ckreuzin","content_type":"image/tiff","checksum":"6d3af95382f070bb63567fbf6b3f9477","success":1,"access_level":"open_access"},{"checksum":"de12b11a75ee3fa775f144e11b68e6ed","content_type":"image/tiff","creator":"ckreuzin","date_updated":"2025-02-27T12:45:46Z","relation":"main_file","date_created":"2025-02-27T12:45:46Z","file_size":12594774,"file_name":"SF8 (12).tif","file_id":"19227","access_level":"open_access","success":1},{"content_type":"image/tiff","creator":"ckreuzin","checksum":"9b79caefb934a8280adcf21b5bbf35ac","file_name":"SF8 (13).tif","file_size":12594778,"file_id":"19228","date_updated":"2025-02-27T12:45:46Z","relation":"main_file","date_created":"2025-02-27T12:45:46Z","access_level":"open_access","success":1},{"success":1,"access_level":"open_access","file_id":"19229","file_name":"SF8 (14).tif","file_size":12594790,"relation":"main_file","date_created":"2025-02-27T12:45:46Z","date_updated":"2025-02-27T12:45:46Z","creator":"ckreuzin","content_type":"image/tiff","checksum":"8e9442cdbd92fd61aacac52c23ca6bec"},{"checksum":"e42c08a6325e82d508221e896bd4f210","creator":"ckreuzin","content_type":"image/tiff","date_created":"2025-02-27T12:45:46Z","relation":"main_file","date_updated":"2025-02-27T12:45:46Z","file_id":"19230","file_size":12594782,"file_name":"SF8 (15).tif","access_level":"open_access","success":1},{"access_level":"open_access","success":1,"checksum":"04657cd0f303f99009cb1c5d4c61551c","creator":"ckreuzin","content_type":"image/tiff","date_updated":"2025-02-27T12:45:58Z","relation":"main_file","date_created":"2025-02-27T12:45:58Z","file_id":"19231","file_name":"SF9_a (1).tif","file_size":12589358},{"access_level":"open_access","success":1,"creator":"ckreuzin","content_type":"image/tiff","checksum":"512247c4f80abeafe17438584f23e09b","file_id":"19232","file_size":977761,"file_name":"SF9_a (2).tif","date_updated":"2025-02-27T12:45:58Z","date_created":"2025-02-27T12:45:58Z","relation":"main_file"},{"success":1,"access_level":"open_access","file_name":"SF9_a (3).tif","file_size":12589346,"file_id":"19233","relation":"main_file","date_created":"2025-02-27T12:45:58Z","date_updated":"2025-02-27T12:45:58Z","content_type":"image/tiff","creator":"ckreuzin","checksum":"3c85543205b21d49dbd99edbc455fc32"},{"checksum":"3cb358e1abafb929493bba73bfef88a4","content_type":"image/tiff","creator":"ckreuzin","relation":"main_file","date_created":"2025-02-27T12:45:58Z","date_updated":"2025-02-27T12:45:58Z","file_name":"SF9_a (4).tif","file_size":977781,"file_id":"19234","access_level":"open_access","success":1},{"success":1,"access_level":"open_access","file_id":"19235","file_size":12589366,"file_name":"SF9_a (5).tif","date_updated":"2025-02-27T12:45:59Z","date_created":"2025-02-27T12:45:59Z","relation":"main_file","creator":"ckreuzin","content_type":"image/tiff","checksum":"d025b195001165d7a1d44af9ad631ab9"},{"success":1,"access_level":"open_access","file_name":"SF9_a (6).tif","file_size":977773,"file_id":"19236","date_updated":"2025-02-27T12:45:59Z","date_created":"2025-02-27T12:45:59Z","relation":"main_file","content_type":"image/tiff","creator":"ckreuzin","checksum":"3f2fb7ce9bf45cfadce35115c12099fd"},{"creator":"ckreuzin","content_type":"image/tiff","checksum":"6fbe1dc7c358f988280c4f8ef04f5be9","file_id":"19237","file_size":977781,"file_name":"SF9_b (1).tif","date_updated":"2025-02-27T12:45:59Z","date_created":"2025-02-27T12:45:59Z","relation":"main_file","access_level":"open_access","success":1},{"success":1,"access_level":"open_access","date_created":"2025-02-27T12:45:59Z","relation":"main_file","date_updated":"2025-02-27T12:45:59Z","file_size":12589366,"file_name":"SF9_b (2).tif","file_id":"19238","checksum":"c02b2420d26ec644e86c569ede14c5ef","content_type":"image/tiff","creator":"ckreuzin"},{"success":1,"access_level":"open_access","date_created":"2025-02-27T12:45:59Z","date_updated":"2025-02-27T12:45:59Z","relation":"main_file","file_name":"SF9_b (3).tif","file_size":977769,"file_id":"19239","checksum":"0ed660389a060890edb85249d468a014","content_type":"image/tiff","creator":"ckreuzin"},{"access_level":"open_access","success":1,"creator":"ckreuzin","content_type":"image/tiff","checksum":"cabf39d2b5d35cd3e5854b3b16001e08","file_id":"19240","file_name":"SF9_b (4).tif","file_size":12589354,"date_created":"2025-02-27T12:45:59Z","relation":"main_file","date_updated":"2025-02-27T12:45:59Z"},{"success":1,"access_level":"open_access","file_id":"19241","file_size":977871,"file_name":"SF9_b (5).tif","date_created":"2025-02-27T12:45:59Z","date_updated":"2025-02-27T12:45:59Z","relation":"main_file","creator":"ckreuzin","content_type":"image/tiff","checksum":"d81c3fce4bd6e2e0109f62efb2b54959"},{"content_type":"image/tiff","creator":"ckreuzin","checksum":"374f2e897f46f6feac9feca0fa8394cd","file_size":12589456,"file_name":"SF9_b (6).tif","file_id":"19242","date_updated":"2025-02-27T12:45:59Z","relation":"main_file","date_created":"2025-02-27T12:45:59Z","access_level":"open_access","success":1},{"success":1,"access_level":"open_access","relation":"main_file","date_created":"2025-02-27T12:46:27Z","date_updated":"2025-02-27T12:46:27Z","file_id":"19243","file_size":827856876,"file_name":"SF11.tif","checksum":"84a880d60f767cfe0665ea2ec595c8d7","creator":"ckreuzin","content_type":"image/tiff"},{"access_level":"open_access","success":1,"checksum":"d18add0f9f824700d0f53d2191466300","content_type":"image/tiff","creator":"ckreuzin","date_updated":"2025-02-27T12:46:38Z","relation":"main_file","date_created":"2025-02-27T12:46:38Z","file_size":3828230,"file_name":"SF12_a (1).tif","file_id":"19244"},{"success":1,"access_level":"open_access","relation":"main_file","date_updated":"2025-02-27T12:46:38Z","date_created":"2025-02-27T12:46:38Z","file_id":"19245","file_size":160112,"file_name":"SF12_a (2).tif","checksum":"042d241d8b3080c8c5ff0a2dbda4a48f","creator":"ckreuzin","content_type":"image/tiff"},{"date_updated":"2025-02-27T12:46:38Z","date_created":"2025-02-27T12:46:38Z","relation":"main_file","file_id":"19246","file_name":"SF12_a (3).tif","file_size":3828230,"checksum":"955d474f43d115fedca614ed6602215f","creator":"ckreuzin","content_type":"image/tiff","success":1,"access_level":"open_access"},{"success":1,"access_level":"open_access","relation":"main_file","date_updated":"2025-02-27T12:46:38Z","date_created":"2025-02-27T12:46:38Z","file_size":160112,"file_name":"SF12_a (4).tif","file_id":"19247","checksum":"325f940b56634b1c33e491dcc58b3404","content_type":"image/tiff","creator":"ckreuzin"},{"creator":"ckreuzin","content_type":"image/tiff","checksum":"1b5524fb3d54489b04afe9f2f7cfebb9","file_id":"19248","file_name":"SF12_b (1).tif","file_size":3821356,"date_created":"2025-02-27T12:46:39Z","date_updated":"2025-02-27T12:46:39Z","relation":"main_file","access_level":"open_access","success":1},{"success":1,"access_level":"open_access","relation":"main_file","date_updated":"2025-02-27T12:46:39Z","date_created":"2025-02-27T12:46:39Z","file_name":"SF12_b (2).tif","file_size":3821356,"file_id":"19249","checksum":"bacb9f4b367c2425df02ad392028e574","content_type":"image/tiff","creator":"ckreuzin"},{"access_level":"open_access","success":1,"checksum":"5cb107bed602073a51a534ceb4c81362","content_type":"image/tiff","creator":"ckreuzin","relation":"main_file","date_updated":"2025-02-27T12:46:39Z","date_created":"2025-02-27T12:46:39Z","file_size":3821356,"file_name":"SF12_b (3).tif","file_id":"19250"},{"success":1,"access_level":"open_access","file_id":"19251","file_name":"SF12_b (4).tif","file_size":3821356,"relation":"main_file","date_created":"2025-02-27T12:46:39Z","date_updated":"2025-02-27T12:46:39Z","creator":"ckreuzin","content_type":"image/tiff","checksum":"26a07d639182a4189650f4c7dba90865"},{"success":1,"access_level":"open_access","date_created":"2025-02-27T12:46:51Z","date_updated":"2025-02-27T12:46:51Z","relation":"main_file","file_name":"SF18_a (1).png","file_size":1245061,"file_id":"19252","checksum":"eba866000a286254545c3f6868f69b9f","content_type":"image/png","creator":"ckreuzin"},{"access_level":"open_access","success":1,"checksum":"8e6c94f552e9dbc34cd0b3853df8d015","content_type":"image/tiff","creator":"ckreuzin","date_updated":"2025-02-27T12:46:51Z","date_created":"2025-02-27T12:46:51Z","relation":"main_file","file_name":"SF18_a (2).tif","file_size":60892,"file_id":"19253"},{"date_updated":"2025-02-27T12:46:51Z","relation":"main_file","date_created":"2025-02-27T12:46:51Z","file_id":"19254","file_size":60892,"file_name":"SF18_a (3).tif","checksum":"079d6c3e2459c71ed27bc3baafa47843","creator":"ckreuzin","content_type":"image/tiff","success":1,"access_level":"open_access"},{"access_level":"open_access","success":1,"checksum":"22602da6be439acf8c3dfbb78fcc4400","creator":"ckreuzin","content_type":"image/tiff","relation":"main_file","date_updated":"2025-02-27T12:46:51Z","date_created":"2025-02-27T12:46:51Z","file_id":"19255","file_size":12583312,"file_name":"SF18_b (1).tif"},{"creator":"ckreuzin","content_type":"image/tiff","checksum":"eed1e333701f9085d69d5239e8719112","file_id":"19256","file_size":811600,"file_name":"SF18_b (2).tif","date_updated":"2025-02-27T12:46:51Z","date_created":"2025-02-27T12:46:51Z","relation":"main_file","access_level":"open_access","success":1},{"access_level":"open_access","success":1,"checksum":"2215b02b1b947caf92e1bbe7185d06e1","creator":"ckreuzin","content_type":"image/tiff","relation":"main_file","date_created":"2025-02-27T12:46:51Z","date_updated":"2025-02-27T12:46:51Z","file_id":"19257","file_name":"SF18_b (3).tif","file_size":811600},{"content_type":"image/tiff","creator":"ckreuzin","checksum":"292e06efed5701eae8e83e02ed7a6e22","file_size":1068146032,"file_name":"SF20.tif","file_id":"19258","relation":"main_file","date_updated":"2025-02-27T12:47:31Z","date_created":"2025-02-27T12:47:31Z","access_level":"open_access","success":1},{"access_level":"open_access","success":1,"creator":"ckreuzin","content_type":"image/png","checksum":"32cbaee7cb8e3ce9385d716b7a54a4bc","file_id":"19259","file_size":219654,"file_name":"SF23 (1).png","date_created":"2025-02-27T12:48:36Z","date_updated":"2025-02-27T12:48:36Z","relation":"main_file"},{"creator":"ckreuzin","content_type":"image/png","checksum":"e0bbf151a4bd261a5cb1c00bed59777d","file_id":"19260","file_name":"SF23 (2).png","file_size":1941088,"relation":"main_file","date_updated":"2025-02-27T12:48:36Z","date_created":"2025-02-27T12:48:36Z","access_level":"open_access","success":1},{"checksum":"73ed6c45b7db745252b61d24f8c40f6f","creator":"ckreuzin","content_type":"image/png","date_created":"2025-02-27T12:48:36Z","date_updated":"2025-02-27T12:48:36Z","relation":"main_file","file_id":"19261","file_size":238170,"file_name":"SF23 (3).png","access_level":"open_access","success":1},{"file_size":2026158,"file_name":"SF23 (4).png","file_id":"19262","date_created":"2025-02-27T12:48:36Z","date_updated":"2025-02-27T12:48:36Z","relation":"main_file","content_type":"image/png","creator":"ckreuzin","checksum":"c871ee6bc9d16b551582ec22b8e1a3bb","success":1,"access_level":"open_access"},{"access_level":"open_access","success":1,"checksum":"448a0397c431153bdf63b0844842feb9","content_type":"image/png","creator":"ckreuzin","date_updated":"2025-02-27T12:48:36Z","relation":"main_file","date_created":"2025-02-27T12:48:36Z","file_size":262037,"file_name":"SF23 (5).png","file_id":"19263"},{"access_level":"open_access","success":1,"creator":"ckreuzin","content_type":"image/png","checksum":"b35f44db5058569ec21550b369beec4b","file_id":"19264","file_name":"SF23 (6).png","file_size":2052749,"date_updated":"2025-02-27T12:48:36Z","date_created":"2025-02-27T12:48:36Z","relation":"main_file"},{"creator":"ckreuzin","content_type":"image/png","checksum":"5dcac37bab7e128a04ba9cdb9b34164f","file_id":"19265","file_name":"SF23_overview.png","file_size":80062038,"date_updated":"2025-02-27T12:49:07Z","relation":"main_file","date_created":"2025-02-27T12:49:07Z","access_level":"open_access","success":1},{"access_level":"open_access","success":1,"checksum":"032c7c52f36298252cc0b19b83ea0648","creator":"ckreuzin","content_type":"image/tiff","relation":"main_file","date_updated":"2025-02-27T12:49:50Z","date_created":"2025-02-27T12:49:50Z","file_id":"19266","file_size":121784120,"file_name":"SF24 (1).tif"},{"creator":"ckreuzin","content_type":"image/tiff","checksum":"5867b6b999d0c3d91354d92ba0d6c30b","file_id":"19267","file_name":"SF24 (2).tif","file_size":121784062,"date_updated":"2025-02-27T12:49:50Z","date_created":"2025-02-27T12:49:50Z","relation":"main_file","access_level":"open_access","success":1},{"success":1,"access_level":"open_access","file_size":2995439929,"file_name":"SF25.tif","file_id":"19268","date_created":"2025-02-27T12:51:29Z","relation":"main_file","date_updated":"2025-02-27T12:51:29Z","content_type":"image/tiff","creator":"ckreuzin","checksum":"bbf1267c8030894e846f2dc95a955014"},{"file_id":"19269","file_size":2400199306,"file_name":"LICONN_gephyrin_test.tif","relation":"main_file","date_updated":"2025-02-28T09:07:23Z","date_created":"2025-02-28T09:07:23Z","creator":"ckreuzin","content_type":"image/tiff","checksum":"3db644adb7181eef3181e1c418856741","success":1,"access_level":"open_access"},{"checksum":"0d716ad1249be4de51e79b6d832340b9","creator":"ckreuzin","content_type":"image/tiff","date_updated":"2025-02-28T09:15:48Z","relation":"main_file","date_created":"2025-02-28T09:15:48Z","file_id":"19270","file_size":588107137,"file_name":"LICONN_test_dataset.tif","access_level":"open_access","success":1}],"file_date_updated":"2025-02-28T16:50:39Z","OA_type":"gold","day":"03","doi":"10.15479/AT:ISTA:18697","date_updated":"2026-04-28T13:33:34Z","date_created":"2024-12-20T09:22:20Z","month":"03","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","corr_author":"1","oa_version":"Published Version","ddc":["570"],"related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"19704"}],"link":[{"description":"Original datasets of large size (>10GB) and datasets in zarr/n5/ims/npz format are provided via this external link.","url":"https://pub.ista.ac.at/group_danzl/data/LICONN/","relation":"research_data"}]},"department":[{"_id":"JoDa"}],"type":"research_data"},{"author":[{"id":"4AC7D980-F248-11E8-B48F-1D18A9856A87","full_name":"Tluckova, Katarina","first_name":"Katarina","last_name":"Tluckova"},{"first_name":"Beata M","last_name":"Kaczmarek","id":"36FA4AFA-F248-11E8-B48F-1D18A9856A87","full_name":"Kaczmarek, Beata M"},{"first_name":"Anita P","last_name":"Testa Salmazo","full_name":"Testa Salmazo, Anita P","id":"41F1F098-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Bernecky, Carrie A","id":"2CB9DFE2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0893-7036","first_name":"Carrie A","last_name":"Bernecky"}],"title":"Mechanism of mammalian transcriptional repression by noncoding RNA","date_published":"2025-04-01T00:00:00Z","publication_status":"published","has_accepted_license":"1","year":"2025","isi":1,"volume":32,"publication":"Nature Structural & Molecular Biology","abstract":[{"text":"Transcription by RNA polymerase II (Pol II) can be repressed by noncoding RNA, including the human RNA Alu. However, the mechanism by which endogenous RNAs repress transcription remains unclear. Here we present cryogenic-electron microscopy structures of Pol II bound to Alu RNA, which reveal that Alu RNA mimics how DNA and RNA bind to Pol II during transcription elongation. Further, we show how distinct domains of the general transcription factor TFIIF control repressive activity. Together, we reveal how a noncoding RNA can regulate mammalian gene expression.","lang":"eng"}],"intvolume":"        32","acknowledgement":"We thank the members of the Bernecky laboratory for helpful discussions and A. Hlavata for providing Pol II for use in the fluorescence anisotropy binding assay. We thank V.-V. Hodirnau for SerialEM data collection and support with EPU data collection. We thank D. Slade (Max Perutz Laboratories and Medical University of Vienna, Vienna, Austria) for the wild-type TFIIF expression plasmid. We thank N. Thompson and R. Burgess (McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI, USA) for the 8WG16 hybridoma cell line. We thank C. Plaschka and M. Loose for critical reading of the manuscript. This work was supported by Austrian Science Fund (FWF) grant no. P34185 (DOI 10.55776/P34185) (C.B.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. This research was further supported by the Scientific Service Units of ISTA through resources provided by the Laboratory Support Facility, Electron Microscopy Facility, Scientific Computing and the Preclinical Facility.","language":[{"iso":"eng"}],"status":"public","external_id":{"isi":["001390268000001"],"pmid":["39762629"]},"quality_controlled":"1","_id":"18778","publisher":"Springer Nature","article_processing_charge":"Yes (in subscription journal)","department":[{"_id":"CaBe"}],"type":"journal_article","related_material":{"record":[{"id":"14644","relation":"earlier_version","status":"public"}]},"pmid":1,"project":[{"_id":"c08a6700-5a5b-11eb-8a69-82a722b2bc30","grant_number":"P34185","name":"Regulation of mammalian transcription by noncoding RNA"}],"page":"607-612","month":"04","ddc":["570"],"oa_version":"Published Version","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","corr_author":"1","doi":"10.1038/s41594-024-01448-7","date_updated":"2025-11-20T10:28:36Z","date_created":"2025-01-08T11:20:20Z","APC_amount":"12348 EUR","article_type":"original","OA_type":"hybrid","day":"01","file":[{"creator":"dernst","content_type":"application/pdf","checksum":"2919b30b271f395888e880076a680d73","file_id":"19573","file_name":"2025_NatureStrucMolBiol_Tluckova.pdf","file_size":9306639,"date_updated":"2025-04-16T08:17:27Z","date_created":"2025-04-16T08:17:27Z","relation":"main_file","access_level":"open_access","success":1}],"file_date_updated":"2025-04-16T08:17:27Z","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"citation":{"ista":"Tluckova K, Kaczmarek BM, Testa Salmazo AP, Bernecky C. 2025. Mechanism of mammalian transcriptional repression by noncoding RNA. Nature Structural &#38; Molecular Biology. 32, 607–612.","chicago":"Tluckova, Katarina, Beata M Kaczmarek, Anita P Testa Salmazo, and Carrie Bernecky. “Mechanism of Mammalian Transcriptional Repression by Noncoding RNA.” <i>Nature Structural &#38; Molecular Biology</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1038/s41594-024-01448-7\">https://doi.org/10.1038/s41594-024-01448-7</a>.","short":"K. Tluckova, B.M. Kaczmarek, A.P. Testa Salmazo, C. Bernecky, Nature Structural &#38; Molecular Biology 32 (2025) 607–612.","ama":"Tluckova K, Kaczmarek BM, Testa Salmazo AP, Bernecky C. Mechanism of mammalian transcriptional repression by noncoding RNA. <i>Nature Structural &#38; Molecular Biology</i>. 2025;32:607-612. doi:<a href=\"https://doi.org/10.1038/s41594-024-01448-7\">10.1038/s41594-024-01448-7</a>","mla":"Tluckova, Katarina, et al. “Mechanism of Mammalian Transcriptional Repression by Noncoding RNA.” <i>Nature Structural &#38; Molecular Biology</i>, vol. 32, Springer Nature, 2025, pp. 607–12, doi:<a href=\"https://doi.org/10.1038/s41594-024-01448-7\">10.1038/s41594-024-01448-7</a>.","apa":"Tluckova, K., Kaczmarek, B. M., Testa Salmazo, A. P., &#38; Bernecky, C. (2025). Mechanism of mammalian transcriptional repression by noncoding RNA. <i>Nature Structural &#38; Molecular Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41594-024-01448-7\">https://doi.org/10.1038/s41594-024-01448-7</a>","ieee":"K. Tluckova, B. M. Kaczmarek, A. P. Testa Salmazo, and C. Bernecky, “Mechanism of mammalian transcriptional repression by noncoding RNA,” <i>Nature Structural &#38; Molecular Biology</i>, vol. 32. Springer Nature, pp. 607–612, 2025."},"fulldoi":"https://doi.org/10.1038/s41594-024-01448-7","publication_identifier":{"issn":["1545-9993"],"eissn":["1545-9985"]},"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"EM-Fac"},{"_id":"ScienComp"},{"_id":"PreCl"}],"scopus_import":"1","oa":1,"OA_place":"publisher"},{"title":"Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory","author":[{"full_name":"Watson, Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","last_name":"Watson","orcid":"0000-0002-8698-3823","first_name":"Jake"},{"last_name":"Vargas Barroso","first_name":"Victor M","id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87","full_name":"Vargas Barroso, Victor M"},{"first_name":"Rebecca","last_name":"Morse","id":"ceb89ae7-dc8d-11ea-abe3-da3301d0eab4","full_name":"Morse, Rebecca"},{"id":"739d26c9-52e8-11ee-8d72-f14d3893b4ce","full_name":"Navas Olivé, Andrea C","last_name":"Navas Olivé","orcid":"0000-0002-9280-8597","first_name":"Andrea C"},{"last_name":"Tavakoli","orcid":"0000-0002-7667-6854","first_name":"Mojtaba","full_name":"Tavakoli, Mojtaba","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Johann G","orcid":"0000-0001-8559-3973","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G"},{"full_name":"Tomschik, Matthias","last_name":"Tomschik","first_name":"Matthias"},{"first_name":"Karl","last_name":"Rössler","full_name":"Rössler, Karl"},{"full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas"}],"date_published":"2025-01-23T00:00:00Z","publication_status":"published","year":"2025","has_accepted_license":"1","isi":1,"publication":"Cell","volume":188,"status":"public","intvolume":"       188","acknowledgement":"We thank Florian Marr for excellent technical assistance, Christina Altmutter and Julia Flor for technical support, Alois Schlögl for programming, Todor Asenov for development of the transportation box for human brain tissue, Tim Vogels for guidance on simulations, Marcus Huber for mathematical advice, Walter Kaufmann for assistance with handling frozen tissue, and Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA, and we are grateful for assistance from Christoph Sommer and the Imaging and Optics Facility, Preclinical Facility, Lab Support Facility, Miba Machine Shop, and Scientific Computing. We are particularly grateful to the patient donors for their support of this project and also acknowledge the excellent support of the Medical University of Vienna Department of Neurosurgery staff; Romana Hoeftberger and the Division of Neuropathology and Neurochemistry; Gregor Kasprian and the Division of Neuroradiology and Musculoskeletal Radiology; and Christoph Baumgartner, Martha Feucht, and Ekaterina Pataraia for their clinical care of the patients included in this study. We thank Laura Jonkman, the NABCA biobank, and postmortem brain sample donors for their support of this research. The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (advanced grant no. 692692 to P.J. and Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 to J.F.W.), the Austrian Science Fund (FWF; grant PAT 4178023 to P.J. and grant DK W1232 to M.R.T. and J.G.D.), the Austrian Academy of Sciences (DOC fellowship 26137 to M.R.T.), and a NOMIS-ISTA fellowship (to A.N.-O.).","language":[{"iso":"eng"}],"abstract":[{"text":"Our brain has remarkable computational power, generating sophisticated behaviors, storing memories over an individual’s lifetime, and producing higher cognitive functions. However, little of our neuroscience knowledge covers the human brain. Is this organ truly unique, or is it a scaled version of the extensively studied rodent brain? Combining multicellular patch-clamp recording with expansion-based superresolution microscopy and full-scale modeling, we determined the cellular and microcircuit properties of the human hippocampal CA3 region, a fundamental circuit for memory storage. In contrast to neocortical networks, human hippocampal CA3 displayed sparse connectivity, providing a circuit architecture that maximizes associational power. Human synapses showed unique reliability, high precision, and long integration times, exhibiting both species- and circuit-specific properties. Together with expanded neuronal numbers, these circuit characteristics greatly enhanced the memory storage capacity of CA3. Our results reveal distinct microcircuit properties of the human hippocampus and begin to unravel the inner workings of our most complex organ. ","lang":"eng"}],"external_id":{"pmid":["39667938"],"isi":["001408395600001"]},"issue":"2","quality_controlled":"1","_id":"18879","publisher":"Elsevier","article_processing_charge":"Yes (via OA deal)","department":[{"_id":"JoDa"},{"_id":"PeJo"},{"_id":"GradSch"}],"ec_funded":1,"type":"journal_article","related_material":{"record":[{"id":"18688","relation":"earlier_version","status":"public"}]},"pmid":1,"page":"501-514.e18","project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"Synaptic computations of the hippocampal CA3 circuitry","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","call_identifier":"H2020","grant_number":"101026635"},{"grant_number":"26137","_id":"6285a163-2b32-11ec-9570-8e204ca2dba5","name":"Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy"},{"name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232"},{"name":"Synaptic networks of human brain","_id":"8d9195e9-16d5-11f0-9cad-d075be887a1e","grant_number":"PAT 4178023"},{"_id":"9B861AAC-BA93-11EA-9121-9846C619BF3A","name":"NOMIS Fellowship Program"}],"month":"01","corr_author":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","ddc":["570"],"date_updated":"2026-04-14T08:34:32Z","date_created":"2025-01-26T23:01:49Z","doi":"10.1016/j.cell.2024.11.022","OA_type":"hybrid","article_type":"original","day":"23","file":[{"access_level":"open_access","success":1,"checksum":"d5a818edc32d249cdf75e1bb5b70a4b7","creator":"dernst","content_type":"application/pdf","date_created":"2025-01-27T08:46:33Z","relation":"main_file","date_updated":"2025-01-27T08:46:33Z","file_id":"18884","file_name":"2025_Cell_Watson.pdf","file_size":14082343}],"file_date_updated":"2025-01-27T08:46:33Z","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"fulldoi":"https://doi.org/10.1016/j.cell.2024.11.022","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"ScienComp"}],"publication_identifier":{"eissn":["1097-4172"],"issn":["0092-8674"]},"citation":{"chicago":"Watson, Jake, Victor M Vargas Barroso, Rebecca Morse, Andrea C Navas Olivé, Mojtaba Tavakoli, Johann G Danzl, Matthias Tomschik, Karl Rössler, and Peter M Jonas. “Human Hippocampal CA3 Uses Specific Functional Connectivity Rules for Efficient Associative Memory.” <i>Cell</i>. Elsevier, 2025. <a href=\"https://doi.org/10.1016/j.cell.2024.11.022\">https://doi.org/10.1016/j.cell.2024.11.022</a>.","ista":"Watson J, Vargas Barroso VM, Morse R, Navas Olivé AC, Tavakoli M, Danzl JG, Tomschik M, Rössler K, Jonas PM. 2025. Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory. Cell. 188(2), 501–514.e18.","short":"J. Watson, V.M. Vargas Barroso, R. Morse, A.C. Navas Olivé, M. Tavakoli, J.G. Danzl, M. Tomschik, K. Rössler, P.M. Jonas, Cell 188 (2025) 501–514.e18.","mla":"Watson, Jake, et al. “Human Hippocampal CA3 Uses Specific Functional Connectivity Rules for Efficient Associative Memory.” <i>Cell</i>, vol. 188, no. 2, Elsevier, 2025, p. 501–514.e18, doi:<a href=\"https://doi.org/10.1016/j.cell.2024.11.022\">10.1016/j.cell.2024.11.022</a>.","ieee":"J. Watson <i>et al.</i>, “Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory,” <i>Cell</i>, vol. 188, no. 2. Elsevier, p. 501–514.e18, 2025.","apa":"Watson, J., Vargas Barroso, V. M., Morse, R., Navas Olivé, A. C., Tavakoli, M., Danzl, J. G., … Jonas, P. M. (2025). Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory. <i>Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cell.2024.11.022\">https://doi.org/10.1016/j.cell.2024.11.022</a>","ama":"Watson J, Vargas Barroso VM, Morse R, et al. Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory. <i>Cell</i>. 2025;188(2):501-514.e18. doi:<a href=\"https://doi.org/10.1016/j.cell.2024.11.022\">10.1016/j.cell.2024.11.022</a>"},"oa":1,"scopus_import":"1","OA_place":"publisher"},{"doi":"10.15479/AT:ISTA:18991","date_created":"2025-02-04T10:36:18Z","date_updated":"2026-05-06T13:12:00Z","month":"02","corr_author":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"oa_version":"Published Version","related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"19453"}]},"department":[{"_id":"GradSch"},{"_id":"JoCs"},{"_id":"GaTk"}],"type":"research_data","oa":1,"OA_place":"repository","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"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"},"fulldoi":"https://doi.org/10.15479/AT:ISTA:18991","citation":{"ama":"Chiossi HSC. Research data for the publication “Learning reshapes the hippocampal representation hierarchy.” 2025. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:18991\">10.15479/AT:ISTA:18991</a>","mla":"Chiossi, Heloisa S. C. <i>Research Data for the Publication “Learning Reshapes the Hippocampal Representation Hierarchy.”</i> Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:18991\">10.15479/AT:ISTA:18991</a>.","ieee":"H. S. C. Chiossi, “Research data for the publication ‘Learning reshapes the hippocampal representation hierarchy.’” Institute of Science and Technology Austria, 2025.","apa":"Chiossi, H. S. C. (2025). Research data for the publication “Learning reshapes the hippocampal representation hierarchy.” Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:18991\">https://doi.org/10.15479/AT:ISTA:18991</a>","short":"H.S.C. Chiossi, (2025).","ista":"Chiossi HSC. 2025. Research data for the publication ‘Learning reshapes the hippocampal representation hierarchy’, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:18991\">10.15479/AT:ISTA:18991</a>.","chicago":"Chiossi, Heloisa S. C. “Research Data for the Publication ‘Learning Reshapes the Hippocampal Representation Hierarchy.’” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT:ISTA:18991\">https://doi.org/10.15479/AT:ISTA:18991</a>."},"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"M-Shop"}],"file":[{"creator":"hchiossi","content_type":"application/zip","checksum":"04d761ed42e8879abffde04a560409ce","file_id":"18992","file_size":769383201,"file_name":"Chiossi_etal_2025_PNAS_data.zip","date_updated":"2025-02-04T10:16:52Z","date_created":"2025-02-04T10:16:52Z","relation":"main_file","access_level":"open_access","success":1},{"file_id":"18993","file_name":"readme.txt","file_size":3215,"date_created":"2025-02-04T10:18:33Z","date_updated":"2025-02-04T10:18:33Z","relation":"main_file","creator":"hchiossi","content_type":"text/plain","checksum":"50602931dcd33e4f009ed46af11335f3","success":1,"access_level":"open_access"}],"file_date_updated":"2025-02-04T10:18:33Z","OA_type":"gold","day":"04","year":"2025","has_accepted_license":"1","date_published":"2025-02-04T00:00:00Z","title":"Research data for the publication \"Learning reshapes the hippocampal representation hierarchy\"","author":[{"last_name":"Chiossi","first_name":"Heloisa","orcid":"0009-0004-2973-278X","full_name":"Chiossi, Heloisa","id":"2BBA502C-F248-11E8-B48F-1D18A9856A87"}],"_id":"18991","publisher":"Institute of Science and Technology Austria","article_processing_charge":"No","contributor":[{"id":"30BD0376-F248-11E8-B48F-1D18A9856A87","contributor_type":"researcher","last_name":"Nardin","first_name":"Michele","orcid":"0000-0001-8849-6570"},{"last_name":"Tkačik","first_name":"Gašper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","contributor_type":"supervisor"},{"id":"3FA14672-F248-11E8-B48F-1D18A9856A87","contributor_type":"supervisor","last_name":"Csicsvari","first_name":"Jozsef L","orcid":"0000-0002-5193-4036"}],"keyword":["hippocampus","electrophysiology","behavior"],"acknowledgement":"Thanks to Rebecca Morse for performing one of the experiments under H.S.C.C. supervision and Jago Wallenschus for technical support, especially with maze design.","status":"public","abstract":[{"text":"Research data for the article \"Learning reshapes the hippocampal representation hierarchy\" from Chiossi et al. (PNAS, 2025). The data includes hippocampal CA1 unit activity and behaviour tracking of 5 Long Evans rats during the learning of an associative memory task. Detailed information can be found in the 'readme.txt' file.","lang":"eng"}]},{"fulldoi":"https://doi.org/10.1038/s41593-025-01874-w","citation":{"chicago":"Vega Zuniga, Tomas A, Anton L Sumser, Olga Symonova, Peter Koppensteiner, Florian Schmidt, and Maximilian A Jösch. “A Thalamic Hub-and-Spoke Network Enables Visual Perception during Action by Coordinating Visuomotor Dynamics.” <i>Nature Neuroscience</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1038/s41593-025-01874-w\">https://doi.org/10.1038/s41593-025-01874-w</a>.","ista":"Vega Zuniga TA, Sumser AL, Symonova O, Koppensteiner P, Schmidt F, Jösch MA. 2025. A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics. Nature Neuroscience. 28, 7278.","short":"T.A. Vega Zuniga, A.L. Sumser, O. Symonova, P. Koppensteiner, F. Schmidt, M.A. Jösch, Nature Neuroscience 28 (2025).","apa":"Vega Zuniga, T. A., Sumser, A. L., Symonova, O., Koppensteiner, P., Schmidt, F., &#38; Jösch, M. A. (2025). A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics. <i>Nature Neuroscience</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41593-025-01874-w\">https://doi.org/10.1038/s41593-025-01874-w</a>","ieee":"T. A. Vega Zuniga, A. L. Sumser, O. Symonova, P. Koppensteiner, F. Schmidt, and M. A. Jösch, “A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics,” <i>Nature Neuroscience</i>, vol. 28. Springer Nature, 2025.","mla":"Vega Zuniga, Tomas A., et al. “A Thalamic Hub-and-Spoke Network Enables Visual Perception during Action by Coordinating Visuomotor Dynamics.” <i>Nature Neuroscience</i>, vol. 28, 7278, Springer Nature, 2025, doi:<a href=\"https://doi.org/10.1038/s41593-025-01874-w\">10.1038/s41593-025-01874-w</a>.","ama":"Vega Zuniga TA, Sumser AL, Symonova O, Koppensteiner P, Schmidt F, Jösch MA. A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics. <i>Nature Neuroscience</i>. 2025;28. doi:<a href=\"https://doi.org/10.1038/s41593-025-01874-w\">10.1038/s41593-025-01874-w</a>"},"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"Bio"}],"publication_identifier":{"eissn":["1546-1726"],"issn":["1097-6256"]},"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"OA_place":"publisher","main_file_link":[{"url":"https://doi.org/10.1038/s41593-025-01874-w","open_access":"1"}],"oa":1,"scopus_import":"1","day":"01","OA_type":"hybrid","article_type":"original","ddc":["570"],"oa_version":"Published Version","corr_author":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"03","date_created":"2025-02-23T23:01:58Z","date_updated":"2026-06-18T18:12:08Z","doi":"10.1038/s41593-025-01874-w","type":"journal_article","ec_funded":1,"department":[{"_id":"MaJö"},{"_id":"PreCl"}],"project":[{"_id":"2634E9D2-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"756502","name":"Circuits of Visual Attention"},{"grant_number":"101086580","_id":"bdaf81a8-d553-11ed-ba76-c95961984540","name":"Action Selection in the Midbrain: Neuromodulation of Visuomotor Senses"},{"name":"Connecting sensory with motor processing in the superior colliculus","grant_number":"ALTF 1098-2017","_id":"264FEA02-B435-11E9-9278-68D0E5697425"},{"grant_number":"LT000256","_id":"266D407A-B435-11E9-9278-68D0E5697425","name":"Neuronal networks of salience and spatial detection in the murine superior colliculus"}],"pmid":1,"related_material":{"record":[{"status":"public","relation":"research_data","id":"18579"}],"link":[{"description":"News on ISTA Website","relation":"press_release","url":"https://ista.ac.at/en/news/high-tech-video-optimization-in-our-brain/"}]},"quality_controlled":"1","article_number":"7278","external_id":{"pmid":["39930095"],"isi":["001416866800001"]},"article_processing_charge":"Yes (via OA deal)","publisher":"Springer Nature","_id":"19076","volume":28,"publication":"Nature Neuroscience","abstract":[{"lang":"eng","text":"For accurate perception and motor control, an animal must distinguish between sensory experiences elicited by external stimuli and those elicited by its own actions. The diversity of behaviors and their complex influences on the senses make this distinction challenging. Here, we uncover an action–cue hub that coordinates motor commands with visual processing in the brain’s first visual relay. We show that the ventral lateral geniculate nucleus (vLGN) acts as a corollary discharge center, integrating visual translational optic flow signals with motor copies from saccades, locomotion and pupil dynamics. The vLGN relays these signals to correct action-specific visual distortions and to refine perception, as shown for the superior colliculus and in a depth-estimation task. Simultaneously, brain-wide vLGN projections drive corrective actions necessary for accurate visuomotor control. Our results reveal an extended corollary discharge architecture that refines early visual transformations and coordinates actions via a distributed hub-and-spoke network to enable visual perception during action."}],"intvolume":"        28","acknowledgement":"We thank Y. Ben-Simon for generously making viral vectors for retrograde tracing available, as well as J. Watson and F. Marr for reagents. We also thank R. Shigemoto, W. Młynarski and members of the Neuroethology group for their comments on the manuscript and L. Burnett for her schematic drawings. This research was supported by the Scientific Service Units of ISTA through resources provided by Scientific Computing, the Preclinical Facility, the Lab Support Facility and the Imaging and Optics Facility, in particular F. Lange, M. Schunn and T. Asenov. This work was supported by European Research Council Starting Grant no. 756502 (M.J.) and European Research Council Consolidator Grant no. 101086580 (M.J.); and EMBO ALTF grant no. 1098-2017 (A.S.) and Human Frontiers Science Program grant no. LT000256/2018-L (A.S.). Open access funding provided by Institute of Science and Technology (IST Austria).","status":"public","language":[{"iso":"eng"}],"has_accepted_license":"1","year":"2025","publication_status":"published","isi":1,"title":"A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics","author":[{"first_name":"Tomas A","last_name":"Vega Zuniga","full_name":"Vega Zuniga, Tomas A","id":"2E7C4E78-F248-11E8-B48F-1D18A9856A87"},{"id":"3320A096-F248-11E8-B48F-1D18A9856A87","full_name":"Sumser, Anton L","first_name":"Anton L","orcid":"0000-0002-4792-1881","last_name":"Sumser"},{"full_name":"Symonova, Olga","id":"3C0C7BC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2012-9947","first_name":"Olga","last_name":"Symonova"},{"id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","full_name":"Koppensteiner, Peter","first_name":"Peter","orcid":"0000-0002-3509-1948","last_name":"Koppensteiner"},{"first_name":"Florian","last_name":"Schmidt","full_name":"Schmidt, Florian","id":"A2EF226A-AF19-11E9-924C-0525E6697425"},{"full_name":"Jösch, Maximilian A","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","last_name":"Jösch","first_name":"Maximilian A","orcid":"0000-0002-3937-1330"}],"date_published":"2025-03-01T00:00:00Z"},{"related_material":{"record":[{"id":"12802","status":"public","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","status":"public","id":"9429"}]},"page":"124","project":[{"name":"Critical windows and reversibility of ASD associated with mutations in chromatin remodelers","_id":"9B91375C-BA93-11EA-9121-9846C619BF3A","grant_number":"707964"},{"_id":"34ba8964-11ca-11ed-8bc3-e15864e7e9a6","grant_number":"101044865","name":"Toward an understanding of the brain interstitial system and the extracellular proteome in health and autism spectrum disorders"},{"name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232"}],"department":[{"_id":"GradSch"},{"_id":"GaNo"}],"type":"dissertation","date_created":"2025-04-14T06:59:06Z","doi":"10.15479/AT-ISTA-19557","date_updated":"2026-04-14T09:07:14Z","month":"04","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","corr_author":"1","oa_version":"Published Version","ddc":["570"],"file":[{"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","creator":"lschwarz","checksum":"50290a8604edb0a720387f01e9d59fe4","file_size":21783427,"file_name":"Schwarz_Thesis_2025_FINAL.docx","file_id":"19561","date_created":"2025-04-15T08:43:36Z","date_updated":"2025-04-15T08:43:36Z","relation":"source_file","access_level":"closed"},{"embargo_to":"open_access","access_level":"closed","content_type":"application/pdf","creator":"lschwarz","checksum":"ed028488180ac4901e018ef1c330cf01","file_name":"Schwarz_Thesis_2025_FINALpdfa.pdf","embargo":"2026-10-15","file_size":11432175,"file_id":"19562","date_updated":"2026-03-27T13:15:08Z","relation":"main_file","date_created":"2025-04-15T08:43:42Z"}],"file_date_updated":"2026-03-27T13:15:08Z","day":"14","OA_place":"publisher","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"supervisor":[{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"}],"fulldoi":"https://doi.org/10.15479/AT-ISTA-19557","citation":{"short":"L.A. Schwarz, Mapping Developmental Dynamics of Autism Spectrum Disorder Mouse Models at Single-Cell Resolution, Institute of Science and Technology Austria, 2025.","ista":"Schwarz LA. 2025. Mapping developmental dynamics of autism spectrum disorder mouse models at single-cell resolution. Institute of Science and Technology Austria.","chicago":"Schwarz, Lena A. “Mapping Developmental Dynamics of Autism Spectrum Disorder Mouse Models at Single-Cell Resolution.” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT-ISTA-19557\">https://doi.org/10.15479/AT-ISTA-19557</a>.","ama":"Schwarz LA. Mapping developmental dynamics of autism spectrum disorder mouse models at single-cell resolution. 2025. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-19557\">10.15479/AT-ISTA-19557</a>","ieee":"L. A. Schwarz, “Mapping developmental dynamics of autism spectrum disorder mouse models at single-cell resolution,” Institute of Science and Technology Austria, 2025.","apa":"Schwarz, L. A. (2025). <i>Mapping developmental dynamics of autism spectrum disorder mouse models at single-cell resolution</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-19557\">https://doi.org/10.15479/AT-ISTA-19557</a>","mla":"Schwarz, Lena A. <i>Mapping Developmental Dynamics of Autism Spectrum Disorder Mouse Models at Single-Cell Resolution</i>. Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-19557\">10.15479/AT-ISTA-19557</a>."},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"ScienComp"}],"publication_identifier":{"issn":["2663-337X"]},"date_published":"2025-04-14T00:00:00Z","title":"Mapping developmental dynamics of autism spectrum disorder mouse models at single-cell resolution","author":[{"last_name":"Schwarz","first_name":"Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","full_name":"Schwarz, Lena A"}],"publication_status":"published","year":"2025","has_accepted_license":"1","acknowledgement":"The work presented in this doctoral thesis was performed at the Institute of Science\r\nand Technology (ISTA) and financially supported by a European Research Council\r\n(ERC) Consolidator Grant (PR1028ERC02), by SFARI (PR1028SIM02) and by the\r\nAustrian Science Fund (FWF) to Gaia Novarino (PE1028W1232). I am very thankful\r\nto the Doctoral Program “Molecular Drug Targets” (MolTag) for offering me financial\r\nsupport to perform essential experiments during my PhD studies and to participate in\r\ninternational conferences and courses.","status":"public","language":[{"iso":"eng"}],"_id":"19557","article_processing_charge":"No","publisher":"Institute of Science and Technology Austria","degree_awarded":"PhD","alternative_title":["ISTA Thesis"]},{"OA_place":"publisher","oa":1,"scopus_import":"1","fulldoi":"https://doi.org/10.1167/iovs.66.3.49","citation":{"short":"F.E. Miteva, M.E. Maes, M. Alamalhoda, A. Firoozi, G. Colombo, S. Siegert, Investigative Ophthalmology &#38; Visual Science 66 (2025).","ista":"Miteva FE, Maes ME, Alamalhoda M, Firoozi A, Colombo G, Siegert S. 2025. Optic nerve crush does not induce retinal ganglion cell loss in the contralateral eye. Investigative Ophthalmology &#38; Visual Science. 66(3), 49.","chicago":"Miteva, Florianne E, Margaret E Maes, Mohammad Alamalhoda, Arsalan Firoozi, Gloria Colombo, and Sandra Siegert. “Optic Nerve Crush Does Not Induce Retinal Ganglion Cell Loss in the Contralateral Eye.” <i>Investigative Ophthalmology &#38; Visual Science</i>. Association for Research in Vision and Ophthalmology, 2025. <a href=\"https://doi.org/10.1167/iovs.66.3.49\">https://doi.org/10.1167/iovs.66.3.49</a>.","ama":"Miteva FE, Maes ME, Alamalhoda M, Firoozi A, Colombo G, Siegert S. Optic nerve crush does not induce retinal ganglion cell loss in the contralateral eye. <i>Investigative Ophthalmology &#38; Visual Science</i>. 2025;66(3). doi:<a href=\"https://doi.org/10.1167/iovs.66.3.49\">10.1167/iovs.66.3.49</a>","ieee":"F. E. Miteva, M. E. Maes, M. Alamalhoda, A. Firoozi, G. Colombo, and S. Siegert, “Optic nerve crush does not induce retinal ganglion cell loss in the contralateral eye,” <i>Investigative Ophthalmology &#38; Visual Science</i>, vol. 66, no. 3. Association for Research in Vision and Ophthalmology, 2025.","apa":"Miteva, F. E., Maes, M. E., Alamalhoda, M., Firoozi, A., Colombo, G., &#38; Siegert, S. (2025). Optic nerve crush does not induce retinal ganglion cell loss in the contralateral eye. <i>Investigative Ophthalmology &#38; Visual Science</i>. Association for Research in Vision and Ophthalmology. <a href=\"https://doi.org/10.1167/iovs.66.3.49\">https://doi.org/10.1167/iovs.66.3.49</a>","mla":"Miteva, Florianne E., et al. “Optic Nerve Crush Does Not Induce Retinal Ganglion Cell Loss in the Contralateral Eye.” <i>Investigative Ophthalmology &#38; Visual Science</i>, vol. 66, no. 3, 49, Association for Research in Vision and Ophthalmology, 2025, doi:<a href=\"https://doi.org/10.1167/iovs.66.3.49\">10.1167/iovs.66.3.49</a>."},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"publication_identifier":{"issn":["1552-5783"]},"DOAJ_listed":"1","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"file_date_updated":"2025-04-15T13:49:10Z","file":[{"creator":"dernst","content_type":"application/pdf","checksum":"e8722ce5792f6c08fe1e191f7de6f147","file_id":"19567","file_size":2721477,"file_name":"2025_IOVS_SchootUiterkamp.pdf","relation":"main_file","date_updated":"2025-04-15T13:49:10Z","date_created":"2025-04-15T13:49:10Z","access_level":"open_access","success":1}],"day":"01","APC_amount":"2236,02 EUR","OA_type":"gold","article_type":"original","doi":"10.1167/iovs.66.3.49","date_updated":"2026-05-20T06:37:12Z","date_created":"2025-04-15T13:40:35Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","corr_author":"1","oa_version":"Published Version","ddc":["570"],"month":"03","project":[{"_id":"7be82147-9f16-11ee-852c-f44682d73140","grant_number":"P37131","name":"Dissecting the morpho-functional relationship of microglia"},{"call_identifier":"FWF","_id":"3AC91DDA-15DF-11EA-824D-93A3E7B544D1","name":"FWF Open Access Fund"}],"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"20467"}],"link":[{"relation":"software","url":"https://github.com/siegert-lab/RGC-Quant"}]},"pmid":1,"type":"journal_article","department":[{"_id":"SaSi"}],"article_processing_charge":"Yes","publisher":"Association for Research in Vision and Ophthalmology","_id":"19566","quality_controlled":"1","external_id":{"pmid":["40126507"]},"issue":"3","article_number":"49","status":"public","intvolume":"        66","acknowledgement":"The authors thank the Scientific Service Units (SSU) of ISTA for the provided resources, specifically the Imaging and Optics Facility (IOF), the Lab Support Facility (LSF), and the Pre-Clinical Facility (PCF) team, specifically Sonja Haslinger, Claudia Gold, and Michael Schunn, for mouse colony management and support. We thank all members of the Siegert group for constant feedback on the project and the manuscript. \r\nSupported in whole or in part by the Austrian Science Fund (FWF) [10.55776/P37131]. For open access purposes, the author has applied a CC BY public copyright license to any author-accepted manuscript version arising from this submission. ","language":[{"iso":"eng"}],"abstract":[{"text":"Purpose: Optic nerve crush (ONC) is a model for studying optic nerve trauma. Unilateral ONC induces massive retinal ganglion cell (RGC) degeneration in the affected eye, leading to vision loss within a month. A common assumption has been that the non-injured contralateral eye is unaffected due to the minimal retino-retinal projections of the RGCs at the chiasm. Yet, recently, microglia, the brain-resident macrophages, have shown a responsive phenotype in the contralateral eye after ONC. Whether RGC loss accompanies this phenotype is still controversial.\r\n\r\nMethods: Using the available RGCode algorithm and developing our own RGC-Quant deep-learning-based tool, we quantify RGC's total number and density across the entire retina after ONC.\r\n\r\nResults: We confirm a short-term microglia response in the contralateral eye after ONC, but this did not affect the microglia number. Furthermore, we cannot confirm the previously reported RGC loss between naïve and contralateral retinas 5 weeks after ONC induction across the commonly used Cx3cr1creERT2 and C57BL6/J mouse models. Neither sex nor the direct comparison of the RGC markers Brn3a and RBPMS, with Brn3a co-labeling, on average, 89% of the RBPMS+-cells, explained this discrepancy, suggesting that the early microglia-responsive phenotype does not have immediate consequences on the RGC number.\r\n\r\nConclusions: Our results corroborate that unilateral optic nerve injury elicits a microglial response in the uninjured contralateral eye but without RGC loss. Therefore, the contralateral eye should be treated separately and not as an ONC control.","lang":"eng"}],"publication":"Investigative Ophthalmology & Visual Science","volume":66,"year":"2025","has_accepted_license":"1","publication_status":"published","date_published":"2025-03-01T00:00:00Z","title":"Optic nerve crush does not induce retinal ganglion cell loss in the contralateral eye","author":[{"id":"3526230C-F248-11E8-B48F-1D18A9856A87","full_name":"Schoot Uiterkamp, Florianne E","first_name":"Florianne E","last_name":"Schoot Uiterkamp"},{"id":"3838F452-F248-11E8-B48F-1D18A9856A87","full_name":"Maes, Margaret E","last_name":"Maes","orcid":"0000-0001-9642-1085","first_name":"Margaret E"},{"first_name":"Mohammad","last_name":"Alamalhoda","full_name":"Alamalhoda, Mohammad"},{"full_name":"Firoozi, Arsalan","last_name":"Firoozi","first_name":"Arsalan"},{"last_name":"Colombo","first_name":"Gloria","orcid":"0000-0001-9434-8902","full_name":"Colombo, Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Sandra","orcid":"0000-0001-8635-0877","last_name":"Siegert","full_name":"Siegert, Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"}]},{"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"citation":{"short":"M. Tavakoli, J. Lyudchik, M. Januszewski, V. Vistunou, N. Agudelo Duenas, J. Vorlaufer, C.M. Sommer, C. Kreuzinger, B. Oliveira, A. Cenameri, G. Novarino, V. Jain, J.G. Danzl, Nature 642 (2025) 398–410.","ista":"Tavakoli M, Lyudchik J, Januszewski M, Vistunou V, Agudelo Duenas N, Vorlaufer J, Sommer CM, Kreuzinger C, Oliveira B, Cenameri A, Novarino G, Jain V, Danzl JG. 2025. Light-microscopy-based connectomic reconstruction of mammalian brain tissue. Nature. 642, 398–410.","chicago":"Tavakoli, Mojtaba, Julia Lyudchik, Michał Januszewski, Vitali Vistunou, Nathalie Agudelo Duenas, Jakob Vorlaufer, Christoph M Sommer, et al. “Light-Microscopy-Based Connectomic Reconstruction of Mammalian Brain Tissue.” <i>Nature</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1038/s41586-025-08985-1\">https://doi.org/10.1038/s41586-025-08985-1</a>.","ama":"Tavakoli M, Lyudchik J, Januszewski M, et al. Light-microscopy-based connectomic reconstruction of mammalian brain tissue. <i>Nature</i>. 2025;642:398-410. doi:<a href=\"https://doi.org/10.1038/s41586-025-08985-1\">10.1038/s41586-025-08985-1</a>","apa":"Tavakoli, M., Lyudchik, J., Januszewski, M., Vistunou, V., Agudelo Duenas, N., Vorlaufer, J., … Danzl, J. G. (2025). Light-microscopy-based connectomic reconstruction of mammalian brain tissue. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-025-08985-1\">https://doi.org/10.1038/s41586-025-08985-1</a>","ieee":"M. Tavakoli <i>et al.</i>, “Light-microscopy-based connectomic reconstruction of mammalian brain tissue,” <i>Nature</i>, vol. 642. Springer Nature, pp. 398–410, 2025.","mla":"Tavakoli, Mojtaba, et al. “Light-Microscopy-Based Connectomic Reconstruction of Mammalian Brain Tissue.” <i>Nature</i>, vol. 642, Springer Nature, 2025, pp. 398–410, doi:<a href=\"https://doi.org/10.1038/s41586-025-08985-1\">10.1038/s41586-025-08985-1</a>."},"fulldoi":"https://doi.org/10.1038/s41586-025-08985-1","publication_identifier":{"issn":["0028-0836"],"eissn":["1476-4687"]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"ScienComp"},{"_id":"PreCl"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"scopus_import":"1","oa":1,"OA_place":"publisher","article_type":"original","PlanS_conform":"1","OA_type":"hybrid","day":"12","file":[{"access_level":"open_access","success":1,"creator":"dernst","content_type":"application/pdf","checksum":"ebc99d7108e728f46db0a009292675ef","file_id":"19959","file_size":133201290,"file_name":"2025_Nature_Tavakoli.pdf","relation":"main_file","date_created":"2025-07-03T06:55:20Z","date_updated":"2025-07-03T06:55:20Z"}],"file_date_updated":"2025-07-03T06:55:20Z","month":"06","corr_author":"1","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","ddc":["570"],"oa_version":"Published Version","date_updated":"2026-04-28T13:33:34Z","date_created":"2025-05-18T22:02:51Z","doi":"10.1038/s41586-025-08985-1","department":[{"_id":"JoDa"},{"_id":"GradSch"},{"_id":"Bio"},{"_id":"GaNo"}],"ec_funded":1,"type":"journal_article","pmid":1,"related_material":{"record":[{"id":"18677","status":"public","relation":"earlier_version"},{"status":"public","relation":"research_data","id":"18697"}],"link":[{"relation":"press_release","url":"https://ista.ac.at/en/news/piecing-together-the-brain-puzzle/","description":"News on ISTA website"}]},"page":"398-410","project":[{"grant_number":"26137","_id":"6285a163-2b32-11ec-9570-8e204ca2dba5","name":"Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy"},{"grant_number":"665385","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program"},{"name":"Toward an understanding of the brain interstitial system and the extracellular proteome in health and autism spectrum disorders","_id":"34ba8964-11ca-11ed-8bc3-e15864e7e9a6","grant_number":"101044865"},{"name":"Molecular Drug Targets","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"W1232-B24"}],"external_id":{"isi":["001483477000001"],"pmid":["40335689"]},"quality_controlled":"1","_id":"19704","publisher":"Springer Nature","article_processing_charge":"Yes (via OA deal)","publication":"Nature","volume":642,"status":"public","intvolume":"       642","language":[{"iso":"eng"}],"acknowledgement":"We thank S. Dorkenwald and P. Li for critical reading of the manuscript, S. Loomba for discussions and E. Miguel for support with data handling. We acknowledge support from ISTA’s scientific service units: Imaging and Optics, Lab Support, Scientific Computing, the preclinical facility, the Miba Machine Shop and the library. We acknowledge funding from the following sources: Austrian Science Fund (FWF) grant DK W1232 (J.G.D. and M.R.T.); Austrian Academy of Sciences DOC fellowship 26137 (M.R.T.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.); the European Union’s Horizon 2020 research and innovation programme and Marie Skłodowska-Curie Actions Fellowship 665385 (J.L.); and the European Union’s Horizon 2020 research and innovation programme and European Research Council (ERC) grant 101044865 ‘SecretAutism’ (G.N.).Open access funding provided by Institute of Science and Technology (IST Austria).","abstract":[{"lang":"eng","text":"The information-processing capability of the brain’s cellular network depends on the physical wiring pattern between neurons and their molecular and functional characteristics. Mapping neurons and resolving their individual synaptic connections can be achieved by volumetric imaging at nanoscale resolution1,2 with dense cellular labelling. Light microscopy is uniquely positioned to visualize specific molecules, but dense, synapse-level circuit reconstruction by light microscopy has been out of reach, owing to limitations in resolution, contrast and volumetric imaging capability. Here we describe light-microscopy-based connectomics (LICONN). We integrated specifically engineered hydrogel embedding and expansion with comprehensive deep-learning-based segmentation and analysis of connectivity, thereby directly incorporating molecular information into synapse-level reconstructions of brain tissue. LICONN will allow synapse-level phenotyping of brain tissue in biological experiments in a readily adoptable manner."}],"publication_status":"published","year":"2025","has_accepted_license":"1","isi":1,"author":[{"last_name":"Tavakoli","first_name":"Mojtaba","orcid":"0000-0002-7667-6854","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","full_name":"Tavakoli, Mojtaba"},{"last_name":"Lyudchik","first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia"},{"full_name":"Januszewski, Michał","last_name":"Januszewski","first_name":"Michał"},{"full_name":"Vistunou, Vitali","id":"7e146587-8972-11ed-ae7b-d7a32ea86a81","first_name":"Vitali","last_name":"Vistunou"},{"last_name":"Agudelo Duenas","first_name":"Nathalie","full_name":"Agudelo Duenas, Nathalie","id":"40E7F008-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Vorlaufer","orcid":"0009-0000-7590-3501","first_name":"Jakob","id":"937696FA-C996-11E9-8C7C-CF13E6697425","full_name":"Vorlaufer, Jakob"},{"full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","orcid":"0000-0003-1216-9105","first_name":"Christoph M"},{"last_name":"Kreuzinger","first_name":"Caroline","full_name":"Kreuzinger, Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87"},{"id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","full_name":"Oliveira, Bárbara","last_name":"Oliveira","first_name":"Bárbara"},{"last_name":"Cenameri","first_name":"Alban","full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino"},{"full_name":"Jain, Viren","first_name":"Viren","last_name":"Jain"},{"first_name":"Johann G","orcid":"0000-0001-8559-3973","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G"}],"title":"Light-microscopy-based connectomic reconstruction of mammalian brain tissue","date_published":"2025-06-12T00:00:00Z"},{"project":[{"grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"name":"Synaptic computations of the hippocampal CA3 circuitry","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","call_identifier":"H2020","grant_number":"101026635"},{"name":"Mechanisms of GABA release in hippocampal circuits","grant_number":"P36232","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5"},{"name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425"}],"type":"journal_article","department":[{"_id":"PeJo"}],"ec_funded":1,"doi":"10.1016/j.celrep.2025.116080","date_created":"2025-08-03T22:01:30Z","date_updated":"2025-09-30T14:12:02Z","corr_author":"1","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","oa_version":"Published Version","ddc":["570"],"month":"08","file_date_updated":"2025-08-04T06:53:07Z","file":[{"content_type":"application/pdf","creator":"dernst","checksum":"556ff9760661ecd23949d75031043b1f","file_size":27695214,"file_name":"2025_CellReports_Watson.pdf","file_id":"20106","relation":"main_file","date_created":"2025-08-04T06:53:07Z","date_updated":"2025-08-04T06:53:07Z","access_level":"open_access","success":1}],"day":"01","PlanS_conform":"1","article_type":"original","OA_type":"gold","OA_place":"publisher","scopus_import":"1","oa":1,"citation":{"ama":"Watson J, Vargas Barroso VM, Jonas PM. Cell-specific wiring routes information flow through hippocampal CA3. <i>Cell Reports</i>. 2025;44(8). doi:<a href=\"https://doi.org/10.1016/j.celrep.2025.116080\">10.1016/j.celrep.2025.116080</a>","mla":"Watson, Jake, et al. “Cell-Specific Wiring Routes Information Flow through Hippocampal CA3.” <i>Cell Reports</i>, vol. 44, no. 8, 116080, Elsevier, 2025, doi:<a href=\"https://doi.org/10.1016/j.celrep.2025.116080\">10.1016/j.celrep.2025.116080</a>.","apa":"Watson, J., Vargas Barroso, V. M., &#38; Jonas, P. M. (2025). Cell-specific wiring routes information flow through hippocampal CA3. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2025.116080\">https://doi.org/10.1016/j.celrep.2025.116080</a>","ieee":"J. Watson, V. M. Vargas Barroso, and P. M. Jonas, “Cell-specific wiring routes information flow through hippocampal CA3,” <i>Cell Reports</i>, vol. 44, no. 8. Elsevier, 2025.","ista":"Watson J, Vargas Barroso VM, Jonas PM. 2025. Cell-specific wiring routes information flow through hippocampal CA3. Cell Reports. 44(8), 116080.","chicago":"Watson, Jake, Victor M Vargas Barroso, and Peter M Jonas. “Cell-Specific Wiring Routes Information Flow through Hippocampal CA3.” <i>Cell Reports</i>. Elsevier, 2025. <a href=\"https://doi.org/10.1016/j.celrep.2025.116080\">https://doi.org/10.1016/j.celrep.2025.116080</a>.","short":"J. Watson, V.M. Vargas Barroso, P.M. Jonas, Cell Reports 44 (2025)."},"fulldoi":"https://doi.org/10.1016/j.celrep.2025.116080","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"publication_identifier":{"eissn":["2211-1247"],"issn":["2639-1856"]},"DOAJ_listed":"1","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"date_published":"2025-08-01T00:00:00Z","author":[{"full_name":"Watson, Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","last_name":"Watson","orcid":"0000-0002-8698-3823","first_name":"Jake"},{"full_name":"Vargas Barroso, Victor M","id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87","first_name":"Victor M","last_name":"Vargas Barroso"},{"orcid":"0000-0001-5001-4804","first_name":"Peter M","last_name":"Jonas","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"title":"Cell-specific wiring routes information flow through hippocampal CA3","isi":1,"year":"2025","has_accepted_license":"1","publication_status":"published","status":"public","intvolume":"        44","language":[{"iso":"eng"}],"acknowledgement":"We thank Andrea Navas-Olive and Rebecca J. Morse-Mora for critically reading an earlier version of the manuscript. We also thank Florian Marr and Christina Altmutter for excellent technical assistance, Alois Schlögl for programming and data-handling assistance, Todor Asenov for technical support, and Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA. We are particularly grateful for assistance from the Imaging and Optics Facility, Preclinical Facility, Lab Support Facility, and Miba Machine Shop. The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 692692 to P.J., Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 to J.F.W., and an ISTplus Fellowship through Marie Skłodowska-Curie grant agreement no. 754411 to V.V.-B.), the Austrian Science Fund (P 36232-B, PAT 4178023, and Cluster of Excellence 10.55776/COE16 to P.J.), and a CONACyT fellowship (289638 to V.V.-B.) and was supported by a non-stipendiary EMBO fellowship (ALTF 756–2020 to J.F.W.).","abstract":[{"lang":"eng","text":"The hippocampus, critical for learning and memory, is dogmatically described as a trisynaptic circuit where dentate gyrus granule cells (GCs), CA3 pyramidal neurons (PNs), and CA1 PNs are serially connected. However, CA3 also forms an autoassociative network, and its PNs have diverse morphologies, intrinsic properties, and GC input levels. How PN subtypes compose this recurrent network is unknown. To determine the synaptic arrangement of identified CA3 PNs, we combine multicellular patch-clamp recording and post hoc morphological analysis in mouse hippocampal slices. PNs can be divided into distinct “superficial” and “deep” subclasses, the latter including previously reported “athorny” cells. Subclasses have distinct input-output transformations and asymmetric connectivity, which is more abundant from superficial to deep PNs, splitting CA3 locally into two parallel recurrent networks. Coincident spontaneous inhibition occurs frequently within but not between subclasses, implying subclass-specific inhibitory innervation. Our results suggest two separately controlled sublayers for parallel information processing in hippocampal CA3."}],"publication":"Cell Reports","volume":44,"publisher":"Elsevier","article_processing_charge":"Yes","_id":"20099","quality_controlled":"1","external_id":{"isi":["001544472300002"]},"issue":"8","article_number":"116080"},{"acknowledgement":"We thank all members of the M.S. and E.H. groups for stimulating discussions.We thank the Imaging and Optics facility, the Pre-clinical and Lab Support facility of the Institute of Science and Technology Austria for their excellent support and provided resources for the experimental research. In particular, we thank Jack Merrin from the Nanofabrication facility who generated the microfabricated channel used in this study. This work received funding fromt he European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 851288 to E.H.). M.C.U.is funded by a University of Sheffield Strategic Research Fellowship in the Physics of Life and Quantitative Biology.","language":[{"iso":"eng"}],"status":"public","intvolume":"       122","abstract":[{"lang":"eng","text":"Cell and tissue movement in development, cancer invasion, and immune response relies on chemical or mechanical guidance cues. In many systems, this behavior is locally directed by self-generated signaling gradients rather than long-range, prepatterned cues. However, how heterogeneous mixtures of cells interact nonreciprocally and navigate through self-generated gradients remains largely unexplored. Here, we introduce a theoretical framework for the self-organized chemotaxis of heterogeneous cell populations. We find that the relative chemotactic sensitivities of different cell populations control their long-time coupling and comigration dynamics, with boundary conditions such as external cell and attractant reservoirs substantially influencing the migration patterns. Our model predicts an optimal parameter regime that enables robust and colocalized migration. We test our theoretical predictions with in vitro experiments demonstrating the comigration of distinct immune cell populations, and quantitatively reproduce observed migration patterns under wild-type and perturbed conditions. Interestingly, immune cell comigration occurs close to the predicted optimal regime. Finally, we incorporate mechanical interactions into our framework, revealing a nontrivial interplay between chemotactic and mechanical nonreciprocity in driving collective migration. Together, our findings suggest that self-generated chemotaxis is a robust strategy for the navigation of mixed cell populations."}],"publication":"Proceedings of the National Academy of Sciences","volume":122,"_id":"20289","publisher":"National Academy of Sciences","article_processing_charge":"Yes (in subscription journal)","external_id":{"isi":["001562181600001"],"pmid":["40838890"]},"article_number":"e2504064122","issue":"34","quality_controlled":"1","date_published":"2025-08-26T00:00:00Z","title":"Self-generated chemotaxis of mixed cell populations","author":[{"id":"50B2A802-6007-11E9-A42B-EB23E6697425","full_name":"Ucar, Mehmet C","last_name":"Ucar","orcid":"0000-0003-0506-4217","first_name":"Mehmet C"},{"first_name":"Alsberga","orcid":"0009-0003-0415-7603","last_name":"Zane","full_name":"Zane, Alsberga","id":"60f7509a-f652-11ea-9d86-b963d6490d7c"},{"last_name":"Alanko","orcid":"0000-0002-7698-3061","first_name":"Jonna H","id":"2CC12E8C-F248-11E8-B48F-1D18A9856A87","full_name":"Alanko, Jonna H"},{"first_name":"Michael K","orcid":"0000-0002-6620-9179","last_name":"Sixt","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Hannezo","first_name":"Edouard B","orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"}],"isi":1,"publication_status":"published","year":"2025","has_accepted_license":"1","file":[{"file_id":"20307","file_name":"2025_PNAS_Ucar.pdf","file_size":16069140,"date_updated":"2025-09-08T07:23:29Z","relation":"main_file","date_created":"2025-09-08T07:23:29Z","creator":"dernst","content_type":"application/pdf","checksum":"b36abd92673b6d76376fc9434bad52cc","success":1,"access_level":"open_access"}],"file_date_updated":"2025-09-08T07:23:29Z","article_type":"original","PlanS_conform":"1","APC_amount":"5766,07 EUR","OA_type":"hybrid","day":"26","scopus_import":"1","oa":1,"OA_place":"publisher","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"fulldoi":"https://doi.org/10.1073/pnas.2504064122","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"NanoFab"}],"publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"citation":{"ama":"Ucar MC, Zane A, Alanko JH, Sixt MK, Hannezo EB. Self-generated chemotaxis of mixed cell populations. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(34). doi:<a href=\"https://doi.org/10.1073/pnas.2504064122\">10.1073/pnas.2504064122</a>","mla":"Ucar, Mehmet C., et al. “Self-Generated Chemotaxis of Mixed Cell Populations.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 34, e2504064122, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2504064122\">10.1073/pnas.2504064122</a>.","ieee":"M. C. Ucar, A. Zane, J. H. Alanko, M. K. Sixt, and E. B. Hannezo, “Self-generated chemotaxis of mixed cell populations,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 34. National Academy of Sciences, 2025.","apa":"Ucar, M. C., Zane, A., Alanko, J. H., Sixt, M. K., &#38; Hannezo, E. B. (2025). Self-generated chemotaxis of mixed cell populations. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2504064122\">https://doi.org/10.1073/pnas.2504064122</a>","short":"M.C. Ucar, A. Zane, J.H. Alanko, M.K. Sixt, E.B. Hannezo, Proceedings of the National Academy of Sciences 122 (2025).","ista":"Ucar MC, Zane A, Alanko JH, Sixt MK, Hannezo EB. 2025. Self-generated chemotaxis of mixed cell populations. Proceedings of the National Academy of Sciences. 122(34), e2504064122.","chicago":"Ucar, Mehmet C, Alsberga Zane, Jonna H Alanko, Michael K Sixt, and Edouard B Hannezo. “Self-Generated Chemotaxis of Mixed Cell Populations.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2504064122\">https://doi.org/10.1073/pnas.2504064122</a>."},"related_material":{"link":[{"url":"https://github.com/mehmetcanucar/Self-generated-chemotaxis","relation":"software"}]},"pmid":1,"project":[{"grant_number":"851288","call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis"}],"department":[{"_id":"EdHa"},{"_id":"MiSi"}],"ec_funded":1,"type":"journal_article","date_updated":"2026-05-20T08:59:54Z","date_created":"2025-09-07T22:01:32Z","doi":"10.1073/pnas.2504064122","month":"08","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","corr_author":"1","ddc":["570"],"oa_version":"Published Version"}]