[{"project":[{"grant_number":"771209","_id":"26580278-B435-11E9-9278-68D0E5697425","name":"Characterizing the fitness landscape on population and global scales","call_identifier":"H2020"},{"call_identifier":"H2020","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385"}],"citation":{"chicago":"Gonzalez Somermeyer, Louisa, Aubin Fleiss, Alexander S Mishin, Nina G Bozhanova, Anna A Igolkina, Jens Meiler, Maria-Elisenda Alaball Pujol, Ekaterina V Putintseva, Karen S Sarkisyan, and Fyodor Kondrashov. “Heterogeneity of the GFP Fitness Landscape and Data-Driven Protein Design.” ELife. eLife Sciences Publications, 2022. https://doi.org/10.7554/elife.75842.","apa":"Gonzalez Somermeyer, L., Fleiss, A., Mishin, A. S., Bozhanova, N. G., Igolkina, A. A., Meiler, J., … Kondrashov, F. (2022). Heterogeneity of the GFP fitness landscape and data-driven protein design. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.75842","mla":"Gonzalez Somermeyer, Louisa, et al. “Heterogeneity of the GFP Fitness Landscape and Data-Driven Protein Design.” ELife, vol. 11, 75842, eLife Sciences Publications, 2022, doi:10.7554/elife.75842.","short":"L. Gonzalez Somermeyer, A. Fleiss, A.S. Mishin, N.G. Bozhanova, A.A. Igolkina, J. Meiler, M.-E. Alaball Pujol, E.V. Putintseva, K.S. Sarkisyan, F. Kondrashov, ELife 11 (2022).","ieee":"L. Gonzalez Somermeyer et al., “Heterogeneity of the GFP fitness landscape and data-driven protein design,” eLife, vol. 11. eLife Sciences Publications, 2022.","ama":"Gonzalez Somermeyer L, Fleiss A, Mishin AS, et al. Heterogeneity of the GFP fitness landscape and data-driven protein design. eLife. 2022;11. doi:10.7554/elife.75842","ista":"Gonzalez Somermeyer L, Fleiss A, Mishin AS, Bozhanova NG, Igolkina AA, Meiler J, Alaball Pujol M-E, Putintseva EV, Sarkisyan KS, Kondrashov F. 2022. Heterogeneity of the GFP fitness landscape and data-driven protein design. eLife. 11, 75842."},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ec_funded":1,"status":"public","day":"05","file_date_updated":"2022-06-20T07:44:19Z","oa":1,"isi":1,"date_updated":"2026-04-07T13:25:01Z","publisher":"eLife Sciences Publications","department":[{"_id":"GradSch"},{"_id":"FyKo"}],"date_published":"2022-05-05T00:00:00Z","month":"05","language":[{"iso":"eng"}],"acknowledgement":"We thank Ondřej Draganov, Rodrigo Redondo, Bor Kavčič, Mia Juračić and Andrea Pauli for discussion and technical advice. We thank Anita Testa Salmazo for advice on resin protein purification, Dmitry Bolotin and the Milaboratory (milaboratory.com) for access to computing and storage infrastructure, and Josef Houser and Eva Fujdiarova for technical assistance and data interpretation. Core facility Biomolecular Interactions and Crystallization of CEITEC Masaryk University is gratefully acknowledged for the obtaining of the scientific data presented in this paper. This research was supported by the Scientific Service Units (SSU) of IST-Austria\r\nthrough resources provided by the Bioimaging Facility (BIF), and the Life Science Facility (LSF). MiSeq and HiSeq NGS sequencing was performed by the Next Generation Sequencing Facility at Vienna BioCenter Core Facilities (VBCF), member of the Vienna BioCenter (VBC), Austria. FACS was performed at the BioOptics Facility of the Institute of Molecular Pathology (IMP), Austria. We also thank the Biomolecular Crystallography Facility in the Vanderbilt University Center for Structural Biology. We are grateful to Joel M Harp for help with X-ray data collection. This work was supported by the ERC Consolidator grant to FAK (771209—CharFL). KSS acknowledges support by President’s Grant МК–5405.2021.1.4, the Imperial College Research Fellowship and the MRC London Institute of Medical Sciences (UKRI MC-A658-5QEA0).\r\nAF is supported by the Marie Skłodowska-Curie Fellowship (H2020-MSCA-IF-2019, Grant Agreement No. 898203, Project acronym \"FLINDIP\"). Experiments were partially carried out using equipment provided by the Institute of Bioorganic Chemistry of the Russian Academy of Sciences Сore Facility (CKP IBCH). This work was supported by a Russian Science Foundation grant 19-74-10102.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 665,385.","type":"journal_article","oa_version":"Published Version","intvolume":" 11","article_type":"original","scopus_import":"1","_id":"11448","file":[{"file_id":"11454","access_level":"open_access","checksum":"7573c28f44028ab0cc81faef30039e44","relation":"main_file","file_size":5297213,"date_updated":"2022-06-20T07:44:19Z","date_created":"2022-06-20T07:44:19Z","content_type":"application/pdf","file_name":"2022_eLife_Somermeyer.pdf","success":1,"creator":"dernst"}],"quality_controlled":"1","corr_author":"1","ddc":["570"],"has_accepted_license":"1","article_number":"75842","date_created":"2022-06-18T09:06:59Z","year":"2022","publication":"eLife","doi":"10.7554/elife.75842","publication_identifier":{"issn":["2050-084X"]},"publication_status":"published","external_id":{"isi":["000799197200001"],"pmid":["35510622"]},"abstract":[{"text":"Studies of protein fitness landscapes reveal biophysical constraints guiding protein evolution and empower prediction of functional proteins. However, generalisation of these findings is limited due to scarceness of systematic data on fitness landscapes of proteins with a defined evolutionary relationship. We characterized the fitness peaks of four orthologous fluorescent proteins with a broad range of sequence divergence. While two of the four studied fitness peaks were sharp, the other two were considerably flatter, being almost entirely free of epistatic interactions. Mutationally robust proteins, characterized by a flat fitness peak, were not optimal templates for machine-learning-driven protein design – instead, predictions were more accurate for fragile proteins with epistatic landscapes. Our work paves insights for practical application of fitness landscape heterogeneity in protein engineering.","lang":"eng"}],"article_processing_charge":"No","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"title":"Heterogeneity of the GFP fitness landscape and data-driven protein design","volume":11,"author":[{"first_name":"Louisa","last_name":"Gonzalez Somermeyer","full_name":"Gonzalez Somermeyer, Louisa","orcid":"0000-0001-9139-5383","id":"4720D23C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Fleiss, Aubin","first_name":"Aubin","last_name":"Fleiss"},{"first_name":"Alexander S","last_name":"Mishin","full_name":"Mishin, Alexander S"},{"full_name":"Bozhanova, Nina G","first_name":"Nina G","last_name":"Bozhanova"},{"first_name":"Anna A","last_name":"Igolkina","full_name":"Igolkina, Anna A"},{"full_name":"Meiler, Jens","first_name":"Jens","last_name":"Meiler"},{"full_name":"Alaball Pujol, Maria-Elisenda","last_name":"Alaball Pujol","first_name":"Maria-Elisenda"},{"first_name":"Ekaterina V","last_name":"Putintseva","full_name":"Putintseva, Ekaterina V"},{"first_name":"Karen S","last_name":"Sarkisyan","full_name":"Sarkisyan, Karen S"},{"full_name":"Kondrashov, Fyodor","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8243-4694","last_name":"Kondrashov","first_name":"Fyodor"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"related_material":{"link":[{"url":"https://github.com/aequorea238/Orthologous_GFP_Fitness_Peaks","relation":"software"}],"record":[{"id":"17850","relation":"dissertation_contains","status":"public"}]},"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}]},{"year":"2022","date_created":"2022-08-07T22:01:57Z","article_number":"e2122460119","issue":"31","doi":"10.1073/pnas.2122460119","publication_identifier":{"eissn":["1091-6490"]},"publication":"Proceedings of the National Academy of Sciences of the United States of America","corr_author":"1","file":[{"success":1,"creator":"dernst","file_name":"2022_PNAS_Abualia.pdf","content_type":"application/pdf","date_created":"2022-08-08T07:09:58Z","file_size":3092330,"date_updated":"2022-08-08T07:09:58Z","access_level":"open_access","relation":"main_file","checksum":"6e97dedc281247fc3fe238a209f14af0","file_id":"11744"}],"quality_controlled":"1","has_accepted_license":"1","ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"first_name":"Rashed","last_name":"Abualia","orcid":"0000-0002-9357-9415","id":"4827E134-F248-11E8-B48F-1D18A9856A87","full_name":"Abualia, Rashed"},{"first_name":"Krisztina","last_name":"Ötvös","full_name":"Ötvös, Krisztina","orcid":"0000-0002-5503-4983","id":"29B901B0-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Ondřej","last_name":"Novák","full_name":"Novák, Ondřej"},{"full_name":"Bouguyon, Eleonore","first_name":"Eleonore","last_name":"Bouguyon"},{"id":"a24c7829-16e8-11ed-8527-c4d36ffb7539","orcid":"0000-0002-1215-4264","full_name":"Domanegg, Kevin","first_name":"Kevin","last_name":"Domanegg"},{"full_name":"Krapp, Anne","last_name":"Krapp","first_name":"Anne"},{"last_name":"Nacry","first_name":"Philip","full_name":"Nacry, Philip"},{"first_name":"Alain","last_name":"Gojon","full_name":"Gojon, Alain"},{"last_name":"Lacombe","first_name":"Benoit","full_name":"Lacombe, Benoit"},{"last_name":"Benková","first_name":"Eva","full_name":"Benková, Eva","orcid":"0000-0002-8510-9739","id":"38F4F166-F248-11E8-B48F-1D18A9856A87"}],"volume":119,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"pmid":1,"article_processing_charge":"No","abstract":[{"lang":"eng","text":"Mineral nutrition is one of the key environmental factors determining plant development and growth. Nitrate is the major form of macronutrient nitrogen that plants take up from the soil. Fluctuating availability or deficiency of this element severely limits plant growth and negatively affects crop production in the agricultural system. To cope with the heterogeneity of nitrate distribution in soil, plants evolved a complex regulatory mechanism that allows rapid adjustment of physiological and developmental processes to the status of this nutrient. The root, as a major exploitation organ that controls the uptake of nitrate to the plant body, acts as a regulatory hub that, according to nitrate availability, coordinates the growth and development of other plant organs. Here, we identified a regulatory framework, where cytokinin response factors (CRFs) play a central role as a molecular readout of the nitrate status in roots to guide shoot adaptive developmental response. We show that nitrate-driven activation of NLP7, a master regulator of nitrate response in plants, fine tunes biosynthesis of cytokinin in roots and its translocation to shoots where it enhances expression of CRFs. CRFs, through direct transcriptional regulation of PIN auxin transporters, promote the flow of auxin and thereby stimulate the development of shoot organs."}],"publication_status":"published","external_id":{"pmid":["35878040"],"isi":["000881496900007"]},"title":"Molecular framework integrating nitrate sensing in root and auxin-guided shoot adaptive responses","tmp":{"short":"CC BY-NC-ND (4.0)","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","image":"/images/cc_by_nc_nd.png"},"day":"25","status":"public","citation":{"mla":"Abualia, Rashed, et al. “Molecular Framework Integrating Nitrate Sensing in Root and Auxin-Guided Shoot Adaptive Responses.” Proceedings of the National Academy of Sciences of the United States of America, vol. 119, no. 31, e2122460119, National Academy of Sciences, 2022, doi:10.1073/pnas.2122460119.","chicago":"Abualia, Rashed, Krisztina Ötvös, Ondřej Novák, Eleonore Bouguyon, Kevin Domanegg, Anne Krapp, Philip Nacry, Alain Gojon, Benoit Lacombe, and Eva Benková. “Molecular Framework Integrating Nitrate Sensing in Root and Auxin-Guided Shoot Adaptive Responses.” Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 2022. https://doi.org/10.1073/pnas.2122460119.","apa":"Abualia, R., Ötvös, K., Novák, O., Bouguyon, E., Domanegg, K., Krapp, A., … Benková, E. (2022). Molecular framework integrating nitrate sensing in root and auxin-guided shoot adaptive responses. Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. https://doi.org/10.1073/pnas.2122460119","ama":"Abualia R, Ötvös K, Novák O, et al. Molecular framework integrating nitrate sensing in root and auxin-guided shoot adaptive responses. Proceedings of the National Academy of Sciences of the United States of America. 2022;119(31). doi:10.1073/pnas.2122460119","ista":"Abualia R, Ötvös K, Novák O, Bouguyon E, Domanegg K, Krapp A, Nacry P, Gojon A, Lacombe B, Benková E. 2022. Molecular framework integrating nitrate sensing in root and auxin-guided shoot adaptive responses. Proceedings of the National Academy of Sciences of the United States of America. 119(31), e2122460119.","ieee":"R. Abualia et al., “Molecular framework integrating nitrate sensing in root and auxin-guided shoot adaptive responses,” Proceedings of the National Academy of Sciences of the United States of America, vol. 119, no. 31. National Academy of Sciences, 2022.","short":"R. Abualia, K. Ötvös, O. Novák, E. Bouguyon, K. Domanegg, A. Krapp, P. Nacry, A. Gojon, B. Lacombe, E. Benková, Proceedings of the National Academy of Sciences of the United States of America 119 (2022)."},"project":[{"grant_number":"I 1774-B16","_id":"2542D156-B435-11E9-9278-68D0E5697425","name":"Hormone cross-talk drives nutrient dependent plant development","call_identifier":"FWF"}],"article_type":"original","intvolume":" 119","oa_version":"Published Version","acknowledgement":"We acknowledge Hana Semeradova, Juan Carlos Montesinos, Nicola Cavallari, Marc¸al Gallem\u0003ı, Kaori Tabata, Andrej Hurn\u0003y, and Sascha Waidmann for sharing materials; and Marina Borges Osorio for critical reading of the manuscript. Work in the E. Benkova laboratory was supported by the Austrian Science Fund (FWF01_I1774S) to K.O., R.A., and E. Benkova. We acknowledge the Bioimaging Facility and Life Science Facilities of the Institute of Science\r\nand Technology Austria. We give sincere thanks to Hana Martınkova and Petra Amakorova for their help with cytokinin analyses. This work was funded by the Czech Science Foundation (Project No. 19-00973S).","type":"journal_article","_id":"11734","scopus_import":"1","isi":1,"oa":1,"file_date_updated":"2022-08-08T07:09:58Z","month":"07","language":[{"iso":"eng"}],"date_published":"2022-07-25T00:00:00Z","publisher":"National Academy of Sciences","department":[{"_id":"EvBe"}],"date_updated":"2025-05-14T11:00:29Z"},{"article_processing_charge":"No","page":"133","publication_status":"published","abstract":[{"lang":"eng","text":"G protein-coupled receptors (GPCRs) respond to specific ligands and regulate multiple processes ranging from cell growth and immune responses to neuronal signal transmission. However, ligands for many GPCRs remain unknown, suffer from off-target effects or have poor bioavailability. Additional challenges exist to dissect cell-type specific responses when the same GPCR is expressed on several cell types within the body. Here, we overcome these limitations by engineering DREADD-based GPCR chimeras that selectively bind their agonist clozapine-N-oxide (CNO) and mimic a GPCR-of-interest in a desired cell type.\r\nWe validated our approach with β2-adrenergic receptor (β2AR/ADRB2) and show that our chimeric DREADD-β2AR triggers comparable responses on second messenger and kinase activity, post-translational modifications, and protein-protein interactions. Since β2AR is also enriched in microglia, which can drive inflammation in the central nervous system, we expressed chimeric DREADD-β2AR in primary microglia and successfully recapitulate β2AR-mediated filopodia formation through CNO stimulation. To dissect the role of selected GPCRs during microglial inflammation, we additionally generated DREADD-based chimeras for microglia-enriched GPR65 and GPR109A/HCAR2. In a microglia cell line, DREADD-β2AR and DREADD-GPR65 both modulated the inflammatory response with a similar profile as endogenously expressed β2AR, while DREADD-GPR109A showed no impact.\r\nOur DREADD-based approach provides the means to obtain mechanistic and functional insights into GPCR signaling on a cell-type specific level."}],"supervisor":[{"last_name":"Siegert","first_name":"Sandra","full_name":"Siegert, Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877"}],"degree_awarded":"PhD","title":"Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function","author":[{"orcid":"0000-0001-5297-733X","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","full_name":"Schulz, Rouven","first_name":"Rouven","last_name":"Schulz"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","OA_place":"publisher","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"}],"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"11995"}]},"corr_author":"1","file":[{"access_level":"open_access","checksum":"61b1b666a210ff7cdd0e95ea75207a13","relation":"main_file","date_updated":"2022-08-25T08:59:57Z","file_size":28079331,"file_id":"11970","success":1,"creator":"rschulz","date_created":"2022-08-25T08:59:57Z","content_type":"application/pdf","file_name":"Thesis_Rouven_Schulz_2022_final.pdf"},{"creator":"rschulz","date_created":"2022-08-25T09:00:11Z","file_name":"Thesis_Rouven_Schulz_2022_final.docx","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","checksum":"2b8f95ea1c134dbdb927b41b1dbeeeb5","relation":"source_file","access_level":"closed","file_size":27226963,"date_updated":"2022-08-25T09:33:31Z","file_id":"11971"}],"has_accepted_license":"1","ddc":["570"],"date_created":"2022-08-23T11:33:11Z","year":"2022","publication_identifier":{"issn":["2663-337X"]},"doi":"10.15479/at:ista:11945","file_date_updated":"2022-08-25T09:33:31Z","oa":1,"date_published":"2022-08-23T00:00:00Z","language":[{"iso":"eng"}],"month":"08","date_updated":"2026-04-07T14:17:59Z","publisher":"Institute of Science and Technology Austria","department":[{"_id":"GradSch"},{"_id":"SaSi"}],"oa_version":"Published Version","type":"dissertation","_id":"11945","citation":{"mla":"Schulz, Rouven. Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling Pathways and Modulate Microglia Function. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:11945.","apa":"Schulz, R. (2022). Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:11945","chicago":"Schulz, Rouven. “Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling Pathways and Modulate Microglia Function.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:11945.","ama":"Schulz R. Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function. 2022. doi:10.15479/at:ista:11945","ista":"Schulz R. 2022. Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function. Institute of Science and Technology Austria.","ieee":"R. Schulz, “Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function,” Institute of Science and Technology Austria, 2022.","short":"R. Schulz, Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling Pathways and Modulate Microglia Function, Institute of Science and Technology Austria, 2022."},"project":[{"_id":"267F75D8-B435-11E9-9278-68D0E5697425","name":"Modulating microglia through G protein-coupled receptor (GPCR) signaling"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"alternative_title":["ISTA Thesis"],"day":"23","status":"public"},{"has_accepted_license":"1","ddc":["570"],"corr_author":"1","quality_controlled":"1","file":[{"file_id":"11990","file_size":5910357,"date_updated":"2022-08-26T11:51:40Z","checksum":"405936d9e4d33625d80c093c9713a91f","relation":"main_file","access_level":"open_access","file_name":"2022_NatureCommunications_BenSimon.pdf","content_type":"application/pdf","date_created":"2022-08-26T11:51:40Z","creator":"dernst","success":1}],"publication_identifier":{"issn":["2041-1723"]},"doi":"10.1038/s41467-022-32559-8","publication":"Nature Communications","year":"2022","date_created":"2022-08-24T08:25:50Z","article_number":"4826","title":"A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory","keyword":["General Physics and Astronomy","General Biochemistry","Genetics and Molecular Biology","General Chemistry","Multidisciplinary"],"article_processing_charge":"No","abstract":[{"text":"The mammalian hippocampal formation (HF) plays a key role in several higher brain functions, such as spatial coding, learning and memory. Its simple circuit architecture is often viewed as a trisynaptic loop, processing input originating from the superficial layers of the entorhinal cortex (EC) and sending it back to its deeper layers. Here, we show that excitatory neurons in layer 6b of the mouse EC project to all sub-regions comprising the HF and receive input from the CA1, thalamus and claustrum. Furthermore, their output is characterized by unique slow-decaying excitatory postsynaptic currents capable of driving plateau-like potentials in their postsynaptic targets. Optogenetic inhibition of the EC-6b pathway affects spatial coding in CA1 pyramidal neurons, while cell ablation impairs not only acquisition of new spatial memories, but also degradation of previously acquired ones. Our results provide evidence of a functional role for cortical layer 6b neurons in the adult brain.","lang":"eng"}],"external_id":{"pmid":["35974109"],"isi":["000841396400008"]},"publication_status":"published","acknowledged_ssus":[{"_id":"Bio"},{"_id":"SSU"}],"pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"full_name":"Ben Simon, Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","last_name":"Ben Simon","first_name":"Yoav"},{"id":"2DAA49AA-F248-11E8-B48F-1D18A9856A87","full_name":"Käfer, Karola","last_name":"Käfer","first_name":"Karola"},{"first_name":"Philipp","last_name":"Velicky","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431","full_name":"Velicky, Philipp"},{"full_name":"Csicsvari, Jozsef L","orcid":"0000-0002-5193-4036","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","first_name":"Jozsef L","last_name":"Csicsvari"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","first_name":"Johann G","last_name":"Danzl"},{"first_name":"Peter M","last_name":"Jonas","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"volume":13,"citation":{"ista":"Ben Simon Y, Käfer K, Velicky P, Csicsvari JL, Danzl JG, Jonas PM. 2022. A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. Nature Communications. 13, 4826.","ama":"Ben Simon Y, Käfer K, Velicky P, Csicsvari JL, Danzl JG, Jonas PM. A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. Nature Communications. 2022;13. doi:10.1038/s41467-022-32559-8","short":"Y. Ben Simon, K. Käfer, P. Velicky, J.L. Csicsvari, J.G. Danzl, P.M. Jonas, Nature Communications 13 (2022).","ieee":"Y. Ben Simon, K. Käfer, P. Velicky, J. L. Csicsvari, J. G. Danzl, and P. M. Jonas, “A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory,” Nature Communications, vol. 13. Springer Nature, 2022.","mla":"Ben Simon, Yoav, et al. “A Direct Excitatory Projection from Entorhinal Layer 6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” Nature Communications, vol. 13, 4826, Springer Nature, 2022, doi:10.1038/s41467-022-32559-8.","apa":"Ben Simon, Y., Käfer, K., Velicky, P., Csicsvari, J. L., Danzl, J. G., & Jonas, P. M. (2022). A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-32559-8","chicago":"Ben Simon, Yoav, Karola Käfer, Philipp Velicky, Jozsef L Csicsvari, Johann G Danzl, and Peter M Jonas. “A Direct Excitatory Projection from Entorhinal Layer 6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-32559-8."},"project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","call_identifier":"H2020","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF"},{"name":"Synaptic communication in neuronal microcircuits","call_identifier":"FWF","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425"}],"status":"public","day":"16","ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"month":"08","language":[{"iso":"eng"}],"date_published":"2022-08-16T00:00:00Z","department":[{"_id":"JoCs"},{"_id":"PeJo"},{"_id":"JoDa"}],"publisher":"Springer Nature","date_updated":"2025-06-12T06:10:44Z","isi":1,"oa":1,"file_date_updated":"2022-08-26T11:51:40Z","_id":"11951","scopus_import":"1","article_type":"original","intvolume":" 13","oa_version":"Published Version","type":"journal_article","acknowledgement":"We thank F. Marr and A. Schlögl for technical assistance, E. Kralli-Beller for manuscript editing, as well as C. Sommer and the Imaging and Optics Facility of the Institute of Science and Technology Austria (ISTA) for image analysis scripts and microscopy support. We extend our gratitude to J. Wallenschus and D. Rangel Guerrero for technical assistance acquiring single-unit data and I. Gridchyn for help with single-unit clustering. Finally, we also thank B. Suter for discussions, A. Saunders, M. Jösch, and H. Monyer for critically reading earlier versions of the manuscript, C. Petersen for sharing clearing protocols, and the Scientific Service Units of ISTA for efficient support. This project was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC advanced grant No 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award for P.J. and I3600-B27 for J.G.D. and P.V.)."},{"title":"Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses","external_id":{"pmid":["35970889"],"isi":["000840984400032"]},"publication_status":"published","abstract":[{"text":"G protein-coupled receptors (GPCRs) regulate processes ranging from immune responses to neuronal signaling. However, ligands for many GPCRs remain unknown, suffer from off-target effects or have poor bioavailability. Additionally, dissecting cell type-specific responses is challenging when the same GPCR is expressed on different cells within a tissue. Here, we overcome these limitations by engineering DREADD-based GPCR chimeras that bind clozapine-N-oxide and mimic a GPCR-of-interest. We show that chimeric DREADD-β2AR triggers responses comparable to β2AR on second messenger and kinase activity, post-translational modifications, and protein-protein interactions. Moreover, we successfully recapitulate β2AR-mediated filopodia formation in microglia, an immune cell capable of driving central nervous system inflammation. When dissecting microglial inflammation, we included two additional DREADD-based chimeras mimicking microglia-enriched GPR65 and GPR109A. DREADD-β2AR and DREADD-GPR65 modulate the inflammatory response with high similarity to endogenous β2AR, while DREADD-GPR109A shows no impact. Our DREADD-based approach allows investigation of cell type-dependent pathways without known endogenous ligands.","lang":"eng"}],"article_processing_charge":"No","pmid":1,"related_material":{"link":[{"url":"https://ista.ac.at/en/news/dreaddful-mimicry/","relation":"press_release","description":"News on ISTA website"}],"record":[{"relation":"research_data","id":"11542","status":"public"},{"relation":"part_of_dissertation","id":"11945","status":"public"}]},"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"LifeSc"}],"volume":13,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"full_name":"Schulz, Rouven","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5297-733X","last_name":"Schulz","first_name":"Rouven"},{"id":"4B51CE74-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4309-2251","full_name":"Korkut, Medina","last_name":"Korkut","first_name":"Medina"},{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2356-9403","full_name":"Venturino, Alessandro","last_name":"Venturino","first_name":"Alessandro"},{"last_name":"Colombo","first_name":"Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9434-8902","full_name":"Colombo, Gloria"},{"last_name":"Siegert","first_name":"Sandra","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Siegert, Sandra"}],"ddc":["570"],"has_accepted_license":"1","quality_controlled":"1","file":[{"checksum":"191d9db0266e14a28d3a56dc7f65da84","relation":"main_file","access_level":"open_access","date_updated":"2022-08-29T06:44:30Z","file_size":7317396,"file_id":"12002","creator":"cchlebak","success":1,"date_created":"2022-08-29T06:44:30Z","file_name":"2022_NatComm_Schulz.pdf","content_type":"application/pdf"}],"corr_author":"1","publication":"Nature Communications","publication_identifier":{"eissn":["2041-1723"]},"doi":"10.1038/s41467-022-32390-1","article_number":"4728","date_created":"2022-08-28T22:01:59Z","year":"2022","date_updated":"2026-04-07T14:17:58Z","department":[{"_id":"SaSi"}],"publisher":"Springer Nature","date_published":"2022-08-15T00:00:00Z","language":[{"iso":"eng"}],"month":"08","file_date_updated":"2022-08-29T06:44:30Z","oa":1,"isi":1,"scopus_import":"1","_id":"11995","type":"journal_article","acknowledgement":"The authors thank the Scientific Service Units at ISTA, in particular the Molecular Biology Service of the Lab Support Facility, Imaging & Optics Facility, and the Preclinical Facility, and the Novarino group, Harald Janoviak, and Marco Benevento for sharing reagents and expertise. This research was supported by a DOC Fellowship (24979) awarded to R.S. by the Austrian Academy of Sciences.","oa_version":"Published Version","intvolume":" 13","article_type":"original","project":[{"name":"Modulating microglia through G protein-coupled receptor (GPCR) signaling","_id":"267F75D8-B435-11E9-9278-68D0E5697425"}],"citation":{"mla":"Schulz, Rouven, et al. “Chimeric GPCRs Mimic Distinct Signaling Pathways and Modulate Microglia Responses.” Nature Communications, vol. 13, 4728, Springer Nature, 2022, doi:10.1038/s41467-022-32390-1.","chicago":"Schulz, Rouven, Medina Korkut, Alessandro Venturino, Gloria Colombo, and Sandra Siegert. “Chimeric GPCRs Mimic Distinct Signaling Pathways and Modulate Microglia Responses.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-32390-1.","apa":"Schulz, R., Korkut, M., Venturino, A., Colombo, G., & Siegert, S. (2022). Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-32390-1","ista":"Schulz R, Korkut M, Venturino A, Colombo G, Siegert S. 2022. Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses. Nature Communications. 13, 4728.","ama":"Schulz R, Korkut M, Venturino A, Colombo G, Siegert S. Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses. Nature Communications. 2022;13. doi:10.1038/s41467-022-32390-1","short":"R. Schulz, M. Korkut, A. Venturino, G. Colombo, S. Siegert, Nature Communications 13 (2022).","ieee":"R. Schulz, M. Korkut, A. Venturino, G. Colombo, and S. Siegert, “Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses,” Nature Communications, vol. 13. Springer Nature, 2022."},"status":"public","day":"15","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"}},{"article_processing_charge":"No","abstract":[{"text":"Proximity-dependent protein labeling provides a powerful in vivo strategy to characterize the interactomes of specific proteins. We previously optimized a proximity labeling protocol for Caenorhabditis elegans using the highly active biotin ligase TurboID. A significant constraint on the sensitivity of TurboID is the presence of abundant endogenously biotinylated proteins that take up bandwidth in the mass spectrometer, notably carboxylases that use biotin as a cofactor. In C. elegans, these comprise POD-2/acetyl-CoA carboxylase alpha, PCCA-1/propionyl-CoA carboxylase alpha, PYC-1/pyruvate carboxylase, and MCCC-1/methylcrotonyl-CoA carboxylase alpha. Here, we developed ways to remove these carboxylases prior to streptavidin purification and mass spectrometry by engineering their corresponding genes to add a C-terminal His10 tag. This allows us to deplete them from C. elegans lysates using immobilized metal affinity chromatography. To demonstrate the method's efficacy, we use it to expand the interactome map of the presynaptic active zone protein ELKS-1. We identify many known active zone proteins, including UNC-10/RIM, SYD-2/liprin-alpha, SAD-1/BRSK1, CLA-1/CLArinet, C16E9.2/Sentryn, as well as previously uncharacterized potentially synaptic proteins such as the ortholog of human angiomotin, F59C12.3 and the uncharacterized protein R148.3. Our approach provides a quick and inexpensive solution to a common contaminant problem in biotin-dependent proximity labeling. The approach may be applicable to other model organisms and will enable deeper and more complete analysis of interactors for proteins of interest.","lang":"eng"}],"publication_status":"published","external_id":{"isi":["000884241800011"],"pmid":["35933017"]},"title":"Depletion of endogenously biotinylated carboxylases enhances the sensitivity of TurboID-mediated proximity labeling in Caenorhabditis elegans","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"full_name":"Artan, Murat","orcid":"0000-0001-8945-6992","id":"C407B586-6052-11E9-B3AE-7006E6697425","last_name":"Artan","first_name":"Murat"},{"full_name":"Hartl, Markus","last_name":"Hartl","first_name":"Markus"},{"full_name":"Chen, Weiqiang","last_name":"Chen","first_name":"Weiqiang"},{"first_name":"Mario","last_name":"De Bono","id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8347-0443","full_name":"De Bono, Mario"}],"volume":298,"acknowledged_ssus":[{"_id":"Bio"}],"pmid":1,"corr_author":"1","file":[{"file_size":2101656,"date_updated":"2022-09-12T08:14:50Z","access_level":"open_access","relation":"main_file","checksum":"e726c7b9315230e6710e0b1f1d1677e9","file_id":"12092","success":1,"creator":"dernst","file_name":"2022_JBC_Artan.pdf","content_type":"application/pdf","date_created":"2022-09-12T08:14:50Z"}],"quality_controlled":"1","has_accepted_license":"1","ddc":["570"],"year":"2022","date_created":"2022-09-11T22:01:55Z","article_number":"102343","issue":"9","publication_identifier":{"issn":["0021-9258"],"eissn":["1083-351X"]},"doi":"10.1016/j.jbc.2022.102343","publication":"Journal of Biological Chemistry","isi":1,"oa":1,"file_date_updated":"2022-09-12T08:14:50Z","month":"09","language":[{"iso":"eng"}],"date_published":"2022-09-01T00:00:00Z","publisher":"Elsevier","department":[{"_id":"MaDe"}],"date_updated":"2025-04-14T07:44:00Z","article_type":"original","oa_version":"Published Version","intvolume":" 298","acknowledgement":"We thank de Bono laboratory members for helpful comments on the article and the Mass Spec Facilities at IST Austria and Max Perutz Labs for invaluable discussions and comments on how to optimize mass spec analyses of worm samples. We are grateful to Ekaterina Lashmanova for designing the degron knock-in constructs and preparing the injection mixes for CRISPR/Cas9-mediated genome editing. All LC–MS/MS analyses were performed on instruments of the Vienna BioCenter Core Facilities instrument pool.\r\nThis work was supported by a Wellcome Investigator Award (grant no.: 209504/Z/17/Z ) to M.d.B. and an ISTplus Fellowship to M.A. (Marie Sklodowska-Curie agreement no.: 754411).","type":"journal_article","_id":"12082","scopus_import":"1","citation":{"short":"M. Artan, M. Hartl, W. Chen, M. de Bono, Journal of Biological Chemistry 298 (2022).","ieee":"M. Artan, M. Hartl, W. Chen, and M. de Bono, “Depletion of endogenously biotinylated carboxylases enhances the sensitivity of TurboID-mediated proximity labeling in Caenorhabditis elegans,” Journal of Biological Chemistry, vol. 298, no. 9. Elsevier, 2022.","ama":"Artan M, Hartl M, Chen W, de Bono M. Depletion of endogenously biotinylated carboxylases enhances the sensitivity of TurboID-mediated proximity labeling in Caenorhabditis elegans. Journal of Biological Chemistry. 2022;298(9). doi:10.1016/j.jbc.2022.102343","ista":"Artan M, Hartl M, Chen W, de Bono M. 2022. Depletion of endogenously biotinylated carboxylases enhances the sensitivity of TurboID-mediated proximity labeling in Caenorhabditis elegans. Journal of Biological Chemistry. 298(9), 102343.","apa":"Artan, M., Hartl, M., Chen, W., & de Bono, M. (2022). Depletion of endogenously biotinylated carboxylases enhances the sensitivity of TurboID-mediated proximity labeling in Caenorhabditis elegans. Journal of Biological Chemistry. Elsevier. https://doi.org/10.1016/j.jbc.2022.102343","chicago":"Artan, Murat, Markus Hartl, Weiqiang Chen, and Mario de Bono. “Depletion of Endogenously Biotinylated Carboxylases Enhances the Sensitivity of TurboID-Mediated Proximity Labeling in Caenorhabditis Elegans.” Journal of Biological Chemistry. Elsevier, 2022. https://doi.org/10.1016/j.jbc.2022.102343.","mla":"Artan, Murat, et al. “Depletion of Endogenously Biotinylated Carboxylases Enhances the Sensitivity of TurboID-Mediated Proximity Labeling in Caenorhabditis Elegans.” Journal of Biological Chemistry, vol. 298, no. 9, 102343, Elsevier, 2022, doi:10.1016/j.jbc.2022.102343."},"project":[{"name":"Molecular mechanisms of neural circuit function","_id":"23870BE8-32DE-11EA-91FC-C7463DDC885E","grant_number":"209504/A/17/Z"},{"call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411"}],"ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","day":"01"},{"date_updated":"2025-06-11T13:58:47Z","publisher":"Elsevier","department":[{"_id":"SaSi"},{"_id":"GradSch"}],"date_published":"2022-12-16T00:00:00Z","month":"12","language":[{"iso":"eng"}],"file_date_updated":"2023-01-23T09:50:51Z","oa":1,"scopus_import":"1","_id":"12117","acknowledgement":"This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant No. 715571 to S.S.) and from the Gesellschaft für Forschungsförderung Niederösterreich (grant No. Sc19-017 to V.H.). We thank Rouven Schulz and Alessandro Venturino for their insights into functional assays and data analysis, Verena Seiboth for insights into necessary institutional permission, and ISTA imaging & optics facility (IOF) especially Bernhard Hochreiter for their support.","type":"journal_article","oa_version":"Published Version","intvolume":" 3","article_type":"letter_note","project":[{"call_identifier":"H2020","name":"Microglia action towards neuronal circuit formation and function in health and disease","_id":"25D4A630-B435-11E9-9278-68D0E5697425","grant_number":"715571"},{"name":"How human microglia shape developing neurons during health and inflammation","grant_number":"SC19-017","_id":"9B99D380-BA93-11EA-9121-9846C619BF3A"}],"citation":{"apa":"Hübschmann, V., Korkut, M., & Siegert, S. (2022). Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. STAR Protocols. Elsevier. https://doi.org/10.1016/j.xpro.2022.101866","chicago":"Hübschmann, Verena, Medina Korkut, and Sandra Siegert. “Assessing Human IPSC-Derived Microglia Identity and Function by Immunostaining, Phagocytosis, Calcium Activity, and Inflammation Assay.” STAR Protocols. Elsevier, 2022. https://doi.org/10.1016/j.xpro.2022.101866.","mla":"Hübschmann, Verena, et al. “Assessing Human IPSC-Derived Microglia Identity and Function by Immunostaining, Phagocytosis, Calcium Activity, and Inflammation Assay.” STAR Protocols, vol. 3, no. 4, 101866, Elsevier, 2022, doi:10.1016/j.xpro.2022.101866.","ieee":"V. Hübschmann, M. Korkut, and S. Siegert, “Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay,” STAR Protocols, vol. 3, no. 4. Elsevier, 2022.","short":"V. Hübschmann, M. Korkut, S. Siegert, STAR Protocols 3 (2022).","ama":"Hübschmann V, Korkut M, Siegert S. Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. STAR Protocols. 2022;3(4). doi:10.1016/j.xpro.2022.101866","ista":"Hübschmann V, Korkut M, Siegert S. 2022. Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. STAR Protocols. 3(4), 101866."},"day":"16","status":"public","tmp":{"short":"CC BY-NC-ND (4.0)","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","image":"/images/cc_by_nc_nd.png"},"ec_funded":1,"keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Neuroscience"],"title":"Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay","publication_status":"published","external_id":{"pmid":["36595902"]},"abstract":[{"text":"To understand how potential gene manipulations affect in vitro microglia, we provide a set of short protocols to evaluate microglia identity and function. We detail steps for immunostaining to determine microglia identity. We describe three functional assays for microglia: phagocytosis, calcium response following ATP stimulation, and cytokine expression upon inflammatory stimuli. We apply these protocols to human induced-pluripotent-stem-cell (hiPSC)-derived microglia, but they can be also applied to other in vitro microglial models including primary mouse microglia.\r\nFor complete details on the use and execution of this protocol, please refer to Bartalska et al. (2022).1","lang":"eng"}],"article_processing_charge":"No","pmid":1,"related_material":{"record":[{"id":"11478","relation":"other","status":"public"}]},"acknowledged_ssus":[{"_id":"Bio"}],"volume":3,"author":[{"last_name":"Hübschmann","first_name":"Verena","id":"32B7C918-F248-11E8-B48F-1D18A9856A87","full_name":"Hübschmann, Verena"},{"first_name":"Medina","last_name":"Korkut","full_name":"Korkut, Medina","id":"4B51CE74-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4309-2251"},{"full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert","first_name":"Sandra"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"has_accepted_license":"1","file":[{"file_id":"12340","access_level":"open_access","checksum":"3c71b8a60633d42c2f77c49025d5559b","relation":"main_file","file_size":6251945,"date_updated":"2023-01-23T09:50:51Z","date_created":"2023-01-23T09:50:51Z","file_name":"2022_STARProtocols_Huebschmann.pdf","content_type":"application/pdf","success":1,"creator":"dernst"}],"quality_controlled":"1","corr_author":"1","publication":"STAR Protocols","publication_identifier":{"issn":["2666-1667"]},"doi":"10.1016/j.xpro.2022.101866","issue":"4","article_number":"101866","date_created":"2023-01-12T11:56:38Z","year":"2022"},{"project":[{"_id":"261099A6-B435-11E9-9278-68D0E5697425","grant_number":"742985","call_identifier":"H2020","name":"Tracing Evolution of Auxin Transport and Polarity in Plants"}],"citation":{"ama":"Qi L, Kwiatkowski M, Chen H, et al. Adenylate cyclase activity of TIR1/AFB auxin receptors in plants. Nature. 2022;611(7934):133-138. doi:10.1038/s41586-022-05369-7","ista":"Qi L, Kwiatkowski M, Chen H, Hörmayer L, Sinclair SA, Zou M, del Genio CI, Kubeš MF, Napier R, Jaworski K, Friml J. 2022. Adenylate cyclase activity of TIR1/AFB auxin receptors in plants. Nature. 611(7934), 133–138.","short":"L. Qi, M. Kwiatkowski, H. Chen, L. Hörmayer, S.A. Sinclair, M. Zou, C.I. del Genio, M.F. Kubeš, R. Napier, K. Jaworski, J. Friml, Nature 611 (2022) 133–138.","ieee":"L. Qi et al., “Adenylate cyclase activity of TIR1/AFB auxin receptors in plants,” Nature, vol. 611, no. 7934. Springer Nature, pp. 133–138, 2022.","mla":"Qi, Linlin, et al. “Adenylate Cyclase Activity of TIR1/AFB Auxin Receptors in Plants.” Nature, vol. 611, no. 7934, Springer Nature, 2022, pp. 133–38, doi:10.1038/s41586-022-05369-7.","apa":"Qi, L., Kwiatkowski, M., Chen, H., Hörmayer, L., Sinclair, S. A., Zou, M., … Friml, J. (2022). Adenylate cyclase activity of TIR1/AFB auxin receptors in plants. Nature. Springer Nature. https://doi.org/10.1038/s41586-022-05369-7","chicago":"Qi, Linlin, Mateusz Kwiatkowski, Huihuang Chen, Lukas Hörmayer, Scott A Sinclair, Minxia Zou, Charo I. del Genio, et al. “Adenylate Cyclase Activity of TIR1/AFB Auxin Receptors in Plants.” Nature. Springer Nature, 2022. https://doi.org/10.1038/s41586-022-05369-7."},"day":"03","status":"public","ec_funded":1,"publisher":"Springer Nature","department":[{"_id":"JiFr"}],"date_updated":"2025-04-14T07:45:02Z","language":[{"iso":"eng"}],"month":"11","date_published":"2022-11-03T00:00:00Z","oa":1,"isi":1,"_id":"12144","scopus_import":"1","acknowledgement":"This research was supported by the Lab Support Facility (LSF) and the Imaging and Optics Facility (IOF) of IST Austria. We thank C. Gehring for suggestions and advice; and K. U. Torii and G. Stacey for seeds and plasmids. This project was funded by a European Research Council Advanced Grant (ETAP-742985). M.F.K. and R.N. acknowledge the support of the EU MSCA-IF project CrysPINs (792329). M.K. was supported by the project POWR.03.05.00-00-Z302/17 Universitas Copernicana Thoruniensis in Futuro–IDS “Academia Copernicana”. CIDG acknowledges support from UKRI under Future Leaders Fellowship grant number MR/T020652/1.","type":"journal_article","article_type":"original","oa_version":"Submitted Version","intvolume":" 611","main_file_link":[{"open_access":"1","url":"http://wrap.warwick.ac.uk/168325/1/WRAP-denylate-cyclase-activity-TIR1-AFB-auxin-receptors-root-growth-22.pdf"}],"quality_controlled":"1","corr_author":"1","publication":"Nature","issue":"7934","doi":"10.1038/s41586-022-05369-7","publication_identifier":{"issn":["0028-0836"],"eissn":["1476-4687"]},"year":"2022","date_created":"2023-01-12T12:06:05Z","title":"Adenylate cyclase activity of TIR1/AFB auxin receptors in plants","abstract":[{"lang":"eng","text":"The phytohormone auxin is the major coordinative signal in plant development1, mediating transcriptional reprogramming by a well-established canonical signalling pathway. TRANSPORT INHIBITOR RESPONSE 1 (TIR1)/AUXIN-SIGNALING F-BOX (AFB) auxin receptors are F-box subunits of ubiquitin ligase complexes. In response to auxin, they associate with Aux/IAA transcriptional repressors and target them for degradation via ubiquitination2,3. Here we identify adenylate cyclase (AC) activity as an additional function of TIR1/AFB receptors across land plants. Auxin, together with Aux/IAAs, stimulates cAMP production. Three separate mutations in the AC motif of the TIR1 C-terminal region, all of which abolish the AC activity, each render TIR1 ineffective in mediating gravitropism and sustained auxin-induced root growth inhibition, and also affect auxin-induced transcriptional regulation. These results highlight the importance of TIR1/AFB AC activity in canonical auxin signalling. They also identify a unique phytohormone receptor cassette combining F-box and AC motifs, and the role of cAMP as a second messenger in plants."}],"publication_status":"published","external_id":{"isi":["000875061600013"],"pmid":["36289340"]},"page":"133-138","article_processing_charge":"No","pmid":1,"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"volume":611,"author":[{"last_name":"Qi","first_name":"Linlin","full_name":"Qi, Linlin","id":"44B04502-A9ED-11E9-B6FC-583AE6697425","orcid":"0000-0001-5187-8401"},{"first_name":"Mateusz","last_name":"Kwiatkowski","full_name":"Kwiatkowski, Mateusz"},{"full_name":"Chen, Huihuang","id":"83c96512-15b2-11ec-abd3-b7eede36184f","last_name":"Chen","first_name":"Huihuang"},{"first_name":"Lukas","last_name":"Hörmayer","id":"2EEE7A2A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8295-2926","full_name":"Hörmayer, Lukas"},{"full_name":"Sinclair, Scott A","id":"2D99FE6A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4566-0593","last_name":"Sinclair","first_name":"Scott A"},{"full_name":"Zou, Minxia","id":"5c243f41-03f3-11ec-841c-96faf48a7ef9","last_name":"Zou","first_name":"Minxia"},{"full_name":"del Genio, Charo I.","first_name":"Charo I.","last_name":"del Genio"},{"last_name":"Kubeš","first_name":"Martin F.","full_name":"Kubeš, Martin F."},{"full_name":"Napier, Richard","last_name":"Napier","first_name":"Richard"},{"first_name":"Krzysztof","last_name":"Jaworski","full_name":"Jaworski, Krzysztof"},{"first_name":"Jiří","last_name":"Friml","id":"4159519E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8302-7596","full_name":"Friml, Jiří"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"date_published":"2022-12-01T00:00:00Z","language":[{"iso":"eng"}],"month":"12","date_updated":"2025-04-14T07:46:59Z","publisher":"Springer Nature","department":[{"_id":"CaHe"},{"_id":"EdHa"}],"isi":1,"file_date_updated":"2023-01-27T07:32:01Z","oa":1,"scopus_import":"1","_id":"12209","oa_version":"Published Version","intvolume":" 18","article_type":"original","acknowledgement":"We thank K. Sampath, A. Pauli and Y. Bellaїche for feedback on the manuscript. We also thank the members of the Heisenberg group, in particular A. Schauer and F. Nur Arslan, for help, technical advice and discussions, and the Bioimaging and Life Science facilities at IST\r\nAustria for continuous support. We thank C. Flandoli for the artwork in the figures. This work was supported by postdoctoral fellowships from EMBO (LTF-850-2017) and HFSP (LT000429/2018-L2) to D.P. and the European Union (European Research Council starting grant 851288 to É.H. and European Research Council advanced grant 742573 to C.-P.H.).","type":"journal_article","citation":{"ista":"Nunes Pinheiro DC, Kardos R, Hannezo EB, Heisenberg C-PJ. 2022. Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming. Nature Physics. 18(12), 1482–1493.","ama":"Nunes Pinheiro DC, Kardos R, Hannezo EB, Heisenberg C-PJ. Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming. Nature Physics. 2022;18(12):1482-1493. doi:10.1038/s41567-022-01787-6","ieee":"D. C. Nunes Pinheiro, R. Kardos, E. B. Hannezo, and C.-P. J. Heisenberg, “Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming,” Nature Physics, vol. 18, no. 12. Springer Nature, pp. 1482–1493, 2022.","short":"D.C. Nunes Pinheiro, R. Kardos, E.B. Hannezo, C.-P.J. Heisenberg, Nature Physics 18 (2022) 1482–1493.","mla":"Nunes Pinheiro, Diana C., et al. “Morphogen Gradient Orchestrates Pattern-Preserving Tissue Morphogenesis via Motility-Driven Unjamming.” Nature Physics, vol. 18, no. 12, Springer Nature, 2022, pp. 1482–93, doi:10.1038/s41567-022-01787-6.","chicago":"Nunes Pinheiro, Diana C, Roland Kardos, Edouard B Hannezo, and Carl-Philipp J Heisenberg. “Morphogen Gradient Orchestrates Pattern-Preserving Tissue Morphogenesis via Motility-Driven Unjamming.” Nature Physics. Springer Nature, 2022. https://doi.org/10.1038/s41567-022-01787-6.","apa":"Nunes Pinheiro, D. C., Kardos, R., Hannezo, E. B., & Heisenberg, C.-P. J. (2022). Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming. Nature Physics. Springer Nature. https://doi.org/10.1038/s41567-022-01787-6"},"project":[{"name":"Coordination of mesendoderm cell fate specification and internalization during zebrafish gastrulation","grant_number":"ALTF 850-2017","_id":"26520D1E-B435-11E9-9278-68D0E5697425"},{"grant_number":"ALTF 850-2017","_id":"26520D1E-B435-11E9-9278-68D0E5697425","name":"Coordination of mesendoderm cell fate specification and internalization during zebrafish gastrulation"},{"_id":"05943252-7A3F-11EA-A408-12923DDC885E","grant_number":"851288","call_identifier":"H2020","name":"Design Principles of Branching Morphogenesis"},{"_id":"260F1432-B435-11E9-9278-68D0E5697425","grant_number":"742573","call_identifier":"H2020","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation"}],"status":"public","day":"01","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ec_funded":1,"keyword":["General Physics and Astronomy"],"title":"Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming","article_processing_charge":"No","page":"1482-1493","publication_status":"published","external_id":{"isi":["000871319900002"]},"abstract":[{"lang":"eng","text":"Embryo development requires biochemical signalling to generate patterns of cell fates and active mechanical forces to drive tissue shape changes. However, how these processes are coordinated, and how tissue patterning is preserved despite the cellular flows occurring during morphogenesis, remains poorly understood. Gastrulation is a crucial embryonic stage that involves both patterning and internalization of the mesendoderm germ layer tissue. Here we show that, in zebrafish embryos, a gradient in Nodal signalling orchestrates pattern-preserving internalization movements by triggering a motility-driven unjamming transition. In addition to its role as a morphogen determining embryo patterning, graded Nodal signalling mechanically subdivides the mesendoderm into a small fraction of highly protrusive leader cells, able to autonomously internalize via local unjamming, and less protrusive followers, which need to be pulled inwards by the leaders. The Nodal gradient further enforces a code of preferential adhesion coupling leaders to their immediate followers, resulting in a collective and ordered mode of internalization that preserves mesendoderm patterning. Integrating this dual mechanical role of Nodal signalling into minimal active particle simulations quantitatively predicts both physiological and experimentally perturbed internalization movements. This provides a quantitative framework for how a morphogen-encoded unjamming transition can bidirectionally couple tissue mechanics with patterning during complex three-dimensional morphogenesis."}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"author":[{"first_name":"Diana C","last_name":"Nunes Pinheiro","id":"2E839F16-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4333-7503","full_name":"Nunes Pinheiro, Diana C"},{"last_name":"Kardos","first_name":"Roland","id":"4039350E-F248-11E8-B48F-1D18A9856A87","full_name":"Kardos, Roland"},{"first_name":"Edouard B","last_name":"Hannezo","full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Carl-Philipp J","last_name":"Heisenberg","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","volume":18,"has_accepted_license":"1","ddc":["570"],"corr_author":"1","file":[{"file_name":"2022_NaturePhysics_Pinheiro.pdf","content_type":"application/pdf","date_created":"2023-01-27T07:32:01Z","success":1,"creator":"dernst","file_id":"12412","file_size":36703569,"date_updated":"2023-01-27T07:32:01Z","access_level":"open_access","checksum":"c86a8e8d80d1bfc46d56a01e88a2526a","relation":"main_file"}],"quality_controlled":"1","doi":"10.1038/s41567-022-01787-6","publication_identifier":{"issn":["1745-2473"],"eissn":["1745-2481"]},"issue":"12","publication":"Nature Physics","date_created":"2023-01-16T09:45:19Z","year":"2022"},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","day":"03","citation":{"mla":"Johnson, Alexander J., et al. “Three-Dimensional Visualization of Planta Clathrin-Coated Vesicles at Ultrastructural Resolution.” Molecular Plant, vol. 15, no. 10, Elsevier, 2022, pp. 1533–42, doi:10.1016/j.molp.2022.09.003.","chicago":"Johnson, Alexander J, Walter Kaufmann, Christoph M Sommer, Tommaso Costanzo, Dana A. Dahhan, Sebastian Y. Bednarek, and Jiří Friml. “Three-Dimensional Visualization of Planta Clathrin-Coated Vesicles at Ultrastructural Resolution.” Molecular Plant. Elsevier, 2022. https://doi.org/10.1016/j.molp.2022.09.003.","apa":"Johnson, A. J., Kaufmann, W., Sommer, C. M., Costanzo, T., Dahhan, D. A., Bednarek, S. Y., & Friml, J. (2022). Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution. Molecular Plant. Elsevier. https://doi.org/10.1016/j.molp.2022.09.003","ista":"Johnson AJ, Kaufmann W, Sommer CM, Costanzo T, Dahhan DA, Bednarek SY, Friml J. 2022. Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution. Molecular Plant. 15(10), 1533–1542.","ama":"Johnson AJ, Kaufmann W, Sommer CM, et al. Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution. Molecular Plant. 2022;15(10):1533-1542. doi:10.1016/j.molp.2022.09.003","ieee":"A. J. Johnson et al., “Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution,” Molecular Plant, vol. 15, no. 10. Elsevier, pp. 1533–1542, 2022.","short":"A.J. Johnson, W. Kaufmann, C.M. Sommer, T. Costanzo, D.A. Dahhan, S.Y. Bednarek, J. Friml, Molecular Plant 15 (2022) 1533–1542."},"project":[{"name":"Molecular mechanisms of endocytic cargo recognition in plants","call_identifier":"FWF","grant_number":"I03630","_id":"26538374-B435-11E9-9278-68D0E5697425"}],"oa_version":"Published Version","intvolume":" 15","article_type":"original","acknowledgement":"A.J. is supported by funding from the Austrian Science Fund I3630B25 (to J.F.). This research was supported by the Scientific Service Units of Institute of Science and Technology Austria (ISTA) through resources provided by the Electron Microscopy Facility, Lab Support Facility, and the Imaging and Optics Facility. We acknowledge Prof. David Robinson (Heidelberg) and Prof. Jan Traas (Lyon) for making us aware of previously published classical on-grid preparation methods. No conflict of interest declared.","type":"journal_article","scopus_import":"1","_id":"12239","isi":1,"file_date_updated":"2023-01-30T07:46:51Z","oa":1,"date_published":"2022-10-03T00:00:00Z","language":[{"iso":"eng"}],"month":"10","date_updated":"2025-04-15T07:32:09Z","department":[{"_id":"JiFr"},{"_id":"EM-Fac"},{"_id":"Bio"}],"publisher":"Elsevier","date_created":"2023-01-16T09:51:49Z","year":"2022","publication_identifier":{"issn":["1674-2052"]},"doi":"10.1016/j.molp.2022.09.003","issue":"10","publication":"Molecular Plant","corr_author":"1","file":[{"creator":"dernst","success":1,"date_created":"2023-01-30T07:46:51Z","content_type":"application/pdf","file_name":"2022_MolecularPlant_Johnson.pdf","relation":"main_file","checksum":"04d5c12490052d03e4dc4412338a43dd","access_level":"open_access","date_updated":"2023-01-30T07:46:51Z","file_size":2307251,"file_id":"12435"}],"quality_controlled":"1","has_accepted_license":"1","ddc":["580"],"author":[{"first_name":"Alexander J","last_name":"Johnson","full_name":"Johnson, Alexander J","id":"46A62C3A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2739-8843"},{"full_name":"Kaufmann, Walter","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","last_name":"Kaufmann","first_name":"Walter"},{"first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M"},{"first_name":"Tommaso","last_name":"Costanzo","full_name":"Costanzo, Tommaso","orcid":"0000-0001-9732-3815","id":"D93824F4-D9BA-11E9-BB12-F207E6697425"},{"full_name":"Dahhan, Dana A.","last_name":"Dahhan","first_name":"Dana A."},{"full_name":"Bednarek, Sebastian Y.","first_name":"Sebastian Y.","last_name":"Bednarek"},{"last_name":"Friml","first_name":"Jiří","full_name":"Friml, Jiří","id":"4159519E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8302-7596"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","volume":15,"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"},{"_id":"Bio"}],"pmid":1,"article_processing_charge":"Yes (via OA deal)","page":"1533-1542","publication_status":"published","external_id":{"isi":["000882769800009"],"pmid":["36081349"]},"abstract":[{"lang":"eng","text":"Biological systems are the sum of their dynamic three-dimensional (3D) parts. Therefore, it is critical to study biological structures in 3D and at high resolution to gain insights into their physiological functions. Electron microscopy of metal replicas of unroofed cells and isolated organelles has been a key technique to visualize intracellular structures at nanometer resolution. However, many of these methods require specialized equipment and personnel to complete them. Here, we present novel accessible methods to analyze biological structures in unroofed cells and biochemically isolated organelles in 3D and at nanometer resolution, focusing on Arabidopsis clathrin-coated vesicles (CCVs). While CCVs are essential trafficking organelles, their detailed structural information is lacking due to their poor preservation when observed via classical electron microscopy protocols experiments. First, we establish a method to visualize CCVs in unroofed cells using scanning transmission electron microscopy tomography, providing sufficient resolution to define the clathrin coat arrangements. Critically, the samples are prepared directly on electron microscopy grids, removing the requirement to use extremely corrosive acids, thereby enabling the use of this method in any electron microscopy lab. Secondly, we demonstrate that this standardized sample preparation allows the direct comparison of isolated CCV samples with those visualized in cells. Finally, to facilitate the high-throughput and robust screening of metal replicated samples, we provide a deep learning analysis method to screen the “pseudo 3D” morphologies of CCVs imaged with 2D modalities. Collectively, our work establishes accessible ways to examine the 3D structure of biological samples and provide novel insights into the structure of plant CCVs."}],"keyword":["Plant Science","Molecular Biology"],"title":"Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution"},{"ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"day":"15","status":"public","citation":{"short":"A.L. Sumser, M.A. Jösch, P.M. Jonas, Y. Ben Simon, ELife 11 (2022).","ieee":"A. L. Sumser, M. A. Jösch, P. M. Jonas, and Y. Ben Simon, “Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling,” eLife, vol. 11. eLife Sciences Publications, 2022.","ista":"Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. 2022. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. eLife. 11, 79848.","ama":"Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. eLife. 2022;11. doi:10.7554/elife.79848","apa":"Sumser, A. L., Jösch, M. A., Jonas, P. M., & Ben Simon, Y. (2022). Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.79848","chicago":"Sumser, Anton L, Maximilian A Jösch, Peter M Jonas, and Yoav Ben Simon. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” ELife. eLife Sciences Publications, 2022. https://doi.org/10.7554/elife.79848.","mla":"Sumser, Anton L., et al. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” ELife, vol. 11, 79848, eLife Sciences Publications, 2022, doi:10.7554/elife.79848."},"project":[{"grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","call_identifier":"H2020"},{"grant_number":"756502","_id":"2634E9D2-B435-11E9-9278-68D0E5697425","name":"Circuits of Visual Attention","call_identifier":"H2020"},{"call_identifier":"FWF","name":"Synaptic communication in neuronal microcircuits","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"},{"_id":"266D407A-B435-11E9-9278-68D0E5697425","grant_number":"LT000256","name":"Neuronal networks of salience and spatial detection in the murine superior colliculus"},{"name":"Connecting sensory with motor processing in the superior colliculus","grant_number":"ALTF 1098-2017","_id":"264FEA02-B435-11E9-9278-68D0E5697425"}],"article_type":"original","intvolume":" 11","oa_version":"Published Version","acknowledgement":"We thank F Marr for technical assistance, A Murray for RVdG-CVS-N2c viruses and Neuro2A packaging cell-lines and J Watson for reading the manuscript. This research was supported by the Scientific Service Units (SSU) of IST-Austria through resources provided by the Imaging and Optics Facility (IOF) and the Preclinical Facility (PCF). This project was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC advanced grant No 692692, PJ, ERC starting grant No 756502, MJ), the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, PJ), the Human Frontier Science Program (LT000256/2018-L, AS) and EMBO (ALTF 1098-2017, AS).","type":"journal_article","_id":"12288","scopus_import":"1","isi":1,"oa":1,"file_date_updated":"2023-01-30T11:50:53Z","month":"09","language":[{"iso":"eng"}],"date_published":"2022-09-15T00:00:00Z","publisher":"eLife Sciences Publications","department":[{"_id":"MaJö"},{"_id":"PeJo"}],"date_updated":"2025-04-15T08:29:05Z","year":"2022","date_created":"2023-01-16T10:04:15Z","article_number":"79848","publication_identifier":{"eissn":["2050-084X"]},"doi":"10.7554/elife.79848","publication":"eLife","corr_author":"1","quality_controlled":"1","file":[{"file_id":"12463","file_size":8506811,"date_updated":"2023-01-30T11:50:53Z","access_level":"open_access","relation":"main_file","checksum":"5a2a65e3e7225090c3d8199f3bbd7b7b","content_type":"application/pdf","file_name":"2022_eLife_Sumser.pdf","date_created":"2023-01-30T11:50:53Z","success":1,"creator":"dernst"}],"has_accepted_license":"1","ddc":["570"],"author":[{"last_name":"Sumser","first_name":"Anton L","full_name":"Sumser, Anton L","id":"3320A096-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4792-1881"},{"first_name":"Maximilian A","last_name":"Jösch","full_name":"Jösch, Maximilian A","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3937-1330"},{"last_name":"Jonas","first_name":"Peter M","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804"},{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","full_name":"Ben Simon, Yoav","first_name":"Yoav","last_name":"Ben Simon"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","volume":11,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"pmid":1,"article_processing_charge":"No","abstract":[{"lang":"eng","text":"To understand the function of neuronal circuits, it is crucial to disentangle the connectivity patterns within the network. However, most tools currently used to explore connectivity have low throughput, low selectivity, or limited accessibility. Here, we report the development of an improved packaging system for the production of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers orders of magnitude higher with no background contamination, at a fraction of the production time, while preserving the efficiency of transsynaptic labeling. Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal populations, tailored for diverse experimental requirements. We demonstrate the power and flexibility of the new system by uncovering hidden local and distal inhibitory connections in the mouse hippocampal formation and by imaging the functional properties of a cortical microcircuit across weeks. Our novel production pipeline provides a convenient approach to generate new rabies vectors, while our toolkit flexibly and efficiently expands the current capacity to label, manipulate and image the neuronal activity of interconnected neuronal circuits in vitro and in vivo."}],"external_id":{"isi":["000892204300001"],"pmid":["36040301"]},"publication_status":"published","title":"Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"]},{"file_date_updated":"2023-01-25T10:52:46Z","oa":1,"date_published":"2022-09-29T00:00:00Z","month":"09","language":[{"iso":"eng"}],"date_updated":"2026-06-18T19:47:50Z","department":[{"_id":"GradSch"},{"_id":"CaHe"}],"publisher":"Institute of Science and Technology Austria","oa_version":"Published Version","type":"dissertation","_id":"12368","citation":{"apa":"Arslan, F. N. (2022). Remodeling of E-cadherin-mediated contacts via cortical flows. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12153","chicago":"Arslan, Feyza N. “Remodeling of E-Cadherin-Mediated Contacts via Cortical Flows.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:12153.","mla":"Arslan, Feyza N. Remodeling of E-Cadherin-Mediated Contacts via Cortical Flows. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:12153.","short":"F.N. Arslan, Remodeling of E-Cadherin-Mediated Contacts via Cortical Flows, Institute of Science and Technology Austria, 2022.","ieee":"F. N. Arslan, “Remodeling of E-cadherin-mediated contacts via cortical flows,” Institute of Science and Technology Austria, 2022.","ama":"Arslan FN. Remodeling of E-cadherin-mediated contacts via cortical flows. 2022. doi:10.15479/at:ista:12153","ista":"Arslan FN. 2022. Remodeling of E-cadherin-mediated contacts via cortical flows. Institute of Science and Technology Austria."},"project":[{"name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","call_identifier":"H2020","grant_number":"742573","_id":"260F1432-B435-11E9-9278-68D0E5697425"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ec_funded":1,"alternative_title":["ISTA Thesis"],"status":"public","day":"29","article_processing_charge":"No","page":"113","publication_status":"published","abstract":[{"lang":"eng","text":"Metazoan development relies on the formation and remodeling of cell-cell contacts. The \r\nbinding of adhesion receptors and remodeling of the actomyosin cell cortex at cell-cell \r\ninteraction sites have been implicated in cell-cell contact formation. Yet, how these two \r\nprocesses functionally interact to drive cell-cell contact expansion and strengthening \r\nremains unclear. Here, we study how primary germ layer progenitor cells from zebrafish \r\nbind to supported lipid bilayers (SLB) functionalized with E-cadherin ectodomains as an \r\nassay system for monitoring cell-cell contact formation at high spatiotemporal resolution. \r\nWe show that cell-cell contact formation represents a two-tiered process: E-cadherin\u0002mediated downregulation of the small GTPase RhoA at the forming contact leads to both \r\ndepletion of Myosin-2 and decrease of F-actin. This is followed by centrifugal actin \r\nnetwork flows at the contact triggered by a sharp gradient of Myosin-2 at the rim of the \r\ncontact zone, with Myosin-2 displaying higher cortical localization outside than inside of \r\nthe contact. These centrifugal cortical actin flows, in turn, not only further dilute the actin \r\nnetwork at the contact disc, but also lead to an accumulation of both F-actin and E\u0002cadherin at the contact rim. Eventually, this combination of actomyosin downregulation \r\nand flows at the contact contribute to the characteristic molecular organization implicated \r\nin contact formation and maintenance: depletion of cortical actomyosin at the contact disc, \r\ndriving contact expansion by lowering interfacial tension at the contact, and accumulation \r\nof both E-cadherin and F-actin at the contact rim, mechanically linking the contractile \r\ncortices of the adhering cells. Thus, using a biomimetic assay, we exemplify how \r\nadhesion signaling and cell mechanics function together to modulate the spatial \r\norganization of cell-cell contacts."}],"supervisor":[{"last_name":"Heisenberg","first_name":"Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87","full_name":"Heisenberg, Carl-Philipp J"}],"title":"Remodeling of E-cadherin-mediated contacts via cortical flows","degree_awarded":"PhD","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","author":[{"full_name":"Arslan, Feyza N","id":"49DA7910-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5809-9566","last_name":"Arslan","first_name":"Feyza N"}],"OA_place":"publisher","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"NanoFab"}],"related_material":{"record":[{"status":"public","id":"9350","relation":"part_of_dissertation"}]},"corr_author":"1","file":[{"file_id":"12369","relation":"main_file","checksum":"e54a3e69b83ebf166544164afd25608e","access_level":"open_access","date_updated":"2023-01-25T10:52:46Z","file_size":14581024,"date_created":"2023-01-25T10:52:46Z","file_name":"THESIS_FINAL_FArslan_pdfa.pdf","content_type":"application/pdf","creator":"cchlebak","success":1}],"has_accepted_license":"1","ddc":["570"],"date_created":"2023-01-25T10:43:24Z","year":"2022","doi":"10.15479/at:ista:12153","publication_identifier":{"isbn":["978-3-99078-025-1 "],"issn":["2663-337X"]}},{"has_accepted_license":"1","ddc":["570"],"corr_author":"1","file":[{"content_type":"application/pdf","file_name":"2022_FrontiersOncol_Roblek.pdf","date_created":"2022-02-08T13:26:40Z","creator":"cchlebak","success":1,"file_id":"10751","date_updated":"2022-02-08T13:26:40Z","file_size":6303227,"checksum":"63dfecf30c5bbf9408b3512bd603f78c","relation":"main_file","access_level":"open_access"}],"quality_controlled":"1","doi":"10.3389/fonc.2022.777634","publication_identifier":{"issn":["2234-943X"]},"publication":"Frontiers in Oncology","year":"2022","date_created":"2022-02-01T10:33:50Z","article_number":"777634","title":"The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis","article_processing_charge":"Yes (via OA deal)","abstract":[{"text":"Solute carriers are increasingly recognized as participating in a plethora of pathologies, including cancer. We describe here the involvement of the orphan solute carrier MFSD1 in the regulation of tumor cell migration. Loss of MFSD1 enabled higher levels of metastasis in a mouse model. We identified an increased migratory potential in MFSD1-/- tumor cells which was mediated by increased focal adhesion turn-over, reduced stability of mature inactive β1 integrin, and the resulting increased integrin activation index. We show that MFSD1 promoted recycling to the cell surface of endocytosed inactive β1 integrin and thereby protected β1 integrin from proteolytic degradation; this led to dampening of the integrin activation index. Furthermore, down-regulation of MFSD1 expression was observed during early steps of tumorigenesis and higher MFSD1 expression levels correlate with a better cancer patient prognosis. In sum, we describe a requirement for endolysosomal MFSD1 in efficient β1 integrin recycling to suppress tumor spread.","lang":"eng"}],"publication_status":"published","external_id":{"isi":["000760618800001"],"pmid":["35211397"]},"acknowledged_ssus":[{"_id":"Bio"}],"related_material":{"link":[{"description":"News on IST Homepage","relation":"confirmation","url":"https://ist.ac.at/en/news/suppressing-the-spread-of-tumors/"}]},"pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"full_name":"Roblek, Marko","orcid":"0000-0001-9588-1389","id":"3047D808-F248-11E8-B48F-1D18A9856A87","first_name":"Marko","last_name":"Roblek"},{"id":"3CCBB46E-F248-11E8-B48F-1D18A9856A87","full_name":"Bicher, Julia","last_name":"Bicher","first_name":"Julia"},{"full_name":"van Gogh, Merel","first_name":"Merel","last_name":"van Gogh"},{"first_name":"Attila","last_name":"György","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1819-198X","full_name":"György, Attila"},{"last_name":"Seeböck","first_name":"Rita","full_name":"Seeböck, Rita"},{"last_name":"Szulc","first_name":"Bozena","full_name":"Szulc, Bozena"},{"full_name":"Damme, Markus","last_name":"Damme","first_name":"Markus"},{"last_name":"Olczak","first_name":"Mariusz","full_name":"Olczak, Mariusz"},{"last_name":"Borsig","first_name":"Lubor","full_name":"Borsig, Lubor"},{"id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353","full_name":"Siekhaus, Daria E","first_name":"Daria E","last_name":"Siekhaus"}],"volume":12,"citation":{"mla":"Roblek, Marko, et al. “The Solute Carrier MFSD1 Decreases Β1 Integrin’s Activation Status and Thus Tumor Metastasis.” Frontiers in Oncology, vol. 12, 777634, Frontiers, 2022, doi:10.3389/fonc.2022.777634.","apa":"Roblek, M., Bicher, J., van Gogh, M., György, A., Seeböck, R., Szulc, B., … Siekhaus, D. E. (2022). The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis. Frontiers in Oncology. Frontiers. https://doi.org/10.3389/fonc.2022.777634","chicago":"Roblek, Marko, Julia Bicher, Merel van Gogh, Attila György, Rita Seeböck, Bozena Szulc, Markus Damme, Mariusz Olczak, Lubor Borsig, and Daria E Siekhaus. “The Solute Carrier MFSD1 Decreases Β1 Integrin’s Activation Status and Thus Tumor Metastasis.” Frontiers in Oncology. Frontiers, 2022. https://doi.org/10.3389/fonc.2022.777634.","ama":"Roblek M, Bicher J, van Gogh M, et al. The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis. Frontiers in Oncology. 2022;12. doi:10.3389/fonc.2022.777634","ista":"Roblek M, Bicher J, van Gogh M, György A, Seeböck R, Szulc B, Damme M, Olczak M, Borsig L, Siekhaus DE. 2022. The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis. Frontiers in Oncology. 12, 777634.","short":"M. Roblek, J. Bicher, M. van Gogh, A. György, R. Seeböck, B. Szulc, M. Damme, M. Olczak, L. Borsig, D.E. Siekhaus, Frontiers in Oncology 12 (2022).","ieee":"M. Roblek et al., “The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis,” Frontiers in Oncology, vol. 12. Frontiers, 2022."},"project":[{"grant_number":"LSC16-021","_id":"2637E9C0-B435-11E9-9278-68D0E5697425","name":"Investigating the role of the novel major superfamily facilitator transporter family member MFSD1 in metastasis"}],"status":"public","day":"08","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"language":[{"iso":"eng"}],"month":"02","date_published":"2022-02-08T00:00:00Z","department":[{"_id":"DaSi"}],"publisher":"Frontiers","date_updated":"2025-06-11T13:56:08Z","isi":1,"oa":1,"file_date_updated":"2022-02-08T13:26:40Z","_id":"10712","scopus_import":"1","article_type":"original","oa_version":"Published Version","intvolume":" 12","type":"journal_article","acknowledgement":"We thank M. Sixt, A. Leithner, and J. Alanko for helpful advice and the BioImaging Facility at IST Austria for technical support and assistance. We thank the Siekhaus Lab for the careful review of the manuscript and their input. MR and DS were funded by the NO Forschungs- und Bildungsges.m.b.H. (LS16-021) and IST core funding. MD was funded by Deutsche Forschungsgemeinschaft (DA 1785-1)."},{"publication":"Science","issue":"6591","publication_identifier":{"issn":["0036-8075"]},"doi":"10.1126/science.abj0425","year":"2022","date_created":"2022-02-01T11:23:18Z","main_file_link":[{"url":"https://doi.org/10.1101/2021.04.19.438995","open_access":"1"}],"quality_controlled":"1","corr_author":"1","pmid":1,"acknowledged_ssus":[{"_id":"Bio"}],"volume":376,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"full_name":"Akhmanova, Maria","id":"3425EC26-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1522-3162","last_name":"Akhmanova","first_name":"Maria"},{"last_name":"Emtenani","first_name":"Shamsi","full_name":"Emtenani, Shamsi","orcid":"0000-0001-6981-6938","id":"49D32318-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Krueger, Daniel","first_name":"Daniel","last_name":"Krueger"},{"first_name":"Attila","last_name":"György","full_name":"György, Attila","orcid":"0000-0002-1819-198X","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Pereira Guarda","first_name":"Mariana","orcid":"0000-0001-8238-480X","id":"6de81d9d-e2f2-11eb-945a-af8bc2a60b26","full_name":"Pereira Guarda, Mariana"},{"first_name":"Mikhail","last_name":"Vlasov","full_name":"Vlasov, Mikhail"},{"full_name":"Vlasov, Fedor","last_name":"Vlasov","first_name":"Fedor"},{"first_name":"Andrei","last_name":"Akopian","full_name":"Akopian, Andrei"},{"full_name":"Ratheesh, Aparna","id":"2F064CFE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7190-0776","last_name":"Ratheesh","first_name":"Aparna"},{"first_name":"Stefano","last_name":"De Renzis","full_name":"De Renzis, Stefano"},{"full_name":"Siekhaus, Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353","first_name":"Daria E","last_name":"Siekhaus"}],"title":"Cell division in tissues enables macrophage infiltration","abstract":[{"text":"Cells migrate through crowded microenvironments within tissues during normal development, immune response, and cancer metastasis. Although migration through pores and tracks in the extracellular matrix (ECM) has been well studied, little is known about cellular traversal into confining cell-dense tissues. We find that embryonic tissue invasion by Drosophila macrophages requires division of an epithelial ectodermal cell at the site of entry. Dividing ectodermal cells disassemble ECM attachment formed by integrin-mediated focal adhesions next to mesodermal cells, allowing macrophages to move their nuclei ahead and invade between two immediately adjacent tissues. Invasion efficiency depends on division frequency, but reduction of adhesion strength allows macrophage entry independently of division. This work demonstrates that tissue dynamics can regulate cellular infiltration.","lang":"eng"}],"external_id":{"pmid":["35446632"],"isi":["000788553700039"]},"publication_status":"published","page":"394-396","article_processing_charge":"No","status":"public","day":"22","tmp":{"short":"CC BY-NC-ND (4.0)","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","image":"/images/cc_by_nc_nd.png"},"project":[{"name":"Modeling epithelial tissue mechanics during cell invasion","call_identifier":"FWF","grant_number":"M02379","_id":"264CBBAC-B435-11E9-9278-68D0E5697425"}],"citation":{"mla":"Akhmanova, Maria, et al. “Cell Division in Tissues Enables Macrophage Infiltration.” Science, vol. 376, no. 6591, American Association for the Advancement of Science, 2022, pp. 394–96, doi:10.1126/science.abj0425.","chicago":"Akhmanova, Maria, Shamsi Emtenani, Daniel Krueger, Attila György, Mariana Pereira Guarda, Mikhail Vlasov, Fedor Vlasov, et al. “Cell Division in Tissues Enables Macrophage Infiltration.” Science. American Association for the Advancement of Science, 2022. https://doi.org/10.1126/science.abj0425.","apa":"Akhmanova, M., Emtenani, S., Krueger, D., György, A., Pereira Guarda, M., Vlasov, M., … Siekhaus, D. E. (2022). Cell division in tissues enables macrophage infiltration. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.abj0425","ama":"Akhmanova M, Emtenani S, Krueger D, et al. Cell division in tissues enables macrophage infiltration. Science. 2022;376(6591):394-396. doi:10.1126/science.abj0425","ista":"Akhmanova M, Emtenani S, Krueger D, György A, Pereira Guarda M, Vlasov M, Vlasov F, Akopian A, Ratheesh A, De Renzis S, Siekhaus DE. 2022. Cell division in tissues enables macrophage infiltration. Science. 376(6591), 394–396.","short":"M. Akhmanova, S. Emtenani, D. Krueger, A. György, M. Pereira Guarda, M. Vlasov, F. Vlasov, A. Akopian, A. Ratheesh, S. De Renzis, D.E. Siekhaus, Science 376 (2022) 394–396.","ieee":"M. Akhmanova et al., “Cell division in tissues enables macrophage infiltration,” Science, vol. 376, no. 6591. American Association for the Advancement of Science, pp. 394–396, 2022."},"_id":"10713","scopus_import":"1","acknowledgement":"We thank J. Friml, C. Guet, T. Hurd, M. Fendrych and members of the laboratory for comments on the manuscript; the Bioimaging Facility of IST Austria for excellent support and T. Lecuit, E. Hafen, R. Levayer and A. Martin for fly strains. This work was supported by a grant from the Austrian Science Fund FWF: Lise Meitner Fellowship M2379-B28 to M.A and D.S., and internal funding from IST Austria to D.S. and EMBL to S.D.R.","type":"journal_article","article_type":"original","oa_version":"Preprint","intvolume":" 376","publisher":"American Association for the Advancement of Science","department":[{"_id":"DaSi"}],"date_updated":"2025-04-15T07:25:41Z","language":[{"iso":"eng"}],"month":"04","date_published":"2022-04-22T00:00:00Z","oa":1,"isi":1},{"title":"Tissue-wide effects override cell-intrinsic gene function in radial neuron migration","external_id":{"pmid":["38596707"]},"publication_status":"published","abstract":[{"lang":"eng","text":"The mammalian neocortex is composed of diverse neuronal and glial cell classes that broadly arrange in six distinct laminae. Cortical layers emerge during development and defects in the developmental programs that orchestrate cortical lamination are associated with neurodevelopmental diseases. The developmental principle of cortical layer formation depends on concerted radial projection neuron migration, from their birthplace to their final target position. Radial migration occurs in defined sequential steps, regulated by a large array of signaling pathways. However, based on genetic loss-of-function experiments, most studies have thus far focused on the role of cell-autonomous gene function. Yet, cortical neuron migration in situ is a complex process and migrating neurons traverse along diverse cellular compartments and environments. The role of tissue-wide properties and genetic state in radial neuron migration is however not clear. Here we utilized mosaic analysis with double markers (MADM) technology to either sparsely or globally delete gene function, followed by quantitative single-cell phenotyping. The MADM-based gene ablation paradigms in combination with computational modeling demonstrated that global tissue-wide effects predominate cell-autonomous gene function albeit in a gene-specific manner. Our results thus suggest that the genetic landscape in a tissue critically affects the overall migration phenotype of individual cortical projection neurons. In a broader context, our findings imply that global tissue-wide effects represent an essential component of the underlying etiology associated with focal malformations of cortical development in particular, and neurological diseases in general."}],"article_processing_charge":"No","pmid":1,"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"12726"},{"status":"public","id":"14530","relation":"dissertation_contains"}]},"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"PreCl"},{"_id":"Bio"}],"volume":1,"author":[{"id":"38853E16-F248-11E8-B48F-1D18A9856A87","full_name":"Hansen, Andi H","last_name":"Hansen","first_name":"Andi H"},{"first_name":"Florian","last_name":"Pauler","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7462-0048"},{"first_name":"Michael","last_name":"Riedl","full_name":"Riedl, Michael","orcid":"0000-0003-4844-6311","id":"3BE60946-F248-11E8-B48F-1D18A9856A87"},{"id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen","first_name":"Carmen","last_name":"Streicher"},{"full_name":"Heger, Anna-Magdalena","id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87","first_name":"Anna-Magdalena","last_name":"Heger"},{"full_name":"Laukoter, Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7903-3010","last_name":"Laukoter","first_name":"Susanne"},{"orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","first_name":"Christoph M","last_name":"Sommer"},{"full_name":"Nicolas, Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87","last_name":"Nicolas","first_name":"Armel"},{"full_name":"Hof, Björn","orcid":"0000-0003-2057-2754","id":"3A374330-F248-11E8-B48F-1D18A9856A87","first_name":"Björn","last_name":"Hof"},{"last_name":"Tsai","first_name":"Li Huei","full_name":"Tsai, Li Huei"},{"last_name":"Rülicke","first_name":"Thomas","full_name":"Rülicke, Thomas"},{"full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"has_accepted_license":"1","file":[{"checksum":"822e76e056c07099d1fb27d1ece5941b","relation":"main_file","access_level":"open_access","file_size":4846551,"date_updated":"2023-08-16T08:00:30Z","file_id":"14061","creator":"dernst","success":1,"date_created":"2023-08-16T08:00:30Z","content_type":"application/pdf","file_name":"2023_OxfordOpenNeuroscience_Hansen.pdf"}],"quality_controlled":"1","corr_author":"1","publication":"Oxford Open Neuroscience","publication_identifier":{"eissn":["2753-149X"]},"doi":"10.1093/oons/kvac009","issue":"1","article_number":"kvac009","date_created":"2022-02-25T07:52:11Z","year":"2022","date_updated":"2026-04-07T13:29:13Z","department":[{"_id":"SiHi"},{"_id":"BjHo"},{"_id":"LifeSc"},{"_id":"EM-Fac"}],"publisher":"Oxford University Press","date_published":"2022-07-07T00:00:00Z","language":[{"iso":"eng"}],"month":"07","file_date_updated":"2023-08-16T08:00:30Z","oa":1,"_id":"10791","type":"journal_article","acknowledgement":"A.H.H. was a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences. This work also received support from IST Austria institutional funds; the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007–2013) under REA grant agreement No 618444 to S.H.\r\nAPC funding was obtained by IST Austria institutional funds.\r\nWe thank A. Sommer and C. Czepe (VBCF GmbH, NGS Unit), L. Andersen, J. Sonntag and J. Renno for technical support and/or initial experiments; M. Sixt, J. Nimpf and all members of the Hippenmeyer lab for discussion. This research was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging and Optics Facility, Lab Support Facility and Preclinical Facility.","intvolume":" 1","oa_version":"Published Version","article_type":"original","project":[{"name":"Molecular Mechanisms of Cerebral Cortex Development","call_identifier":"FP7","grant_number":"618444","_id":"25D61E48-B435-11E9-9278-68D0E5697425"},{"name":"Molecular mechanisms of radial neuronal migration","grant_number":"24812","_id":"2625A13E-B435-11E9-9278-68D0E5697425"}],"citation":{"mla":"Hansen, Andi H., et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function in Radial Neuron Migration.” Oxford Open Neuroscience, vol. 1, no. 1, kvac009, Oxford University Press, 2022, doi:10.1093/oons/kvac009.","chicago":"Hansen, Andi H, Florian Pauler, Michael Riedl, Carmen Streicher, Anna-Magdalena Heger, Susanne Laukoter, Christoph M Sommer, et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function in Radial Neuron Migration.” Oxford Open Neuroscience. Oxford University Press, 2022. https://doi.org/10.1093/oons/kvac009.","apa":"Hansen, A. H., Pauler, F., Riedl, M., Streicher, C., Heger, A.-M., Laukoter, S., … Hippenmeyer, S. (2022). Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. Oxford Open Neuroscience. Oxford University Press. https://doi.org/10.1093/oons/kvac009","ama":"Hansen AH, Pauler F, Riedl M, et al. Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. Oxford Open Neuroscience. 2022;1(1). doi:10.1093/oons/kvac009","ista":"Hansen AH, Pauler F, Riedl M, Streicher C, Heger A-M, Laukoter S, Sommer CM, Nicolas A, Hof B, Tsai LH, Rülicke T, Hippenmeyer S. 2022. Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. Oxford Open Neuroscience. 1(1), kvac009.","short":"A.H. Hansen, F. Pauler, M. Riedl, C. Streicher, A.-M. Heger, S. Laukoter, C.M. Sommer, A. Nicolas, B. Hof, L.H. Tsai, T. Rülicke, S. Hippenmeyer, Oxford Open Neuroscience 1 (2022).","ieee":"A. H. Hansen et al., “Tissue-wide effects override cell-intrinsic gene function in radial neuron migration,” Oxford Open Neuroscience, vol. 1, no. 1. Oxford University Press, 2022."},"day":"07","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ec_funded":1},{"oa":1,"file_date_updated":"2022-07-25T07:11:32Z","isi":1,"publisher":"Springer Nature","department":[{"_id":"SiHi"},{"_id":"CaHe"},{"_id":"EdHa"},{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"MiSi"}],"date_updated":"2025-06-11T13:52:43Z","month":"07","language":[{"iso":"eng"}],"date_published":"2022-07-11T00:00:00Z","type":"journal_article","acknowledgement":"This research was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging and Optics, Electron Microscopy, Preclinical and Life Science Facilities. We thank C. Moussion for providing anti-PNAd antibody and D. Critchley for Talin1-floxed mice, and E. Papusheva for providing a custom 3D channel alignment script. This work was supported by a European Research Council grant ERC-CoG-72437 to M.S. M.H. was supported by Czech Sciencundation GACR 20-24603Y and Charles University PRIMUS/20/MED/013.","article_type":"original","intvolume":" 23","oa_version":"Published Version","_id":"9794","scopus_import":"1","project":[{"call_identifier":"H2020","name":"Cellular Navigation Along Spatial Gradients","_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373"}],"citation":{"apa":"Assen, F. P., Abe, J., Hons, M., Hauschild, R., Shamipour, S., Kaufmann, W., … Sixt, M. K. (2022). Multitier mechanics control stromal adaptations in swelling lymph nodes. Nature Immunology. Springer Nature. https://doi.org/10.1038/s41590-022-01257-4","chicago":"Assen, Frank P, Jun Abe, Miroslav Hons, Robert Hauschild, Shayan Shamipour, Walter Kaufmann, Tommaso Costanzo, et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” Nature Immunology. Springer Nature, 2022. https://doi.org/10.1038/s41590-022-01257-4.","mla":"Assen, Frank P., et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” Nature Immunology, vol. 23, Springer Nature, 2022, pp. 1246–55, doi:10.1038/s41590-022-01257-4.","ieee":"F. P. Assen et al., “Multitier mechanics control stromal adaptations in swelling lymph nodes,” Nature Immunology, vol. 23. Springer Nature, pp. 1246–1255, 2022.","short":"F.P. Assen, J. Abe, M. Hons, R. Hauschild, S. Shamipour, W. Kaufmann, T. Costanzo, G. Krens, M. Brown, B. Ludewig, S. Hippenmeyer, C.-P.J. Heisenberg, W. Weninger, E.B. Hannezo, S.A. Luther, J.V. Stein, M.K. Sixt, Nature Immunology 23 (2022) 1246–1255.","ista":"Assen FP, Abe J, Hons M, Hauschild R, Shamipour S, Kaufmann W, Costanzo T, Krens G, Brown M, Ludewig B, Hippenmeyer S, Heisenberg C-PJ, Weninger W, Hannezo EB, Luther SA, Stein JV, Sixt MK. 2022. Multitier mechanics control stromal adaptations in swelling lymph nodes. Nature Immunology. 23, 1246–1255.","ama":"Assen FP, Abe J, Hons M, et al. Multitier mechanics control stromal adaptations in swelling lymph nodes. Nature Immunology. 2022;23:1246-1255. doi:10.1038/s41590-022-01257-4"},"ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"day":"11","status":"public","abstract":[{"lang":"eng","text":"Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular cells that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. Immunological challenge causes LNs to increase more than tenfold in size within a few days. Here, we characterized the biomechanics of LN swelling on the cellular and organ scale. We identified lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing fibroblastic reticular cells of the T-zone (TRCs) and their associated conduits to stretch. After an initial phase of relaxation, TRCs sensed the resulting strain through cell matrix adhesions, which coordinated local growth and remodeling of the stromal network. While the expanded TRC network readopted its typical configuration, a massive fibrotic reaction of the organ capsule set in and countered further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multitier fashion."}],"publication_status":"published","external_id":{"pmid":["35817845"],"isi":["000822975900002"]},"page":"1246-1255","article_processing_charge":"No","title":"Multitier mechanics control stromal adaptations in swelling lymph nodes","volume":23,"author":[{"id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3470-6119","full_name":"Assen, Frank P","first_name":"Frank P","last_name":"Assen"},{"first_name":"Jun","last_name":"Abe","full_name":"Abe, Jun"},{"orcid":"0000-0002-6625-3348","id":"4167FE56-F248-11E8-B48F-1D18A9856A87","full_name":"Hons, Miroslav","first_name":"Miroslav","last_name":"Hons"},{"orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","full_name":"Hauschild, Robert","first_name":"Robert","last_name":"Hauschild"},{"last_name":"Shamipour","first_name":"Shayan","full_name":"Shamipour, Shayan","id":"40B34FE2-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Kaufmann","first_name":"Walter","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","full_name":"Kaufmann, Walter"},{"first_name":"Tommaso","last_name":"Costanzo","id":"D93824F4-D9BA-11E9-BB12-F207E6697425","orcid":"0000-0001-9732-3815","full_name":"Costanzo, Tommaso"},{"first_name":"Gabriel","last_name":"Krens","full_name":"Krens, Gabriel","orcid":"0000-0003-4761-5996","id":"2B819732-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Brown, Markus","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","last_name":"Brown","first_name":"Markus"},{"full_name":"Ludewig, Burkhard","first_name":"Burkhard","last_name":"Ludewig"},{"first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon"},{"last_name":"Heisenberg","first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J"},{"full_name":"Weninger, Wolfgang","last_name":"Weninger","first_name":"Wolfgang"},{"full_name":"Hannezo, Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","last_name":"Hannezo","first_name":"Edouard B"},{"full_name":"Luther, Sanjiv A.","first_name":"Sanjiv A.","last_name":"Luther"},{"last_name":"Stein","first_name":"Jens V.","full_name":"Stein, Jens V."},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4561-241X","full_name":"Sixt, Michael K","first_name":"Michael K","last_name":"Sixt"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"LifeSc"}],"file":[{"content_type":"application/pdf","file_name":"2022_NatureImmunology_Assen.pdf","date_created":"2022-07-25T07:11:32Z","creator":"dernst","success":1,"file_id":"11642","file_size":11475325,"date_updated":"2022-07-25T07:11:32Z","checksum":"628e7b49809f22c75b428842efe70c68","relation":"main_file","access_level":"open_access"}],"quality_controlled":"1","corr_author":"1","ddc":["570"],"has_accepted_license":"1","year":"2022","date_created":"2021-08-06T09:09:11Z","publication":"Nature Immunology","doi":"10.1038/s41590-022-01257-4","publication_identifier":{"eissn":["1529-2916"],"issn":["1529-2908"]}},{"title":"Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells","article_processing_charge":"No","external_id":{"isi":["000766926900009"],"pmid":["35165179"]},"publication_status":"published","abstract":[{"lang":"eng","text":"Tension of the actomyosin cell cortex plays a key role in determining cell–cell contact growth and size. The level of cortical tension outside of the cell–cell contact, when pulling at the contact edge, scales with the total size to which a cell–cell contact can grow [J.-L. Maître et al., Science 338, 253–256 (2012)]. Here, we show in zebrafish primary germ-layer progenitor cells that this monotonic relationship only applies to a narrow range of cortical tension increase and that above a critical threshold, contact size inversely scales with cortical tension. This switch from cortical tension increasing to decreasing progenitor cell–cell contact size is caused by cortical tension promoting E-cadherin anchoring to the actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin at the contact. After tension-mediated E-cadherin stabilization at the contact exceeds a critical threshold level, the rate by which the contact expands in response to pulling forces from the cortex sharply drops, leading to smaller contacts at physiologically relevant timescales of contact formation. Thus, the activity of cortical tension in expanding cell–cell contact size is limited by tension-stabilizing E-cadherin–actin complexes at the contact."}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"PreCl"}],"pmid":1,"related_material":{"record":[{"status":"public","relation":"earlier_version","id":"9750"}]},"author":[{"last_name":"Slovakova","first_name":"Jana","id":"30F3F2F0-F248-11E8-B48F-1D18A9856A87","full_name":"Slovakova, Jana"},{"full_name":"Sikora, Mateusz K","id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87","first_name":"Mateusz K","last_name":"Sikora"},{"last_name":"Arslan","first_name":"Feyza N","full_name":"Arslan, Feyza N","orcid":"0000-0001-5809-9566","id":"49DA7910-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Caballero Mancebo","first_name":"Silvia","orcid":"0000-0002-5223-3346","id":"2F1E1758-F248-11E8-B48F-1D18A9856A87","full_name":"Caballero Mancebo, Silvia"},{"first_name":"Gabriel","last_name":"Krens","full_name":"Krens, Gabriel","id":"2B819732-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4761-5996"},{"full_name":"Kaufmann, Walter","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","last_name":"Kaufmann","first_name":"Walter"},{"full_name":"Merrin, Jack","orcid":"0000-0001-5145-4609","id":"4515C308-F248-11E8-B48F-1D18A9856A87","first_name":"Jack","last_name":"Merrin"},{"last_name":"Heisenberg","first_name":"Carl-Philipp J","full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","volume":119,"has_accepted_license":"1","ddc":["570"],"corr_author":"1","file":[{"file_id":"10780","relation":"main_file","checksum":"d49f83c3580613966f71768ddb9a55a5","access_level":"open_access","file_size":1609678,"date_updated":"2022-02-21T08:45:11Z","date_created":"2022-02-21T08:45:11Z","file_name":"2022_PNAS_Slovakova.pdf","content_type":"application/pdf","creator":"dernst","success":1}],"quality_controlled":"1","doi":"10.1073/pnas.2122030119","publication_identifier":{"eissn":["1091-6490"]},"issue":"8","publication":"Proceedings of the National Academy of Sciences of the United States of America","date_created":"2022-02-20T23:01:31Z","year":"2022","article_number":"e2122030119","date_published":"2022-02-14T00:00:00Z","language":[{"iso":"eng"}],"month":"02","date_updated":"2026-07-06T12:45:39Z","department":[{"_id":"CaHe"},{"_id":"EM-Fac"},{"_id":"Bio"}],"publisher":"National Academy of Sciences","isi":1,"file_date_updated":"2022-02-21T08:45:11Z","oa":1,"scopus_import":"1","_id":"10766","intvolume":" 119","oa_version":"Published Version","article_type":"original","type":"journal_article","acknowledgement":"We thank Guillaume Salbreaux, Silvia Grigolon, Edouard Hannezo, and Vanessa Barone for discussions and comments on the manuscript and Shayan Shamipour and Daniel Capek for help with data analysis. We also thank the Imaging & Optics, Electron Microscopy, and Zebrafish Facility Scientific Service Units at the Institute of Science and Technology Austria (ISTA)Nasser Darwish-Miranda for continuous support. We acknowledge Hitoshi Morita for the gift of VinculinB-GFP plasmid. This research was supported by an ISTA Fellow Marie-Curie Co-funding of regional, national, and international programmes Grant P_IST_EU01 (to J.S.), European Molecular Biology Organization Long-Term Fellowship Grant, ALTF reference number: 187-2013 (to M.S.), Schroedinger Fellowship J4332-B28 (to M.S.), and European Research Council Advanced Grant (MECSPEC; to C.-P.H.).","citation":{"chicago":"Slovakova, Jana, Mateusz K Sikora, Feyza N Arslan, Silvia Caballero Mancebo, Gabriel Krens, Walter Kaufmann, Jack Merrin, and Carl-Philipp J Heisenberg. “Tension-Dependent Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion in Zebrafish Germ-Layer Progenitor Cells.” Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 2022. https://doi.org/10.1073/pnas.2122030119.","apa":"Slovakova, J., Sikora, M. K., Arslan, F. N., Caballero Mancebo, S., Krens, G., Kaufmann, W., … Heisenberg, C.-P. J. (2022). Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells. Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. https://doi.org/10.1073/pnas.2122030119","mla":"Slovakova, Jana, et al. “Tension-Dependent Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion in Zebrafish Germ-Layer Progenitor Cells.” Proceedings of the National Academy of Sciences of the United States of America, vol. 119, no. 8, e2122030119, National Academy of Sciences, 2022, doi:10.1073/pnas.2122030119.","short":"J. Slovakova, M.K. Sikora, F.N. Arslan, S. Caballero Mancebo, G. Krens, W. Kaufmann, J. Merrin, C.-P.J. Heisenberg, Proceedings of the National Academy of Sciences of the United States of America 119 (2022).","ieee":"J. Slovakova et al., “Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 119, no. 8. National Academy of Sciences, 2022.","ama":"Slovakova J, Sikora MK, Arslan FN, et al. Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells. Proceedings of the National Academy of Sciences of the United States of America. 2022;119(8). doi:10.1073/pnas.2122030119","ista":"Slovakova J, Sikora MK, Arslan FN, Caballero Mancebo S, Krens G, Kaufmann W, Merrin J, Heisenberg C-PJ. 2022. Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells. Proceedings of the National Academy of Sciences of the United States of America. 119(8), e2122030119."},"project":[{"call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"},{"grant_number":"742573","_id":"260F1432-B435-11E9-9278-68D0E5697425","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","call_identifier":"H2020"},{"_id":"2521E28E-B435-11E9-9278-68D0E5697425","grant_number":"187-2013","name":"Modulation of adhesion function in cell-cell contact formation by cortical tension"}],"day":"14","status":"public","tmp":{"short":"CC BY-NC-ND (4.0)","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","image":"/images/cc_by_nc_nd.png"},"ec_funded":1},{"citation":{"ieee":"K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” eLife, vol. 11. eLife Sciences Publications, 2022.","short":"K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, ELife 11 (2022).","ama":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. eLife. 2022;11. doi:10.7554/eLife.78995","ista":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. 2022. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. eLife. 11, e78995.","chicago":"Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” ELife. eLife Sciences Publications, 2022. https://doi.org/10.7554/eLife.78995.","apa":"Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., & Sixt, M. K. (2022). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.78995","mla":"Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” ELife, vol. 11, e78995, eLife Sciences Publications, 2022, doi:10.7554/eLife.78995."},"project":[{"grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425","name":"Cellular Navigation Along Spatial Gradients","call_identifier":"H2020"},{"call_identifier":"FWF","name":"Mechanical adaptation of lamellipodial actin","_id":"26018E70-B435-11E9-9278-68D0E5697425","grant_number":"P29911"}],"ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"day":"26","status":"public","isi":1,"oa":1,"file_date_updated":"2022-08-16T08:57:37Z","language":[{"iso":"eng"}],"month":"07","date_published":"2022-07-26T00:00:00Z","publisher":"eLife Sciences Publications","department":[{"_id":"MiSi"},{"_id":"CaGu"}],"date_updated":"2026-07-06T12:48:19Z","article_type":"original","intvolume":" 11","oa_version":"Published Version","acknowledgement":"We thank Ulrich Dobrindt for providing UPEC strains CFT073, UTI89, and 536, Frank Assen, Vlad Gavra, Maximilian Götz, Bor Kavčič, Jonna Alanko, and Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp, and Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific Service Units, especially the Bioimaging facility, the Preclinical facility and the Electron microscopy facility for technical support, Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically reading the manuscript. This work was supported by grants from the Austrian Research Promotion Agency (FEMtech 868984) to IG, the European Research Council (CoG 724373), and the Austrian Science Fund (FWF P29911) to MS.","type":"journal_article","_id":"11843","scopus_import":"1","corr_author":"1","quality_controlled":"1","file":[{"checksum":"002a3c7c7ea5caa9af9cfbea308f6ea4","relation":"main_file","access_level":"open_access","date_updated":"2022-08-16T08:57:37Z","file_size":2057577,"file_id":"11861","creator":"cchlebak","success":1,"date_created":"2022-08-16T08:57:37Z","content_type":"application/pdf","file_name":"2022_eLife_Tomasek.pdf"}],"has_accepted_license":"1","ddc":["570"],"year":"2022","date_created":"2022-08-14T22:01:46Z","article_number":"e78995","publication_identifier":{"eissn":["2050-084X"]},"doi":"10.7554/eLife.78995","publication":"eLife","article_processing_charge":"Yes","abstract":[{"text":"A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on mouse dendritic cells (DCs) as a binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of the pathogenic strain CFT073 to CD14 reduced DC migration by overactivation of integrins and blunted expression of co-stimulatory molecules by overactivating the NFAT (nuclear factor of activated T-cells) pathway, both rate-limiting factors of T cell activation. This response was binary at the single-cell level, but averaged in larger populations exposed to both piliated and non-piliated pathogens, presumably via the exchange of immunomodulatory cytokines. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease.","lang":"eng"}],"publication_status":"published","external_id":{"pmid":["35881547"],"isi":["000838410200001"]},"title":"Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14","author":[{"first_name":"Kathrin","last_name":"Tomasek","orcid":"0000-0003-3768-877X","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","full_name":"Tomasek, Kathrin"},{"full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1073-744X","last_name":"Leithner","first_name":"Alexander F"},{"id":"727b3c7d-4939-11ec-89b3-b9b0750ab74d","full_name":"Glatzová, Ivana","first_name":"Ivana","last_name":"Glatzová"},{"first_name":"Michael S.","last_name":"Lukesch","full_name":"Lukesch, Michael S."},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","last_name":"Guet","first_name":"Calin C"},{"orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","last_name":"Sixt","first_name":"Michael K"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","volume":11,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"related_material":{"record":[{"relation":"earlier_version","id":"10316","status":"public"}]},"pmid":1},{"citation":{"short":"K. Bartalska, V. Hübschmann, M. Korkut, R.J. Cubero, A. Venturino, K. Rössler, T. Czech, S. Siegert, IScience 25 (2022).","ieee":"K. Bartalska et al., “A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation,” iScience, vol. 25, no. 7. Elsevier, 2022.","ista":"Bartalska K, Hübschmann V, Korkut M, Cubero RJ, Venturino A, Rössler K, Czech T, Siegert S. 2022. A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation. iScience. 25(7), 104580.","ama":"Bartalska K, Hübschmann V, Korkut M, et al. A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation. iScience. 2022;25(7). doi:10.1016/j.isci.2022.104580","apa":"Bartalska, K., Hübschmann, V., Korkut, M., Cubero, R. J., Venturino, A., Rössler, K., … Siegert, S. (2022). A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation. IScience. Elsevier. https://doi.org/10.1016/j.isci.2022.104580","chicago":"Bartalska, Katarina, Verena Hübschmann, Medina Korkut, Ryan J Cubero, Alessandro Venturino, Karl Rössler, Thomas Czech, and Sandra Siegert. “A Systematic Characterization of Microglia-like Cell Occurrence during Retinal Organoid Differentiation.” IScience. Elsevier, 2022. https://doi.org/10.1016/j.isci.2022.104580.","mla":"Bartalska, Katarina, et al. “A Systematic Characterization of Microglia-like Cell Occurrence during Retinal Organoid Differentiation.” IScience, vol. 25, no. 7, 104580, Elsevier, 2022, doi:10.1016/j.isci.2022.104580."},"project":[{"call_identifier":"H2020","name":"Microglia action towards neuronal circuit formation and function in health and disease","_id":"25D4A630-B435-11E9-9278-68D0E5697425","grant_number":"715571"},{"name":"IST Austria Open Access Fund","_id":"B67AFEDC-15C9-11EA-A837-991A96BB2854"},{"_id":"9B99D380-BA93-11EA-9121-9846C619BF3A","grant_number":"SC19-017","name":"How human microglia shape developing neurons during health and inflammation"}],"ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"day":"15","status":"public","isi":1,"oa":1,"file_date_updated":"2022-07-04T08:19:25Z","language":[{"iso":"eng"}],"month":"07","date_published":"2022-07-15T00:00:00Z","department":[{"_id":"SaSi"}],"publisher":"Elsevier","date_updated":"2026-08-12T08:45:16Z","article_type":"original","intvolume":" 25","oa_version":"Published Version","type":"journal_article","acknowledgement":"We thank the scientific service units at ISTA, specifically the lab support facility and imaging & optics facility for their support; Nicolas Armel for performing the Mass Spectrometry. We thank Alexandra Lang and Tanja Peilnsteiner for their help in human brain tissue collection, Rouven Schulz for his insights into the functional assays We thank all members of the Siegert group for constant feedback on the project and Margaret Maes, Rouven Schulz, and Marco Benevento for feedback on the manuscript. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant No. 715571 to S.S.) and from the Gesellschaft für Forschungsförderung Niederösterreich (grant No. Sc19-017 to V.H.).","_id":"11478","scopus_import":"1","corr_author":"1","quality_controlled":"1","file":[{"date_created":"2022-07-04T08:19:25Z","file_name":"2022_iScience_Bartalska.pdf","content_type":"application/pdf","success":1,"creator":"cchlebak","file_id":"11480","access_level":"open_access","checksum":"a470b74e1b3796c710189c81a4cd4329","relation":"main_file","date_updated":"2022-07-04T08:19:25Z","file_size":19400048}],"has_accepted_license":"1","ddc":["610"],"year":"2022","date_created":"2022-07-03T22:01:33Z","article_number":"104580","issue":"7","doi":"10.1016/j.isci.2022.104580","publication_identifier":{"eissn":["2589-0042"]},"publication":"iScience","article_processing_charge":"Yes","abstract":[{"text":"Cerebral organoids differentiated from human-induced pluripotent stem cells (hiPSC) provide a unique opportunity to investigate brain development. However, organoids usually lack microglia, brain-resident immune cells, which are present in the early embryonic brain and participate in neuronal circuit development. Here, we find IBA1+ microglia-like cells alongside retinal cups between week 3 and 4 in 2.5D culture with an unguided retinal organoid differentiation protocol. Microglia do not infiltrate the neuroectoderm and instead enrich within non-pigmented, 3D-cystic compartments that develop in parallel to the 3D-retinal organoids. When we guide the retinal organoid differentiation with low-dosed BMP4, we prevent cup development and enhance microglia and 3D-cysts formation. Mass spectrometry identifies these 3D-cysts to express mesenchymal and epithelial markers. We confirmed this microglia-preferred environment also within the unguided protocol, providing insight into microglial behavior and migration and offer a model to study how they enter and distribute within the human brain.","lang":"eng"}],"external_id":{"pmid":["35789843"],"isi":["000830428500005"]},"publication_status":"published","title":"A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"first_name":"Katarina","last_name":"Bartalska","id":"4D883232-F248-11E8-B48F-1D18A9856A87","full_name":"Bartalska, Katarina"},{"id":"32B7C918-F248-11E8-B48F-1D18A9856A87","full_name":"Hübschmann, Verena","first_name":"Verena","last_name":"Hübschmann"},{"orcid":"0000-0003-4309-2251","id":"4B51CE74-F248-11E8-B48F-1D18A9856A87","full_name":"Korkut, Medina","first_name":"Medina","last_name":"Korkut"},{"last_name":"Cubero","first_name":"Ryan J","orcid":"0000-0003-0002-1867","id":"850B2E12-9CD4-11E9-837F-E719E6697425","full_name":"Cubero, Ryan J"},{"full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","first_name":"Alessandro","last_name":"Venturino"},{"last_name":"Rössler","first_name":"Karl","full_name":"Rössler, Karl"},{"first_name":"Thomas","last_name":"Czech","full_name":"Czech, Thomas"},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","first_name":"Sandra","last_name":"Siegert"}],"volume":25,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"related_material":{"record":[{"relation":"other","id":"12117","status":"public"},{"id":"20074","relation":"dissertation_contains","status":"public"}]},"pmid":1},{"ddc":["580"],"has_accepted_license":"1","file":[{"file_id":"14483","checksum":"a6055c606aefb900bf62ae3e7d15f921","relation":"main_file","access_level":"open_access","file_size":79774945,"date_updated":"2023-11-02T17:12:37Z","date_created":"2023-11-02T17:12:37Z","content_type":"application/pdf","file_name":"Friml Nature 2022_merged.pdf","creator":"amally","success":1}],"quality_controlled":"1","corr_author":"1","publication":"Nature","publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"doi":"10.1038/s41586-022-05187-x","issue":"7927","date_created":"2023-01-16T10:04:48Z","year":"2022","title":"ABP1–TMK auxin perception for global phosphorylation and auxin canalization","publication_status":"published","external_id":{"isi":["000851357500002"],"pmid":["36071161"]},"abstract":[{"text":"The phytohormone auxin triggers transcriptional reprogramming through a well-characterized perception machinery in the nucleus. By contrast, mechanisms that underlie fast effects of auxin, such as the regulation of ion fluxes, rapid phosphorylation of proteins or auxin feedback on its transport, remain unclear1,2,3. Whether auxin-binding protein 1 (ABP1) is an auxin receptor has been a source of debate for decades1,4. Here we show that a fraction of Arabidopsis thaliana ABP1 is secreted and binds auxin specifically at an acidic pH that is typical of the apoplast. ABP1 and its plasma-membrane-localized partner, transmembrane kinase 1 (TMK1), are required for the auxin-induced ultrafast global phospho-response and for downstream processes that include the activation of H+-ATPase and accelerated cytoplasmic streaming. abp1 and tmk mutants cannot establish auxin-transporting channels and show defective auxin-induced vasculature formation and regeneration. An ABP1(M2X) variant that lacks the capacity to bind auxin is unable to complement these defects in abp1 mutants. These data indicate that ABP1 is the auxin receptor for TMK1-based cell-surface signalling, which mediates the global phospho-response and auxin canalization.","lang":"eng"}],"article_processing_charge":"No","page":"575-581","pmid":1,"related_material":{"record":[{"id":"20364","relation":"dissertation_contains","status":"public"},{"status":"public","relation":"dissertation_contains","id":"19395"}]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"LifeSc"}],"volume":609,"author":[{"last_name":"Friml","first_name":"Jiří","id":"4159519E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8302-7596","full_name":"Friml, Jiří"},{"full_name":"Gallei, Michelle C","orcid":"0000-0003-1286-7368","id":"35A03822-F248-11E8-B48F-1D18A9856A87","last_name":"Gallei","first_name":"Michelle C"},{"id":"0AE74790-0E0B-11E9-ABC7-1ACFE5697425","orcid":"0000-0003-4783-1752","full_name":"Gelová, Zuzana","first_name":"Zuzana","last_name":"Gelová"},{"full_name":"Johnson, Alexander J","orcid":"0000-0002-2739-8843","id":"46A62C3A-F248-11E8-B48F-1D18A9856A87","last_name":"Johnson","first_name":"Alexander J"},{"full_name":"Mazur, Ewa","last_name":"Mazur","first_name":"Ewa"},{"full_name":"Monzer, Aline","id":"2DB5D88C-D7B3-11E9-B8FD-7907E6697425","last_name":"Monzer","first_name":"Aline"},{"full_name":"Rodriguez Solovey, Lesia","id":"3922B506-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7244-7237","first_name":"Lesia","last_name":"Rodriguez Solovey"},{"first_name":"Mark","last_name":"Roosjen","full_name":"Roosjen, Mark"},{"id":"362BF7FE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7241-2328","full_name":"Verstraeten, Inge","last_name":"Verstraeten","first_name":"Inge"},{"full_name":"Živanović, Branka D.","last_name":"Živanović","first_name":"Branka D."},{"first_name":"Minxia","last_name":"Zou","full_name":"Zou, Minxia","id":"5c243f41-03f3-11ec-841c-96faf48a7ef9"},{"full_name":"Fiedler, Lukas","id":"7c417475-8972-11ed-ae7b-8b674ca26986","last_name":"Fiedler","first_name":"Lukas"},{"last_name":"Giannini","first_name":"Caterina","id":"e3fdddd5-f6e0-11ea-865d-ca99ee6367f4","full_name":"Giannini, Caterina"},{"first_name":"Peter","last_name":"Grones","full_name":"Grones, Peter"},{"first_name":"Mónika","last_name":"Hrtyan","id":"45A71A74-F248-11E8-B48F-1D18A9856A87","full_name":"Hrtyan, Mónika"},{"last_name":"Kaufmann","first_name":"Walter","full_name":"Kaufmann, Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315"},{"first_name":"Andre","last_name":"Kuhn","full_name":"Kuhn, Andre"},{"full_name":"Narasimhan, Madhumitha","orcid":"0000-0002-8600-0671","id":"44BF24D0-F248-11E8-B48F-1D18A9856A87","first_name":"Madhumitha","last_name":"Narasimhan"},{"first_name":"Marek","last_name":"Randuch","id":"6ac4636d-15b2-11ec-abd3-fb8df79972ae","full_name":"Randuch, Marek"},{"full_name":"Rýdza, Nikola","last_name":"Rýdza","first_name":"Nikola"},{"full_name":"Takahashi, Koji","last_name":"Takahashi","first_name":"Koji"},{"full_name":"Tan, Shutang","id":"2DE75584-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0471-8285","first_name":"Shutang","last_name":"Tan"},{"last_name":"Teplova","first_name":"Anastasiia","full_name":"Teplova, Anastasiia","id":"e3736151-106c-11ec-b916-c2558e2762c6"},{"full_name":"Kinoshita, Toshinori","first_name":"Toshinori","last_name":"Kinoshita"},{"first_name":"Dolf","last_name":"Weijers","full_name":"Weijers, Dolf"},{"first_name":"Hana","last_name":"Rakusová","full_name":"Rakusová, Hana"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","project":[{"_id":"261099A6-B435-11E9-9278-68D0E5697425","grant_number":"742985","call_identifier":"H2020","name":"Tracing Evolution of Auxin Transport and Polarity in Plants"},{"_id":"262EF96E-B435-11E9-9278-68D0E5697425","grant_number":"P29988","call_identifier":"FWF","name":"RNA-directed DNA methylation in plant development"}],"citation":{"ieee":"J. Friml et al., “ABP1–TMK auxin perception for global phosphorylation and auxin canalization,” Nature, vol. 609, no. 7927. Springer Nature, pp. 575–581, 2022.","short":"J. Friml, M.C. Gallei, Z. Gelová, A.J. Johnson, E. Mazur, A. Monzer, L. Rodriguez Solovey, M. Roosjen, I. Verstraeten, B.D. Živanović, M. Zou, L. Fiedler, C. Giannini, P. Grones, M. Hrtyan, W. Kaufmann, A. Kuhn, M. Narasimhan, M. Randuch, N. Rýdza, K. Takahashi, S. Tan, A. Teplova, T. Kinoshita, D. Weijers, H. Rakusová, Nature 609 (2022) 575–581.","ama":"Friml J, Gallei MC, Gelová Z, et al. ABP1–TMK auxin perception for global phosphorylation and auxin canalization. Nature. 2022;609(7927):575-581. doi:10.1038/s41586-022-05187-x","ista":"Friml J, Gallei MC, Gelová Z, Johnson AJ, Mazur E, Monzer A, Rodriguez Solovey L, Roosjen M, Verstraeten I, Živanović BD, Zou M, Fiedler L, Giannini C, Grones P, Hrtyan M, Kaufmann W, Kuhn A, Narasimhan M, Randuch M, Rýdza N, Takahashi K, Tan S, Teplova A, Kinoshita T, Weijers D, Rakusová H. 2022. ABP1–TMK auxin perception for global phosphorylation and auxin canalization. Nature. 609(7927), 575–581.","apa":"Friml, J., Gallei, M. C., Gelová, Z., Johnson, A. J., Mazur, E., Monzer, A., … Rakusová, H. (2022). ABP1–TMK auxin perception for global phosphorylation and auxin canalization. Nature. Springer Nature. https://doi.org/10.1038/s41586-022-05187-x","chicago":"Friml, Jiří, Michelle C Gallei, Zuzana Gelová, Alexander J Johnson, Ewa Mazur, Aline Monzer, Lesia Rodriguez Solovey, et al. “ABP1–TMK Auxin Perception for Global Phosphorylation and Auxin Canalization.” Nature. Springer Nature, 2022. https://doi.org/10.1038/s41586-022-05187-x.","mla":"Friml, Jiří, et al. “ABP1–TMK Auxin Perception for Global Phosphorylation and Auxin Canalization.” Nature, vol. 609, no. 7927, Springer Nature, 2022, pp. 575–81, doi:10.1038/s41586-022-05187-x."},"day":"15","status":"public","ec_funded":1,"date_updated":"2026-08-14T09:33:45Z","publisher":"Springer Nature","department":[{"_id":"JiFr"},{"_id":"GradSch"},{"_id":"EvBe"},{"_id":"EM-Fac"}],"date_published":"2022-09-15T00:00:00Z","month":"09","language":[{"iso":"eng"}],"file_date_updated":"2023-11-02T17:12:37Z","oa":1,"isi":1,"scopus_import":"1","_id":"12291","acknowledgement":"We acknowledge K. Kubiasová for excellent technical assistance, J. Neuhold, A. Lehner and A. Sedivy for technical assistance with protein production and purification at Vienna Biocenter Core Facilities; Creoptix for performing GCI; and the Bioimaging, Electron Microscopy and Life Science Facilities at ISTA, the Plant Sciences Core Facility of CEITEC Masaryk University, the Core Facility CELLIM (MEYS CR, LM2018129 Czech-BioImaging) and J. Sprakel for their assistance. J.F. is grateful to R. Napier for many insightful suggestions and support. We thank all past and present members of the Friml group for their support and for other contributions to this effort to clarify the controversial role of ABP1 over the past seven years. The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 742985 to J.F. and 833867 to D.W.); the Austrian Science Fund (FWF; P29988 to J.F.); the Netherlands Organization for Scientific Research (NWO; VICI grant 865.14.001 to D.W. and VENI grant VI.Veni.212.003 to A.K.); the Ministry of Education, Science and Technological Development of the Republic of Serbia (contract no. 451-03-68/2022-14/200053 to B.D.Ž.); and the MEXT/JSPS KAKENHI to K.T. (20K06685) and T.K. (20H05687 and 20H05910).","type":"journal_article","oa_version":"Submitted Version","intvolume":" 609","article_type":"original"}]