[{"volume":26,"date_created":"2023-09-24T22:01:11Z","date_updated":"2023-12-13T12:27:30Z","author":[{"orcid":"0000-0001-9642-1085","id":"3838F452-F248-11E8-B48F-1D18A9856A87","last_name":"Maes","first_name":"Margaret E","full_name":"Maes, Margaret E"},{"full_name":"Colombo, Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9434-8902","first_name":"Gloria","last_name":"Colombo"},{"full_name":"Schoot Uiterkamp, Florianne E","id":"3526230C-F248-11E8-B48F-1D18A9856A87","last_name":"Schoot Uiterkamp","first_name":"Florianne E"},{"full_name":"Sternberg, Felix","last_name":"Sternberg","first_name":"Felix"},{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2356-9403","first_name":"Alessandro","last_name":"Venturino","full_name":"Venturino, Alessandro"},{"first_name":"Elena E.","last_name":"Pohl","full_name":"Pohl, Elena E."},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","first_name":"Sandra","last_name":"Siegert","full_name":"Siegert, Sandra"}],"department":[{"_id":"SaSi"}],"publisher":"Elsevier","publication_status":"published","pmid":1,"year":"2023","acknowledgement":"We thank the Scientific Service Units (SSU) of ISTA through resources provided by the Imaging and Optics Facility (IOF), the Lab Support Facility (LSF), and the Pre-Clinical Facility (PCF) team, specifically Sonja Haslinger and Michael Schunn for excellent mouse colony management and support. This research was supported by the FWF Sonderforschungsbereich F83 (to E.E.P). We thank Bálint Nagy, Ryan John A. Cubero, Marco Benevento and all members of the Siegert group for constant feedback on the project and article.","file_date_updated":"2023-11-07T08:53:21Z","article_number":"107780","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"doi":"10.1016/j.isci.2023.107780","quality_controlled":"1","isi":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"isi":["001080403500001"],"pmid":["37731609"]},"publication_identifier":{"eissn":["2589-0042"]},"month":"10","oa_version":"Published Version","file":[{"file_id":"14497","relation":"main_file","success":1,"checksum":"be1a560efdd96d20712311f4fc54aac2","date_created":"2023-11-07T08:53:21Z","date_updated":"2023-11-07T08:53:21Z","access_level":"open_access","file_name":"2023_iScience_Maes.pdf","creator":"dernst","content_type":"application/pdf","file_size":8197935}],"intvolume":" 26","ddc":["570"],"title":"Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout","status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"14363","issue":"10","abstract":[{"text":"Mitochondrial networks remodel their connectivity, content, and subcellular localization to support optimized energy production in conditions of increased environmental or cellular stress. Microglia rely on mitochondria to respond to these stressors, however our knowledge about mitochondrial networks and their adaptations in microglia in vivo is limited. Here, we generate a mouse model that selectively labels mitochondria in microglia. We identify that mitochondrial networks are more fragmented with increased content and perinuclear localization in vitro vs. in vivo. Mitochondrial networks adapt similarly in microglia closest to the injury site after optic nerve crush. Preventing microglial UCP2 increase after injury by selective knockout induces cellular stress. This results in mitochondrial hyperfusion in male microglia, a phenotype absent in females due to circulating estrogens. Our results establish the foundation for mitochondrial network analysis of microglia in vivo, emphasizing the importance of mitochondrial-based sex effects of microglia in other pathologies.","lang":"eng"}],"type":"journal_article","date_published":"2023-10-20T00:00:00Z","article_type":"original","citation":{"chicago":"Maes, Margaret E, Gloria Colombo, Florianne E Schoot Uiterkamp, Felix Sternberg, Alessandro Venturino, Elena E. Pohl, and Sandra Siegert. “Mitochondrial Network Adaptations of Microglia Reveal Sex-Specific Stress Response after Injury and UCP2 Knockout.” IScience. Elsevier, 2023. https://doi.org/10.1016/j.isci.2023.107780.","mla":"Maes, Margaret E., et al. “Mitochondrial Network Adaptations of Microglia Reveal Sex-Specific Stress Response after Injury and UCP2 Knockout.” IScience, vol. 26, no. 10, 107780, Elsevier, 2023, doi:10.1016/j.isci.2023.107780.","short":"M.E. Maes, G. Colombo, F.E. Schoot Uiterkamp, F. Sternberg, A. Venturino, E.E. Pohl, S. Siegert, IScience 26 (2023).","ista":"Maes ME, Colombo G, Schoot Uiterkamp FE, Sternberg F, Venturino A, Pohl EE, Siegert S. 2023. Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout. iScience. 26(10), 107780.","ieee":"M. E. Maes et al., “Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout,” iScience, vol. 26, no. 10. Elsevier, 2023.","apa":"Maes, M. E., Colombo, G., Schoot Uiterkamp, F. E., Sternberg, F., Venturino, A., Pohl, E. E., & Siegert, S. (2023). Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout. IScience. Elsevier. https://doi.org/10.1016/j.isci.2023.107780","ama":"Maes ME, Colombo G, Schoot Uiterkamp FE, et al. Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout. iScience. 2023;26(10). doi:10.1016/j.isci.2023.107780"},"publication":"iScience","article_processing_charge":"Yes","has_accepted_license":"1","day":"20","scopus_import":"1"},{"date_created":"2023-10-08T22:01:15Z","date_updated":"2024-01-30T14:34:21Z","volume":18,"author":[{"full_name":"Maes, Margaret E","first_name":"Margaret E","last_name":"Maes","id":"3838F452-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9642-1085"},{"first_name":"Ryan J.","last_name":"Donahue","full_name":"Donahue, Ryan J."},{"full_name":"Schlamp, Cassandra L.","last_name":"Schlamp","first_name":"Cassandra L."},{"last_name":"Marola","first_name":"Olivia J.","full_name":"Marola, Olivia J."},{"first_name":"Richard T.","last_name":"Libby","full_name":"Libby, Richard T."},{"full_name":"Nickells, Robert W.","first_name":"Robert W.","last_name":"Nickells"}],"publication_status":"published","publisher":"Springer Nature","department":[{"_id":"SaSi"}],"year":"2023","acknowledgement":"The authors would like to thank Mr. Joel Dietz for management of the mouse colony and helpful advice for conducting quantitative PCR studies and Mr. Santoshi Kinoshita at the Translational Research Initiative in Pathology laboratory at the University of Wisconsin-Madison for cutting sections analyzed in this study.\r\nThis work was supported by National Eye Institute grants R01 EY030123 (RWN), R01 EY018606 (RTL), P30 EY016665 (Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison), T32 EY027721 (RJD) and F31 EY030739 (OJM). Additional funding was provided by the BrightFocus Foundation (RWN) and unrestricted grants from Research to Prevent Blindness, Inc to the Department of Ophthalmology and Visual Sciences (University of Wisconsin-Madison) and to the Department of Ophthalmology (University of Rochester).","pmid":1,"file_date_updated":"2024-01-30T14:33:31Z","article_number":"67","language":[{"iso":"eng"}],"doi":"10.1186/s13024-023-00659-8","quality_controlled":"1","isi":1,"external_id":{"isi":["001071403800001"],"pmid":["37292963"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"month":"09","publication_identifier":{"eissn":["1750-1326"]},"file":[{"file_id":"14917","relation":"main_file","success":1,"checksum":"3aa218ddea4a082d8fd5e196ae55ca06","date_created":"2024-01-30T14:33:31Z","date_updated":"2024-01-30T14:33:31Z","access_level":"open_access","file_name":"2023_MolecularNeurodegeneration_Maes.pdf","creator":"dernst","file_size":11568350,"content_type":"application/pdf"}],"oa_version":"Published Version","ddc":["570"],"status":"public","title":"BAX activation in mouse retinal ganglion cells occurs in two temporally and mechanistically distinct steps","intvolume":" 18","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"14401","abstract":[{"text":"Background: \r\nPro-apoptotic BAX is a central mediator of retinal ganglion cell (RGC) death after optic nerve damage. BAX activation occurs in two stages including translocation of latent BAX to the mitochondrial outer membrane (MOM) and then permeabilization of the MOM to facilitate the release of apoptotic signaling molecules. As a critical component of RGC death, BAX is an attractive target for neuroprotective therapies and an understanding of the kinetics of BAX activation and the mechanisms controlling the two stages of this process in RGCs is potentially valuable in informing the development of a neuroprotective strategy.\r\nMethods:\r\nThe kinetics of BAX translocation were assessed by both static and live-cell imaging of a GFP-BAX fusion protein introduced into RGCs using AAV2-mediated gene transfer in mice. Activation of BAX was achieved using an acute optic nerve crush (ONC) protocol. Live-cell imaging of GFP-BAX was achieved using explants of mouse retina harvested 7 days after ONC. Kinetics of translocation in RGCs were compared to GFP-BAX translocation in 661W tissue culture cells. Permeabilization of GFP-BAX was assessed by staining with the 6A7 monoclonal antibody, which recognizes a conformational change in this protein after MOM insertion. Assessment of individual kinases associated with both stages of activation was made using small molecule inhibitors injected into the vitreous either independently or in concert with ONC surgery. The contribution of the Dual Leucine Zipper-JUN-N-Terminal Kinase cascade was evaluated using mice with a double conditional knock-out of both Mkk4 and Mkk7.\r\nResults:\r\nONC induces the translocation of GFP-BAX in RGCs at a slower rate and with less intracellular synchronicity than 661W cells, but exhibits less variability among mitochondrial foci within a single cell. GFP-BAX was also found to translocate in all compartments of an RGC including the dendritic arbor and axon. Approximately 6% of translocating RGCs exhibited retrotranslocation of BAX immediately following translocation. Unlike tissue culture cells, which exhibit simultaneous translocation and permeabilization, RGCs exhibited a significant delay between these two stages, similar to detached cells undergoing anoikis. Translocation, with minimal permeabilization could be induced in a subset of RGCs using an inhibitor of Focal Adhesion Kinase (PF573228). Permeabilization after ONC, in a majority of RGCs, could be inhibited with a broad spectrum kinase inhibitor (sunitinib) or a selective inhibitor for p38/MAPK14 (SB203580). Intervention of DLK-JNK axis signaling abrogated GFP-BAX translocation after ONC.\r\nConclusions:\r\nA comparison between BAX activation kinetics in tissue culture cells and in cells of a complex tissue environment shows distinct differences indicating that caution should be used when translating findings from one condition to the other. RGCs exhibit both a delay between translocation and permeabilization and the ability for translocated BAX to be retrotranslocated, suggesting several stages at which intervention of the activation process could be exploited in the design of a therapeutic strategy.","lang":"eng"}],"type":"journal_article","date_published":"2023-09-26T00:00:00Z","article_type":"original","publication":"Molecular Neurodegeneration","citation":{"chicago":"Maes, Margaret E, Ryan J. Donahue, Cassandra L. Schlamp, Olivia J. Marola, Richard T. Libby, and Robert W. Nickells. “BAX Activation in Mouse Retinal Ganglion Cells Occurs in Two Temporally and Mechanistically Distinct Steps.” Molecular Neurodegeneration. Springer Nature, 2023. https://doi.org/10.1186/s13024-023-00659-8.","mla":"Maes, Margaret E., et al. “BAX Activation in Mouse Retinal Ganglion Cells Occurs in Two Temporally and Mechanistically Distinct Steps.” Molecular Neurodegeneration, vol. 18, 67, Springer Nature, 2023, doi:10.1186/s13024-023-00659-8.","short":"M.E. Maes, R.J. Donahue, C.L. Schlamp, O.J. Marola, R.T. Libby, R.W. Nickells, Molecular Neurodegeneration 18 (2023).","ista":"Maes ME, Donahue RJ, Schlamp CL, Marola OJ, Libby RT, Nickells RW. 2023. BAX activation in mouse retinal ganglion cells occurs in two temporally and mechanistically distinct steps. Molecular Neurodegeneration. 18, 67.","ieee":"M. E. Maes, R. J. Donahue, C. L. Schlamp, O. J. Marola, R. T. Libby, and R. W. Nickells, “BAX activation in mouse retinal ganglion cells occurs in two temporally and mechanistically distinct steps,” Molecular Neurodegeneration, vol. 18. Springer Nature, 2023.","apa":"Maes, M. E., Donahue, R. J., Schlamp, C. L., Marola, O. J., Libby, R. T., & Nickells, R. W. (2023). BAX activation in mouse retinal ganglion cells occurs in two temporally and mechanistically distinct steps. Molecular Neurodegeneration. Springer Nature. https://doi.org/10.1186/s13024-023-00659-8","ama":"Maes ME, Donahue RJ, Schlamp CL, Marola OJ, Libby RT, Nickells RW. BAX activation in mouse retinal ganglion cells occurs in two temporally and mechanistically distinct steps. Molecular Neurodegeneration. 2023;18. doi:10.1186/s13024-023-00659-8"},"day":"26","has_accepted_license":"1","article_processing_charge":"Yes","scopus_import":"1"},{"ec_funded":1,"file_date_updated":"2023-08-04T13:19:47Z","publisher":"Institute of Science and Technology Austria","department":[{"_id":"JoDa"},{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"Bio"},{"_id":"RySh"}],"acknowledgement":"We thank Jakob Vorlaufer, Nathalie Agudelo-Dueñas, Wiebke Jahr, Andreas Wartak for microscope maintenance and troubleshooting, Caroline Kreuzinger, Anna Freeman, and Irene Erber for technical assistance and Matthias Tomschik for support with obtaining human samples. We gratefully acknowledge Eder Miguel for setting up webKnossos and Marek Šuplata for computational support and hardware control. We are grateful to Ryuichi Shigemoto and Bernd Bickel for generous support, and Michael Sixt and Scott Boyd (Stanford University) for discussions and critical reading of the manuscript. PSD95-HaloTag mice were kindly provided by Seth Grant (University of Edinburgh). We acknowledge expert support by IST Austria’s scientific computing, imaging and optics, preclinical, and lab support facilities, and by the Library and Miba machine shop.\r\nWe gratefully acknowledge funding by the following sources: \r\nAustrian Science Fund (FWF) grant I3600-B27 (JGD)\r\nAustrian Science Fund (FWF) grant DK W1232 (JGD, JMM)\r\nAustrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (PJ)\r\nAustrian Science Funds (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (RH)\r\nGesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (JGD)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (GN)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (PJ)\r\nMarie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (JMM, JL)\r\nMarie Skłodowska-Curie Actions Individual Fellowship 101026635 under the EU Horizon 2020 program (JFW)","year":"2023","date_updated":"2024-02-21T12:18:19Z","date_created":"2023-06-07T07:15:12Z","related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"14257"}],"link":[{"url":"https://pub.ista.ac.at/group_danzl/data/CATS/","relation":"research_data","description":"Original data for Fig. 5d, Fig. 5d (N2V) and Fig. 5f-i, provided via an external link due to the large size (>10GB) of the datasets. "}]},"contributor":[{"last_name":"Michalska","first_name":"Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Julia","last_name":"Lyudchik","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Philipp","last_name":"Velicky","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431"},{"id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","first_name":"Hana","last_name":"Stefanickova"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823","first_name":"Jake","last_name":"Watson"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","last_name":"Cenameri","first_name":"Alban"},{"orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","first_name":"Christoph M"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207","first_name":"Nicole","last_name":"Amberg"},{"first_name":"Alessandro","last_name":"Venturino","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2356-9403"},{"first_name":"Karl","last_name":"Roessler"},{"last_name":"Czech","first_name":"Thomas"},{"last_name":"Höftberger","first_name":"Romana"},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","first_name":"Sandra","last_name":"Siegert"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia"},{"orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","first_name":"Peter M"}],"author":[{"last_name":"Danzl","first_name":"Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G"}],"month":"08","project":[{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600","call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules"},{"_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24","name":"Molecular Drug Targets","call_identifier":"FWF"},{"call_identifier":"FWF","name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"},{"_id":"23889792-32DE-11EA-91FC-C7463DDC885E","name":"High content imaging to decode human immune cell interactions in health and allergic disease"},{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glumatergic synapse"},{"grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"International IST Doctoral Program"},{"_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","grant_number":"101026635","name":"Synaptic computations of the hippocampal CA3 circuitry","call_identifier":"H2020"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","image":"/images/cc_by_nc_sa.png","short":"CC BY-NC-SA (4.0)"},"oa":1,"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"doi":"10.15479/AT:ISTA:13126","type":"research_data","abstract":[{"lang":"eng","text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here, we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease."}],"status":"public","title":"Research data for the publication \"Imaging brain tissue architecture across millimeter to nanometer 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Research Data for the Publication “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Institute of Science and Technology Austria, 2023, doi:10.15479/AT:ISTA:13126.","chicago":"Danzl, Johann G. “Research Data for the Publication ‘Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.’” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/AT:ISTA:13126."},"date_published":"2023-08-04T00:00:00Z"},{"month":"08","publication_identifier":{"issn":["1087-0156"],"eissn":["1546-1696"]},"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"language":[{"iso":"eng"}],"doi":"10.1038/s41587-023-01911-8","isi":1,"quality_controlled":"1","project":[{"call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425"},{"grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Drug Targets"},{"name":"The Wittgenstein Prize","call_identifier":"FWF","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"_id":"23889792-32DE-11EA-91FC-C7463DDC885E","name":"High content imaging to decode human immune cell interactions in health and allergic disease"},{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020"},{"call_identifier":"H2020","name":"International IST Doctoral Program","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"},{"name":"Synaptic computations of the hippocampal CA3 circuitry","call_identifier":"H2020","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","grant_number":"101026635"}],"main_file_link":[{"url":"https://doi.org/10.1038/s41587-023-01911-8","open_access":"1"}],"external_id":{"isi":["001065254200001"]},"oa":1,"ec_funded":1,"date_updated":"2024-02-21T12:18:18Z","date_created":"2023-09-03T22:01:15Z","author":[{"orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","last_name":"Michalska","first_name":"Julia M","full_name":"Michalska, Julia M"},{"full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","last_name":"Lyudchik","first_name":"Julia"},{"full_name":"Velicky, Philipp","last_name":"Velicky","first_name":"Philipp","orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Korinkova, Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","last_name":"Korinkova","first_name":"Hana"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823","first_name":"Jake","last_name":"Watson","full_name":"Watson, Jake"},{"full_name":"Cenameri, Alban","last_name":"Cenameri","first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M"},{"last_name":"Amberg","first_name":"Nicole","orcid":"0000-0002-3183-8207","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","full_name":"Amberg, Nicole"},{"full_name":"Venturino, Alessandro","first_name":"Alessandro","last_name":"Venturino","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2356-9403"},{"full_name":"Roessler, Karl","last_name":"Roessler","first_name":"Karl"},{"full_name":"Czech, Thomas","last_name":"Czech","first_name":"Thomas"},{"first_name":"Romana","last_name":"Höftberger","full_name":"Höftberger, Romana"},{"last_name":"Siegert","first_name":"Sandra","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Siegert, Sandra"},{"full_name":"Novarino, Gaia","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178"},{"first_name":"Peter M","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M"},{"full_name":"Danzl, Johann G","first_name":"Johann G","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973"}],"related_material":{"link":[{"relation":"software","url":"https://github.com/danzllab/CATS"}],"record":[{"relation":"research_data","status":"public","id":"13126"}]},"publication_status":"epub_ahead","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}],"publisher":"Springer Nature","acknowledgement":"We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I. Erber for technical assistance; and M. Tomschik for support with obtaining human samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata for computational support and hardware control. We are grateful to R. Shigemoto and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University) for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly provided by S. Grant (University of Edinburgh). We acknowledge expert support by Institute of Science and Technology Austria’s scientific computing, imaging and optics, preclinical and lab support facilities and by the Miba machine shop and library. We gratefully acknowledge funding by the following sources: Austrian Science Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232 (J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).","year":"2023","day":"31","article_processing_charge":"Yes (in subscription journal)","scopus_import":"1","date_published":"2023-08-31T00:00:00Z","article_type":"original","publication":"Nature Biotechnology","citation":{"ieee":"J. M. Michalska et al., “Imaging brain tissue architecture across millimeter to nanometer scales,” Nature Biotechnology. Springer Nature, 2023.","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (2023). Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. Springer Nature. https://doi.org/10.1038/s41587-023-01911-8","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino G, Jonas PM, Danzl JG. 2023. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology.","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. 2023. doi:10.1038/s41587-023-01911-8","chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Nature Biotechnology. Springer Nature, 2023. https://doi.org/10.1038/s41587-023-01911-8.","short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology (2023).","mla":"Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Nature Biotechnology, Springer Nature, 2023, doi:10.1038/s41587-023-01911-8."},"abstract":[{"text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease.","lang":"eng"}],"type":"journal_article","oa_version":"Published Version","title":"Imaging brain tissue architecture across millimeter to nanometer scales","status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"14257"},{"day":"23","has_accepted_license":"1","article_processing_charge":"No","page":"133","citation":{"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.","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.","short":"R. Schulz, Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling Pathways and Modulate Microglia Function, Institute of Science and Technology Austria, 2022.","ista":"Schulz R. 2022. Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function. Institute of Science and Technology Austria.","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","ieee":"R. Schulz, “Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function,” Institute of Science and Technology Austria, 2022.","ama":"Schulz R. Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function. 2022. doi:10.15479/at:ista:11945"},"date_published":"2022-08-23T00:00:00Z","alternative_title":["ISTA Thesis"],"type":"dissertation","abstract":[{"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.","lang":"eng"}],"status":"public","ddc":["570"],"title":"Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function","_id":"11945","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","file":[{"file_name":"Thesis_Rouven_Schulz_2022_final.pdf","access_level":"open_access","file_size":28079331,"content_type":"application/pdf","creator":"rschulz","relation":"main_file","file_id":"11970","date_created":"2022-08-25T08:59:57Z","date_updated":"2022-08-25T08:59:57Z","checksum":"61b1b666a210ff7cdd0e95ea75207a13","success":1},{"date_updated":"2022-08-25T09:33:31Z","date_created":"2022-08-25T09:00:11Z","checksum":"2b8f95ea1c134dbdb927b41b1dbeeeb5","relation":"source_file","file_id":"11971","file_size":27226963,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","creator":"rschulz","file_name":"Thesis_Rouven_Schulz_2022_final.docx","access_level":"closed"}],"oa_version":"Published Version","month":"08","publication_identifier":{"issn":["2663-337X"]},"project":[{"_id":"267F75D8-B435-11E9-9278-68D0E5697425","name":"Modulating microglia through G protein-coupled receptor (GPCR) signaling"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"supervisor":[{"orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert","first_name":"Sandra","full_name":"Siegert, Sandra"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"}],"degree_awarded":"PhD","language":[{"iso":"eng"}],"doi":"10.15479/at:ista:11945","file_date_updated":"2022-08-25T09:33:31Z","publication_status":"published","department":[{"_id":"GradSch"},{"_id":"SaSi"}],"publisher":"Institute of Science and Technology Austria","year":"2022","date_created":"2022-08-23T11:33:11Z","date_updated":"2023-08-03T13:02:26Z","author":[{"first_name":"Rouven","last_name":"Schulz","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5297-733X","full_name":"Schulz, Rouven"}],"related_material":{"record":[{"id":"11995","relation":"dissertation_contains","status":"public"}]}}]