[{"day":"16","page":"601–605","ddc":["540"],"type":"journal_article","scopus_import":"1","isi":1,"language":[{"iso":"eng"}],"date_published":"2025-10-16T00:00:00Z","issue":"8085","publisher":"Springer Nature","publication_status":"published","project":[{"_id":"8df062be-16d5-11f0-9cad-f559b6612c7e","name":"Singlet oxygen in non-aqueous oxygen redox chemistry","grant_number":"P37169"},{"grant_number":"CZI01","name":"Tools for automation and feedback microscopy","_id":"c08e9ad1-5a5b-11eb-8a69-9d1cf3b07473"}],"acknowledgement":"S.A.F. thanks the Institute of Science and Technology Austria (ISTA) for the support. The Scientific Service Units of ISTA supported this research through resources provided by the Imaging and Optics Facility, the Lab Support Facility, the Miba Machine Shop and Scientific Computing. This research was partly funded by the Austrian Science Fund (FWF) (10.55776/P37169 and 10.55776/COE5). For open access purposes, the author has applied for a CC BY public copyright licence to any author-accepted manuscript version arising from this submission. R.H. acknowledges funding through CZI grant DAF2020-225401 (10.37921/120055ratwvi) from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation (10.13039/100014989). H.T.K.N. acknowledges funding by the European Commission Erasmus Mundus Joint Masters programme. We thank M. Sixt and M. Chinon for the discussions about O-redox in life and R. Jethwa for proofreading. Open access funding was provided by ISTA.","status":"public","date_created":"2024-08-29T10:40:23Z","OA_place":"publisher","author":[{"last_name":"Mondal","id":"d25d21ef-dc8d-11ea-abe3-ec4576307f48","full_name":"Mondal, Soumyadip","first_name":"Soumyadip"},{"last_name":"Nguyen","first_name":"Huyen T.K.","full_name":"Nguyen, Huyen T.K."},{"last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","full_name":"Hauschild, Robert","first_name":"Robert","orcid":"0000-0001-9843-3522"},{"orcid":"0000-0003-2902-5319","first_name":"Stefan Alexander","full_name":"Freunberger, Stefan Alexander","id":"A8CA28E6-CE23-11E9-AD2D-EC27E6697425","last_name":"Freunberger"}],"year":"2025","article_processing_charge":"Yes (via OA deal)","title":"Marcus kinetics control singlet and triplet oxygen evolving from superoxide","oa_version":"Published Version","pmid":1,"article_type":"original","month":"10","file":[{"file_id":"20500","content_type":"application/pdf","date_created":"2025-10-20T10:26:13Z","file_size":3809247,"success":1,"creator":"dernst","checksum":"b507ddd23df0388aa65d04dc9b00fe3d","file_name":"2025_Nature_Mondal.pdf","relation":"main_file","date_updated":"2025-10-20T10:26:13Z","access_level":"open_access"}],"_id":"17468","intvolume":"       646","abstract":[{"lang":"eng","text":"Oxygen redox chemistry is central to life1 and many human-made technologies, such as in energy storage2,3,4. The large energy gain from oxygen redox reactions is often connected with the occurrence of harmful reactive oxygen species3,5,6. Key species are superoxide and the highly reactive singlet oxygen3,4,5,6,7, which may evolve from superoxide. However, the factors determining the formation of singlet oxygen, rather than the relatively unreactive triplet oxygen, are unknown. Here we report that the release of triplet or singlet oxygen is governed by individual Marcus normal and inverted region behaviour. We found that as the driving force for the reaction increases, the initially dominant evolution of triplet oxygen slows down, and singlet oxygen evolution becomes predominant with higher maximum kinetics. This behaviour also applies to the widely observed superoxide disproportionation, in which one superoxide is oxidized by another, in both non-aqueous and aqueous systems, with Lewis and Brønsted acidity controlling the driving forces. Singlet oxygen yields governed by these conditions are relevant, for example, in batteries or cellular organelles in which superoxide forms. Our findings suggest ways to understand and control spin states and kinetics in oxygen redox chemistry, with implications for fields, including life sciences, pure chemistry and energy storage."}],"publication":"Nature","department":[{"_id":"StFr"},{"_id":"Bio"}],"volume":646,"related_material":{"link":[{"url":"https://ista.ac.at/en/news/taming-the-bad-oxygen/","relation":"press_release","description":"News on ISTA website"}]},"date_updated":"2026-04-28T13:18:33Z","external_id":{"pmid":["41044415"],"isi":["001586378900001"]},"corr_author":"1","oa":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"has_accepted_license":"1","doi":"10.1038/s41586-025-09587-7","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"ScienComp"}],"publication_identifier":{"issn":["0028-0836"],"eissn":["1476-4687"]},"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","citation":{"ieee":"S. Mondal, H. T. K. Nguyen, R. Hauschild, and S. A. Freunberger, “Marcus kinetics control singlet and triplet oxygen evolving from superoxide,” <i>Nature</i>, vol. 646, no. 8085. Springer Nature, pp. 601–605, 2025.","chicago":"Mondal, Soumyadip, Huyen T.K. Nguyen, Robert Hauschild, and Stefan Alexander Freunberger. “Marcus Kinetics Control Singlet and Triplet Oxygen Evolving from Superoxide.” <i>Nature</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1038/s41586-025-09587-7\">https://doi.org/10.1038/s41586-025-09587-7</a>.","apa":"Mondal, S., Nguyen, H. T. K., Hauschild, R., &#38; Freunberger, S. A. (2025). Marcus kinetics control singlet and triplet oxygen evolving from superoxide. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-025-09587-7\">https://doi.org/10.1038/s41586-025-09587-7</a>","mla":"Mondal, Soumyadip, et al. “Marcus Kinetics Control Singlet and Triplet Oxygen Evolving from Superoxide.” <i>Nature</i>, vol. 646, no. 8085, Springer Nature, 2025, pp. 601–605, doi:<a href=\"https://doi.org/10.1038/s41586-025-09587-7\">10.1038/s41586-025-09587-7</a>.","ista":"Mondal S, Nguyen HTK, Hauschild R, Freunberger SA. 2025. Marcus kinetics control singlet and triplet oxygen evolving from superoxide. Nature. 646(8085), 601–605.","ama":"Mondal S, Nguyen HTK, Hauschild R, Freunberger SA. Marcus kinetics control singlet and triplet oxygen evolving from superoxide. <i>Nature</i>. 2025;646(8085):601–605. doi:<a href=\"https://doi.org/10.1038/s41586-025-09587-7\">10.1038/s41586-025-09587-7</a>","short":"S. Mondal, H.T.K. Nguyen, R. Hauschild, S.A. Freunberger, Nature 646 (2025) 601–605."},"file_date_updated":"2025-10-20T10:26:13Z","quality_controlled":"1","OA_type":"hybrid","PlanS_conform":"1"},{"scopus_import":"1","isi":1,"language":[{"iso":"eng"}],"page":"1258–1266","ddc":["570"],"day":"01","type":"journal_article","date_published":"2025-08-01T00:00:00Z","project":[{"name":"Pushing from within: Control of cell shape, integrity and motility by cytoskeletal pushing forces","grant_number":"101071793","_id":"bd91e723-d553-11ed-ba76-fe7eeb2185fd"},{"name":"Bioelectric patrolling: the role of the local membrane potential in immune cell migration","grant_number":"944-2020","_id":"c092d618-5a5b-11eb-8a69-f92e1e843fc8"}],"acknowledgement":"This research was supported by the Scientific Service Units of ISTA through resources provided by the Imaging and Optics, Preclinical and Lab Support Facilities. In particular, we thank M. A. Symth and F. G. G. Leite, from the Virus Service Team, who helped generating the lentiviral particles used in this study. We thank all the members of the Sixt group for valuable discussions and feedback, in particular, I. Mayer, for helping with T cell isolation and Z. (P.) Li for providing the Actin–GFP DC line. We are also thankful to J. Mandl and C. Shen for their feedback during the writing of this manuscript. This work was supported by a European Research Council grant ERC-SyG 101071793 to M.S. M.J.A. was supported by an HFSP Postdoctoral Fellowship LTF 177 2021 and A.J.G. by a Lise Meitner Fellowship of the FWF (Austrian Science Fund). Y.F. was supported by the AMED-CREST (JP19gm1310005), the Medical Research Center Initiative for High Depth Omics and CURE:JPMXP1323015486 for MIB, Kyushu University. Open access funding provided by Institute of Science and Technology (IST Austria).","status":"public","date_created":"2025-07-27T22:01:26Z","publisher":"Springer Nature","publication_status":"published","title":"Migrating immune cells globally coordinate protrusive forces","article_processing_charge":"Yes (via OA deal)","oa_version":"Published Version","pmid":1,"OA_place":"publisher","author":[{"id":"26E95904-5160-11E9-9C0B-C5B0DC97E90F","last_name":"Dos Reis Rodrigues","first_name":"Patricia","full_name":"Dos Reis Rodrigues, Patricia","orcid":"0000-0003-1681-508X"},{"id":"DC4BA84C-56E6-11EA-AD5D-348C3DDC885E","last_name":"Avellaneda Sarrió","first_name":"Mario","full_name":"Avellaneda Sarrió, Mario","orcid":"0000-0001-6406-524X"},{"orcid":"0000-0002-8518-5926","last_name":"Canigova","id":"3795523E-F248-11E8-B48F-1D18A9856A87","full_name":"Canigova, Nikola","first_name":"Nikola"},{"orcid":"0000-0001-6120-3723","first_name":"Florian R","full_name":"Gärtner, Florian R","id":"397A88EE-F248-11E8-B48F-1D18A9856A87","last_name":"Gärtner"},{"orcid":"0000-0001-7829-3518","first_name":"Kari","full_name":"Vaahtomeri, Kari","last_name":"Vaahtomeri","id":"368EE576-F248-11E8-B48F-1D18A9856A87"},{"id":"3BE60946-F248-11E8-B48F-1D18A9856A87","last_name":"Riedl","first_name":"Michael","full_name":"Riedl, Michael","orcid":"0000-0003-4844-6311"},{"id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","last_name":"De Vries","first_name":"Ingrid","full_name":"De Vries, Ingrid"},{"orcid":"0000-0001-5145-4609","id":"4515C308-F248-11E8-B48F-1D18A9856A87","last_name":"Merrin","first_name":"Jack","full_name":"Merrin, Jack"},{"orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert","first_name":"Robert","last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Yoshinori","full_name":"Fukui, Yoshinori","last_name":"Fukui"},{"id":"40F05888-F248-11E8-B48F-1D18A9856A87","last_name":"Juanes Garcia","full_name":"Juanes Garcia, Alba","first_name":"Alba","orcid":"0000-0002-1009-9652"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","full_name":"Sixt, Michael K","first_name":"Michael K","orcid":"0000-0002-6620-9179"}],"year":"2025","publication":"Nature Immunology","department":[{"_id":"MiSi"},{"_id":"NanoFab"},{"_id":"Bio"}],"volume":26,"month":"08","article_type":"letter_note","file":[{"checksum":"0c725123dca7797c682609bff2c4c5ac","creator":"dernst","content_type":"application/pdf","success":1,"file_size":13514646,"date_created":"2025-07-31T08:00:33Z","file_id":"20096","date_updated":"2025-07-31T08:00:33Z","access_level":"open_access","relation":"main_file","file_name":"2025_NatureImmunology_ReisRodrigues.pdf"}],"abstract":[{"lang":"eng","text":"Efficient immune responses rely on the capacity of leukocytes to traverse diverse and complex tissues. To meet such changing environmental conditions, leukocytes usually adopt an ameboid configuration, using their forward-positioned nucleus as a probe to identify and follow the path of least resistance among pre-existing pores. We show that, in dense environments where even the largest pores preclude free passage, leukocytes position their nucleus behind the centrosome and organelles. The local compression imposed on the cell body by its surroundings triggers assembly of a central F-actin pool, located between cell front and nucleus. Central actin pushes outward to transiently dilate a path for organelles and nucleus. Pools of central and front actin are tightly coupled and experimental depletion of the central pool enhances actin accumulation and protrusion formation at the cell front. Although this shifted balance speeds up cells in permissive environments, migration in restrictive environments is impaired, as the unleashed leading edge dissociates from the trapped cell body. Our findings establish an actin regulatory loop that balances path dilation with advancement of the leading edge to maintain cellular coherence."}],"_id":"20082","intvolume":"        26","corr_author":"1","oa":1,"related_material":{"record":[{"relation":"dissertation_contains","id":"20149","status":"public"}],"link":[{"description":"News on ISTA website","url":"https://ista.ac.at/en/news/bench-pressing-cells/","relation":"press_release"}]},"date_updated":"2026-04-28T13:26:50Z","external_id":{"isi":["001529134300001"],"pmid":["40664976"]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"publication_identifier":{"issn":["1529-2908"],"eissn":["1529-2916"]},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"has_accepted_license":"1","doi":"10.1038/s41590-025-02211-w","quality_controlled":"1","OA_type":"hybrid","PlanS_conform":"1","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","file_date_updated":"2025-07-31T08:00:33Z","citation":{"ista":"Dos Reis Rodrigues P, Avellaneda Sarrió M, Canigova N, Gärtner FR, Vaahtomeri K, Riedl M, de Vries I, Merrin J, Hauschild R, Fukui Y, Juanes Garcia A, Sixt MK. 2025. Migrating immune cells globally coordinate protrusive forces. Nature Immunology. 26, 1258–1266.","apa":"Dos Reis Rodrigues, P., Avellaneda Sarrió, M., Canigova, N., Gärtner, F. R., Vaahtomeri, K., Riedl, M., … Sixt, M. K. (2025). Migrating immune cells globally coordinate protrusive forces. <i>Nature Immunology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41590-025-02211-w\">https://doi.org/10.1038/s41590-025-02211-w</a>","mla":"Dos Reis Rodrigues, Patricia, et al. “Migrating Immune Cells Globally Coordinate Protrusive Forces.” <i>Nature Immunology</i>, vol. 26, Springer Nature, 2025, pp. 1258–1266, doi:<a href=\"https://doi.org/10.1038/s41590-025-02211-w\">10.1038/s41590-025-02211-w</a>.","chicago":"Dos Reis Rodrigues, Patricia, Mario Avellaneda Sarrió, Nikola Canigova, Florian R Gärtner, Kari Vaahtomeri, Michael Riedl, Ingrid de Vries, et al. “Migrating Immune Cells Globally Coordinate Protrusive Forces.” <i>Nature Immunology</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1038/s41590-025-02211-w\">https://doi.org/10.1038/s41590-025-02211-w</a>.","ieee":"P. Dos Reis Rodrigues <i>et al.</i>, “Migrating immune cells globally coordinate protrusive forces,” <i>Nature Immunology</i>, vol. 26. Springer Nature, pp. 1258–1266, 2025.","short":"P. Dos Reis Rodrigues, M. Avellaneda Sarrió, N. Canigova, F.R. Gärtner, K. Vaahtomeri, M. Riedl, I. de Vries, J. Merrin, R. Hauschild, Y. Fukui, A. Juanes Garcia, M.K. Sixt, Nature Immunology 26 (2025) 1258–1266.","ama":"Dos Reis Rodrigues P, Avellaneda Sarrió M, Canigova N, et al. Migrating immune cells globally coordinate protrusive forces. <i>Nature Immunology</i>. 2025;26:1258–1266. doi:<a href=\"https://doi.org/10.1038/s41590-025-02211-w\">10.1038/s41590-025-02211-w</a>"}},{"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","degree_awarded":"PhD","citation":{"ieee":"P. Dos Reis Rodrigues, “Coordination of protrusive forces in immune cell migration ,” Institute of Science and Technology Austria, 2025.","chicago":"Dos Reis Rodrigues, Patricia. “Coordination of Protrusive Forces in Immune Cell Migration .” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT-ISTA-20149\">https://doi.org/10.15479/AT-ISTA-20149</a>.","mla":"Dos Reis Rodrigues, Patricia. <i>Coordination of Protrusive Forces in Immune Cell Migration </i>. Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-20149\">10.15479/AT-ISTA-20149</a>.","apa":"Dos Reis Rodrigues, P. (2025). <i>Coordination of protrusive forces in immune cell migration </i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-20149\">https://doi.org/10.15479/AT-ISTA-20149</a>","ista":"Dos Reis Rodrigues P. 2025. Coordination of protrusive forces in immune cell migration . Institute of Science and Technology Austria.","ama":"Dos Reis Rodrigues P. Coordination of protrusive forces in immune cell migration . 2025. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-20149\">10.15479/AT-ISTA-20149</a>","short":"P. Dos Reis Rodrigues, Coordination of Protrusive Forces in Immune Cell Migration , Institute of Science and Technology Austria, 2025."},"file_date_updated":"2025-08-27T13:02:28Z","tmp":{"image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)"},"has_accepted_license":"1","doi":"10.15479/AT-ISTA-20149","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"NanoFab"}],"publication_identifier":{"issn":["2663-337X"]},"alternative_title":["ISTA Thesis"],"date_updated":"2026-04-28T13:26:50Z","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"10703"},{"status":"public","id":"20082","relation":"part_of_dissertation"}]},"oa":1,"corr_author":"1","month":"08","file":[{"file_name":"2025_ReisRodrigues_Patricia_Thesis.pdf","relation":"main_file","access_level":"open_access","date_updated":"2025-08-27T12:59:10Z","file_id":"20232","file_size":63885565,"success":1,"date_created":"2025-08-27T12:59:10Z","content_type":"application/pdf","creator":"prodrigu","checksum":"fda8a1070667c3562263f4867609b41b"},{"relation":"source_file","access_level":"closed","date_updated":"2025-08-27T13:02:28Z","file_name":"2025_ReisRodrigues_Patricia_Thesis.docx","creator":"prodrigu","checksum":"e8b65affcbce846a926454df4b2867b9","file_id":"20233","file_size":50483434,"date_created":"2025-08-27T13:00:30Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document"}],"_id":"20149","abstract":[{"text":"Immune responses depend on the coordinated and efficient migration of leukocytes. These\r\ncells, which are embedded and tightly confined within tissues, must navigate and traverse\r\ndiverse and complex three-dimensional environments. Leukocytes adapt their locomotory\r\nbehavior to the mechanical, geometrical, and biochemical characteristics of their\r\nsurroundings. In low-density environments, where the pore size of the interstitial matrix\r\nallows free passage, these cells position the nucleus directly behind the lamellipodium, the\r\nprotrusive actin structure that forms the leading front of the cell. In this configuration, they\r\nuse the nucleus as a gauge to identify the path of least resistance.\r\nHere, we show that in high-density environments, where the pore size precludes free passage\r\nof the cell body, leukocytes reposition the microtubule-organizing center (MTOC) and\r\nassociated organelles in front of the nucleus. In this configuration, they use actin structures\r\nprotruding orthogonally to the direction of migration in order to open a path for the cell body.\r\nWe identify two distinct actin populations that serve this purpose at different subcellular\r\nlocalizations. At the leading edge, local indentation of the plasma membrane leads to\r\nrecruitment of the Wiskott-Aldrich syndrome protein (WASp), which, via Arp2/3, results in\r\nthe formation of individual actin foci. At the cell body, actin polymerization is triggered by\r\nDOCK8, a Cdc42 exchange factor, resulting in the formation of a central actin pool.\r\nWe demonstrate that the central and peripheral actin pools are functionally communicating\r\nand that depletion of the central actin pool leads to increased actin accumulation at the cell\r\nfront, resulting in excessive extension of the leading edge.","lang":"eng"}],"department":[{"_id":"GradSch"},{"_id":"MiSi"}],"supervisor":[{"full_name":"Sixt, Michael K","first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179"}],"OA_place":"publisher","author":[{"last_name":"Dos Reis Rodrigues","id":"26E95904-5160-11E9-9C0B-C5B0DC97E90F","first_name":"Patricia","full_name":"Dos Reis Rodrigues, Patricia","orcid":"0000-0003-1681-508X"}],"year":"2025","title":"Coordination of protrusive forces in immune cell migration ","article_processing_charge":"No","oa_version":"Published Version","publisher":"Institute of Science and Technology Austria","publication_status":"published","project":[{"_id":"bd91e723-d553-11ed-ba76-fe7eeb2185fd","name":"Pushing from within: Control of cell shape, integrity and motility by cytoskeletal pushing forces","grant_number":"101071793"}],"acknowledgement":"I would like to acknowledge the\r\nfinancial support of the European Research Council through the ERC-SyG grant “Pushing from\r\nwithin: Control of cell shape, integrity and motility by cytoskeletal pushing forces”\r\n(01071793), which made this research possible. 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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."}],"month":"03","department":[{"_id":"JoDa"}],"citation":{"short":"J.G. Danzl, J. Lyudchik, C. Kreuzinger, (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>","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>.","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>.","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>","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>.","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."},"file_date_updated":"2025-02-28T16:50:39Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","OA_type":"gold","has_accepted_license":"1","doi":"10.15479/AT:ISTA:18697","tmp":{"name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","image":"/images/cc_by_nc_sa.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","short":"CC BY-NC-SA (4.0)"},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"ScienComp"},{"_id":"PreCl"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"date_published":"2025-03-03T00:00:00Z","day":"03","ddc":["570"],"type":"research_data","license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","author":[{"last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973"},{"first_name":"Julia","full_name":"Lyudchik, Julia","last_name":"Lyudchik","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Kreuzinger","id":"382077BA-F248-11E8-B48F-1D18A9856A87","full_name":"Kreuzinger, Caroline","first_name":"Caroline"}],"year":"2025","contributor":[{"orcid":"0000-0002-7667-6854","contributor_type":"researcher","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","last_name":"Tavakoli","first_name":"Mojtaba"},{"last_name":"Lyudchik","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","contributor_type":"researcher"},{"last_name":"Januszewski","first_name":"Michal","contributor_type":"researcher"},{"contributor_type":"researcher","id":"7e146587-8972-11ed-ae7b-d7a32ea86a81","last_name":"Vistunou","first_name":"Vitali"},{"contributor_type":"researcher","first_name":"Nathalie","last_name":"Agudelo Duenas","id":"40E7F008-F248-11E8-B48F-1D18A9856A87"},{"contributor_type":"researcher","last_name":"Vorlaufer","id":"937696FA-C996-11E9-8C7C-CF13E6697425","first_name":"Jakob"},{"contributor_type":"researcher","orcid":"0000-0003-1216-9105","first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"id":"382077BA-F248-11E8-B48F-1D18A9856A87","last_name":"Kreuzinger","first_name":"Caroline","contributor_type":"researcher"},{"contributor_type":"researcher","first_name":"Bárbara","last_name":"Oliveira","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Alban","last_name":"Cenameri","contributor_type":"researcher"},{"contributor_type":"researcher","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Jain","first_name":"Viren","contributor_type":"researcher"},{"orcid":"0000-0001-8559-3973","contributor_type":"researcher","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G"}],"OA_place":"repository","article_processing_charge":"No","title":"Light-microscopy based connectomic reconstruction of mammalian brain tissue","oa_version":"Published Version","publisher":"Institute of Science and Technology Austria","date_created":"2024-12-20T09:22:20Z","status":"public"},{"oa":1,"corr_author":"1","external_id":{"isi":["001483477000001"],"pmid":["40335689"]},"related_material":{"link":[{"description":"News on ISTA website","url":"https://ista.ac.at/en/news/piecing-together-the-brain-puzzle/","relation":"press_release"}],"record":[{"id":"18677","relation":"earlier_version","status":"public"},{"status":"public","id":"18697","relation":"research_data"}]},"date_updated":"2026-04-28T13:33:34Z","department":[{"_id":"JoDa"},{"_id":"GradSch"},{"_id":"Bio"},{"_id":"GaNo"}],"publication":"Nature","volume":642,"article_type":"original","month":"06","intvolume":"       642","_id":"19704","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."}],"file":[{"file_name":"2025_Nature_Tavakoli.pdf","relation":"main_file","access_level":"open_access","date_updated":"2025-07-03T06:55:20Z","file_id":"19959","file_size":133201290,"success":1,"date_created":"2025-07-03T06:55:20Z","content_type":"application/pdf","creator":"dernst","checksum":"ebc99d7108e728f46db0a009292675ef"}],"quality_controlled":"1","PlanS_conform":"1","OA_type":"hybrid","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","citation":{"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>","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.","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.","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>.","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.","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>.","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>"},"file_date_updated":"2025-07-03T06:55:20Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"ScienComp"},{"_id":"PreCl"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"publication_identifier":{"issn":["0028-0836"],"eissn":["1476-4687"]},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"doi":"10.1038/s41586-025-08985-1","has_accepted_license":"1","date_published":"2025-06-12T00:00:00Z","scopus_import":"1","language":[{"iso":"eng"}],"isi":1,"type":"journal_article","ddc":["570"],"day":"12","page":"398-410","oa_version":"Published Version","ec_funded":1,"article_processing_charge":"Yes (via OA deal)","title":"Light-microscopy-based connectomic reconstruction of mammalian brain tissue","pmid":1,"OA_place":"publisher","year":"2025","author":[{"orcid":"0000-0002-7667-6854","first_name":"Mojtaba","full_name":"Tavakoli, Mojtaba","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","last_name":"Tavakoli"},{"full_name":"Lyudchik, Julia","first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","last_name":"Lyudchik"},{"last_name":"Januszewski","first_name":"Michał","full_name":"Januszewski, Michał"},{"first_name":"Vitali","full_name":"Vistunou, Vitali","id":"7e146587-8972-11ed-ae7b-d7a32ea86a81","last_name":"Vistunou"},{"full_name":"Agudelo Duenas, Nathalie","first_name":"Nathalie","id":"40E7F008-F248-11E8-B48F-1D18A9856A87","last_name":"Agudelo Duenas"},{"full_name":"Vorlaufer, Jakob","first_name":"Jakob","id":"937696FA-C996-11E9-8C7C-CF13E6697425","last_name":"Vorlaufer","orcid":"0009-0000-7590-3501"},{"orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer"},{"id":"382077BA-F248-11E8-B48F-1D18A9856A87","last_name":"Kreuzinger","full_name":"Kreuzinger, Caroline","first_name":"Caroline"},{"last_name":"Oliveira","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","full_name":"Oliveira, Bárbara","first_name":"Bárbara"},{"full_name":"Cenameri, Alban","first_name":"Alban","last_name":"Cenameri","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","full_name":"Novarino, Gaia","first_name":"Gaia"},{"full_name":"Jain, Viren","first_name":"Viren","last_name":"Jain"},{"first_name":"Johann G","full_name":"Danzl, Johann G","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973"}],"project":[{"grant_number":"26137","name":"Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy","_id":"6285a163-2b32-11ec-9570-8e204ca2dba5"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"665385","name":"International IST Doctoral Program"},{"grant_number":"101044865","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"},{"call_identifier":"FWF","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24","name":"Molecular Drug Targets"}],"status":"public","date_created":"2025-05-18T22:02:51Z","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).","publisher":"Springer Nature","publication_status":"published"},{"date_published":"2025-05-29T00:00:00Z","issue":"11","page":"2890-2906.e14","day":"29","ddc":["570"],"type":"journal_article","scopus_import":"1","isi":1,"language":[{"iso":"eng"}],"OA_place":"publisher","author":[{"first_name":"James","full_name":"Walker, James","last_name":"Walker"},{"last_name":"Zhang","full_name":"Zhang, Jingyi","first_name":"Jingyi"},{"last_name":"Liu","full_name":"Liu, Yalin","first_name":"Yalin"},{"id":"9724dd9d-f591-11ee-bd51-e97ed0652286","last_name":"Xu","full_name":"Xu, Shujuan","first_name":"Shujuan"},{"full_name":"Yu, Yiming","first_name":"Yiming","id":"318e643b-8b61-11ed-b69e-aafa103ec8dd","last_name":"Yu","orcid":"0000-0002-9919-7282"},{"last_name":"Vickers","first_name":"Martin","full_name":"Vickers, Martin"},{"first_name":"Weizhi","full_name":"Ouyang, Weizhi","id":"fec73395-8b60-11ed-b69e-927fda99c743","last_name":"Ouyang"},{"first_name":"Judit","full_name":"Tálas, Judit","last_name":"Tálas"},{"first_name":"Liam","full_name":"Dolan, Liam","last_name":"Dolan"},{"last_name":"Nakajima","full_name":"Nakajima, Keiji","first_name":"Keiji"},{"orcid":"0000-0002-4008-1234","full_name":"Feng, Xiaoqi","first_name":"Xiaoqi","id":"e0164712-22ee-11ed-b12a-d80fcdf35958","last_name":"Feng"}],"year":"2025","article_processing_charge":"Yes (via OA deal)","title":"Extensive N4 cytosine methylation is essential for Marchantia sperm function","ec_funded":1,"oa_version":"Published Version","pmid":1,"publisher":"Elsevier","publication_status":"published","project":[{"name":"Establishment, modulation and inheritance of sexual lineage specific DNA methylation in plants","grant_number":"804981","call_identifier":"H2020","_id":"bdb51a6e-d553-11ed-ba76-c2025f3d5725"}],"acknowledgement":"We thank Sir Richard Roberts (NEB) for the kind gift of anti-4mC antibodies. We are also grateful to the JIC Small Molecule Mass Spectrometry (Lionel Hill) and Chemistry (Martin Rejzek) platforms as well as the High Resolution Metabolomics Laboratory (Manfred Beckmann, Aberystwyth University) for their assistance with LC-MS. Additionally, we acknowledge the assistance of the JIC Bioimaging Facility and ISTA Imaging and Optics Facility for microscopy. Finally, we appreciate the High Performance Computing resources provided by the ISTA Scientific Computing Facility and Norwich BioScience Institute Partnership Computing Infrastructure. This work was funded by a Sainsbury Charitable Foundation studentship (J.W.), a UKRI-BBSRC Doctoral Training Partnerships studentship (BBT0087171 to J.T.), a European Research Council Starting Grant (“SexMeth” 804981 to J.W., S.X., and X.F.), two Biotechnology and Biological Sciences Research Council (BBSRC) grants (BBS0096201 and BBP0135111 to J.Z., M.V., and X.F.), an EMBO Long Term Fellowship (Y.L.), an ISTA Bridge Fellowship (S.X.), and ISTA core funding (Y.Y. and X.F.).","date_created":"2025-04-20T22:01:28Z","status":"public","date_updated":"2026-04-28T13:36:51Z","related_material":{"link":[{"relation":"press_release","url":"https://ista.ac.at/en/news/from-bacterial-immunity-to-plant-sex/","description":"News on ISTA website"}]},"external_id":{"pmid":["40209706"],"isi":["001504744800006"]},"corr_author":"1","oa":1,"month":"05","article_type":"original","file":[{"access_level":"open_access","date_updated":"2025-12-29T13:40:32Z","relation":"main_file","file_name":"2025_Cell_Walker.pdf","checksum":"0dcc2feb368dfe7c4890093366b2dacb","creator":"dernst","content_type":"application/pdf","file_size":11622960,"date_created":"2025-12-29T13:40:32Z","success":1,"file_id":"20871"}],"abstract":[{"lang":"eng","text":"N4-methylcytosine (4mC) is an important DNA modification in prokaryotes, but its relevance and even its presence in eukaryotes have been mysterious. Here we show that spermatogenesis in the liverwort Marchantia polymorpha involves two waves of extensive DNA methylation reprogramming. First, 5-methylcytosine (5mC) expands from transposons to the entire genome. Notably, the second wave installs 4mC throughout genic regions, covering over 50% of CG sites in sperm. 4mC requires a methyltransferase (MpDN4MT1a) that is specifically expressed during late spermiogenesis. Deletion of MpDN4MT1a alters the sperm transcriptome, causes sperm swimming and fertility defects, and impairs post-fertilization development. Our results reveal extensive 4mC in a eukaryote, identify a family of eukaryotic methyltransferases, and elucidate the biological functions of 4mC in reproductive development, thereby expanding the repertoire of functional eukaryotic DNA modifications."}],"_id":"19602","intvolume":"       188","publication":"Cell","department":[{"_id":"XiFe"}],"volume":188,"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","citation":{"ieee":"J. Walker <i>et al.</i>, “Extensive N4 cytosine methylation is essential for Marchantia sperm function,” <i>Cell</i>, vol. 188, no. 11. Elsevier, p. 2890–2906.e14, 2025.","ista":"Walker J, Zhang J, Liu Y, Xu S, Yu Y, Vickers M, Ouyang W, Tálas J, Dolan L, Nakajima K, Feng X. 2025. Extensive N4 cytosine methylation is essential for Marchantia sperm function. Cell. 188(11), 2890–2906.e14.","apa":"Walker, J., Zhang, J., Liu, Y., Xu, S., Yu, Y., Vickers, M., … Feng, X. (2025). Extensive N4 cytosine methylation is essential for Marchantia sperm function. <i>Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cell.2025.03.014\">https://doi.org/10.1016/j.cell.2025.03.014</a>","mla":"Walker, James, et al. “Extensive N4 Cytosine Methylation Is Essential for Marchantia Sperm Function.” <i>Cell</i>, vol. 188, no. 11, Elsevier, 2025, p. 2890–2906.e14, doi:<a href=\"https://doi.org/10.1016/j.cell.2025.03.014\">10.1016/j.cell.2025.03.014</a>.","chicago":"Walker, James, Jingyi Zhang, Yalin Liu, Shujuan Xu, Yiming Yu, Martin Vickers, Weizhi Ouyang, et al. “Extensive N4 Cytosine Methylation Is Essential for Marchantia Sperm Function.” <i>Cell</i>. Elsevier, 2025. <a href=\"https://doi.org/10.1016/j.cell.2025.03.014\">https://doi.org/10.1016/j.cell.2025.03.014</a>.","ama":"Walker J, Zhang J, Liu Y, et al. Extensive N4 cytosine methylation is essential for Marchantia sperm function. <i>Cell</i>. 2025;188(11):2890-2906.e14. doi:<a href=\"https://doi.org/10.1016/j.cell.2025.03.014\">10.1016/j.cell.2025.03.014</a>","short":"J. Walker, J. Zhang, Y. Liu, S. Xu, Y. Yu, M. Vickers, W. Ouyang, J. Tálas, L. Dolan, K. Nakajima, X. Feng, Cell 188 (2025) 2890–2906.e14."},"file_date_updated":"2025-12-29T13:40:32Z","quality_controlled":"1","OA_type":"hybrid","PlanS_conform":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"has_accepted_license":"1","doi":"10.1016/j.cell.2025.03.014","acknowledged_ssus":[{"_id":"Bio"},{"_id":"ScienComp"}],"publication_identifier":{"issn":["0092-8674"],"eissn":["1097-4172"]}},{"oa":1,"corr_author":"1","date_updated":"2026-04-28T13:42:45Z","related_material":{"record":[{"relation":"dissertation_contains","id":"19478","status":"public"}],"link":[{"description":"News on ISTA website","relation":"press_release","url":"https://ista.ac.at/en/news/updating-the-textbook/"}]},"external_id":{"isi":["001437493900001"],"pmid":["40044868"]},"volume":640,"publication":"Nature","department":[{"_id":"JiFr"}],"file":[{"file_id":"20132","file_size":13549245,"date_created":"2025-08-05T12:29:35Z","success":1,"content_type":"application/pdf","creator":"dernst","checksum":"f5f18081003e7a1b8e372ecb7da82e7d","file_name":"2025_Nature_Chen.pdf","relation":"main_file","access_level":"open_access","date_updated":"2025-08-05T12:29:35Z"}],"intvolume":"       640","_id":"19421","abstract":[{"text":"The phytohormone auxin (Aux) is a principal endogenous developmental signal in plants. It mediates transcriptional reprogramming by a well-established canonical signalling mechanism. TIR1/AFB auxin receptors are F-box subunits of an ubiquitin ligase complex; after auxin perception, they associate with Aux/IAA transcriptional repressors and ubiquitinate them for degradation, thus enabling the activation of auxin response factor (ARF) transcription factors1,2,3. Here we revise this paradigm by showing that without TIR1 adenylate cyclase (AC) activity4, auxin-induced degradation of Aux/IAAs is not sufficient to mediate the transcriptional auxin response. Abolishing the TIR1 AC activity does not affect auxin-induced degradation of Aux/IAAs but renders TIR1 non-functional in mediating transcriptional reprogramming and auxin-regulated development, including shoot, root, root hair growth and lateral root formation. Transgenic plants show that local cAMP production in the vicinity of the Aux/IAA–ARF complex by unrelated AC enzymes bypasses the need for auxin perception and is sufficient to induce ARF-mediated transcription. These discoveries revise the canonical model of auxin signalling and establish TIR1/AFB-produced cAMP as a second messenger essential for transcriptional reprograming.","lang":"eng"}],"article_type":"original","month":"04","OA_type":"hybrid","PlanS_conform":"1","quality_controlled":"1","file_date_updated":"2025-08-05T12:29:35Z","citation":{"ama":"Chen H, Qi L, Zou M, et al. TIR1-produced cAMP as a second messenger in transcriptional auxin signalling. <i>Nature</i>. 2025;640:1011-1016. doi:<a href=\"https://doi.org/10.1038/s41586-025-08669-w\">10.1038/s41586-025-08669-w</a>","short":"H. Chen, L. Qi, M. Zou, M. Lu, M. Kwiatkowski, Y. Pei, K. Jaworski, J. Friml, Nature 640 (2025) 1011–1016.","ieee":"H. Chen <i>et al.</i>, “TIR1-produced cAMP as a second messenger in transcriptional auxin signalling,” <i>Nature</i>, vol. 640. Springer Nature, pp. 1011–1016, 2025.","mla":"Chen, Huihuang, et al. “TIR1-Produced CAMP as a Second Messenger in Transcriptional Auxin Signalling.” <i>Nature</i>, vol. 640, Springer Nature, 2025, pp. 1011–16, doi:<a href=\"https://doi.org/10.1038/s41586-025-08669-w\">10.1038/s41586-025-08669-w</a>.","apa":"Chen, H., Qi, L., Zou, M., Lu, M., Kwiatkowski, M., Pei, Y., … Friml, J. (2025). TIR1-produced cAMP as a second messenger in transcriptional auxin signalling. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-025-08669-w\">https://doi.org/10.1038/s41586-025-08669-w</a>","ista":"Chen H, Qi L, Zou M, Lu M, Kwiatkowski M, Pei Y, Jaworski K, Friml J. 2025. TIR1-produced cAMP as a second messenger in transcriptional auxin signalling. Nature. 640, 1011–1016.","chicago":"Chen, Huihuang, Linlin Qi, Minxia Zou, Mengting Lu, M Kwiatkowski, Yuanrong Pei, K Jaworski, and Jiří Friml. “TIR1-Produced CAMP as a Second Messenger in Transcriptional Auxin Signalling.” <i>Nature</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1038/s41586-025-08669-w\">https://doi.org/10.1038/s41586-025-08669-w</a>."},"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","publication_identifier":{"issn":["0028-0836"],"eissn":["1476-4687"]},"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"has_accepted_license":"1","doi":"10.1038/s41586-025-08669-w","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2025-04-24T00:00:00Z","isi":1,"language":[{"iso":"eng"}],"day":"24","ddc":["580"],"page":"1011-1016","type":"journal_article","pmid":1,"article_processing_charge":"Yes (via OA deal)","title":"TIR1-produced cAMP as a second messenger in transcriptional auxin signalling","oa_version":"Published Version","author":[{"last_name":"Chen","id":"83c96512-15b2-11ec-abd3-b7eede36184f","first_name":"Huihuang","full_name":"Chen, Huihuang"},{"last_name":"Qi","id":"44B04502-A9ED-11E9-B6FC-583AE6697425","first_name":"Linlin","full_name":"Qi, Linlin","orcid":"0000-0001-5187-8401"},{"last_name":"Zou","id":"5c243f41-03f3-11ec-841c-96faf48a7ef9","full_name":"Zou, Minxia","first_name":"Minxia"},{"last_name":"Lu","id":"a8198a14-1ffe-11ee-8b67-d2bdff9d9178","full_name":"Lu, Mengting","first_name":"Mengting"},{"last_name":"Kwiatkowski","full_name":"Kwiatkowski, M","first_name":"M"},{"first_name":"Yuanrong","full_name":"Pei, Yuanrong","last_name":"Pei","id":"98605edc-6ce7-11ee-95f3-cc16b866efcd"},{"full_name":"Jaworski, K","first_name":"K","last_name":"Jaworski"},{"orcid":"0000-0002-8302-7596","last_name":"Friml","id":"4159519E-F248-11E8-B48F-1D18A9856A87","full_name":"Friml, Jiří","first_name":"Jiří"}],"year":"2025","OA_place":"publisher","acknowledgement":"We are grateful to J. Callis and H.-Q. Yang for sharing materials and to M. Estelle and S. Kepinski for inspiring discussions. This research was supported by the Laboratory Support Facility, the Plant Facility and the Imaging and Optics Facility of the Institute of Science and Technology Austria. This project has received funding from the European Research Council (101142681 CYNIPS) and Austrian Science Fund (P 37051-B). L.Q. was supported by the National Natural Science Foundation of China (grant no. 32470327). M.Z. was supported by the Interdisciplinary Project Committee of the Institute of Science and Technology Austria, and Y.P. was supported by an EMBO Postdoctoral Fellowship (ALTF 38-2023). Open access funding provided by Institute of Science and Technology (IST Austria).","date_created":"2025-03-19T09:44:39Z","status":"public","project":[{"_id":"7bcece63-9f16-11ee-852c-ae94e099eeb6","grant_number":"P37051","name":"Guanylate cyclase activity of TIR1/AFBs auxin receptors"}],"publication_status":"published","publisher":"Springer Nature"},{"degree_awarded":"PhD","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","file_date_updated":"2025-04-09T13:53:38Z","citation":{"ista":"Chen H. 2025. The cAMP second messenger in auxin signalling. Institute of Science and Technology Austria.","apa":"Chen, H. (2025). <i>The cAMP second messenger in auxin signalling</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-19478\">https://doi.org/10.15479/AT-ISTA-19478</a>","mla":"Chen, Huihuang. <i>The CAMP Second Messenger in Auxin Signalling</i>. Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-19478\">10.15479/AT-ISTA-19478</a>.","chicago":"Chen, Huihuang. “The CAMP Second Messenger in Auxin Signalling.” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT-ISTA-19478\">https://doi.org/10.15479/AT-ISTA-19478</a>.","ieee":"H. Chen, “The cAMP second messenger in auxin signalling,” Institute of Science and Technology Austria, 2025.","short":"H. Chen, The CAMP Second Messenger in Auxin Signalling, Institute of Science and Technology Austria, 2025.","ama":"Chen H. The cAMP second messenger in auxin signalling. 2025. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-19478\">10.15479/AT-ISTA-19478</a>"},"doi":"10.15479/AT-ISTA-19478","has_accepted_license":"1","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"publication_identifier":{"issn":["2663-337X"]},"date_updated":"2026-04-28T13:42:45Z","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"13212"},{"id":"19421","relation":"part_of_dissertation","status":"public"}]},"alternative_title":["ISTA Thesis"],"corr_author":"1","month":"04","_id":"19478","file":[{"file_name":"Thesis_0403_Huihuang.docx","access_level":"closed","date_updated":"2025-04-08T08:22:37Z","relation":"source_file","file_size":16344814,"date_created":"2025-04-08T08:00:07Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_id":"19526","checksum":"b154973663a1bba505683faab7ae5ead","creator":"hchen"},{"file_name":"Thesis_0406_PDFA_Huihuang_1.pdf","embargo":"2026-10-08","relation":"main_file","embargo_to":"local","date_updated":"2025-04-09T13:53:38Z","access_level":"closed","file_id":"19527","file_size":8482147,"date_created":"2025-04-08T08:00:06Z","content_type":"application/pdf","creator":"hchen","checksum":"0099565f024388830c125ec17375c1a0"}],"supervisor":[{"full_name":"Friml, Jiří","first_name":"Jiří","last_name":"Friml","id":"4159519E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8302-7596"}],"department":[{"_id":"GradSch"},{"_id":"JiFr"}],"OA_place":"publisher","year":"2025","author":[{"id":"83c96512-15b2-11ec-abd3-b7eede36184f","last_name":"Chen","full_name":"Chen, Huihuang","first_name":"Huihuang"}],"oa_version":"Published Version","ec_funded":1,"title":"The cAMP second messenger in auxin signalling","article_processing_charge":"No","publisher":"Institute of Science and Technology Austria","publication_status":"published","project":[{"call_identifier":"H2020","_id":"261099A6-B435-11E9-9278-68D0E5697425","name":"Tracing Evolution of Auxin Transport and Polarity in Plants","grant_number":"742985"},{"_id":"7bcece63-9f16-11ee-852c-ae94e099eeb6","grant_number":"P37051","name":"Guanylate cyclase activity of TIR1/AFBs auxin receptors"},{"grant_number":"101142681","name":"Cyclic nucleotides as second messengers in plants","_id":"8f347782-16d5-11f0-9cad-8c19706ee739"}],"date_created":"2025-04-04T07:48:24Z","status":"public","acknowledgement":"This project was funded by the European Research Council Advanced Grant (ETAP-742985),\r\nEuropean Research Council (ERC; 101142681 CYNIPS), Austrian Science Fund (FWF; P\r\n37051-B).","date_published":"2025-04-04T00:00:00Z","type":"dissertation","day":"04","page":"118","ddc":["580"],"language":[{"iso":"eng"}]},{"quality_controlled":"1","OA_type":"gold","PlanS_conform":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_number":"98","file_date_updated":"2025-04-22T09:46:27Z","citation":{"short":"V. Schmied, M. Korkut, A. Venturino, J.P. Maya-Arteaga, S. Siegert, Journal of Neuroinflammation 22 (2025).","ama":"Schmied V, Korkut M, Venturino A, Maya-Arteaga JP, Siegert S. Microglia determine an immune-challenged environment and facilitate ibuprofen action in human retinal organoids. <i>Journal of Neuroinflammation</i>. 2025;22(1). doi:<a href=\"https://doi.org/10.1186/s12974-025-03366-x\">10.1186/s12974-025-03366-x</a>","apa":"Schmied, V., Korkut, M., Venturino, A., Maya-Arteaga, J. P., &#38; Siegert, S. (2025). Microglia determine an immune-challenged environment and facilitate ibuprofen action in human retinal organoids. <i>Journal of Neuroinflammation</i>. Springer Nature. <a href=\"https://doi.org/10.1186/s12974-025-03366-x\">https://doi.org/10.1186/s12974-025-03366-x</a>","ista":"Schmied V, Korkut M, Venturino A, Maya-Arteaga JP, Siegert S. 2025. Microglia determine an immune-challenged environment and facilitate ibuprofen action in human retinal organoids. Journal of Neuroinflammation. 22(1), 98.","mla":"Schmied, Verena, et al. “Microglia Determine an Immune-Challenged Environment and Facilitate Ibuprofen Action in Human Retinal Organoids.” <i>Journal of Neuroinflammation</i>, vol. 22, no. 1, 98, Springer Nature, 2025, doi:<a href=\"https://doi.org/10.1186/s12974-025-03366-x\">10.1186/s12974-025-03366-x</a>.","chicago":"Schmied, Verena, Medina Korkut, Alessandro Venturino, Juan Pablo Maya-Arteaga, and Sandra Siegert. “Microglia Determine an Immune-Challenged Environment and Facilitate Ibuprofen Action in Human Retinal Organoids.” <i>Journal of Neuroinflammation</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1186/s12974-025-03366-x\">https://doi.org/10.1186/s12974-025-03366-x</a>.","ieee":"V. Schmied, M. Korkut, A. Venturino, J. P. Maya-Arteaga, and S. Siegert, “Microglia determine an immune-challenged environment and facilitate ibuprofen action in human retinal organoids,” <i>Journal of Neuroinflammation</i>, vol. 22, no. 1. Springer Nature, 2025."},"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"publication_identifier":{"eissn":["1742-2094"]},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"has_accepted_license":"1","doi":"10.1186/s12974-025-03366-x","oa":1,"corr_author":"1","date_updated":"2026-05-06T12:49:37Z","related_material":{"record":[{"relation":"dissertation_contains","id":"20074","status":"public"}],"link":[{"relation":"press_release","url":"https://ista.ac.at/en/news/pink-skies/","description":"News on ISTA website"}]},"external_id":{"isi":["001459311800002"],"pmid":["40181459"]},"publication":"Journal of Neuroinflammation","department":[{"_id":"SaSi"}],"DOAJ_listed":"1","volume":22,"article_type":"original","month":"04","file":[{"checksum":"dcc355c21ab713e45fda5c61b5fa5299","creator":"dernst","content_type":"application/pdf","file_size":4482167,"date_created":"2025-04-22T09:46:27Z","success":1,"file_id":"19607","date_updated":"2025-04-22T09:46:27Z","access_level":"open_access","relation":"main_file","file_name":"2025_JourNeuroinflammation_Schmied.pdf"}],"_id":"19593","intvolume":"        22","abstract":[{"text":"Prenatal immune challenges pose significant risks to human embryonic brain and eye development. However, our knowledge about the safe usage of anti-inflammatory drugs during pregnancy is still limited. While human induced pluripotent stem cells (hIPSC)-derived brain organoid models have started to explore functional consequences upon viral stimulation, these models commonly lack microglia, which are susceptible to and promote inflammation. Furthermore, microglia are actively involved in neuronal development. Here, we generate hIPSC-derived microglia precursor cells and assemble them into retinal organoids. Once the outer plexiform layer forms, these hIPSC-derived microglia (iMG) fully integrate into the retinal organoids. Since the ganglion cell survival declines by this time in 3D-retinal organoids, we adapted the model into 2D and identify that the improved ganglion cell number significantly decreases only with iMG presence. In parallel, we applied the immunostimulant POLY(I:C) to mimic a fetal viral infection. While POLY(I:C) exposure alters the iMG phenotype, it does not hinder their interaction with ganglion cells. Furthermore, iMG significantly enhance the supernatant’s inflammatory secretome and increase retinal cell proliferation. Simultaneous exposure with the non-steroidal anti-inflammatory drug (NSAID) ibuprofen dampens POLY(I:C)-mediated changes of the iMG phenotype and ameliorates cell proliferation. Remarkably, while POLY(I:C) disrupts neuronal calcium dynamics independent of iMG, ibuprofen rescues this effect only if iMG are present. Mechanistically, ibuprofen targets the enzymes cyclooxygenase 1 and 2 (COX1/PTGS1 and COX2/PTGS2) simultaneously, from which iMG mainly express COX1. Selective COX1 blockage fails to restore the calcium peak amplitude upon POLY(I:C) stimulation, suggesting ibuprofen’s beneficial effect depends on the presence and interplay of COX1 and COX2. These findings underscore the importance of microglia in the context of prenatal immune challenges and provide insight into the mechanisms by which ibuprofen exerts its protective effects during embryonic development.","lang":"eng"}],"article_processing_charge":"Yes","title":"Microglia determine an immune-challenged environment and facilitate ibuprofen action in human retinal organoids","oa_version":"Published Version","pmid":1,"OA_place":"publisher","author":[{"last_name":"Hübschmann","id":"32B7C918-F248-11E8-B48F-1D18A9856A87","first_name":"Verena","full_name":"Hübschmann, Verena"},{"first_name":"Medina","full_name":"Korkut, Medina","last_name":"Korkut","id":"4B51CE74-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4309-2251"},{"orcid":"0000-0003-2356-9403","first_name":"Alessandro","full_name":"Venturino, Alessandro","last_name":"Venturino","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Juan Pablo","full_name":"Maya-Arteaga, Juan Pablo","id":"c815d433-1f5d-11f0-a875-dad18b1e5924","last_name":"Maya-Arteaga"},{"first_name":"Sandra","full_name":"Siegert, Sandra","last_name":"Siegert","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877"}],"year":"2025","project":[{"_id":"9B99D380-BA93-11EA-9121-9846C619BF3A","grant_number":"SC19-017","name":"How human microglia shape developing neurons during health and inflammation"},{"name":"IST Austria Open Access Fund","_id":"B67AFEDC-15C9-11EA-A837-991A96BB2854"}],"acknowledgement":"We thank the scientific service units at ISTA, specifically the Lab Support Facility (LSF), the Molecular Biology Services/Virus Services Team, specifically Flavia Gama Gomes Leite and Mark Andrew Smyth, for the virus production, and the Imaging and Optics Facility (IOF). We thank all members of the Siegert group and Marco Benevento for their constant feedback on the project and comments on the manuscript. A special thanks to Rouven Schulz for input on statistical analysis and sharing R-scripts, Gloria Colombo for the introduction to cell sorting, Negar Vehdani and Florianne Schoot Uiterkamp for their support in cell culture. This research was supported by the Gesellschaft für Forschungsförderung Niederösterreich (grant No. Sc19-017 to V.H.).","status":"public","date_created":"2025-04-20T22:01:28Z","publisher":"Springer Nature","publication_status":"published","issue":"1","APC_amount":"3948 EUR","date_published":"2025-04-03T00:00:00Z","scopus_import":"1","isi":1,"language":[{"iso":"eng"}],"ddc":["570"],"day":"03","type":"journal_article"},{"volume":66,"DOAJ_listed":"1","department":[{"_id":"SaSi"}],"publication":"Investigative Ophthalmology & Visual Science","intvolume":"        66","_id":"19566","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"}],"file":[{"checksum":"e8722ce5792f6c08fe1e191f7de6f147","creator":"dernst","content_type":"application/pdf","success":1,"file_size":2721477,"date_created":"2025-04-15T13:49:10Z","file_id":"19567","access_level":"open_access","date_updated":"2025-04-15T13:49:10Z","relation":"main_file","file_name":"2025_IOVS_SchootUiterkamp.pdf"}],"month":"03","article_type":"original","oa":1,"corr_author":"1","external_id":{"pmid":["40126507"]},"related_material":{"link":[{"relation":"software","url":"https://github.com/siegert-lab/RGC-Quant"}],"record":[{"relation":"dissertation_contains","id":"20467","status":"public"}]},"date_updated":"2026-05-20T06:37:12Z","publication_identifier":{"issn":["1552-5783"]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"doi":"10.1167/iovs.66.3.49","has_accepted_license":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"OA_type":"gold","quality_controlled":"1","file_date_updated":"2025-04-15T13:49:10Z","citation":{"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>.","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>.","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>","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.","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.","short":"F.E. Miteva, M.E. Maes, M. Alamalhoda, A. Firoozi, G. Colombo, S. Siegert, Investigative Ophthalmology &#38; Visual Science 66 (2025).","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>"},"article_number":"49","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","language":[{"iso":"eng"}],"scopus_import":"1","type":"journal_article","ddc":["570"],"day":"01","issue":"3","date_published":"2025-03-01T00:00:00Z","APC_amount":"2236,02 EUR","date_created":"2025-04-15T13:40:35Z","status":"public","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. ","project":[{"_id":"7be82147-9f16-11ee-852c-f44682d73140","grant_number":"P37131","name":"Dissecting the morpho-functional relationship of microglia"},{"_id":"3AC91DDA-15DF-11EA-824D-93A3E7B544D1","call_identifier":"FWF","name":"FWF Open Access Fund"}],"publication_status":"published","publisher":"Association for Research in Vision and Ophthalmology","pmid":1,"oa_version":"Published Version","article_processing_charge":"Yes","title":"Optic nerve crush does not induce retinal ganglion cell loss in the contralateral eye","year":"2025","author":[{"first_name":"Florianne E","full_name":"Schoot Uiterkamp, Florianne E","id":"3526230C-F248-11E8-B48F-1D18A9856A87","last_name":"Schoot Uiterkamp"},{"orcid":"0000-0001-9642-1085","last_name":"Maes","id":"3838F452-F248-11E8-B48F-1D18A9856A87","full_name":"Maes, Margaret E","first_name":"Margaret E"},{"first_name":"Mohammad","full_name":"Alamalhoda, Mohammad","last_name":"Alamalhoda"},{"full_name":"Firoozi, Arsalan","first_name":"Arsalan","last_name":"Firoozi"},{"orcid":"0000-0001-9434-8902","full_name":"Colombo, Gloria","first_name":"Gloria","last_name":"Colombo","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Siegert","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877"}],"OA_place":"publisher"},{"ddc":["570"],"day":"14","page":"99","type":"dissertation","language":[{"iso":"eng"}],"date_published":"2025-10-14T00:00:00Z","publisher":"Institute of Science and Technology Austria","publication_status":"published","project":[{"name":"Dissecting the morpho-functional relationship of microglia","grant_number":"P37131","_id":"7be82147-9f16-11ee-852c-f44682d73140"}],"acknowledgement":"The work presented in this Thesis was carried out at the Institute of Science and Technology\r\nAustria (ISTA), and was supported by the Austrian Science Fund (FWF) [10.55776/P37131].\r\nI would like to thank the Scientific Service Units (SSU) of ISTA for the provided resources,\r\nspecifically the Imaging and Optics Facility (IOF), the Lab Support Facility (LSF), and the\r\nPre-Clinical Facility (PCF) team, specifically Sonja Haslinger, Claudia Gold, and Michael\r\nSchunn, for mouse colony management and support. ","date_created":"2025-10-14T10:24:41Z","status":"public","OA_place":"publisher","author":[{"id":"3526230C-F248-11E8-B48F-1D18A9856A87","last_name":"Miteva","first_name":"Florianne E","full_name":"Miteva, Florianne E"}],"year":"2025","title":"The role of cyclooxygenase 1 on microglial response to inflammatory stressors","article_processing_charge":"No","oa_version":"Published Version","month":"10","file":[{"checksum":"03537697be8c688d3a05cf948288e48f","creator":"fschootu","content_type":"application/pdf","file_size":13668588,"date_created":"2025-10-17T11:09:11Z","file_id":"20484","date_updated":"2025-10-17T11:13:25Z","access_level":"closed","embargo_to":"open_access","relation":"main_file","embargo":"2026-10-14","file_name":"2025_Miteva_Florianne_thesis.pdf"},{"creator":"fschootu","checksum":"df4930d7211cf9cfe1254b77204dc1d3","file_id":"20525","file_size":28991918,"date_created":"2025-10-23T11:33:06Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","access_level":"closed","date_updated":"2025-10-23T11:33:06Z","file_name":"2025_Miteva_florianne_thesis.docx"}],"_id":"20467","department":[{"_id":"GradSch"},{"_id":"SaSi"}],"supervisor":[{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert","first_name":"Sandra","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877"}],"alternative_title":["ISTA Thesis"],"date_updated":"2026-05-20T06:37:12Z","related_material":{"record":[{"relation":"part_of_dissertation","id":"19566","status":"public"}]},"corr_author":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"has_accepted_license":"1","doi":"10.15479/AT-ISTA-20467","acknowledged_ssus":[{"_id":"Bio"},{"_id":"SSU"},{"_id":"PreCl"},{"_id":"LifeSc"}],"publication_identifier":{"issn":["2663-337X"]},"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","degree_awarded":"PhD","citation":{"short":"F.E. Miteva, The Role of Cyclooxygenase 1 on Microglial Response to Inflammatory Stressors, Institute of Science and Technology Austria, 2025.","ama":"Miteva FE. The role of cyclooxygenase 1 on microglial response to inflammatory stressors. 2025. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-20467\">10.15479/AT-ISTA-20467</a>","mla":"Miteva, Florianne E. <i>The Role of Cyclooxygenase 1 on Microglial Response to Inflammatory Stressors</i>. Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-20467\">10.15479/AT-ISTA-20467</a>.","apa":"Miteva, F. E. (2025). <i>The role of cyclooxygenase 1 on microglial response to inflammatory stressors</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-20467\">https://doi.org/10.15479/AT-ISTA-20467</a>","ista":"Miteva FE. 2025. The role of cyclooxygenase 1 on microglial response to inflammatory stressors. Institute of Science and Technology Austria.","chicago":"Miteva, Florianne E. “The Role of Cyclooxygenase 1 on Microglial Response to Inflammatory Stressors.” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT-ISTA-20467\">https://doi.org/10.15479/AT-ISTA-20467</a>.","ieee":"F. E. Miteva, “The role of cyclooxygenase 1 on microglial response to inflammatory stressors,” Institute of Science and Technology Austria, 2025."},"file_date_updated":"2025-10-23T11:33:06Z"},{"has_accepted_license":"1","doi":"10.3389/fpls.2025.1612366","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"publication_identifier":{"eissn":["1664-462X"]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"E-Lib"}],"article_number":"1612366","file_date_updated":"2025-07-31T07:28:54Z","citation":{"ama":"Gallemi M, Montesinos López JC, Zarevski N, et al. Dual role of pectin methyl esterase activity in the regulation of plant cell wall biophysical properties. <i>Frontiers in Plant Science</i>. 2025;16. doi:<a href=\"https://doi.org/10.3389/fpls.2025.1612366\">10.3389/fpls.2025.1612366</a>","short":"M. Gallemi, J.C. Montesinos López, N. Zarevski, J. Pribyl, P. Skládal, E.B. Hannezo, E. Benková, Frontiers in Plant Science 16 (2025).","ieee":"M. Gallemi <i>et al.</i>, “Dual role of pectin methyl esterase activity in the regulation of plant cell wall biophysical properties,” <i>Frontiers in Plant Science</i>, vol. 16. Frontiers Media, 2025.","ista":"Gallemi M, Montesinos López JC, Zarevski N, Pribyl J, Skládal P, Hannezo EB, Benková E. 2025. Dual role of pectin methyl esterase activity in the regulation of plant cell wall biophysical properties. Frontiers in Plant Science. 16, 1612366.","mla":"Gallemi, Marçal, et al. “Dual Role of Pectin Methyl Esterase Activity in the Regulation of Plant Cell Wall Biophysical Properties.” <i>Frontiers in Plant Science</i>, vol. 16, 1612366, Frontiers Media, 2025, doi:<a href=\"https://doi.org/10.3389/fpls.2025.1612366\">10.3389/fpls.2025.1612366</a>.","apa":"Gallemi, M., Montesinos López, J. C., Zarevski, N., Pribyl, J., Skládal, P., Hannezo, E. B., &#38; Benková, E. (2025). Dual role of pectin methyl esterase activity in the regulation of plant cell wall biophysical properties. <i>Frontiers in Plant Science</i>. Frontiers Media. <a href=\"https://doi.org/10.3389/fpls.2025.1612366\">https://doi.org/10.3389/fpls.2025.1612366</a>","chicago":"Gallemi, Marçal, Juan C Montesinos López, Nikola Zarevski, Jan Pribyl, Petr Skládal, Edouard B Hannezo, and Eva Benková. “Dual Role of Pectin Methyl Esterase Activity in the Regulation of Plant Cell Wall Biophysical Properties.” <i>Frontiers in Plant Science</i>. Frontiers Media, 2025. <a href=\"https://doi.org/10.3389/fpls.2025.1612366\">https://doi.org/10.3389/fpls.2025.1612366</a>."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","OA_type":"gold","PlanS_conform":"1","quality_controlled":"1","file":[{"success":1,"date_created":"2025-07-31T07:28:54Z","file_size":3665187,"content_type":"application/pdf","file_id":"20093","checksum":"9e6b8b53ba56d4a24a9bd91cf6d2dc58","creator":"dernst","file_name":"2025_FrontiersPlantSc_Gallemi.pdf","access_level":"open_access","date_updated":"2025-07-31T07:28:54Z","relation":"main_file"}],"_id":"20080","intvolume":"        16","abstract":[{"lang":"eng","text":"Introduction: Acid-growth theory has been postulated in the 70s to explain the rapid elongation of plant cells in response to the hormone auxin. More recently, it has been demonstrated that activation of the proton ATPs pump (H+-ATPs) promoting acidification of the apoplast is the principal mechanism by which auxin and other hormones such as brassinosteroids (BR) induce cell elongation. Despite these advances, the impact of this acidification on the mechanical properties of the cell wall remained largely unexplored.\r\n\r\nMethods: Here, we use elongation assays of Arabidopsis thaliana hypocotyls and Atomic Force Microscopy (AFM) to correlate hormone-induced tissue elongation and local changes in cell wall mechanical properties. Furthermore, employing transgenic lines over-expressing Pectin Methyl Esterase (PME), along with calcium chelators, we investigate the effect of pectin modification in hormone-driven cell elongation.\r\n\r\nResults: We demonstrate that acidification of apoplast is necessary and sufficient to induce cell elongation through promoting cell wall softening. Moreover, we show that enhanced PME activity can induce both cell wall softening or stiffening in extracellular calcium dependent-manner and that tight control of PME activity is required for proper hypocotyl elongation.\r\n\r\nDiscussion: Our results confirm a dual role of PME in plant cell elongation. However, further investigation is needed to assess the status of pectin following short- or long-term PME treatments in order to determine if pectin methyl-esterification might promote its degradation as well as the role of PME inhibitors upon PME induction."}],"month":"07","article_type":"original","DOAJ_listed":"1","volume":16,"publication":"Frontiers in Plant Science","department":[{"_id":"EdHa"},{"_id":"EvBe"},{"_id":"CaGu"}],"date_updated":"2026-05-20T07:53:03Z","external_id":{"pmid":["40688689"],"isi":["001530690900001"]},"oa":1,"corr_author":"1","publication_status":"published","publisher":"Frontiers Media","acknowledgement":"The author(s) declare that financial support was received for the research and/or publication of this article. This work was supported by grants from the European Research Council (Starting Independent Research Grant ERC-2007-Stg- 207362-HCPO to EB) and MG was recipient of an IST Interdisciplinary project (IC1022IPC03).\r\nWe acknowledge Jaume F. Martı́nez Garcı́a for phyAphyB mutant seeds. We acknowledge CF Nanobiotechnology of CIISB, Instruct-CZ Centre, supported by MEYS CR (LM2018127). We gratefully acknowledge support by the Scientific Service Units at ISTA, including the Imaging and Optics and Lab Support facilities and Library. We thank Stefan Riegler for the efforts to establish immunodetection method.","date_created":"2025-07-27T22:01:26Z","status":"public","project":[{"name":"Hormonal cross-talk in plant organogenesis","grant_number":"207362","_id":"253FCA6A-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"_id":"B67AFEDC-15C9-11EA-A837-991A96BB2854","name":"IST Austria Open Access Fund"}],"author":[{"orcid":"0000-0003-4675-6893","full_name":"Gallemi, Marçal","first_name":"Marçal","id":"460C6802-F248-11E8-B48F-1D18A9856A87","last_name":"Gallemi"},{"orcid":"0000-0001-9179-6099","id":"310A8E3E-F248-11E8-B48F-1D18A9856A87","last_name":"Montesinos López","first_name":"Juan C","full_name":"Montesinos López, Juan C"},{"full_name":"Zarevski, Nikola","first_name":"Nikola","last_name":"Zarevski","id":"18e95355-e05a-11ea-a9c0-8fba1b89e83a"},{"last_name":"Pribyl","full_name":"Pribyl, Jan","first_name":"Jan"},{"full_name":"Skládal, Petr","first_name":"Petr","last_name":"Skládal"},{"orcid":"0000-0001-6005-1561","first_name":"Edouard B","full_name":"Hannezo, Edouard B","last_name":"Hannezo","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Eva","full_name":"Benková, Eva","last_name":"Benková","id":"38F4F166-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8510-9739"}],"year":"2025","OA_place":"publisher","pmid":1,"article_processing_charge":"Yes","title":"Dual role of pectin methyl esterase activity in the regulation of plant cell wall biophysical properties","oa_version":"Published Version","ec_funded":1,"ddc":["580"],"day":"04","type":"journal_article","isi":1,"language":[{"iso":"eng"}],"scopus_import":"1","APC_amount":"3642,79 EUR","date_published":"2025-07-04T00:00:00Z"},{"_id":"20929","intvolume":"        16","abstract":[{"lang":"eng","text":"Insulin/insulin-like growth factor signaling inhibits FOXO transcription factors to control development, homeostasis, and aging. Here, we use proximity labeling to identify proteins interacting with the C. elegans FOXO DAF-16. We show that in well-fed, unstressed animals harboring active insulin signaling, DAF-16 forms a complex with the PAR-1/MARK serine/threonine kinase, a key regulator of cell polarity. PAR-1 inhibits DAF-16 accumulation and promotes DAF-16 phosphorylation at S249, at a conserved motif that PAR-1/human MARK2 phosphorylates in vitro. DAF-2 insulin-like receptor signaling stimulates DAF-16 S249 phosphorylation, suggesting DAF-2 activates PAR-1. DAF-2 also promotes PAR-1 expression by inhibiting DAF-16. PAR-1 knockdown, or DAF-16 S249A, prolong lifespan, whereas phosphomimetic DAF-16 S249D suppresses the longevity of daf-2 mutants. At low insulin signaling, DAF-16 proximity labeling highlights transcription factors, chromatin regulators, and DNA repair proteins. One interactor, the zinc finger/homeobox protein ZFH-2/ZFHX3, forms a complex with DAF-16 and prolongs lifespan. Our work provides entry points for hypothesis-driven studies of FOXO function and longevity."}],"file":[{"access_level":"open_access","date_updated":"2026-01-05T10:58:28Z","relation":"main_file","file_name":"2025_NatureComm_Artan.pdf","checksum":"748e2e003b878b85b6048d51621d6aae","creator":"dernst","content_type":"application/pdf","file_size":1642352,"success":1,"date_created":"2026-01-05T10:58:28Z","file_id":"20941"}],"month":"12","article_type":"original","volume":16,"DOAJ_listed":"1","department":[{"_id":"MaDe"}],"publication":"Nature Communications","external_id":{"pmid":["41381452"]},"date_updated":"2026-05-20T08:10:18Z","corr_author":"1","oa":1,"doi":"10.1038/s41467-025-66409-0","has_accepted_license":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"publication_identifier":{"eissn":["2041-1723"]},"acknowledged_ssus":[{"_id":"Bio"}],"citation":{"ieee":"M. Artan, H. Schön, and M. de Bono, “Proximity labeling of DAF-16 FOXO highlights aging regulatory proteins,” <i>Nature Communications</i>, vol. 16. Springer Nature, 2025.","chicago":"Artan, Murat, Hanna Schön, and Mario de Bono. “Proximity Labeling of DAF-16 FOXO Highlights Aging Regulatory Proteins.” <i>Nature Communications</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1038/s41467-025-66409-0\">https://doi.org/10.1038/s41467-025-66409-0</a>.","mla":"Artan, Murat, et al. “Proximity Labeling of DAF-16 FOXO Highlights Aging Regulatory Proteins.” <i>Nature Communications</i>, vol. 16, 11355, Springer Nature, 2025, doi:<a href=\"https://doi.org/10.1038/s41467-025-66409-0\">10.1038/s41467-025-66409-0</a>.","apa":"Artan, M., Schön, H., &#38; de Bono, M. (2025). Proximity labeling of DAF-16 FOXO highlights aging regulatory proteins. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-025-66409-0\">https://doi.org/10.1038/s41467-025-66409-0</a>","ista":"Artan M, Schön H, de Bono M. 2025. Proximity labeling of DAF-16 FOXO highlights aging regulatory proteins. Nature Communications. 16, 11355.","ama":"Artan M, Schön H, de Bono M. Proximity labeling of DAF-16 FOXO highlights aging regulatory proteins. <i>Nature Communications</i>. 2025;16. doi:<a href=\"https://doi.org/10.1038/s41467-025-66409-0\">10.1038/s41467-025-66409-0</a>","short":"M. Artan, H. Schön, M. de Bono, Nature Communications 16 (2025)."},"file_date_updated":"2026-01-05T10:58:28Z","article_number":"11355","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","PlanS_conform":"1","OA_type":"gold","quality_controlled":"1","type":"journal_article","day":"11","ddc":["570"],"language":[{"iso":"eng"}],"scopus_import":"1","date_published":"2025-12-11T00:00:00Z","APC_amount":"7068 EUR","publication_status":"published","publisher":"Springer Nature","status":"public","date_created":"2026-01-04T23:01:34Z","acknowledgement":"We thank de Bono lab members for helpful comments on the manuscript, and the Mass Spec Facility at the Max Perutz Labs, notably WeiQiang Chen and Markus Hartl, for invaluable discussions and comments on mass spec analyses of worm samples. All LC-MS/MS analyses were performed on instruments of the Vienna BioCenter Core Facilities (VBCF). Microscopy was supported by the Scientific Services Units (SSU) of ISTA through resources provided by the Imaging & Optics Facility (IOF). We are grateful to Dr. Geraldine Seydoux (Johns Hopkins University) for worm strains and plasmids, and Dr. Seung-Jae V. Lee (KAIST) for RNAi clones. We are grateful to Ekaterina Lashmanova for designing the daf-16::TbID::mNG::3xFLAG knock-in construct and for her outstanding support in the lab. This work was supported by a Wellcome Investigator Award (209504/A/17/Z) to MdB and an ISTplus Fellowship to MA (Marie Sklodowska-Curie agreement No 754411).","project":[{"call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411"},{"_id":"23870BE8-32DE-11EA-91FC-C7463DDC885E","name":"Molecular mechanisms of neural circuit function","grant_number":"209504/A/17/Z"}],"year":"2025","author":[{"orcid":"0000-0001-8945-6992","last_name":"Artan","id":"C407B586-6052-11E9-B3AE-7006E6697425","full_name":"Artan, Murat","first_name":"Murat"},{"full_name":"Schön, Hanna","first_name":"Hanna","id":"C8E17EDC-D7AA-11E9-B7B7-45ECE5697425","last_name":"Schön"},{"orcid":"0000-0001-8347-0443","id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87","last_name":"De Bono","first_name":"Mario","full_name":"De Bono, Mario"}],"OA_place":"publisher","pmid":1,"ec_funded":1,"oa_version":"Published Version","article_processing_charge":"Yes","title":"Proximity labeling of DAF-16 FOXO highlights aging regulatory proteins"},{"acknowledged_ssus":[{"_id":"Bio"}],"publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"doi":"10.1073/pnas.2413709122","has_accepted_license":"1","quality_controlled":"1","OA_type":"hybrid","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file_date_updated":"2025-06-24T07:27:43Z","citation":{"ieee":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, and C. C. Guet, “Pulsatile basal gene expression as a fitness determinant in bacteria,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 15. National Academy of Sciences, 2025.","chicago":"Jain, Kirti, Robert Hauschild, Olga Bochkareva, Roderich Römhild, Gašper Tkačik, and Calin C Guet. “Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2413709122\">https://doi.org/10.1073/pnas.2413709122</a>.","apa":"Jain, K., Hauschild, R., Bochkareva, O., Römhild, R., Tkačik, G., &#38; Guet, C. C. (2025). Pulsatile basal gene expression as a fitness determinant in bacteria. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2413709122\">https://doi.org/10.1073/pnas.2413709122</a>","ista":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. 2025. Pulsatile basal gene expression as a fitness determinant in bacteria. Proceedings of the National Academy of Sciences. 122(15), e2413709122.","mla":"Jain, Kirti, et al. “Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 15, e2413709122, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2413709122\">10.1073/pnas.2413709122</a>.","ama":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. Pulsatile basal gene expression as a fitness determinant in bacteria. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(15). doi:<a href=\"https://doi.org/10.1073/pnas.2413709122\">10.1073/pnas.2413709122</a>","short":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, C.C. Guet, Proceedings of the National Academy of Sciences 122 (2025)."},"article_number":"e2413709122","department":[{"_id":"CaGu"},{"_id":"Bio"},{"_id":"FyKo"},{"_id":"GaTk"}],"publication":"Proceedings of the National Academy of Sciences","volume":122,"month":"04","article_type":"original","_id":"19626","abstract":[{"lang":"eng","text":"Active regulation of gene expression, orchestrated by complex interactions of activators and repressors at promoters, controls the fate of organisms. In contrast, basal expression at uninduced promoters is considered to be a dynamically inert mode of nonfunctional “promoter leakiness,” merely a byproduct of transcriptional regulation. Here, we investigate the basal expression mode of the mar operon, the main regulator of intrinsic multiple antibiotic resistance in Escherichia coli, and link its dynamic properties to the noncanonical, yet highly conserved start codon of marR across Enterobacteriaceae. Real-time, single-cell measurements across tens of generations reveal that basal expression consists of rare stochastic gene expression pulses, which maximize variability in wildtype and, surprisingly, transiently accelerate cellular elongation rates. Competition experiments show that basal expression confers fitness advantages to wildtype across several transitions between exponential and stationary growth by shortening lag times. The dynamically rich basal expression of the mar operon has likely been evolutionarily maintained for its role in growth homeostasis of Enterobacteria within the gut environment, thereby allowing other ancillary gene regulatory roles to evolve, e.g., control of costly-to-induce multidrug efflux pumps. Understanding the complex selection forces governing genetic systems involved in intrinsic multidrug resistance is crucial for effective public health measures."}],"intvolume":"       122","file":[{"access_level":"open_access","date_updated":"2025-06-24T07:27:43Z","relation":"main_file","file_name":"2025_PNAS_Jain.pdf","checksum":"115a687f40009660eb4b38b4f6559d41","creator":"dernst","content_type":"application/pdf","success":1,"file_size":2949523,"date_created":"2025-06-24T07:27:43Z","file_id":"19888"}],"oa":1,"corr_author":"1","external_id":{"pmid":["40193613"],"isi":["001471235200001"]},"related_material":{"link":[{"description":"News on ISTA website","relation":"press_release","url":"https://ista.ac.at/en/news/clockwork-just-for-antibiotic-resistance/"}],"record":[{"status":"public","relation":"research_data","id":"19294"}]},"date_updated":"2026-05-20T08:33:08Z","project":[{"_id":"c08e9ad1-5a5b-11eb-8a69-9d1cf3b07473","name":"Tools for automation and feedback microscopy","grant_number":"CZI01"},{"_id":"bd6f94d1-d553-11ed-ba76-ae9f07250f74","name":"Non-canonical antibiotic interactions","grant_number":"E219"},{"_id":"34e076d6-11ca-11ed-8bc3-aec76c41a181","grant_number":"I05127","name":"Evolutionary analysis of gene regulation"}],"date_created":"2025-04-27T22:02:13Z","status":"public","acknowledgement":"K.J. thanks B. Wu, I. Tomanek, K. Tomasek for detailed discussions on the manuscript, all other members from the Guet laboratory for valuable feedback, R. Chait, & Imaging and Optics Facility, Institute of Science and Technology Austria for helping with microscopy, Dr. Sudha Rao and Dr. Raja Mugasimangalam, Genotypic Technology India for allowing time off to address the revisions. K.J. acknowledges Institute of Science and Technology fellowship IC1006FELL02, R.H. was supported in part by Chan Zuckerberg Initiative and Donor Advised-Fund grant 2020-225401 (https://doi.org/10.37921/120055ratwvi), O.O.B. acknowledges Fonds Zur Förderung der Wissenschaftlichen Forschung (FWF) Grant ESP253-B, R.R. acknowledges FWF Grant 10.55776/ESP219, C.C.G. acknowledges FWF I5127-B.","publisher":"National Academy of Sciences","publication_status":"published","oa_version":"Published Version","title":"Pulsatile basal gene expression as a fitness determinant in bacteria","article_processing_charge":"Yes (in subscription journal)","pmid":1,"OA_place":"publisher","year":"2025","author":[{"orcid":"0000-0002-3809-0449","id":"330F0278-F248-11E8-B48F-1D18A9856A87","last_name":"Jain","full_name":"Jain, Kirti","first_name":"Kirti"},{"last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","first_name":"Robert","full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522"},{"orcid":"0000-0003-1006-6639","id":"C4558D3C-6102-11E9-A62E-F418E6697425","last_name":"Bochkareva","full_name":"Bochkareva, Olga","first_name":"Olga"},{"id":"68E56E44-62B0-11EA-B963-444F3DDC885E","last_name":"Römhild","full_name":"Römhild, Roderich","first_name":"Roderich","orcid":"0000-0001-9480-5261"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkačik","first_name":"Gašper","full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455"},{"orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","full_name":"Guet, Calin C","first_name":"Calin C"}],"scopus_import":"1","language":[{"iso":"eng"}],"isi":1,"type":"journal_article","ddc":["570"],"day":"15","issue":"15","date_published":"2025-04-15T00:00:00Z","APC_amount":"5949 EUR"},{"article_type":"original","month":"09","file":[{"date_updated":"2025-12-30T09:17:09Z","access_level":"open_access","relation":"main_file","file_name":"2025_LifeScienceAlliance_Kuhn.pdf","checksum":"591d47aa39fc969986c7d3b966890f5f","creator":"dernst","content_type":"application/pdf","success":1,"file_size":5471288,"date_created":"2025-12-30T09:17:09Z","file_id":"20904"}],"_id":"19963","intvolume":"         8","abstract":[{"text":"The acquisition of cellular identity requires large-scale alterations in cellular state. The noncanonical proteasome activator PSME3 is known to regulate diverse cellular processes, but its importance for differentiation remains unclear. Here, we demonstrate that PSME3 binds dynamically to highly active promoters over the course of differentiation. However, loss of PSME3 does not globally affect mRNA transcription. We find instead that PSME3 influences the levels of several adhesion-related proteins and acts upstream of the HSP90 co-chaperone NUDC to regulate cell motility and myoblast differentiation in a proteasome-independent manner. Our findings reveal several new facets of PSME3 functionality and highlight its importance for the differentiation of myogenic cells.","lang":"eng"}],"publication":"Life Science Alliance","department":[{"_id":"MaHe"}],"DOAJ_listed":"1","volume":8,"date_updated":"2026-05-20T08:38:04Z","external_id":{"isi":["001511452100001"],"pmid":["40537284"]},"corr_author":"1","oa":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"has_accepted_license":"1","doi":"10.26508/lsa.202503208","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"publication_identifier":{"eissn":["2575-1077"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_number":"e202503208","file_date_updated":"2025-12-30T09:17:09Z","citation":{"ama":"Kuhn KD, Cho UH, Hetzer M. PSME3 regulates migration and differentiation of myoblasts. <i>Life Science Alliance</i>. 2025;8(9). doi:<a href=\"https://doi.org/10.26508/lsa.202503208\">10.26508/lsa.202503208</a>","short":"K.D. Kuhn, U.H. Cho, M. Hetzer, Life Science Alliance 8 (2025).","ieee":"K. D. Kuhn, U. H. Cho, and M. Hetzer, “PSME3 regulates migration and differentiation of myoblasts,” <i>Life Science Alliance</i>, vol. 8, no. 9. Embo Press, 2025.","apa":"Kuhn, K. D., Cho, U. H., &#38; Hetzer, M. (2025). PSME3 regulates migration and differentiation of myoblasts. <i>Life Science Alliance</i>. Embo Press. <a href=\"https://doi.org/10.26508/lsa.202503208\">https://doi.org/10.26508/lsa.202503208</a>","ista":"Kuhn KD, Cho UH, Hetzer M. 2025. PSME3 regulates migration and differentiation of myoblasts. Life Science Alliance. 8(9), e202503208.","mla":"Kuhn, Kenneth D., et al. “PSME3 Regulates Migration and Differentiation of Myoblasts.” <i>Life Science Alliance</i>, vol. 8, no. 9, e202503208, Embo Press, 2025, doi:<a href=\"https://doi.org/10.26508/lsa.202503208\">10.26508/lsa.202503208</a>.","chicago":"Kuhn, Kenneth D, Ukrae H. Cho, and Martin Hetzer. “PSME3 Regulates Migration and Differentiation of Myoblasts.” <i>Life Science Alliance</i>. Embo Press, 2025. <a href=\"https://doi.org/10.26508/lsa.202503208\">https://doi.org/10.26508/lsa.202503208</a>."},"quality_controlled":"1","OA_type":"gold","PlanS_conform":"1","ddc":["570"],"day":"01","type":"journal_article","scopus_import":"1","isi":1,"language":[{"iso":"eng"}],"APC_amount":"4215,38 EUR","date_published":"2025-09-01T00:00:00Z","issue":"9","publisher":"Embo Press","publication_status":"published","project":[{"name":"IST Austria Open Access Fund","_id":"B67AFEDC-15C9-11EA-A837-991A96BB2854"}],"acknowledgement":"All proteomics analysis was done by the ISTA LSF Mass Spectrometry Service: Ewelina Dutkiewicz-Kopczynska processed the samples (digest and cleanup); Bella Bruszel optimized the acquisition methods, acquired the data, and performed all searches; and Armel Nicolas provided pre- and post-project consulting and post-processed the search results using a development version of their data analysis package, proteoCraft (publication pending). The authors would like to thank Saki for their clarity of thought and insight, as well as Dr. Lorenzo Puri and the members of his laboratory for invaluable discussions relating to the project. This research was further supported by the Lab Support Facility and the Imaging and Optics Facility of ISTA.","status":"public","date_created":"2025-07-06T22:01:22Z","OA_place":"publisher","author":[{"id":"7deed7e0-0133-11f0-8590-c4600b08d0f4","last_name":"Kuhn","full_name":"Kuhn, Kenneth D","first_name":"Kenneth D"},{"last_name":"Cho","first_name":"Ukrae H.","full_name":"Cho, Ukrae H."},{"full_name":"Hetzer, Martin W","first_name":"Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","last_name":"Hetzer","orcid":"0000-0002-2111-992X"}],"year":"2025","article_processing_charge":"Yes","title":"PSME3 regulates migration and differentiation of myoblasts","oa_version":"Published Version","pmid":1},{"publication":"Proceedings of the National Academy of Sciences","department":[{"_id":"EdHa"},{"_id":"MiSi"}],"volume":122,"month":"08","article_type":"original","file":[{"file_name":"2025_PNAS_Ucar.pdf","relation":"main_file","access_level":"open_access","date_updated":"2025-09-08T07:23:29Z","file_id":"20307","content_type":"application/pdf","success":1,"date_created":"2025-09-08T07:23:29Z","file_size":16069140,"creator":"dernst","checksum":"b36abd92673b6d76376fc9434bad52cc"}],"_id":"20289","abstract":[{"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.","lang":"eng"}],"intvolume":"       122","corr_author":"1","oa":1,"related_material":{"link":[{"url":"https://github.com/mehmetcanucar/Self-generated-chemotaxis","relation":"software"}]},"date_updated":"2026-05-20T08:59:54Z","external_id":{"isi":["001562181600001"],"pmid":["40838890"]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"NanoFab"}],"publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"has_accepted_license":"1","doi":"10.1073/pnas.2504064122","quality_controlled":"1","OA_type":"hybrid","PlanS_conform":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_number":"e2504064122","citation":{"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>.","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>.","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>","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.","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.","short":"M.C. Ucar, A. Zane, J.H. Alanko, M.K. Sixt, E.B. Hannezo, Proceedings of the National Academy of Sciences 122 (2025).","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>"},"file_date_updated":"2025-09-08T07:23:29Z","scopus_import":"1","isi":1,"language":[{"iso":"eng"}],"ddc":["570"],"day":"26","type":"journal_article","issue":"34","APC_amount":"5766,07 EUR","date_published":"2025-08-26T00:00:00Z","project":[{"_id":"05943252-7A3F-11EA-A408-12923DDC885E","call_identifier":"H2020","name":"Design Principles of Branching Morphogenesis","grant_number":"851288"}],"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.","status":"public","date_created":"2025-09-07T22:01:32Z","publisher":"National Academy of Sciences","publication_status":"published","article_processing_charge":"Yes (in subscription journal)","title":"Self-generated chemotaxis of mixed cell populations","ec_funded":1,"oa_version":"Published Version","pmid":1,"OA_place":"publisher","author":[{"last_name":"Ucar","id":"50B2A802-6007-11E9-A42B-EB23E6697425","full_name":"Ucar, Mehmet C","first_name":"Mehmet C","orcid":"0000-0003-0506-4217"},{"last_name":"Zane","id":"60f7509a-f652-11ea-9d86-b963d6490d7c","first_name":"Alsberga","full_name":"Zane, Alsberga","orcid":"0009-0003-0415-7603"},{"orcid":"0000-0002-7698-3061","last_name":"Alanko","id":"2CC12E8C-F248-11E8-B48F-1D18A9856A87","full_name":"Alanko, Jonna H","first_name":"Jonna H"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179"},{"last_name":"Hannezo","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","full_name":"Hannezo, Edouard B","first_name":"Edouard B","orcid":"0000-0001-6005-1561"}],"year":"2025"},{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file_date_updated":"2025-10-13T12:37:04Z","citation":{"ieee":"P. Sahu, S. Monteiro-Ferreira, S. Canato, R. M. Soares, A. Sánchez-Danés, and E. B. Hannezo, “Mechanical control of cell fate decisions in the skin epidermis,” <i>Nature Communications</i>, vol. 16. Springer Nature, 2025.","mla":"Sahu, Preeti, et al. “Mechanical Control of Cell Fate Decisions in the Skin Epidermis.” <i>Nature Communications</i>, vol. 16, 8440, Springer Nature, 2025, doi:<a href=\"https://doi.org/10.1038/s41467-025-62882-9\">10.1038/s41467-025-62882-9</a>.","ista":"Sahu P, Monteiro-Ferreira S, Canato S, Soares RM, Sánchez-Danés A, Hannezo EB. 2025. Mechanical control of cell fate decisions in the skin epidermis. Nature Communications. 16, 8440.","apa":"Sahu, P., Monteiro-Ferreira, S., Canato, S., Soares, R. M., Sánchez-Danés, A., &#38; Hannezo, E. B. (2025). Mechanical control of cell fate decisions in the skin epidermis. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-025-62882-9\">https://doi.org/10.1038/s41467-025-62882-9</a>","chicago":"Sahu, Preeti, Sara Monteiro-Ferreira, Sara Canato, Raquel Maia Soares, Adriana Sánchez-Danés, and Edouard B Hannezo. “Mechanical Control of Cell Fate Decisions in the Skin Epidermis.” <i>Nature Communications</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1038/s41467-025-62882-9\">https://doi.org/10.1038/s41467-025-62882-9</a>.","ama":"Sahu P, Monteiro-Ferreira S, Canato S, Soares RM, Sánchez-Danés A, Hannezo EB. Mechanical control of cell fate decisions in the skin epidermis. <i>Nature Communications</i>. 2025;16. doi:<a href=\"https://doi.org/10.1038/s41467-025-62882-9\">10.1038/s41467-025-62882-9</a>","short":"P. Sahu, S. Monteiro-Ferreira, S. Canato, R.M. Soares, A. Sánchez-Danés, E.B. Hannezo, Nature Communications 16 (2025)."},"article_number":"8440","quality_controlled":"1","OA_type":"gold","tmp":{"image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)"},"doi":"10.1038/s41467-025-62882-9","has_accepted_license":"1","acknowledged_ssus":[{"_id":"Bio"}],"publication_identifier":{"eissn":["2041-1723"]},"external_id":{"isi":["001582555200011"],"pmid":["41006218"]},"date_updated":"2026-05-20T08:52:01Z","corr_author":"1","oa":1,"article_type":"original","month":"09","_id":"20424","abstract":[{"lang":"eng","text":"Homeostasis relies on a precise balance of fate choices between renewal and differentiation. Although progress has been done to characterize the dynamics of single-cell fate choices, their underlying mechanistic basis often remains unclear. Concentrating on skin epidermis as a paradigm for multilayered tissues with complex fate choices, we develop a 3D vertex-based model with proliferation in the basal layer, showing that mechanical competition for space naturally gives rise to homeostasis and neutral drift dynamics that are seen experimentally. We then explore the effect of introducing mechanical heterogeneities between cellular subpopulations. We uncover that relatively small tension heterogeneities, reflected by distinct morphological changes in single-cell shapes, can be sufficient to heavily tilt cellular dynamics towards exponential growth. We thus derive a master relationship between cell shape and long-term clonal dynamics, which we validated during basal cell carcinoma initiation in mouse epidermis. Altogether, we propose a theoretical framework to link mechanical forces, quantitative cellular morphologies and cellular fate outcomes in complex tissues."}],"intvolume":"        16","file":[{"file_name":"2025_NatureComm_Sahu.pdf","relation":"main_file","date_updated":"2025-10-13T12:37:04Z","access_level":"open_access","file_id":"20464","success":1,"date_created":"2025-10-13T12:37:04Z","file_size":2816813,"content_type":"application/pdf","creator":"dernst","checksum":"d1656576883b23902545328e2d640234"}],"department":[{"_id":"EdHa"}],"publication":"Nature Communications","volume":16,"DOAJ_listed":"1","OA_place":"publisher","year":"2025","author":[{"first_name":"Preeti","full_name":"Sahu, Preeti","last_name":"Sahu","id":"55BA52EE-A185-11EA-88FD-18AD3DDC885E"},{"last_name":"Monteiro-Ferreira","first_name":"Sara","full_name":"Monteiro-Ferreira, Sara"},{"last_name":"Canato","first_name":"Sara","full_name":"Canato, Sara"},{"first_name":"Raquel Maia","full_name":"Soares, Raquel Maia","last_name":"Soares"},{"last_name":"Sánchez-Danés","full_name":"Sánchez-Danés, Adriana","first_name":"Adriana"},{"full_name":"Hannezo, Edouard B","first_name":"Edouard B","last_name":"Hannezo","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561"}],"oa_version":"Published Version","ec_funded":1,"title":"Mechanical control of cell fate decisions in the skin epidermis","article_processing_charge":"Yes","pmid":1,"publisher":"Springer Nature","publication_status":"published","project":[{"name":"Biomechanics of stem cell fate determination","grant_number":"ALTF 522-2021","_id":"628f3fb1-2b32-11ec-9570-83ce778803f7"},{"name":"Design Principles of Branching Morphogenesis","grant_number":"851288","call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E"}],"status":"public","date_created":"2025-10-05T22:01:34Z","acknowledgement":"We thank Alois Schlögl, Paula Sanematsu, Susana Moreno Flores, Bernat Corominas-Murtra, Stefania Tavano, Gayathri Singharaju, and Hannezo group members for helpful discussions, the Bioimaging facility at ISTA, as well as Matthias Merkel and Lisa Manning for sharing the 3D Voronoi code. We also thank the Champalimaud animal facility, Anna Pezzarossa and the Champalimaud ABBE platform for the help with microscopy and image processing. This work was supported by EMBO (ALTF 522-2021), a Fundação para a Ciência e Tecnologia grant to A.S.D. (PTDC/MED-ONC/5553/2020), as well as the European Research Council (grant 851288 to EH). A.S.D., S.C., and R.M.S. are supported by QuantOCancer Project Horizon European Union’s Horizon 2020 program (grant agreement No 810653).","date_published":"2025-09-26T00:00:00Z","APC_amount":"7068 EUR","type":"journal_article","day":"26","ddc":["570"],"scopus_import":"1","language":[{"iso":"eng"}],"isi":1},{"status":"public","date_created":"2025-03-25T11:22:38Z","OA_embargo":"6 months","publication_status":"published","publisher":"Institute of Science and Technology Austria","oa_version":"Published Version","title":"The role of prefrontal spatial coding in supporting a contextual association task","article_processing_charge":"No","year":"2025","author":[{"last_name":"Cumpelik","id":"3F158B32-F248-11E8-B48F-1D18A9856A87","full_name":"Cumpelik, Andrea D","first_name":"Andrea D","orcid":"0000-0003-1727-6612"}],"OA_place":"publisher","language":[{"iso":"eng"}],"type":"dissertation","day":"18","page":"96","ddc":["612"],"date_published":"2025-02-18T00:00:00Z","publication_identifier":{"isbn":["978-3-99078-056-5"],"issn":["2663-337X"]},"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"doi":"10.15479/AT-ISTA-19456","has_accepted_license":"1","file_date_updated":"2025-09-30T22:30:02Z","citation":{"ieee":"A. D. Cumpelik, “The role of prefrontal spatial coding in supporting a contextual association task,” Institute of Science and Technology Austria, 2025.","chicago":"Cumpelik, Andrea D. “The Role of Prefrontal Spatial Coding in Supporting a Contextual Association Task.” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT-ISTA-19456\">https://doi.org/10.15479/AT-ISTA-19456</a>.","ista":"Cumpelik AD. 2025. The role of prefrontal spatial coding in supporting a contextual association task. Institute of Science and Technology Austria.","mla":"Cumpelik, Andrea D. <i>The Role of Prefrontal Spatial Coding in Supporting a Contextual Association Task</i>. Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-19456\">10.15479/AT-ISTA-19456</a>.","apa":"Cumpelik, A. D. (2025). <i>The role of prefrontal spatial coding in supporting a contextual association task</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-19456\">https://doi.org/10.15479/AT-ISTA-19456</a>","ama":"Cumpelik AD. The role of prefrontal spatial coding in supporting a contextual association task. 2025. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-19456\">10.15479/AT-ISTA-19456</a>","short":"A.D. Cumpelik, The Role of Prefrontal Spatial Coding in Supporting a Contextual Association Task, Institute of Science and Technology Austria, 2025."},"degree_awarded":"PhD","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","keyword":["neuroscience","decision making","learning","cognitive flexibility","medial prefrontal cortex","hippocampus","electrophysiology"],"supervisor":[{"first_name":"Jozsef L","full_name":"Csicsvari, Jozsef L","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","last_name":"Csicsvari","orcid":"0000-0002-5193-4036"}],"department":[{"_id":"GradSch"},{"_id":"JoCs"}],"_id":"19456","abstract":[{"text":"Making decisions requires flexibly adapting to changing environments, a process that\r\ndepends on accurately interpreting current contingencies and integrating them with\r\npast experience. Two brain regions are particularly critical for this process, the medial\r\nprefrontal cortex (mPFC) and the hippocampus. Using contextual information from the\r\nhippocampus, the mPFC selects relevant cognitive frameworks and suppresses\r\nirrelevant ones to guide appropriate actions. Several studies have shown that some\r\nmPFC pyramidal neurons become spatially tuned when spatial information is required\r\nto guide goal-directed behavior. However, the role of prefrontal spatial representations\r\nin learning and decision making is not well understood. This work aims to characterize\r\nthe role of mPFC spatial tuning in supporting a contextual association task. Rats were\r\ntrained to learn two cue–location associations on a radial arm maze over multiple days,\r\nwhile we simultaneously recorded from dorsal CA1 of the hippocampus and the\r\nprelimbic area of the mPFC. We describe a subset of spatially tuned hippocampal and\r\nprefrontal pyramidal neurons that “flicker” between multiple spatial representations on\r\ndifferent trials, suggesting dynamic, context-dependent coding. This flickering may\r\nprovide a substrate for how the network reorganizes in response to task demands,\r\nlikely by enabling the flexible evaluation of competing representations. ","lang":"eng"}],"file":[{"creator":"acumpeli","checksum":"1c7573303d8e5f6da3eb03d59055390f","file_id":"19457","content_type":"application/pdf","date_created":"2025-03-25T11:07:55Z","file_size":11869040,"relation":"main_file","access_level":"open_access","date_updated":"2025-09-30T22:30:02Z","file_name":"2025_Thesis_Cumpelik_corrections_PDFA.pdf","embargo":"2025-09-30"},{"creator":"acumpeli","checksum":"b93265ebd9a53f7a14100d0d48b4ff5b","file_id":"19458","date_created":"2025-03-25T11:08:05Z","file_size":20436467,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","embargo_to":"open_access","access_level":"closed","date_updated":"2025-09-30T22:30:02Z","file_name":"2025_Thesis_Cumpelik_corrections.docx"}],"month":"02","corr_author":"1","oa":1,"alternative_title":["ISTA Thesis"],"date_updated":"2026-04-07T12:37:58Z"},{"corr_author":"1","oa":1,"date_updated":"2026-04-14T09:50:53Z","alternative_title":["ISTA Thesis"],"related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"18601"},{"relation":"part_of_dissertation","id":"17148","status":"public"},{"id":"18807","relation":"part_of_dissertation","status":"public"},{"id":"13136","relation":"part_of_dissertation","status":"public"}]},"department":[{"_id":"AnKi"},{"_id":"GradSch"}],"supervisor":[{"id":"3959A2A0-F248-11E8-B48F-1D18A9856A87","last_name":"Kicheva","first_name":"Anna","full_name":"Kicheva, Anna","orcid":"0000-0003-4509-4998"}],"file":[{"creator":"cchlebak","checksum":"8cd7fe3ca990adbcafdece119aa0973d","file_id":"19764","content_type":"application/pdf","file_size":42879974,"date_created":"2025-05-30T09:10:22Z","relation":"main_file","access_level":"open_access","date_updated":"2025-11-30T23:30:02Z","embargo":"2025-11-30","file_name":"Thesis_Lehr_PDFA.pdf"},{"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":18731094,"date_created":"2025-05-30T09:31:15Z","file_id":"19765","checksum":"0c87dd5fc803450a47b20736b5f86a2f","creator":"cchlebak","file_name":"Thesis_Lehr_emptyPages.docx","access_level":"closed","date_updated":"2025-11-30T23:30:02Z","embargo_to":"open_access","relation":"source_file"}],"abstract":[{"text":"Pattern formation in developing organs is controlled by morphogens. These signalling\r\nmolecules form concentration gradients across tissues, thereby providing positional\r\ninformation that instructs the pattern of cell differentiation. Morphogen gradients are highly\r\ndynamic in space and time. Many factors such as morphogen production, spreading,\r\ndegradation, cellular rearrangements and others could contribute to changes in the gradient\r\nshape, yet how the spatiotemporal signalling dynamics arise in many systems is still unclear.\r\nWe studied the dynamics of morphogen signalling and tissue patterning in the developing\r\nvertebrate neural tube. In this system, neural crest, roof plate and distinct dorsal progenitor\r\nsubtypes are specified in a spatially and temporally ordered manner in response to dorsal-toventral gradients of BMP and WNT signalling activity. How the BMP and WNT gradients are\r\nestablished and interpreted to ensure ordered cell specification is poorly understood.\r\nTo address this question, we developed a 2D embryonic stem cell differentiation system that\r\ncaptures key features of dorsal neural tube development. In this system, differentiated\r\ncolonies display remarkable self-organised pattern formation in response to uniformly\r\napplied BMP ligand. We established a method of differentiating the colonies using\r\nmicrofabricated stencils, which allowed us to control the initial size and shape of colonies\r\nwithout confining cell migration and colony growth. This led to highly reproducible pattern\r\nformation that facilitates quantification.\r\nUsing this approach, we observed striking two-phase temporal dynamics of BMP signalling in\r\nour colonies: a BMP gradient rapidly forms from the periphery to the centre of colonies,\r\nsubsequently disappears and is re-established again in the second phase. By combining our\r\nquantitative data with a data-driven theoretical model, we uncovered a temporal relay\r\nmechanism that underlies this biphasic BMP signalling dynamics. The first signalling phase is\r\ncontrolled by fast tissue-autonomous negative feedback that restricts the duration of the\r\ninitial response to BMP. The early BMP activity gradient moreover controls the spatial\r\norganisation of the cell type pattern: the absence of a first phase results in disordered cell\r\ntype pattern. The second phase is controlled by slow positive regulation of BMP signalling by\r\nthe transcription factor LMX1A, a key regulator of roof plate identity. WNT promotes the\r\nsecond phase of BMP signalling via positive feedback on LMX1A.\r\nAltogether, the mechanism that we uncovered ensures the coupling of sequential\r\ndevelopmental events, making pattern formation spatially and temporally organised.\r\nFurthermore, this mechanism allows the BMP signalling pathway to be reused in different\r\ncontexts – first for the establishment of the neural plate border, and subsequently for dorsal\r\nneural progenitor patterning. Our study supports a general developmental principle in which\r\nmultiple morphogens interact with transcriptional networks resulting in complex\r\nspatiotemporal signalling dynamics that ultimately drive organised pattern formation.","lang":"eng"}],"_id":"19763","month":"05","citation":{"apa":"Rus, S. (2025). <i>Dynamics of morphogen signalling and cell fate decisions in the dorsal neural tube</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-19763\">https://doi.org/10.15479/AT-ISTA-19763</a>","ista":"Rus S. 2025. Dynamics of morphogen signalling and cell fate decisions in the dorsal neural tube. Institute of Science and Technology Austria.","mla":"Rus, Stefanie. <i>Dynamics of Morphogen Signalling and Cell Fate Decisions in the Dorsal Neural Tube</i>. Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-19763\">10.15479/AT-ISTA-19763</a>.","chicago":"Rus, Stefanie. “Dynamics of Morphogen Signalling and Cell Fate Decisions in the Dorsal Neural Tube.” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT-ISTA-19763\">https://doi.org/10.15479/AT-ISTA-19763</a>.","ieee":"S. Rus, “Dynamics of morphogen signalling and cell fate decisions in the dorsal neural tube,” Institute of Science and Technology Austria, 2025.","short":"S. Rus, Dynamics of Morphogen Signalling and Cell Fate Decisions in the Dorsal Neural Tube, Institute of Science and Technology Austria, 2025.","ama":"Rus S. Dynamics of morphogen signalling and cell fate decisions in the dorsal neural tube. 2025. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-19763\">10.15479/AT-ISTA-19763</a>"},"file_date_updated":"2025-11-30T23:30:02Z","degree_awarded":"PhD","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","publication_identifier":{"issn":["2663-337X"]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"}],"has_accepted_license":"1","doi":"10.15479/AT-ISTA-19763","tmp":{"image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)"},"date_published":"2025-05-29T00:00:00Z","language":[{"iso":"eng"}],"day":"29","page":"129","ddc":["570"],"type":"dissertation","article_processing_charge":"No","title":"Dynamics of morphogen signalling and cell fate decisions in the dorsal neural tube","oa_version":"Published Version","author":[{"orcid":"0000-0001-8703-1093","full_name":"Rus, Stefanie","first_name":"Stefanie","last_name":"Rus","id":"4D9EC9B6-F248-11E8-B48F-1D18A9856A87"}],"year":"2025","OA_place":"publisher","acknowledgement":"My work would also not have been possible without the Imaging and Optics, the Life Science\r\nand the Preclinical Facility of ISTA. Your support has facilitated my research substantially. I\r\nalso want to thank the Graduate School Office for their never-ending support and their sincere\r\neffort to improve the PhD programme of the ISTA even further.\r\nThis work was supported by the Gesellschaft für Forschungsförderung Niederösterreich\r\nm.b.H. fellowship (SC19-011). Thank you for recognizing the importance of this project.","date_created":"2025-05-30T09:14:58Z","status":"public","project":[{"name":"The regulatory logic of pattern formation in the vertebrate dorsal neural tube","grant_number":"SC19-011","_id":"9B9B39FA-BA93-11EA-9121-9846C619BF3A"}],"publication_status":"published","publisher":"Institute of Science and Technology Austria"},{"_id":"18579","abstract":[{"lang":"eng","text":"Electrophysiological, calcium two-photon recordings and behavioral data for Vega-Zuniga et al.  Relevant information can be found in the 'README.txt' files. "}],"file":[{"date_created":"2024-12-06T13:28:18Z","file_size":800647957,"content_type":"application/x-zip-compressed","file_id":"18625","checksum":"8b13990ca1a458ae3f3ae54c2e888564","creator":"symonova","file_name":"electro_physiology_data.zip","date_updated":"2024-12-09T10:24:25Z","access_level":"open_access","relation":"main_file"},{"file_name":"NN_vLGN_Ca_data.zip","access_level":"open_access","date_updated":"2024-12-09T10:21:10Z","relation":"main_file","date_created":"2024-12-09T10:21:10Z","file_size":828410832,"success":1,"content_type":"application/x-zip-compressed","file_id":"18636","checksum":"c5a4d71c5f29c009c3d96a3244532afa","creator":"symonova"},{"relation":"main_file","date_updated":"2024-12-09T12:54:55Z","access_level":"open_access","file_name":"readme.txt","creator":"symonova","checksum":"63651df0186196969553dc48b467f6ab","file_id":"18637","content_type":"text/plain","success":1,"date_created":"2024-12-09T12:54:55Z","file_size":505}],"month":"12","department":[{"_id":"MaJö"}],"related_material":{"record":[{"relation":"used_in_publication","id":"19076","status":"public"}]},"date_updated":"2025-09-30T10:40:48Z","corr_author":"1","oa":1,"doi":"10.15479/AT:ISTA:18579","has_accepted_license":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"PreCl"},{"_id":"M-Shop"},{"_id":"Bio"},{"_id":"LifeSc"}],"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.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/AT:ISTA:18579\">https://doi.org/10.15479/AT:ISTA:18579</a>.","apa":"Vega Zuniga, T. A., Sumser, A. L., Symonova, O., Koppensteiner, P., Schmidt, F., &#38; Jösch, M. A. (2024). A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:18579\">https://doi.org/10.15479/AT:ISTA:18579</a>","mla":"Vega Zuniga, Tomas A., et al. <i>A Thalamic Hub-and-Spoke Network Enables Visual Perception during Action by Coordinating Visuomotor Dynamics</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:18579\">10.15479/AT:ISTA:18579</a>.","ista":"Vega Zuniga TA, Sumser AL, Symonova O, Koppensteiner P, Schmidt F, Jösch MA. 2024. A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:18579\">10.15479/AT:ISTA:18579</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.” Institute of Science and Technology Austria, 2024.","short":"T.A. Vega Zuniga, A.L. Sumser, O. Symonova, P. Koppensteiner, F. Schmidt, M.A. Jösch, (2024).","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. 2024. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:18579\">10.15479/AT:ISTA:18579</a>"},"file_date_updated":"2024-12-09T12:54:55Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","type":"research_data","day":"09","ddc":["570"],"date_published":"2024-12-09T00:00:00Z","publisher":"Institute of Science and Technology Austria","status":"public","date_created":"2024-11-22T13:48:12Z","acknowledgement":"Freyja Lange, Michael Schunn, and Todor Asenov","project":[{"_id":"264FEA02-B435-11E9-9278-68D0E5697425","grant_number":"ALTF 1098-2017","name":"Connecting sensory with motor processing in the superior colliculus"},{"grant_number":"LT000256","name":"Neuronal networks of salience and spatial detection in the murine superior colliculus","_id":"266D407A-B435-11E9-9278-68D0E5697425"},{"name":"Circuits of Visual Attention","grant_number":"756502","_id":"2634E9D2-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"101086580","name":"Action Selection in the Midbrain: Neuromodulation of Visuomotor Senses","_id":"bdaf81a8-d553-11ed-ba76-c95961984540"}],"year":"2024","author":[{"full_name":"Vega Zuniga, Tomas A","first_name":"Tomas A","id":"2E7C4E78-F248-11E8-B48F-1D18A9856A87","last_name":"Vega Zuniga"},{"first_name":"Anton L","full_name":"Sumser, Anton L","id":"3320A096-F248-11E8-B48F-1D18A9856A87","last_name":"Sumser","orcid":"0000-0002-4792-1881"},{"last_name":"Symonova","id":"3C0C7BC6-F248-11E8-B48F-1D18A9856A87","first_name":"Olga","full_name":"Symonova, Olga","orcid":"0000-0003-2012-9947"},{"orcid":"0000-0002-3509-1948","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","last_name":"Koppensteiner","full_name":"Koppensteiner, Peter","first_name":"Peter"},{"id":"A2EF226A-AF19-11E9-924C-0525E6697425","last_name":"Schmidt","first_name":"Florian","full_name":"Schmidt, Florian"},{"full_name":"Jösch, Maximilian A","first_name":"Maximilian A","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","last_name":"Jösch","orcid":"0000-0002-3937-1330"}],"OA_place":"publisher","oa_version":"Published Version","ec_funded":1,"article_processing_charge":"No","title":"A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics"}]