--- _id: '15084' abstract: - lang: eng text: "GABAB receptor (GBR) activation inhibits neurotransmitter release in axon terminals in the brain, except in medial habenula (MHb) terminals, which show robust potentiation. However, mechanisms underlying this enigmatic potentiation remain elusive. Here, we report that GBR activation on MHb terminals induces an activity-dependent transition from a facilitating, tonic to a depressing, phasic neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked synaptic vesicles (SVs) at the presynaptic active zone (AZ). Strikingly, the depressing phasic release exhibits looser coupling distance than the tonic release. Furthermore, the tonic and phasic release are selectively affected by deletion of synaptoporin (SPO) and Ca\r\n 2+\r\n -dependent activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation, the short-term plasticity associated with tonic release, and CAPS2 retains the increased RRP for initial responses in phasic response trains. The cytosolic protein CAPS2 showed a SV-associated distribution similar to the vesicular transmembrane protein SPO, and they were colocalized in the same terminals. We developed the “Flash and Freeze-fracture” method, and revealed the release of SPO-associated vesicles in both tonic and phasic modes and activity-dependent recruitment of CAPS2 to the AZ during phasic release, which lasted several minutes. Overall, these results indicate that GBR activation translocates CAPS2 to the AZ along with the fusion of CAPS2-associated SVs, contributing to persistency of the RRP increase. Thus, we identified structural and molecular mechanisms underlying tonic and phasic neurotransmitter release and their transition by GBR activation in MHb terminals." acknowledged_ssus: - _id: M-Shop - _id: PreCl - _id: EM-Fac acknowledgement: We thank Erwin Neher and Ipe Ninan for critical comments on the manuscript. This project has received funding from the European Research Council (ERC) and European Commission, under the European Union’s Horizon 2020 research and innovation program (ERC grant agreement no. 694539 to R.S. and the Marie Skłodowska-Curie grant agreement no. 665385 to C.Ö.). This study was supported by the Cooperative Study Program of Center for Animal Resources and Collaborative Study of NINS. We thank Kohgaku Eguchi for statistical analysis, Yu Kasugai for additional EM imaging, Robert Beattie for the design of the slice recovery chamber for Flash and Freeze experiments, Todor Asenov from the ISTA machine shop for custom part preparations for high-pressure freezing, the ISTA preclinical facility for animal caretaking, and the ISTA EM facilities for technical support. article_number: e2301449121 article_processing_charge: Yes (in subscription journal) article_type: original author: - first_name: Peter full_name: Koppensteiner, Peter id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87 last_name: Koppensteiner orcid: 0000-0002-3509-1948 - first_name: Pradeep full_name: Bhandari, Pradeep id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87 last_name: Bhandari orcid: 0000-0003-0863-4481 - first_name: Hüseyin C full_name: Önal, Hüseyin C id: 4659D740-F248-11E8-B48F-1D18A9856A87 last_name: Önal orcid: 0000-0002-2771-2011 - first_name: Carolina full_name: Borges Merjane, Carolina id: 4305C450-F248-11E8-B48F-1D18A9856A87 last_name: Borges Merjane orcid: 0000-0003-0005-401X - first_name: Elodie full_name: Le Monnier, Elodie id: 3B59276A-F248-11E8-B48F-1D18A9856A87 last_name: Le Monnier - first_name: Utsa full_name: Roy, Utsa id: 4d26cf11-5355-11ee-ae5a-eb05e255b9b2 last_name: Roy - first_name: Yukihiro full_name: Nakamura, Yukihiro last_name: Nakamura - first_name: Tetsushi full_name: Sadakata, Tetsushi last_name: Sadakata - first_name: Makoto full_name: Sanbo, Makoto last_name: Sanbo - first_name: Masumi full_name: Hirabayashi, Masumi last_name: Hirabayashi - first_name: JeongSeop full_name: Rhee, JeongSeop last_name: Rhee - first_name: Nils full_name: Brose, Nils last_name: Brose - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: Koppensteiner P, Bhandari P, Önal C, et al. GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. Proceedings of the National Academy of Sciences. 2024;121(8). doi:10.1073/pnas.2301449121 apa: Koppensteiner, P., Bhandari, P., Önal, C., Borges Merjane, C., Le Monnier, E., Roy, U., … Shigemoto, R. (2024). GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. Proceedings of the National Academy of Sciences. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2301449121 chicago: Koppensteiner, Peter, Pradeep Bhandari, Cihan Önal, Carolina Borges Merjane, Elodie Le Monnier, Utsa Roy, Yukihiro Nakamura, et al. “GABAB Receptors Induce Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.” Proceedings of the National Academy of Sciences. Proceedings of the National Academy of Sciences, 2024. https://doi.org/10.1073/pnas.2301449121. ieee: P. Koppensteiner et al., “GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles,” Proceedings of the National Academy of Sciences, vol. 121, no. 8. Proceedings of the National Academy of Sciences, 2024. ista: Koppensteiner P, Bhandari P, Önal C, Borges Merjane C, Le Monnier E, Roy U, Nakamura Y, Sadakata T, Sanbo M, Hirabayashi M, Rhee J, Brose N, Jonas PM, Shigemoto R. 2024. GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. Proceedings of the National Academy of Sciences. 121(8), e2301449121. mla: Koppensteiner, Peter, et al. “GABAB Receptors Induce Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.” Proceedings of the National Academy of Sciences, vol. 121, no. 8, e2301449121, Proceedings of the National Academy of Sciences, 2024, doi:10.1073/pnas.2301449121. short: P. Koppensteiner, P. Bhandari, C. Önal, C. Borges Merjane, E. Le Monnier, U. Roy, Y. Nakamura, T. Sadakata, M. Sanbo, M. Hirabayashi, J. Rhee, N. Brose, P.M. Jonas, R. Shigemoto, Proceedings of the National Academy of Sciences 121 (2024). date_created: 2024-03-05T09:23:55Z date_published: 2024-02-20T00:00:00Z date_updated: 2024-03-12T13:44:18Z day: '20' ddc: - '570' department: - _id: RySh - _id: PeJo doi: 10.1073/pnas.2301449121 ec_funded: 1 external_id: pmid: - '38346189' file: - access_level: open_access checksum: b25b2a057c266ff317a48b0d54d6fc8a content_type: application/pdf creator: dernst date_created: 2024-03-12T13:42:42Z date_updated: 2024-03-12T13:42:42Z file_id: '15110' file_name: 2024_PNAS_Koppensteiner.pdf file_size: 13648221 relation: main_file success: 1 file_date_updated: 2024-03-12T13:42:42Z has_accepted_license: '1' intvolume: ' 121' issue: '8' language: - iso: eng month: '02' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication: Proceedings of the National Academy of Sciences publication_identifier: eissn: - 1091-6490 issn: - 0027-8424 publication_status: published publisher: Proceedings of the National Academy of Sciences quality_controlled: '1' related_material: link: - description: News on ISTA Website relation: press_release url: https://ista.ac.at/en/news/neuronal-insights-flash-and-freeze-fracture/ record: - id: '13173' relation: research_data status: public status: public title: GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 121 year: '2024' ... --- _id: '14843' abstract: - lang: eng text: The coupling between Ca2+ channels and release sensors is a key factor defining the signaling properties of a synapse. However, the coupling nanotopography at many synapses remains unknown, and it is unclear how it changes during development. To address these questions, we examined coupling at the cerebellar inhibitory basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission by paired recording and intracellular pipette perfusion revealed that the effects of exogenous Ca2+ chelators decreased during development, despite constant reliance of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission. acknowledged_ssus: - _id: EM-Fac - _id: PreCl - _id: M-Shop acknowledgement: We thank Drs. David DiGregorio and Erwin Neher for critically reading an earlier version of the manuscript, Ralf Schneggenburger for helpful discussions, Benjamin Suter and Katharina Lichter for support with image analysis, Chris Wojtan for advice on numerical solution of partial differential equations, Maria Reva for help with Ripley analysis, Alois Schlögl for programming, and Akari Hagiwara and Toshihisa Ohtsuka for anti-ELKS antibody. We are grateful to Florian Marr, Christina Altmutter, and Vanessa Zheden for excellent technical assistance and to Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA (Electron Microscopy Facility, Preclinical Facility, and Machine Shop). The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 692692), the Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award; P 36232-B), all to P.J., and a DOC fellowship of the Austrian Academy of Sciences to J.-J.C. article_processing_charge: No article_type: original author: - first_name: JingJing full_name: Chen, JingJing id: 2C4E65C8-F248-11E8-B48F-1D18A9856A87 last_name: Chen - first_name: Walter full_name: Kaufmann, Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - first_name: Chong full_name: Chen, Chong id: 3DFD581A-F248-11E8-B48F-1D18A9856A87 last_name: Chen - first_name: Itaru full_name: Arai, Itaru id: 32A73F6C-F248-11E8-B48F-1D18A9856A87 last_name: Arai - first_name: Olena full_name: Kim, Olena id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87 last_name: Kim - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: Chen J, Kaufmann W, Chen C, et al. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron. doi:10.1016/j.neuron.2023.12.002 apa: Chen, J., Kaufmann, W., Chen, C., Arai, itaru, Kim, O., Shigemoto, R., & Jonas, P. M. (n.d.). Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2023.12.002 chicago: Chen, JingJing, Walter Kaufmann, Chong Chen, itaru Arai, Olena Kim, Ryuichi Shigemoto, and Peter M Jonas. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” Neuron. Elsevier, n.d. https://doi.org/10.1016/j.neuron.2023.12.002. ieee: J. Chen et al., “Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse,” Neuron. Elsevier. ista: Chen J, Kaufmann W, Chen C, Arai itaru, Kim O, Shigemoto R, Jonas PM. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron. mla: Chen, JingJing, et al. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” Neuron, Elsevier, doi:10.1016/j.neuron.2023.12.002. short: J. Chen, W. Kaufmann, C. Chen, itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas, Neuron (n.d.). date_created: 2024-01-21T23:00:56Z date_published: 2024-01-11T00:00:00Z date_updated: 2024-03-14T13:14:18Z day: '11' department: - _id: PeJo - _id: EM-Fac - _id: RySh doi: 10.1016/j.neuron.2023.12.002 ec_funded: 1 external_id: pmid: - '38215739' language: - iso: eng month: '01' oa_version: None pmid: 1 project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize - _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5 grant_number: P36232 name: Mechanisms of GABA release in hippocampal circuits - _id: 26B66A3E-B435-11E9-9278-68D0E5697425 grant_number: '25383' name: Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse publication: Neuron publication_identifier: eissn: - 1097-4199 issn: - 0896-6273 publication_status: inpress publisher: Elsevier quality_controlled: '1' related_material: link: - description: News on ISTA Website relation: press_release url: https://ista.ac.at/en/news/synapses-brought-to-the-point/ record: - id: '15101' relation: dissertation_contains status: public scopus_import: '1' status: public title: Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2024' ... --- _id: '15101' acknowledged_ssus: - _id: EM-Fac alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: JingJing full_name: Chen, JingJing id: 2C4E65C8-F248-11E8-B48F-1D18A9856A87 last_name: Chen citation: ama: Chen J. Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse. 2024. doi:10.15479/at:ista:15101 apa: Chen, J. (2024). Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:15101 chicago: Chen, JingJing. “Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse.” Institute of Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:15101. ieee: J. Chen, “Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse,” Institute of Science and Technology Austria, 2024. ista: Chen J. 2024. Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse. Institute of Science and Technology Austria. mla: Chen, JingJing. Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse. Institute of Science and Technology Austria, 2024, doi:10.15479/at:ista:15101. short: J. Chen, Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse, Institute of Science and Technology Austria, 2024. date_created: 2024-03-11T10:09:54Z date_published: 2024-03-11T00:00:00Z date_updated: 2024-03-14T13:14:19Z day: '11' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: PeJo doi: 10.15479/at:ista:15101 ec_funded: 1 file: - access_level: closed checksum: db4947474ffa271e66c254b6fe876a55 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: jchen date_created: 2024-03-11T14:10:58Z date_updated: 2024-03-12T07:12:17Z file_id: '15104' file_name: Thesis_Jingjing CHEN.docx file_size: 11271363 relation: source_file - access_level: closed checksum: a5eeae8b5702cd540f5d03469bc33dde content_type: application/pdf creator: jchen date_created: 2024-03-11T14:11:06Z date_updated: 2024-03-11T14:11:06Z embargo: 2024-04-01 embargo_to: open_access file_id: '15105' file_name: Thesis_Jingjing CHEN_merged.pdf file_size: 16627311 relation: main_file file_date_updated: 2024-03-12T07:12:17Z has_accepted_license: '1' language: - iso: eng month: '03' oa_version: Published Version page: '84' project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize - _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5 grant_number: P36232 name: Mechanisms of GABA release in hippocampal circuits - _id: 26B66A3E-B435-11E9-9278-68D0E5697425 grant_number: '25383' name: Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse publication_identifier: issn: - 2663 - 337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '14843' relation: part_of_dissertation status: public status: public supervisor: - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 title: Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 year: '2024' ... --- _id: '15117' abstract: - lang: eng text: 'The hippocampal mossy fiber synapse, formed between axons of dentate gyrus granule cells and dendrites of CA3 pyramidal neurons, is a key synapse in the trisynaptic circuitry of the hippocampus. Because of its comparatively large size, this synapse is accessible to direct presynaptic recording, allowing a rigorous investigation of the biophysical mechanisms of synaptic transmission and plasticity. Furthermore, because of its placement in the very center of the hippocampal memory circuit, this synapse seems to be critically involved in several higher network functions, such as learning, memory, pattern separation, and pattern completion. Recent work based on new technologies in both nanoanatomy and nanophysiology, including presynaptic patch-clamp recording, paired recording, super-resolution light microscopy, and freeze-fracture and “flash-and-freeze” electron microscopy, has provided new insights into the structure, biophysics, and network function of this intriguing synapse. This brings us one step closer to answering a fundamental question in neuroscience: how basic synaptic properties shape higher network computations.' acknowledgement: "We thank previous students, postdocs, and collaborators, particularly J. Geiger, and (in alphabetical order) H. Alle, J. Bischofberger, C. Borges-Merjane, D. Engel, M. Frotscher, S. Hallermann, M. Heckmann, S. Jamrichova, O. Kim, L. Li, K. Lichter, P. Lin, J. Lübke, Y. Okamoto, C. Pawlu, C. Schmidt-Hieber, N. Spruston, and N. Vyleta for their outstanding experimental contributions. We also thank P. Castillo, J. Geiger, T. Sakaba, S. Siegert, T. Vogels, and J. Watson for critically reading the manuscript, E. Kralli-Beller for text editing, and J. Malikovic and L. Slomianka for useful discussions. We apologize that, due to space constraints, not all relevant papers could be cited.\r\nThis project was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement 692692, AdG “GIANTSYN”) and the Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein Award; P 36232-B, stand-alone grant), both to P.J." article_processing_charge: No article_type: review author: - first_name: David H full_name: Vandael, David H id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87 last_name: Vandael orcid: 0000-0001-7577-1676 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: Vandael DH, Jonas PM. Structure, biophysics, and circuit function of a “giant” cortical presynaptic terminal. Science. 2024;383(6687):eadg6757. doi:10.1126/science.adg6757 apa: Vandael, D. H., & Jonas, P. M. (2024). Structure, biophysics, and circuit function of a “giant” cortical presynaptic terminal. Science. AAAS. https://doi.org/10.1126/science.adg6757 chicago: Vandael, David H, and Peter M Jonas. “Structure, Biophysics, and Circuit Function of a ‘Giant’ Cortical Presynaptic Terminal.” Science. AAAS, 2024. https://doi.org/10.1126/science.adg6757. ieee: D. H. Vandael and P. M. Jonas, “Structure, biophysics, and circuit function of a ‘giant’ cortical presynaptic terminal,” Science, vol. 383, no. 6687. AAAS, p. eadg6757, 2024. ista: Vandael DH, Jonas PM. 2024. Structure, biophysics, and circuit function of a ‘giant’ cortical presynaptic terminal. Science. 383(6687), eadg6757. mla: Vandael, David H., and Peter M. Jonas. “Structure, Biophysics, and Circuit Function of a ‘Giant’ Cortical Presynaptic Terminal.” Science, vol. 383, no. 6687, AAAS, 2024, p. eadg6757, doi:10.1126/science.adg6757. short: D.H. Vandael, P.M. Jonas, Science 383 (2024) eadg6757. date_created: 2024-03-17T23:00:57Z date_published: 2024-03-08T00:00:00Z date_updated: 2024-03-20T07:42:52Z day: '08' department: - _id: PeJo doi: 10.1126/science.adg6757 ec_funded: 1 external_id: pmid: - '38452088' intvolume: ' 383' issue: '6687' language: - iso: eng month: '03' oa_version: None page: eadg6757 pmid: 1 project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize - _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5 grant_number: P36232 name: Mechanisms of GABA release in hippocampal circuits publication: Science publication_identifier: eissn: - 1095-9203 publication_status: published publisher: AAAS quality_controlled: '1' scopus_import: '1' status: public title: Structure, biophysics, and circuit function of a "giant" cortical presynaptic terminal type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 383 year: '2024' ... --- _id: '12720' abstract: - lang: eng text: Here we describe the in vivo DNA assembly approach, where molecular cloning procedures are performed using an E. coli recA-independent recombination pathway, which assembles linear fragments of DNA with short homologous termini. This pathway is present in all standard laboratory E. coli strains and, by bypassing the need for in vitro DNA assembly, allows simplified molecular cloning to be performed without the plasmid instability issues associated with specialized recombination-cloning bacterial strains. The methodology requires specific primer design and can perform all standard plasmid modifications (insertions, deletions, mutagenesis, and sub-cloning) in a rapid, simple, and cost-efficient manner, as it does not require commercial kits or specialized bacterial strains. Additionally, this approach can be used to perform complex procedures such as multiple modifications to a plasmid, as up to 6 linear fragments can be assembled in vivo by this recombination pathway. Procedures generally require less than 3 h, involving PCR amplification, DpnI digestion of template DNA, and transformation, upon which circular plasmids are assembled. In this chapter we describe the requirements, procedure, and potential pitfalls when using this technique, as well as protocol variations to overcome the most common issues. alternative_title: - Methods in Molecular Biology article_processing_charge: No author: - first_name: Sandra full_name: Arroyo-Urea, Sandra last_name: Arroyo-Urea - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Javier full_name: García-Nafría, Javier last_name: García-Nafría citation: ama: 'Arroyo-Urea S, Watson J, García-Nafría J. Molecular Cloning Using In Vivo DNA Assembly. In: Scarlett G, ed. DNA Manipulation and Analysis. Vol 2633. MIMB. New York, NY, United States: Springer Nature; 2023:33-44. doi:10.1007/978-1-0716-3004-4_3' apa: 'Arroyo-Urea, S., Watson, J., & García-Nafría, J. (2023). Molecular Cloning Using In Vivo DNA Assembly. In G. Scarlett (Ed.), DNA Manipulation and Analysis (Vol. 2633, pp. 33–44). New York, NY, United States: Springer Nature. https://doi.org/10.1007/978-1-0716-3004-4_3' chicago: 'Arroyo-Urea, Sandra, Jake Watson, and Javier García-Nafría. “Molecular Cloning Using In Vivo DNA Assembly.” In DNA Manipulation and Analysis, edited by Garry Scarlett, 2633:33–44. MIMB. New York, NY, United States: Springer Nature, 2023. https://doi.org/10.1007/978-1-0716-3004-4_3.' ieee: 'S. Arroyo-Urea, J. Watson, and J. García-Nafría, “Molecular Cloning Using In Vivo DNA Assembly,” in DNA Manipulation and Analysis, vol. 2633, G. Scarlett, Ed. New York, NY, United States: Springer Nature, 2023, pp. 33–44.' ista: 'Arroyo-Urea S, Watson J, García-Nafría J. 2023.Molecular Cloning Using In Vivo DNA Assembly. In: DNA Manipulation and Analysis. Methods in Molecular Biology, vol. 2633, 33–44.' mla: Arroyo-Urea, Sandra, et al. “Molecular Cloning Using In Vivo DNA Assembly.” DNA Manipulation and Analysis, edited by Garry Scarlett, vol. 2633, Springer Nature, 2023, pp. 33–44, doi:10.1007/978-1-0716-3004-4_3. short: S. Arroyo-Urea, J. Watson, J. García-Nafría, in:, G. Scarlett (Ed.), DNA Manipulation and Analysis, Springer Nature, New York, NY, United States, 2023, pp. 33–44. date_created: 2023-03-12T23:01:02Z date_published: 2023-03-01T00:00:00Z date_updated: 2023-03-16T08:34:24Z day: '01' department: - _id: PeJo doi: 10.1007/978-1-0716-3004-4_3 editor: - first_name: Garry full_name: Scarlett, Garry last_name: Scarlett external_id: pmid: - '36853454' intvolume: ' 2633' language: - iso: eng month: '03' oa_version: None page: 33-44 place: New York, NY, United States pmid: 1 publication: DNA Manipulation and Analysis publication_identifier: eisbn: - 978-1-0716-3004-4 eissn: - 1940-6029 isbn: - 978-1-0716-3003-7 issn: - 1064-3745 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' series_title: MIMB status: public title: Molecular Cloning Using In Vivo DNA Assembly type: book_chapter user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 2633 year: '2023' ... --- _id: '12567' abstract: - lang: eng text: Single-molecule localization microscopy (SMLM) greatly advances structural studies of diverse biological tissues. For example, presynaptic active zone (AZ) nanotopology is resolved in increasing detail. Immunofluorescence imaging of AZ proteins usually relies on epitope preservation using aldehyde-based immunocompetent fixation. Cryofixation techniques, such as high-pressure freezing (HPF) and freeze substitution (FS), are widely used for ultrastructural studies of presynaptic architecture in electron microscopy (EM). HPF/FS demonstrated nearer-to-native preservation of AZ ultrastructure, e.g., by facilitating single filamentous structures. Here, we present a protocol combining the advantages of HPF/FS and direct stochastic optical reconstruction microscopy (dSTORM) to quantify nanotopology of the AZ scaffold protein Bruchpilot (Brp) at neuromuscular junctions (NMJs) of Drosophila melanogaster. Using this standardized model, we tested for preservation of Brp clusters in different FS protocols compared to classical aldehyde fixation. In HPF/FS samples, presynaptic boutons were structurally well preserved with ~22% smaller Brp clusters that allowed quantification of subcluster topology. In summary, we established a standardized near-to-native preparation and immunohistochemistry protocol for SMLM analyses of AZ protein clusters in a defined model synapse. Our protocol could be adapted to study protein arrangements at single-molecule resolution in other intact tissue preparations. acknowledgement: This work has been supported by funding of the German Research Foundation (Deutsche Forschungsgemeinschaft [DFG], CRC 166, Project B06 to M.H. and A.-L.S., FOR 3004 SYNABS P1 to M.H.) and by the Interdisciplinary Clinical Research Center (IZKF) Würzburg (Z-3/69 to M.M.P., N-229 to M.H. and A.-L.S.). A.M. is funded by the University of Leipzig Clinician Scientist Program. article_number: '2128' article_processing_charge: No article_type: original author: - first_name: Achmed full_name: Mrestani, Achmed last_name: Mrestani - first_name: Katharina full_name: Lichter, Katharina id: 39302e62-fcfc-11ec-8196-8b01447dbd3d last_name: Lichter - first_name: Anna Leena full_name: Sirén, Anna Leena last_name: Sirén - first_name: Manfred full_name: Heckmann, Manfred last_name: Heckmann - first_name: Mila M. full_name: Paul, Mila M. last_name: Paul - first_name: Martin full_name: Pauli, Martin last_name: Pauli citation: ama: Mrestani A, Lichter K, Sirén AL, Heckmann M, Paul MM, Pauli M. Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation. International Journal of Molecular Sciences. 2023;24(3). doi:10.3390/ijms24032128 apa: Mrestani, A., Lichter, K., Sirén, A. L., Heckmann, M., Paul, M. M., & Pauli, M. (2023). Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation. International Journal of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms24032128 chicago: Mrestani, Achmed, Katharina Lichter, Anna Leena Sirén, Manfred Heckmann, Mila M. Paul, and Martin Pauli. “Single-Molecule Localization Microscopy of Presynaptic Active Zones in Drosophila Melanogaster after Rapid Cryofixation.” International Journal of Molecular Sciences. MDPI, 2023. https://doi.org/10.3390/ijms24032128. ieee: A. Mrestani, K. Lichter, A. L. Sirén, M. Heckmann, M. M. Paul, and M. Pauli, “Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation,” International Journal of Molecular Sciences, vol. 24, no. 3. MDPI, 2023. ista: Mrestani A, Lichter K, Sirén AL, Heckmann M, Paul MM, Pauli M. 2023. Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation. International Journal of Molecular Sciences. 24(3), 2128. mla: Mrestani, Achmed, et al. “Single-Molecule Localization Microscopy of Presynaptic Active Zones in Drosophila Melanogaster after Rapid Cryofixation.” International Journal of Molecular Sciences, vol. 24, no. 3, 2128, MDPI, 2023, doi:10.3390/ijms24032128. short: A. Mrestani, K. Lichter, A.L. Sirén, M. Heckmann, M.M. Paul, M. Pauli, International Journal of Molecular Sciences 24 (2023). date_created: 2023-02-19T23:00:56Z date_published: 2023-01-21T00:00:00Z date_updated: 2023-08-01T13:16:36Z day: '21' ddc: - '570' department: - _id: PeJo doi: 10.3390/ijms24032128 external_id: isi: - '000930324700001' file: - access_level: open_access checksum: 69a35dcd3e0249f902ab881b06ee2e58 content_type: application/pdf creator: dernst date_created: 2023-02-20T07:09:27Z date_updated: 2023-02-20T07:09:27Z file_id: '12569' file_name: 2023_IJMS_Mrestani.pdf file_size: 2823025 relation: main_file success: 1 file_date_updated: 2023-02-20T07:09:27Z has_accepted_license: '1' intvolume: ' 24' isi: 1 issue: '3' language: - iso: eng month: '01' oa: 1 oa_version: Published Version publication: International Journal of Molecular Sciences publication_identifier: eissn: - 1422-0067 publication_status: published publisher: MDPI quality_controlled: '1' scopus_import: '1' status: public title: Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 24 year: '2023' ... --- _id: '12759' abstract: - lang: eng text: Stereological methods for estimating the 3D particle size and density from 2D projections are essential to many research fields. These methods are, however, prone to errors arising from undetected particle profiles due to sectioning and limited resolution, known as ‘lost caps’. A potential solution developed by Keiding, Jensen, and Ranek in 1972, which we refer to as the Keiding model, accounts for lost caps by quantifying the smallest detectable profile in terms of its limiting ‘cap angle’ (ϕ), a size-independent measure of a particle’s distance from the section surface. However, this simple solution has not been widely adopted nor tested. Rather, model-independent design-based stereological methods, which do not explicitly account for lost caps, have come to the fore. Here, we provide the first experimental validation of the Keiding model by comparing the size and density of particles estimated from 2D projections with direct measurement from 3D EM reconstructions of the same tissue. We applied the Keiding model to estimate the size and density of somata, nuclei and vesicles in the cerebellum of mice and rats, where high packing density can be problematic for design-based methods. Our analysis reveals a Gaussian distribution for ϕ rather than a single value. Nevertheless, curve fits of the Keiding model to the 2D diameter distribution accurately estimate the mean ϕ and 3D diameter distribution. While systematic testing using simulations revealed an upper limit to determining ϕ, our analysis shows that estimated ϕ can be used to determine the 3D particle density from the 2D density under a wide range of conditions, and this method is potentially more accurate than minimum-size-based lost-cap corrections and disector methods. Our results show the Keiding model provides an efficient means of accurately estimating the size and density of particles from 2D projections even under conditions of a high density. acknowledged_ssus: - _id: EM-Fac acknowledgement: "We thank the IST Austria Electron Microscopy Facility for technical support, and Diccon Coyle, Andrea Lőrincz and Zoltan Nusser for their helpful comments and discussions.\r\nFunding for JSR and RAS was from the Wellcome Trust (203048; 224499; https://\r\nwellcome.org/). RAS is in receipt of a Wellcome Trust Principal Research Fellowship (224499).\r\nFunding for CBM and PJ was from Fond zur Förderung der Wissenschaftlichen Forschung (V\r\n739-B27 Elise-Richter Programme to CBM, Z 312-B27 Wittgenstein Award to PJ; \r\nhttps://www.fwf.ac.at). PJ received funding from the European Research Council (ERC; https://erc.europa.eu) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 692692). NH was supported by a European\r\nResearch Council Advanced Grant (ERC-AG787157)." article_number: e0277148 article_processing_charge: No article_type: original author: - first_name: Jason Seth full_name: Rothman, Jason Seth last_name: Rothman - first_name: Carolina full_name: Borges Merjane, Carolina id: 4305C450-F248-11E8-B48F-1D18A9856A87 last_name: Borges Merjane orcid: 0000-0003-0005-401X - first_name: Noemi full_name: Holderith, Noemi last_name: Holderith - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 - first_name: R. full_name: Angus Silver, R. last_name: Angus Silver citation: ama: Rothman JS, Borges Merjane C, Holderith N, Jonas PM, Angus Silver R. Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy. PLoS ONE. 2023;18(3 March). doi:10.1371/journal.pone.0277148 apa: Rothman, J. S., Borges Merjane, C., Holderith, N., Jonas, P. M., & Angus Silver, R. (2023). Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy. PLoS ONE. Public Library of Science. https://doi.org/10.1371/journal.pone.0277148 chicago: Rothman, Jason Seth, Carolina Borges Merjane, Noemi Holderith, Peter M Jonas, and R. Angus Silver. “Validation of a Stereological Method for Estimating Particle Size and Density from 2D Projections with High Accuracy.” PLoS ONE. Public Library of Science, 2023. https://doi.org/10.1371/journal.pone.0277148. ieee: J. S. Rothman, C. Borges Merjane, N. Holderith, P. M. Jonas, and R. Angus Silver, “Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy,” PLoS ONE, vol. 18, no. 3 March. Public Library of Science, 2023. ista: Rothman JS, Borges Merjane C, Holderith N, Jonas PM, Angus Silver R. 2023. Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy. PLoS ONE. 18(3 March), e0277148. mla: Rothman, Jason Seth, et al. “Validation of a Stereological Method for Estimating Particle Size and Density from 2D Projections with High Accuracy.” PLoS ONE, vol. 18, no. 3 March, e0277148, Public Library of Science, 2023, doi:10.1371/journal.pone.0277148. short: J.S. Rothman, C. Borges Merjane, N. Holderith, P.M. Jonas, R. Angus Silver, PLoS ONE 18 (2023). date_created: 2023-03-26T22:01:07Z date_published: 2023-03-17T00:00:00Z date_updated: 2023-08-01T13:46:39Z day: '17' ddc: - '570' department: - _id: PeJo doi: 10.1371/journal.pone.0277148 ec_funded: 1 external_id: isi: - '001024737400001' file: - access_level: open_access checksum: 2380331ec27cc87808826fc64419ac1c content_type: application/pdf creator: dernst date_created: 2023-03-27T06:51:09Z date_updated: 2023-03-27T06:51:09Z file_id: '12770' file_name: 2023_PLoSOne_Rothman.pdf file_size: 7290413 relation: main_file success: 1 file_date_updated: 2023-03-27T06:51:09Z has_accepted_license: '1' intvolume: ' 18' isi: 1 issue: 3 March language: - iso: eng month: '03' oa: 1 oa_version: Published Version project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize - _id: 2696E7FE-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: V00739 name: Structural plasticity at mossy fiber-CA3 synapses publication: PLoS ONE publication_identifier: eissn: - 1932-6203 publication_status: published publisher: Public Library of Science quality_controlled: '1' scopus_import: '1' status: public title: Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 18 year: '2023' ... --- _id: '12515' abstract: - lang: eng text: "Introduction: The olfactory system in most mammals is divided into several subsystems based on the anatomical locations of the neuroreceptor cells involved and the receptor families that are expressed. In addition to the main olfactory system and the vomeronasal system, a range of olfactory subsystems converge onto the transition zone located between the main olfactory bulb (MOB) and the accessory olfactory bulb (AOB), which has been termed the olfactory limbus (OL). The OL contains specialized glomeruli that receive noncanonical sensory afferences and which interact with the MOB and AOB. Little is known regarding the olfactory subsystems of mammals other than laboratory rodents.\r\nMethods: We have focused on characterizing the OL in the red fox by performing general and specific histological stainings on serial sections, using both single and double immunohistochemical and lectin-histochemical labeling techniques.\r\nResults: As a result, we have been able to determine that the OL of the red fox (Vulpes vulpes) displays an uncommonly high degree of development and complexity.\r\nDiscussion: This makes this species a novel mammalian model, the study of which could improve our understanding of the noncanonical pathways involved in the processing of chemosensory cues." acknowledgement: This work was partially supported by a grant from “Consello Social Universidade de Santiago de Compostela” 2022-PU004.We would like to show special gratitude to Prof. Ludwig Wagner (Medical University, Vienna) for kindly providing us with the secretagogin antibody. We thank the Wildlife Recovery Centres of Galicia, Dirección Xeral de Patrimonio Natural (Xunta de Galicia, Spain), and Federación Galega de Caza for providing the red foxes used in this study. article_number: '1097467' article_processing_charge: No article_type: original author: - first_name: Irene full_name: Ortiz-Leal, Irene last_name: Ortiz-Leal - first_name: Mateo V. full_name: Torres, Mateo V. last_name: Torres - first_name: Victor M full_name: Vargas Barroso, Victor M id: 2F55A9DE-F248-11E8-B48F-1D18A9856A87 last_name: Vargas Barroso - first_name: Luis Eusebio full_name: Fidalgo, Luis Eusebio last_name: Fidalgo - first_name: Ana María full_name: López-Beceiro, Ana María last_name: López-Beceiro - first_name: Jorge A. full_name: Larriva-Sahd, Jorge A. last_name: Larriva-Sahd - first_name: Pablo full_name: Sánchez-Quinteiro, Pablo last_name: Sánchez-Quinteiro citation: ama: Ortiz-Leal I, Torres MV, Vargas Barroso VM, et al. The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway. Frontiers in Neuroanatomy. 2023;16. doi:10.3389/fnana.2022.1097467 apa: Ortiz-Leal, I., Torres, M. V., Vargas Barroso, V. M., Fidalgo, L. E., López-Beceiro, A. M., Larriva-Sahd, J. A., & Sánchez-Quinteiro, P. (2023). The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway. Frontiers in Neuroanatomy. Frontiers. https://doi.org/10.3389/fnana.2022.1097467 chicago: Ortiz-Leal, Irene, Mateo V. Torres, Victor M Vargas Barroso, Luis Eusebio Fidalgo, Ana María López-Beceiro, Jorge A. Larriva-Sahd, and Pablo Sánchez-Quinteiro. “The Olfactory Limbus of the Red Fox (Vulpes Vulpes). New Insights Regarding a Noncanonical Olfactory Bulb Pathway.” Frontiers in Neuroanatomy. Frontiers, 2023. https://doi.org/10.3389/fnana.2022.1097467. ieee: I. Ortiz-Leal et al., “The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway,” Frontiers in Neuroanatomy, vol. 16. Frontiers, 2023. ista: Ortiz-Leal I, Torres MV, Vargas Barroso VM, Fidalgo LE, López-Beceiro AM, Larriva-Sahd JA, Sánchez-Quinteiro P. 2023. The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway. Frontiers in Neuroanatomy. 16, 1097467. mla: Ortiz-Leal, Irene, et al. “The Olfactory Limbus of the Red Fox (Vulpes Vulpes). New Insights Regarding a Noncanonical Olfactory Bulb Pathway.” Frontiers in Neuroanatomy, vol. 16, 1097467, Frontiers, 2023, doi:10.3389/fnana.2022.1097467. short: I. Ortiz-Leal, M.V. Torres, V.M. Vargas Barroso, L.E. Fidalgo, A.M. López-Beceiro, J.A. Larriva-Sahd, P. Sánchez-Quinteiro, Frontiers in Neuroanatomy 16 (2023). date_created: 2023-02-05T23:01:00Z date_published: 2023-01-10T00:00:00Z date_updated: 2023-08-16T11:37:52Z day: '10' ddc: - '570' department: - _id: PeJo doi: 10.3389/fnana.2022.1097467 external_id: isi: - '000919786900001' pmid: - '36704406' file: - access_level: open_access checksum: 49cd40f3bda6f267079427042e7d15e3 content_type: application/pdf creator: dernst date_created: 2023-02-06T07:56:14Z date_updated: 2023-02-06T07:56:14Z file_id: '12518' file_name: 2022_FrontiersNeuroanatomy_OrtizLeal.pdf file_size: 21943473 relation: main_file success: 1 file_date_updated: 2023-02-06T07:56:14Z has_accepted_license: '1' intvolume: ' 16' isi: 1 language: - iso: eng month: '01' oa: 1 oa_version: Published Version pmid: 1 publication: Frontiers in Neuroanatomy publication_identifier: eissn: - 1662-5129 publication_status: published publisher: Frontiers quality_controlled: '1' scopus_import: '1' status: public title: The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 16 year: '2023' ... --- _id: '12786' abstract: - lang: eng text: AMPA glutamate receptors (AMPARs) mediate excitatory neurotransmission throughout the brain. Their signalling is uniquely diversified by brain region-specific auxiliary subunits, providing an opportunity for the development of selective therapeutics. AMPARs associated with TARP γ8 are enriched in the hippocampus, and are targets of emerging anti-epileptic drugs. To understand their therapeutic activity, we determined cryo-EM structures of the GluA1/2-γ8 receptor associated with three potent, chemically diverse ligands. We find that despite sharing a lipid-exposed and water-accessible binding pocket, drug action is differentially affected by binding-site mutants. Together with patch-clamp recordings and MD simulations we also demonstrate that ligand-triggered reorganisation of the AMPAR-TARP interface contributes to modulation. Unexpectedly, one ligand (JNJ-61432059) acts bifunctionally, negatively affecting GluA1 but exerting positive modulatory action on GluA2-containing AMPARs, in a TARP stoichiometry-dependent manner. These results further illuminate the action of TARPs, demonstrate the sensitive balance between positive and negative modulatory action, and provide a mechanistic platform for development of both positive and negative selective AMPAR modulators. acknowledgement: We thank James Krieger for generating the ‘proDy’ interaction maps in Fig. 5B and S7C, and Jan-Niklas Dohrke for critically reading the manuscript. We thank members of the Greger lab for insightful comments during this study. We acknowledge Trevor Rutherford for confirming ligand integrity by NMR. We are also grateful to LMB scientific computing and the EM facility for their support. This research was funded in part by the Wellcome Trust (223194/Z/21/Z) to I.H.G. For the purpose of Open Access, the MRC Laboratory of Molecular Biology has applied a CC BY public copyright licence to any Author Accepted Manuscript (AAM) version arising from this submission. Further funding came from the Medical Research Council (MRU105174197) to I.H.G, and NIH grant (R56/R01MH123474) to T.N. article_number: '1659' article_processing_charge: No article_type: original author: - first_name: Danyang full_name: Zhang, Danyang last_name: Zhang - first_name: Remigijus full_name: Lape, Remigijus last_name: Lape - first_name: Saher A. full_name: Shaikh, Saher A. last_name: Shaikh - first_name: Bianka K. full_name: Kohegyi, Bianka K. last_name: Kohegyi - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Ondrej full_name: Cais, Ondrej last_name: Cais - first_name: Terunaga full_name: Nakagawa, Terunaga last_name: Nakagawa - first_name: Ingo H. full_name: Greger, Ingo H. last_name: Greger citation: ama: Zhang D, Lape R, Shaikh SA, et al. Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics. Nature Communications. 2023;14. doi:10.1038/s41467-023-37259-5 apa: Zhang, D., Lape, R., Shaikh, S. A., Kohegyi, B. K., Watson, J., Cais, O., … Greger, I. H. (2023). Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-023-37259-5 chicago: Zhang, Danyang, Remigijus Lape, Saher A. Shaikh, Bianka K. Kohegyi, Jake Watson, Ondrej Cais, Terunaga Nakagawa, and Ingo H. Greger. “Modulatory Mechanisms of TARP Γ8-Selective AMPA Receptor Therapeutics.” Nature Communications. Springer Nature, 2023. https://doi.org/10.1038/s41467-023-37259-5. ieee: D. Zhang et al., “Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics,” Nature Communications, vol. 14. Springer Nature, 2023. ista: Zhang D, Lape R, Shaikh SA, Kohegyi BK, Watson J, Cais O, Nakagawa T, Greger IH. 2023. Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics. Nature Communications. 14, 1659. mla: Zhang, Danyang, et al. “Modulatory Mechanisms of TARP Γ8-Selective AMPA Receptor Therapeutics.” Nature Communications, vol. 14, 1659, Springer Nature, 2023, doi:10.1038/s41467-023-37259-5. short: D. Zhang, R. Lape, S.A. Shaikh, B.K. Kohegyi, J. Watson, O. Cais, T. Nakagawa, I.H. Greger, Nature Communications 14 (2023). date_created: 2023-04-02T22:01:09Z date_published: 2023-03-25T00:00:00Z date_updated: 2023-12-13T11:15:58Z day: '25' ddc: - '570' department: - _id: PeJo doi: 10.1038/s41467-023-37259-5 external_id: isi: - '001066658700003' file: - access_level: open_access checksum: 0a97b31191432dae5853bbb5ccb7698d content_type: application/pdf creator: dernst date_created: 2023-04-03T06:38:56Z date_updated: 2023-04-03T06:38:56Z file_id: '12797' file_name: 2023_NatureComm_Zhang.pdf file_size: 2613996 relation: main_file success: 1 file_date_updated: 2023-04-03T06:38:56Z has_accepted_license: '1' intvolume: ' 14' isi: 1 language: - iso: eng month: '03' oa: 1 oa_version: Published Version publication: Nature Communications publication_identifier: eissn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 14 year: '2023' ... --- _id: '13267' abstract: - lang: eng text: Three-dimensional (3D) reconstruction of living brain tissue down to an individual synapse level would create opportunities for decoding the dynamics and structure–function relationships of the brain’s complex and dense information processing network; however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise ratio and prohibitive light burden in optical imaging, whereas electron microscopy is inherently static. Here we solved these challenges by developing an integrated optical/machine-learning technology, LIONESS (live information-optimized nanoscopy enabling saturated segmentation). This leverages optical modifications to stimulated emission depletion microscopy in comprehensively, extracellularly labeled tissue and previous information on sample structure via machine learning to simultaneously achieve isotropic super-resolution, high signal-to-noise ratio and compatibility with living tissue. This allows dense deep-learning-based instance segmentation and 3D reconstruction at a synapse level, incorporating molecular, activity and morphodynamic information. LIONESS opens up avenues for studying the dynamic functional (nano-)architecture of living brain tissue. acknowledged_ssus: - _id: ScienComp - _id: Bio - _id: PreCl - _id: E-Lib - _id: LifeSc - _id: M-Shop acknowledgement: "We thank J. Vorlaufer, N. Agudelo and A. Wartak for microscope maintenance and troubleshooting, C. Kreuzinger and A. Freeman for technical assistance, M. Šuplata for hardware control support and M. Cunha dos Santos for initial exploration of software. We\r\nthank P. Henderson for advice on deep-learning training and M. Sixt, S. Boyd and T. Weiss for discussions and critical reading of the manuscript. L. Lavis (Janelia Research Campus) generously provided the JF585-HaloTag ligand. We acknowledge expert support by IST\r\nAustria’s scientific computing, imaging and optics, preclinical, library and laboratory support facilities and by the Miba machine shop. We gratefully acknowledge funding by the following sources: Austrian Science Fund (F.W.F.) grant no. I3600-B27 (J.G.D.), grant no. DK W1232\r\n(J.G.D. and J.M.M.) and grant no. Z 312-B27, Wittgenstein award (P.J.); the Gesellschaft für Forschungsförderung NÖ grant no. LSC18-022 (J.G.D.); an ISTA Interdisciplinary project grant (J.G.D. and B.B.); the European Union’s Horizon 2020 research and innovation programme,\r\nMarie-Skłodowska Curie grant 665385 (J.M.M. and J.L.); the European Union’s Horizon 2020 research and innovation programme, European Research Council grant no. 715767, MATERIALIZABLE (B.B.); grant no. 715508, REVERSEAUTISM (G.N.); grant no. 695568, SYNNOVATE (S.G.N.G.); and grant no. 692692, GIANTSYN (P.J.); the Simons\r\nFoundation Autism Research Initiative grant no. 529085 (S.G.N.G.); the Wellcome Trust Technology Development grant no. 202932 (S.G.N.G.); the Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.);\r\nthe Human Frontier Science Program postdoctoral fellowship LT000557/2018 (W.J.); and the National Science Foundation grant no. IIS-1835231 (H.P.) and NCS-FO-2124179 (H.P.)." article_processing_charge: Yes article_type: original author: - first_name: Philipp full_name: Velicky, Philipp id: 39BDC62C-F248-11E8-B48F-1D18A9856A87 last_name: Velicky orcid: 0000-0002-2340-7431 - first_name: Eder full_name: Miguel Villalba, Eder id: 3FB91342-F248-11E8-B48F-1D18A9856A87 last_name: Miguel Villalba orcid: 0000-0001-5665-0430 - first_name: Julia M full_name: Michalska, Julia M id: 443DB6DE-F248-11E8-B48F-1D18A9856A87 last_name: Michalska orcid: 0000-0003-3862-1235 - first_name: Julia full_name: Lyudchik, Julia id: 46E28B80-F248-11E8-B48F-1D18A9856A87 last_name: Lyudchik - first_name: Donglai full_name: Wei, Donglai last_name: Wei - first_name: Zudi full_name: Lin, Zudi last_name: Lin - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Jakob full_name: Troidl, Jakob last_name: Troidl - first_name: Johanna full_name: Beyer, Johanna last_name: Beyer - first_name: Yoav full_name: Ben Simon, Yoav id: 43DF3136-F248-11E8-B48F-1D18A9856A87 last_name: Ben Simon - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Wiebke full_name: Jahr, Wiebke id: 425C1CE8-F248-11E8-B48F-1D18A9856A87 last_name: Jahr - first_name: Alban full_name: Cenameri, Alban id: 9ac8f577-2357-11eb-997a-e566c5550886 last_name: Cenameri - first_name: Johannes full_name: Broichhagen, Johannes last_name: Broichhagen - first_name: Seth G.N. full_name: Grant, Seth G.N. last_name: Grant - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Hanspeter full_name: Pfister, Hanspeter last_name: Pfister - first_name: Bernd full_name: Bickel, Bernd id: 49876194-F248-11E8-B48F-1D18A9856A87 last_name: Bickel orcid: 0000-0001-6511-9385 - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 citation: ama: Velicky P, Miguel Villalba E, Michalska JM, et al. Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. 2023;20:1256-1265. doi:10.1038/s41592-023-01936-6 apa: Velicky, P., Miguel Villalba, E., Michalska, J. M., Lyudchik, J., Wei, D., Lin, Z., … Danzl, J. G. (2023). Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. Springer Nature. https://doi.org/10.1038/s41592-023-01936-6 chicago: Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Julia Lyudchik, Donglai Wei, Zudi Lin, Jake Watson, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” Nature Methods. Springer Nature, 2023. https://doi.org/10.1038/s41592-023-01936-6. ieee: P. Velicky et al., “Dense 4D nanoscale reconstruction of living brain tissue,” Nature Methods, vol. 20. Springer Nature, pp. 1256–1265, 2023. ista: Velicky P, Miguel Villalba E, Michalska JM, Lyudchik J, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. 2023. Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. 20, 1256–1265. mla: Velicky, Philipp, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” Nature Methods, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:10.1038/s41592-023-01936-6. short: P. Velicky, E. Miguel Villalba, J.M. Michalska, J. Lyudchik, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, Nature Methods 20 (2023) 1256–1265. date_created: 2023-07-23T22:01:13Z date_published: 2023-08-01T00:00:00Z date_updated: 2024-01-10T08:37:48Z day: '01' department: - _id: PeJo - _id: GaNo - _id: BeBi - _id: JoDa - _id: Bio doi: 10.1038/s41592-023-01936-6 ec_funded: 1 external_id: isi: - '001025621500001' pmid: - '37429995' intvolume: ' 20' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1038/s41592-023-01936-6 month: '08' oa: 1 oa_version: Published Version page: 1256-1265 pmid: 1 project: - _id: 265CB4D0-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03600 name: Optical control of synaptic function via adhesion molecules - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize - _id: 23889792-32DE-11EA-91FC-C7463DDC885E name: High content imaging to decode human immune cell interactions in health and allergic disease - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: 24F9549A-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715767' name: 'MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling' - _id: 25444568-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715508' name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9 call_identifier: H2020 grant_number: '101026635' name: Synaptic computations of the hippocampal CA3 circuitry - _id: 2668BFA0-B435-11E9-9278-68D0E5697425 grant_number: LT00057 name: High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration publication: Nature Methods publication_identifier: eissn: - 1548-7105 issn: - 1548-7091 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: software url: https://github.com/danzllab/LIONESS record: - id: '12817' relation: research_data status: public - id: '14770' relation: shorter_version status: public scopus_import: '1' status: public title: Dense 4D nanoscale reconstruction of living brain tissue type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 20 year: '2023' ... --- _id: '13126' 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. acknowledged_ssus: - _id: ScienComp - _id: Bio - _id: PreCl - _id: LifeSc - _id: M-Shop - _id: E-Lib 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)" article_processing_charge: No author: - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 citation: ama: Danzl JG. Research data for the publication “Imaging brain tissue architecture across millimeter to nanometer scales.” 2023. doi:10.15479/AT:ISTA:13126 apa: Danzl, J. G. (2023). Research data for the publication “Imaging brain tissue architecture across millimeter to nanometer scales.” Institute of Science and Technology Austria. https://doi.org/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. ieee: J. G. Danzl, “Research data for the publication ‘Imaging brain tissue architecture across millimeter to nanometer scales.’” Institute of Science and Technology Austria, 2023. ista: Danzl JG. 2023. Research data for the publication ‘Imaging brain tissue architecture across millimeter to nanometer scales’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:13126. mla: Danzl, Johann G. 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. short: J.G. Danzl, (2023). contributor: - first_name: Julia M id: 443DB6DE-F248-11E8-B48F-1D18A9856A87 last_name: Michalska - first_name: Julia id: 46E28B80-F248-11E8-B48F-1D18A9856A87 last_name: Lyudchik - first_name: Philipp id: 39BDC62C-F248-11E8-B48F-1D18A9856A87 last_name: Velicky orcid: 0000-0002-2340-7431 - first_name: Hana id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed last_name: Stefanickova - first_name: Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Alban id: 9ac8f577-2357-11eb-997a-e566c5550886 last_name: Cenameri - first_name: Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Alessandro id: 41CB84B2-F248-11E8-B48F-1D18A9856A87 last_name: Venturino orcid: 0000-0003-2356-9403 - first_name: Karl last_name: Roessler - first_name: Thomas last_name: Czech - first_name: Romana last_name: Höftberger - first_name: Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 - first_name: Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 date_created: 2023-06-07T07:15:12Z date_published: 2023-08-04T00:00:00Z date_updated: 2024-02-21T12:18:19Z day: '04' ddc: - '610' department: - _id: JoDa - _id: SaSi - _id: GaNo - _id: PeJo - _id: Bio - _id: RySh doi: 10.15479/AT:ISTA:13126 ec_funded: 1 file: - access_level: open_access checksum: 6f18ce9b89b47ce5abeb379869ff5c49 content_type: text/plain creator: jdanzl date_created: 2023-08-04T13:19:47Z date_updated: 2023-08-04T13:19:47Z file_id: '13961' file_name: Readme_Michalska_2023.txt file_size: 541 relation: main_file success: 1 - access_level: open_access checksum: 2098e8c5285c5e86cb69075e1b5dcf39 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:29:29Z date_updated: 2023-08-03T11:29:29Z file_id: '13482' file_name: Fig1_b_top-left.tif file_size: 64582744 relation: main_file success: 1 - access_level: open_access checksum: 9affab3dacf847096cc8e8d5ff99467e content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:29:28Z date_updated: 2023-08-03T11:29:28Z file_id: '13483' file_name: Fig1_b_top-right.tif file_size: 1442113 relation: main_file success: 1 - access_level: open_access checksum: d7fec0296123a17f6bcdbfee17411424 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:29:29Z date_updated: 2023-08-03T11:29:29Z file_id: '13484' file_name: Fig1_c_1.tif file_size: 40078276 relation: main_file success: 1 - access_level: open_access checksum: 5195a180c4f26a7adc994bad0b3c53c7 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:29:29Z date_updated: 2023-08-03T11:29:29Z file_id: '13485' file_name: Fig1_c_2.tif file_size: 7984315 relation: main_file success: 1 - access_level: open_access checksum: df1105d8f41ebd5373cacc597ffa91f3 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:29:29Z date_updated: 2023-08-03T11:29:29Z file_id: '13486' file_name: Fig1_c_3.tif file_size: 8693320 relation: main_file success: 1 - access_level: open_access checksum: 00edbb0c9f42032c830d2291ec55c4c0 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:29:30Z date_updated: 2023-08-03T11:29:30Z file_id: '13487' file_name: Fig1_c_4.tif file_size: 6003063 relation: main_file success: 1 - access_level: open_access checksum: a58399e98ec4b6506a5dae13e387f391 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:29:30Z date_updated: 2023-08-03T11:29:30Z file_id: '13488' file_name: Fig1_d.tif file_size: 24003063 relation: main_file success: 1 - access_level: open_access checksum: 699df4bc104df14607359678963b3d2d content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:29:30Z date_updated: 2023-08-03T11:29:30Z file_id: '13489' file_name: Fig1_e_zoom.tif file_size: 18063 relation: main_file success: 1 - access_level: open_access checksum: ea7b1278da490d221fc7698fd6bc39a4 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:29:30Z date_updated: 2023-08-03T11:29:30Z file_id: '13490' file_name: Fig1_e.tif file_size: 186813 relation: main_file success: 1 - access_level: open_access checksum: 37b05ef3a36b9f6bf4ec46199230874a content_type: application/vnd.openxmlformats-officedocument.spreadsheetml.sheet creator: jdanzl date_created: 2023-08-03T11:29:30Z date_updated: 2023-08-03T11:29:30Z file_id: '13491' file_name: Fig1_f.xlsx file_size: 17494 relation: main_file success: 1 - access_level: open_access checksum: 872eb3dc1a94afb26947a365bfae581a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:40:43Z date_updated: 2023-08-03T11:40:43Z file_id: '13492' file_name: Fig2_a_1.tif file_size: 816786862 relation: main_file success: 1 - access_level: open_access checksum: cab6f72d7d546a81c105c229747949ef content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:40:13Z date_updated: 2023-08-03T11:40:13Z file_id: '13493' file_name: Fig2_a_2.tif file_size: 8654692 relation: main_file success: 1 - access_level: open_access checksum: c85bc3ffe7f6bdf16a81290761ed6253 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:40:14Z date_updated: 2023-08-03T11:40:14Z file_id: '13494' file_name: Fig2_a_3.tif file_size: 8654692 relation: main_file success: 1 - access_level: open_access checksum: 5a3fd5484e566c34e210a4acb2b97791 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:40:24Z date_updated: 2023-08-03T11:40:24Z file_id: '13495' file_name: Fig2_a_4.tif file_size: 272262438 relation: main_file success: 1 - access_level: open_access checksum: ae5cbacf56e3fdf934a6d6fd489f5fe0 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:40:37Z date_updated: 2023-08-03T11:40:37Z file_id: '13496' file_name: Fig2_a_5.tif file_size: 272262438 relation: main_file success: 1 - access_level: open_access checksum: e6da436b83bbe3a34138b52e5de49d69 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:40:44Z date_updated: 2023-08-03T11:40:44Z file_id: '13497' file_name: Fig2_a_6.tif file_size: 204301228 relation: main_file success: 1 - access_level: open_access checksum: 855f0a0bcf5b3d7cc7d50561f2c8f625 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:40:49Z date_updated: 2023-08-03T11:40:49Z file_id: '13498' file_name: Fig2_a_7-8.tif file_size: 68094350 relation: main_file success: 1 - access_level: open_access checksum: ff709f9f8ebaa8cf50a4b2fca5ce9813 content_type: application/octet-stream creator: jdanzl date_created: 2023-08-03T11:40:48Z date_updated: 2023-08-03T11:40:48Z file_id: '13499' file_name: Fig2_a_roi.roi file_size: 156 relation: main_file success: 1 - access_level: open_access checksum: ce9b774ff5163ebfa4e3fb162f4cfffe content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:41:37Z date_updated: 2023-08-03T11:41:37Z file_id: '13500' file_name: Fig2_c-i_1_n2v.tif file_size: 1036927887 relation: main_file success: 1 - access_level: open_access checksum: 21f1bb8d2a00c88bdd6febe6285acc2a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:41:25Z date_updated: 2023-08-03T11:41:25Z file_id: '13501' file_name: Fig2_c-i_1.tif file_size: 518519275 relation: main_file success: 1 - access_level: open_access checksum: 9af5b66b74c2ff4b2b99b0d94f2864e6 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:42:48Z date_updated: 2023-08-03T11:42:48Z file_id: '13502' file_name: Fig2_c-i_3_n2v.tif file_size: 1444202302 relation: main_file success: 1 - access_level: open_access checksum: c83261e88821747b301197314d92f2b2 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:42:57Z date_updated: 2023-08-03T11:42:57Z file_id: '13503' file_name: Fig2_c-i_3.tif file_size: 1075338708 relation: main_file success: 1 - access_level: open_access checksum: 5d1278ba4b7e085c0c186ea49fce535b content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:44:05Z date_updated: 2023-08-03T11:44:05Z file_id: '13504' file_name: Fig2_c-i_2_n2v.tif file_size: 851145493 relation: main_file success: 1 - access_level: open_access checksum: 5aaf1eba65582cf437ff3ce753eba4d7 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:43:47Z date_updated: 2023-08-03T11:43:47Z file_id: '13505' file_name: Fig2_c-i_2.tif file_size: 432099834 relation: main_file success: 1 - access_level: open_access checksum: ce9b774ff5163ebfa4e3fb162f4cfffe content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:44:41Z date_updated: 2023-08-03T11:44:41Z file_id: '13506' file_name: Fig2_h_n2v.tif file_size: 1036927887 relation: main_file success: 1 - access_level: open_access checksum: 21f1bb8d2a00c88bdd6febe6285acc2a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:44:36Z date_updated: 2023-08-03T11:44:36Z file_id: '13507' file_name: Fig2_h.tif file_size: 518519275 relation: main_file success: 1 - access_level: open_access checksum: b37f25a90ef42fa4358649fdd6b41f35 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:44:40Z date_updated: 2023-08-03T11:44:40Z file_id: '13508' file_name: Fig2_j_1.tif file_size: 19287397 relation: main_file success: 1 - access_level: open_access checksum: 50f0969c6c2c1209ff776bec4861030a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:44:41Z date_updated: 2023-08-03T11:44:41Z file_id: '13509' file_name: Fig2_j_2.tif file_size: 617552 relation: main_file success: 1 - access_level: open_access checksum: 2a8cc93471378ac4c3b640e4318d89eb content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:44:41Z date_updated: 2023-08-03T11:44:41Z file_id: '13510' file_name: Fig2_j_3.tif file_size: 19287392 relation: main_file success: 1 - access_level: open_access checksum: b90965d20133fea73c99050c32eb7695 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:44:42Z date_updated: 2023-08-03T11:44:42Z file_id: '13511' file_name: Fig2_j_4.tif file_size: 617552 relation: main_file success: 1 - access_level: open_access checksum: 568a1e0efaa62527b51e66a7aabfd05c content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:44:43Z date_updated: 2023-08-03T11:44:43Z file_id: '13512' file_name: Fig2_j_coCATS_N2V.tif file_size: 19287339 relation: main_file success: 1 - access_level: open_access checksum: c70447cebe073dd78e0ac34ecc36ad85 content_type: application/octet-stream creator: jdanzl date_created: 2023-08-03T11:44:44Z date_updated: 2023-08-03T11:44:44Z file_id: '13513' file_name: Fig2_j_roi.roi file_size: 148 relation: main_file success: 1 - access_level: open_access checksum: 505252cc4b443b76c2e41ecf5879a542 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:44:52Z date_updated: 2023-08-03T11:44:52Z file_id: '13514' file_name: Fig3_a_n2v.tif file_size: 316842690 relation: main_file success: 1 - access_level: open_access checksum: 35463183611e8ee4fba2025772c40eb2 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:45:01Z date_updated: 2023-08-03T11:45:01Z file_id: '13515' file_name: Fig3_a.tif file_size: 172839057 relation: main_file success: 1 - access_level: open_access checksum: e0469102a87332b46904b4ba35b8fb2f content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:45:05Z date_updated: 2023-08-03T11:45:05Z file_id: '13516' file_name: Fig3_g_n2v.tif file_size: 309407894 relation: main_file success: 1 - access_level: open_access checksum: 854c8fe02acd920f8e8f6a3173458e86 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:51:15Z date_updated: 2023-08-03T11:51:15Z file_id: '13517' file_name: Fig4_a_MIP.tif file_size: 11327792 relation: main_file success: 1 - access_level: open_access checksum: ab35811ffbe3f40733d0e054d9d6c4e6 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:51:18Z date_updated: 2023-08-03T11:51:18Z file_id: '13518' file_name: Fig4_c_dghilus_bouton2_n2v.tif file_size: 106696700 relation: main_file success: 1 - access_level: open_access checksum: e3b6410d68e42004ef3857967707aeb3 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:51:17Z date_updated: 2023-08-03T11:51:17Z file_id: '13519' file_name: Fig4_c_dghilus_bouton2.tif file_size: 53367287 relation: main_file success: 1 - access_level: open_access checksum: 9ef0e3f3ec6f0b7b2666e3a0d7e6f355 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:51:20Z date_updated: 2023-08-03T11:51:20Z file_id: '13520' file_name: Fig4_c_dghilus_bouton5_n2v.tif file_size: 103816699 relation: main_file success: 1 - access_level: open_access checksum: d5d846a4edaf0168ca6cc53d8cc39dde content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:51:21Z date_updated: 2023-08-03T11:51:21Z file_id: '13521' file_name: Fig4_c_dghilus_bouton5.tif file_size: 51927287 relation: main_file success: 1 - access_level: open_access checksum: 690a87182441c9742da2550189641e5a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:51:24Z date_updated: 2023-08-03T11:51:24Z file_id: '13522' file_name: Fig4_c_stratum_bouton11_n2v.tif file_size: 76391971 relation: main_file success: 1 - access_level: open_access checksum: 4dc575424729c5ba181bd9a3962d4781 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:51:23Z date_updated: 2023-08-03T11:51:23Z file_id: '13523' file_name: Fig4_c_stratum_bouton11.tif file_size: 38217920 relation: main_file success: 1 - access_level: open_access checksum: 9fdd51636928f45e8e534cc5a37a48ff content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:51:29Z date_updated: 2023-08-03T11:51:29Z file_id: '13524' file_name: Fig4_c_stratum_bouton13_n2v.tif file_size: 154149020 relation: main_file success: 1 - access_level: open_access checksum: 643169464252d67753ac6f8493668f34 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:51:28Z date_updated: 2023-08-03T11:51:28Z file_id: '13525' file_name: Fig4_c_stratum_bouton13.tif file_size: 77099447 relation: main_file success: 1 - access_level: open_access checksum: ab35811ffbe3f40733d0e054d9d6c4e6 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:51:32Z date_updated: 2023-08-03T11:51:32Z file_id: '13526' file_name: Fig4_d.tif file_size: 106696700 relation: main_file success: 1 - access_level: open_access checksum: 9fdd51636928f45e8e534cc5a37a48ff content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:51:35Z date_updated: 2023-08-03T11:51:35Z file_id: '13527' file_name: Fig4_e.tif file_size: 154149020 relation: main_file success: 1 - access_level: open_access checksum: 5380d0a98e97d7d8462b38bd0a96644c content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:51:32Z date_updated: 2023-08-03T11:51:32Z file_id: '13528' file_name: Fig4_f_1_top.tif file_size: 5986760 relation: main_file success: 1 - access_level: open_access checksum: 7d1309e806eb31588ebafcf40388e13f content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:51:33Z date_updated: 2023-08-03T11:51:33Z file_id: '13529' file_name: Fig4_f_2_top.tif file_size: 6001178 relation: main_file success: 1 - access_level: open_access checksum: a71c80207655d508cbc7626bc144d7a1 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:51:33Z date_updated: 2023-08-03T11:51:33Z file_id: '13530' file_name: Fig4_f_3_top.tif file_size: 6023318 relation: main_file success: 1 - access_level: open_access checksum: 5d76b2ad7d7acbb1afa27cf52194b1cb content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:51:34Z date_updated: 2023-08-03T11:51:34Z file_id: '13531' file_name: Fig4_f_4_top.tif file_size: 6038186 relation: main_file success: 1 - access_level: open_access checksum: 9cee6b3387bd880843f2c6cdfa0d4a8d content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:51:34Z date_updated: 2023-08-03T11:51:34Z file_id: '13532' file_name: Fig4_f_5_top.tif file_size: 2324158 relation: main_file success: 1 - access_level: open_access checksum: a48fc9e1bb2710cf28466ae6d2a20c19 content_type: image/png creator: jdanzl date_created: 2023-08-03T11:51:34Z date_updated: 2023-08-03T11:51:34Z file_id: '13533' file_name: Fig4_f_1_bottom.png file_size: 1150264 relation: main_file success: 1 - access_level: open_access checksum: ff47ca30f814e17561974b73b0913a1a content_type: image/png creator: jdanzl date_created: 2023-08-03T11:51:34Z date_updated: 2023-08-03T11:51:34Z file_id: '13534' file_name: Fig4_f_2_bottom.png file_size: 1157424 relation: main_file success: 1 - access_level: open_access checksum: 2ea3fb8d79cee8ae9de7ca31d003910f content_type: image/png creator: jdanzl date_created: 2023-08-03T11:51:34Z date_updated: 2023-08-03T11:51:34Z file_id: '13535' file_name: Fig4_f_3_bottom.png file_size: 1152715 relation: main_file success: 1 - access_level: open_access checksum: d25e5ecf2f0c3be7c20a7e25a7a334b8 content_type: image/png creator: jdanzl date_created: 2023-08-03T11:51:34Z date_updated: 2023-08-03T11:51:34Z file_id: '13536' file_name: Fig4_f_4_bottom.png file_size: 1105240 relation: main_file success: 1 - access_level: open_access checksum: 76535f569a57b967e378df89b7d2982a content_type: image/png creator: jdanzl date_created: 2023-08-03T11:51:35Z date_updated: 2023-08-03T11:51:35Z file_id: '13537' file_name: Fig4_f_5_bottom.png file_size: 1228157 relation: main_file success: 1 - access_level: open_access checksum: d46fefe73daa3ec08b847631e9de6828 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:53:52Z date_updated: 2023-08-03T11:53:52Z file_id: '13538' file_name: Fig5_a_1.tif file_size: 91181184 relation: main_file success: 1 - access_level: open_access checksum: 354c0ba876a33672eca37cd61dac7073 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:53:54Z date_updated: 2023-08-03T11:53:54Z file_id: '13539' file_name: Fig5_a_2.tif file_size: 176024124 relation: main_file success: 1 - access_level: open_access checksum: d07925040ef0c3c51edbdca8cf3ec1fa content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:53:53Z date_updated: 2023-08-03T11:53:53Z file_id: '13540' file_name: Fig5_a_3.tif file_size: 15812494 relation: main_file success: 1 - access_level: open_access checksum: 7c34b19a1764e2f501f11dcabd442ce2 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:53:53Z date_updated: 2023-08-03T11:53:53Z file_id: '13541' file_name: Fig5_a_4.tif file_size: 11117689 relation: main_file success: 1 - access_level: open_access checksum: c49af4b96532e00b3a51574a2a94decb content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:53:53Z date_updated: 2023-08-03T11:53:53Z file_id: '13542' file_name: Fig5_a_5.tif file_size: 111665 relation: main_file success: 1 - access_level: open_access checksum: 1b42eadcdd71f2dc00d82784673aa577 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:53:54Z date_updated: 2023-08-03T11:53:54Z file_id: '13543' file_name: Fig5_b_1.tif file_size: 16676449 relation: main_file success: 1 - access_level: open_access checksum: 0d27266bf216f71fcb5496731ce76dd5 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:53:54Z date_updated: 2023-08-03T11:53:54Z file_id: '13544' file_name: Fig5_b_2-4.tif file_size: 427651 relation: main_file success: 1 - access_level: open_access checksum: c4232930068a0a8f7c8a70ce0ea48dc2 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:53:55Z date_updated: 2023-08-03T11:53:55Z file_id: '13545' file_name: Fig5_c_1-3.tif file_size: 11117705 relation: main_file success: 1 - access_level: open_access checksum: c9caad749be0ef04ef8013cfdb69f8fc content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:53:55Z date_updated: 2023-08-03T11:53:55Z file_id: '13546' file_name: Fig5_c_2-4.tif file_size: 254153 relation: main_file success: 1 - access_level: open_access checksum: 5c6d36b96bde1e090cc428b269aba6ec content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:54:14Z date_updated: 2023-08-03T11:54:14Z file_id: '13547' file_name: Fig5_e_1.tif file_size: 737290746 relation: main_file success: 1 - access_level: open_access checksum: f97632984b6a73e06cc0c8c947cdcc71 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:53:57Z date_updated: 2023-08-03T11:53:57Z file_id: '13548' file_name: Fig5_e_2.tif file_size: 31366288 relation: main_file success: 1 - access_level: open_access checksum: 8c471eeaa59008eed9e91afe5e1f1698 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:53:57Z date_updated: 2023-08-03T11:53:57Z file_id: '13549' file_name: Fig5_e_3.tif file_size: 1216304 relation: main_file success: 1 - access_level: open_access checksum: 31c10c3a1d874b5028e35e2dd8800a68 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:53:59Z date_updated: 2023-08-03T11:53:59Z file_id: '13550' file_name: Fig5_g.tif file_size: 35669193 relation: main_file success: 1 - access_level: open_access checksum: 0e9fe7b7ee06a630837e9d3c41b80e01 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:53:59Z date_updated: 2023-08-03T11:53:59Z file_id: '13551' file_name: Fig5_h.tif file_size: 7492349 relation: main_file success: 1 - access_level: open_access checksum: d25b3d04bb8364089cafdf8deb6846b6 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:59:18Z date_updated: 2023-08-03T11:59:18Z file_id: '13552' file_name: Fig6_a_1.tif file_size: 121446390 relation: main_file success: 1 - access_level: open_access checksum: 4361e10db6ec48c2d4579ac089ff3ca3 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:59:22Z date_updated: 2023-08-03T11:59:22Z file_id: '13553' file_name: Fig6_a_2.tif file_size: 264412158 relation: main_file success: 1 - access_level: open_access checksum: fe3a00ae75fb3388438e53ced92a9498 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:59:21Z date_updated: 2023-08-03T11:59:21Z file_id: '13554' file_name: Fig6_a_3.tif file_size: 57399051 relation: main_file success: 1 - access_level: open_access checksum: 4372c13d6dd2274aa749799b8e96bf06 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:59:21Z date_updated: 2023-08-03T11:59:21Z file_id: '13555' file_name: Fig6_b_left.tif file_size: 6003163 relation: main_file success: 1 - access_level: open_access checksum: f7ae4e50f2f4d414c598bddd691b722a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:59:21Z date_updated: 2023-08-03T11:59:21Z file_id: '13556' file_name: Fig6_b_right.tif file_size: 511265 relation: main_file success: 1 - access_level: open_access checksum: cde658a9ca666bdef1b29613ab72092d content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:59:39Z date_updated: 2023-08-03T11:59:39Z file_id: '13557' file_name: Fig6_c_n2v.tif file_size: 467125933 relation: main_file success: 1 - access_level: open_access checksum: 57e73c1fedcee4bd8ab62518baa0e0e5 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:59:36Z date_updated: 2023-08-03T11:59:36Z file_id: '13558' file_name: Fig6_c.tif file_size: 322251440 relation: main_file success: 1 - access_level: open_access checksum: 53175073b83ab569241ae64ef7f180b3 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:59:38Z date_updated: 2023-08-03T11:59:38Z file_id: '13559' file_name: Fig6_d_1.tif file_size: 37641738 relation: main_file success: 1 - access_level: open_access checksum: af97423e1077af85465a5e39fa25d1e4 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:59:40Z date_updated: 2023-08-03T11:59:40Z file_id: '13560' file_name: Fig6_d_2.tif file_size: 70596929 relation: main_file success: 1 - access_level: open_access checksum: f1fd7a9fa2a12a930fe35bdf53ba3ff7 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:59:42Z date_updated: 2023-08-03T11:59:42Z file_id: '13561' file_name: Fig6_d_3.tif file_size: 15303146 relation: main_file success: 1 - access_level: open_access checksum: 95655df5cdb05f09912298de9a3711b4 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:59:41Z date_updated: 2023-08-03T11:59:41Z file_id: '13562' file_name: Fig6_d_4.tif file_size: 893051 relation: main_file success: 1 - access_level: open_access checksum: 4d722b4e09ce617252d284f78ea2ee30 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:59:58Z date_updated: 2023-08-03T11:59:58Z file_id: '13563' file_name: Fig6_e.tif file_size: 381232200 relation: main_file success: 1 - access_level: open_access checksum: d1eda9599f422a614404dd112f0c3185 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:59:58Z date_updated: 2023-08-03T11:59:58Z file_id: '13564' file_name: Fig6_f.tif file_size: 345804470 relation: main_file success: 1 - access_level: open_access checksum: 1cd202570f964b78e1f55c987d5d5de1 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:00:08Z date_updated: 2023-08-03T12:00:08Z file_id: '13565' file_name: Fig6_g.tif file_size: 346119927 relation: main_file success: 1 - access_level: open_access checksum: 78cbf1906ff8746ed524c62f8f580f52 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:00:02Z date_updated: 2023-08-03T12:00:02Z file_id: '13566' file_name: Fig6_h.tif file_size: 7064977 relation: main_file success: 1 - access_level: open_access checksum: 21635ce59f1ae5a334aaad3f4c0b171c content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:00:03Z date_updated: 2023-08-03T12:00:03Z file_id: '13567' file_name: Fig6_i.tif file_size: 7110129 relation: main_file success: 1 - access_level: open_access checksum: 704962856f2a024ce1f321a1785556e3 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:00:07Z date_updated: 2023-08-03T12:00:07Z file_id: '13568' file_name: Fig6_j.tif file_size: 110297540 relation: main_file success: 1 - access_level: open_access checksum: 4b74ba5ae1e2bb2201bf51c74d733268 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:00:07Z date_updated: 2023-08-03T12:00:07Z file_id: '13569' file_name: Fig6_k.tif file_size: 11117689 relation: main_file success: 1 - access_level: open_access checksum: a8efa3007df4e9e0f80c7a2bbc451178 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:05:41Z date_updated: 2023-08-03T12:05:41Z file_id: '13570' file_name: Extdata_01_a_1.tif file_size: 1287107 relation: main_file success: 1 - access_level: open_access checksum: 7f24b6c84ce96a67347eb5ef4c43fac1 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:05:41Z date_updated: 2023-08-03T12:05:41Z file_id: '13571' file_name: Extdata_01_a_2.tif file_size: 58307 relation: main_file success: 1 - access_level: open_access checksum: fa7ae4eefc11b9b60c4ab80f6e839b73 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:05:41Z date_updated: 2023-08-03T12:05:41Z file_id: '13572' file_name: Extdata_01_a_3.tif file_size: 1283209 relation: main_file success: 1 - access_level: open_access checksum: cec9a5eb87f1b56e64626a00c6d0e53d content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:05:41Z date_updated: 2023-08-03T12:05:41Z file_id: '13573' file_name: Extdata_01_a_4.tif file_size: 54409 relation: main_file success: 1 - access_level: open_access checksum: 450e4786d66d5059028420153908a4dc content_type: image/png creator: jdanzl date_created: 2023-08-03T12:05:41Z date_updated: 2023-08-03T12:05:41Z file_id: '13574' file_name: Extdata_01_c_1.png file_size: 2431 relation: main_file success: 1 - access_level: open_access checksum: feb758609b399cf644dd3ae7cd75fb96 content_type: image/png creator: jdanzl date_created: 2023-08-03T12:05:41Z date_updated: 2023-08-03T12:05:41Z file_id: '13575' file_name: Extdata_01_c_2.png file_size: 612 relation: main_file success: 1 - access_level: open_access checksum: 52f43300a50f83f9a6ff1409324086ee content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:05:41Z date_updated: 2023-08-03T12:05:41Z file_id: '13576' file_name: Extdata_01_d_1.tif file_size: 433981 relation: main_file success: 1 - access_level: open_access checksum: 28925dcf8792f524e286beb16b0c532c content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:05:41Z date_updated: 2023-08-03T12:05:41Z file_id: '13577' file_name: Extdata_01_d_2.tif file_size: 19649 relation: main_file success: 1 - access_level: open_access checksum: c93b2f0426c80d18e252435f1e146568 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:05:41Z date_updated: 2023-08-03T12:05:41Z file_id: '13578' file_name: Extdata_01_d_3.tif file_size: 433981 relation: main_file success: 1 - access_level: open_access checksum: c0ed722a768001431f47646ef98c44da content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:05:41Z date_updated: 2023-08-03T12:05:41Z file_id: '13579' file_name: Extdata_01_d_4.tif file_size: 19649 relation: main_file success: 1 - access_level: open_access checksum: db9d386276b985b8e702f797e910bd0b content_type: image/png creator: jdanzl date_created: 2023-08-03T12:05:41Z date_updated: 2023-08-03T12:05:41Z file_id: '13580' file_name: Extdata_01_f_1.png file_size: 4752 relation: main_file success: 1 - access_level: open_access checksum: 244f6645d191c50d997c0dc6a15535ec content_type: image/png creator: jdanzl date_created: 2023-08-03T12:05:41Z date_updated: 2023-08-03T12:05:41Z file_id: '13581' file_name: Extdata_01_f_2.png file_size: 2698 relation: main_file success: 1 - access_level: open_access checksum: 3d6100b836d850b38e66e0f5a7919495 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:07:27Z date_updated: 2023-08-03T12:07:27Z file_id: '13582' file_name: Extdata_02_a.tif file_size: 24003247 relation: main_file success: 1 - access_level: open_access checksum: 3cd6a3b7bf2061cf5c7810c0001236e5 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:07:27Z date_updated: 2023-08-03T12:07:27Z file_id: '13583' file_name: Extdata_02_b.tif file_size: 1164723 relation: main_file success: 1 - access_level: open_access checksum: d87c82d663ffea379cc86c56981e2e16 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:10:32Z date_updated: 2023-08-03T12:10:32Z file_id: '13584' file_name: Extdata_03_SYPH1_xy_1.tif file_size: 7109763 relation: main_file success: 1 - access_level: open_access checksum: a3703d0d26393578d4ba466681fc6be8 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:10:32Z date_updated: 2023-08-03T12:10:32Z file_id: '13585' file_name: Extdata_03_SYPH1_xz_1-2.tif file_size: 27791 relation: main_file success: 1 - access_level: open_access checksum: f653ac7d531cf9896cbd6a9edf2a7759 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:10:32Z date_updated: 2023-08-03T12:10:32Z file_id: '13586' file_name: Extdata_03_SYPH1_xz_3-4.tif file_size: 27721 relation: main_file success: 1 - access_level: open_access checksum: 04edbb337df4d5470e033a4f53c07300 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:10:33Z date_updated: 2023-08-03T12:10:33Z file_id: '13587' file_name: Extdata_03_SYPH1_xz_n2v.tif file_size: 57657482 relation: main_file success: 1 - access_level: open_access checksum: 09e1fe2dd3a1e8349693fda55d0985ca content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:10:34Z date_updated: 2023-08-03T12:10:34Z file_id: '13588' file_name: Extdata_03_SYPH1_xz.tif file_size: 57657527 relation: main_file success: 1 - access_level: open_access checksum: 458f8d486cb63876c6664cde4a9be27c content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:12:25Z date_updated: 2023-08-03T12:12:25Z file_id: '13589' file_name: Extdata_03_SYP1_xy_1.tif file_size: 7109763 relation: main_file success: 1 - access_level: open_access checksum: e2dfccc882d85b660d65a596e1a8cbac content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:12:25Z date_updated: 2023-08-03T12:12:25Z file_id: '13590' file_name: Extdata_03_SYP1_xy_2-3.tif file_size: 72963 relation: main_file success: 1 - access_level: open_access checksum: a331be6052c68cc027cdb79f15447d9a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:12:25Z date_updated: 2023-08-03T12:12:25Z file_id: '13591' file_name: Extdata_03_SYP1_xz_1-2.tif file_size: 27724 relation: main_file success: 1 - access_level: open_access checksum: 4de626b035b43feaacd923fca411e6a2 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:12:25Z date_updated: 2023-08-03T12:12:25Z file_id: '13592' file_name: Extdata_03_SYP1_xz_3-4.tif file_size: 27724 relation: main_file success: 1 - access_level: open_access checksum: d8076e927a074f024924d9bdb6fdd5e6 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:12:30Z date_updated: 2023-08-03T12:12:30Z file_id: '13593' file_name: Extdata_03_SYP1_xz_n2v.tif file_size: 214613644 relation: main_file success: 1 - access_level: open_access checksum: 79cf7d0f450c397caa877dd06b52f8df content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:12:30Z date_updated: 2023-08-03T12:12:30Z file_id: '13594' file_name: Extdata_03_SYP1_xz.tif file_size: 214613687 relation: main_file success: 1 - access_level: open_access checksum: 60ac6ea988d9b8bdaba2f09e0e1ef370 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:14:29Z date_updated: 2023-08-03T12:14:29Z file_id: '13595' file_name: Extdata03_VAMP2_xy_1.tif file_size: 7109747 relation: main_file success: 1 - access_level: open_access checksum: 92bf312da2dd356aa4fc9a0e7d811af2 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:14:29Z date_updated: 2023-08-03T12:14:29Z file_id: '13596' file_name: Extdata03_VAMP2_xy_2-3.tif file_size: 72947 relation: main_file success: 1 - access_level: open_access checksum: 9319e293092eeee24e3c658fc178af1a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:14:29Z date_updated: 2023-08-03T12:14:29Z file_id: '13597' file_name: Extdata03_VAMP2_xz_1-2.tif file_size: 27724 relation: main_file success: 1 - access_level: open_access checksum: a627d7fd9a89bdde968e6d9bff846254 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:14:29Z date_updated: 2023-08-03T12:14:29Z file_id: '13598' file_name: Extdata03_VAMP2_xz_3-4.tif file_size: 27708 relation: main_file success: 1 - access_level: open_access checksum: 7a5363a185edce59ce57535f7d855092 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:14:32Z date_updated: 2023-08-03T12:14:32Z file_id: '13599' file_name: Extdata03_VAMP2_xz_n2v.tif file_size: 102457485 relation: main_file success: 1 - access_level: open_access checksum: 8e7fc4d00fff8ec6d9340e969f37e176 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:14:32Z date_updated: 2023-08-03T12:14:32Z file_id: '13600' file_name: Extdata03_VAMP2_xz.tif file_size: 102457527 relation: main_file success: 1 - access_level: open_access checksum: be17472f73ed8cd02a700b861f1dbac0 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:16:08Z date_updated: 2023-08-03T12:16:08Z file_id: '13601' file_name: Extdata04_VGLUT_xy_1.tif file_size: 11117763 relation: main_file success: 1 - access_level: open_access checksum: dbc3ec477f491ce3e98ab40475bd90ca content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:16:08Z date_updated: 2023-08-03T12:16:08Z file_id: '13602' file_name: Extdata04_VGLUT_xy_2-3.tif file_size: 72947 relation: main_file success: 1 - access_level: open_access checksum: 8ee877e6b843bb0e38febb0481962d69 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:16:08Z date_updated: 2023-08-03T12:16:08Z file_id: '13603' file_name: Extdata04_VGLUT_xz_1-2.tif file_size: 53367 relation: main_file success: 1 - access_level: open_access checksum: 9873f54d50955a2c204d0559c87aa13d content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:16:08Z date_updated: 2023-08-03T12:16:08Z file_id: '13604' file_name: Extdata04_VGLUT_xz_3-4.tif file_size: 53358 relation: main_file success: 1 - access_level: open_access checksum: 8eda08ae5981fcfa3758d0320b1923af content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:16:11Z date_updated: 2023-08-03T12:16:11Z file_id: '13605' file_name: Extdata04_VGLUT_xz_n2v.tif file_size: 144076208 relation: main_file success: 1 - access_level: open_access checksum: bc0b10229d498f60996a5b05cb87c428 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:16:10Z date_updated: 2023-08-03T12:16:10Z file_id: '13606' file_name: Extdata04_VGLUT_xz.tif file_size: 72071440 relation: main_file success: 1 - access_level: open_access checksum: e8d093ce7d98ea5647d8a80e3084c40b content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:32:32Z date_updated: 2023-08-03T12:32:32Z file_id: '13607' file_name: Extdata03_VGAT_xy_1.tif file_size: 7109763 relation: main_file success: 1 - access_level: open_access checksum: 36590ca7a586de7ad76d3ad659c38995 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:32:32Z date_updated: 2023-08-03T12:32:32Z file_id: '13608' file_name: Extdata03_VGAT_xy_2-3.tif file_size: 72947 relation: main_file success: 1 - access_level: open_access checksum: 3914c7709f69d4d18f23a9fb6dc64572 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:32:32Z date_updated: 2023-08-03T12:32:32Z file_id: '13609' file_name: Extdata03_VGAT_xz_1-2.tif file_size: 53355 relation: main_file success: 1 - access_level: open_access checksum: fa98aa521adaefb9e4476fe519e88e59 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:32:32Z date_updated: 2023-08-03T12:32:32Z file_id: '13610' file_name: Extdata03_VGAT_xz_3-4.tif file_size: 53339 relation: main_file success: 1 - access_level: open_access checksum: cd6f384c51756977e37f45043c913252 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:32:36Z date_updated: 2023-08-03T12:32:36Z file_id: '13611' file_name: Extdata03_VGAT_xz_n2v.tif file_size: 204861338 relation: main_file success: 1 - access_level: open_access checksum: fb7e46feda5ac07877a91ad963da0e31 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:32:35Z date_updated: 2023-08-03T12:32:35Z file_id: '13612' file_name: Extdata03_VGAT_xz.tif file_size: 102457527 relation: main_file success: 1 - access_level: open_access checksum: fe033e0a377d391cd8e4af04987d9900 content_type: image/png creator: jdanzl date_created: 2023-08-03T12:36:46Z date_updated: 2023-08-03T12:36:46Z file_id: '13613' file_name: Extdata04_MUNC_xy_1.png file_size: 4348932 relation: main_file success: 1 - access_level: open_access checksum: 771d8e2b9192b6620f54ab30e4fad594 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:35:58Z date_updated: 2023-08-03T12:35:58Z file_id: '13614' file_name: Extdata04_MUNC_xy_2-3.tif file_size: 72947 relation: main_file success: 1 - access_level: open_access checksum: 4256d8f06fa2077b352776cf76b46618 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:35:58Z date_updated: 2023-08-03T12:35:58Z file_id: '13615' file_name: Extdata04_MUNC_xz_1-2.tif file_size: 53435 relation: main_file success: 1 - access_level: open_access checksum: 0b9365638c81d545e773170cf04b04b8 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:35:58Z date_updated: 2023-08-03T12:35:58Z file_id: '13616' file_name: Extdata04_MUNC_xz_3-4.tif file_size: 55941 relation: main_file success: 1 - access_level: open_access checksum: 9fa62688dab03c592cec47bf5d1c304d content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:36:04Z date_updated: 2023-08-03T12:36:04Z file_id: '13617' file_name: Extdata04_MUNC_xz_n2v.tif file_size: 204861404 relation: main_file success: 1 - access_level: open_access checksum: 39f710080a26136dbbe4c8916b434c65 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:36:02Z date_updated: 2023-08-03T12:36:02Z file_id: '13618' file_name: Extdata04_MUNC_xz.tif file_size: 102457527 relation: main_file success: 1 - access_level: open_access checksum: eaabc8112645a73f4326e621b4e6ad0a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:38:39Z date_updated: 2023-08-03T12:38:39Z file_id: '13619' file_name: Extdata04_BASSOON_xy_1.tif file_size: 11117757 relation: main_file success: 1 - access_level: open_access checksum: 15f624d29c473ce6e0ae7e466efc059a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:38:39Z date_updated: 2023-08-03T12:38:39Z file_id: '13620' file_name: Extdata04_BASSOON_xy_2-3.tif file_size: 74041 relation: main_file success: 1 - access_level: open_access checksum: 1cb4b4d219767a30072c804a07140240 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:38:39Z date_updated: 2023-08-03T12:38:39Z file_id: '13621' file_name: Extdata04_BASSOON_xz_1-2.tif file_size: 53435 relation: main_file success: 1 - access_level: open_access checksum: 1bac9c192da9375d81cb3747f48c9be4 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:38:39Z date_updated: 2023-08-03T12:38:39Z file_id: '13622' file_name: Extdata04_BASSOON_xz_3-4.tif file_size: 53362 relation: main_file success: 1 - access_level: open_access checksum: 57fa91bfb1e2937e3449e57096b6fc74 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:38:50Z date_updated: 2023-08-03T12:38:50Z file_id: '13623' file_name: Extdata04_BASSOON_xz_n2v.tif file_size: 576071410 relation: main_file success: 1 - access_level: open_access checksum: ac51a734dcf7d1b94afcd4a471f10626 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:38:46Z date_updated: 2023-08-03T12:38:46Z file_id: '13624' file_name: Extdata04_BASSOON_xz.tif file_size: 288066640 relation: main_file success: 1 - access_level: open_access checksum: 244043f7acba250d560e29123702dcd7 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:40:57Z date_updated: 2023-08-03T12:40:57Z file_id: '13625' file_name: Extdata04_HOMER1_xy_1.tif file_size: 7109763 relation: main_file success: 1 - access_level: open_access checksum: eff51ff97539f6491989bfc3d3f88860 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:40:57Z date_updated: 2023-08-03T12:40:57Z file_id: '13626' file_name: Extdata04_HOMER1_xy_2-3.tif file_size: 72963 relation: main_file success: 1 - access_level: open_access checksum: df35046d9bca4e97a5625c5a55218cfb content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:40:57Z date_updated: 2023-08-03T12:40:57Z file_id: '13627' file_name: Extdata04_HOMER1_xz_1-2.tif file_size: 53375 relation: main_file success: 1 - access_level: open_access checksum: 5dc7536f7aaea084dfc329537d8412ce content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:40:57Z date_updated: 2023-08-03T12:40:57Z file_id: '13628' file_name: Extdata04_HOMER1_xz_3-4.tif file_size: 53359 relation: main_file success: 1 - access_level: open_access checksum: 0b407669a26b9d7730a41361ceffda9a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:41:00Z date_updated: 2023-08-03T12:41:00Z file_id: '13629' file_name: Extdata04_HOMER1_xz_n2v.tif file_size: 204861339 relation: main_file success: 1 - access_level: open_access checksum: f95a0da9bea8b605fc2ed310190836b3 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:40:59Z date_updated: 2023-08-03T12:40:59Z file_id: '13630' file_name: Extdata04_HOMER1_xz.tif file_size: 102457527 relation: main_file success: 1 - access_level: open_access checksum: cf74307696548e7aa90e59a0935a74a1 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:45:08Z date_updated: 2023-08-03T12:45:08Z file_id: '13631' file_name: Extdata04_SHANK2_xy_1.tif file_size: 7120361 relation: main_file success: 1 - access_level: open_access checksum: 7b3490246df4f5bb68d0df682161820f content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:45:08Z date_updated: 2023-08-03T12:45:08Z file_id: '13632' file_name: Extdata04_SHANK2_xy_2-3.tif file_size: 72973 relation: main_file success: 1 - access_level: open_access checksum: c599d6830e61c386219e266f4717fe7c content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:45:08Z date_updated: 2023-08-03T12:45:08Z file_id: '13633' file_name: Extdata04_SHANK2_xz_1-2.tif file_size: 53443 relation: main_file success: 1 - access_level: open_access checksum: 5b9912b2a408d224ad669f39dc8d5bc6 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:45:08Z date_updated: 2023-08-03T12:45:08Z file_id: '13634' file_name: Extdata04_SHANK2_xz_3-4.tif file_size: 53362 relation: main_file success: 1 - access_level: open_access checksum: 17f2064ceeb99cbb51208c27b1961ed5 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:45:30Z date_updated: 2023-08-03T12:45:30Z file_id: '13635' file_name: Extdata04_SHANK2_xz_n2v.tif file_size: 691291157 relation: main_file success: 1 - access_level: open_access checksum: 21f1bb8d2a00c88bdd6febe6285acc2a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:45:26Z date_updated: 2023-08-03T12:45:26Z file_id: '13636' file_name: Extdata04_SHANK2_xz.tif file_size: 518519275 relation: main_file success: 1 - access_level: open_access checksum: 47597ca873f1ea81cd4f7e9bfbb34aa4 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:46:25Z date_updated: 2023-08-03T12:46:25Z file_id: '13637' file_name: Extdata04_GEPHYRIN_xy_1.tif file_size: 752109 relation: main_file success: 1 - access_level: open_access checksum: 14ed7ae64eb783e6b30f824f21959d0f content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:46:25Z date_updated: 2023-08-03T12:46:25Z file_id: '13638' file_name: Extdata04_GEPHYRIN_xy_2-3.tif file_size: 72909 relation: main_file success: 1 - access_level: open_access checksum: e361e226428d7b23618eed35b1cad080 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:46:25Z date_updated: 2023-08-03T12:46:25Z file_id: '13639' file_name: Extdata04_GEPHYRIN_xz_1-2.tif file_size: 53375 relation: main_file success: 1 - access_level: open_access checksum: abe7cee22f69fc2bf1a3ff9955ccf45a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:46:25Z date_updated: 2023-08-03T12:46:25Z file_id: '13640' file_name: Extdata04_GEPHYRIN_xz_3-4.tif file_size: 53360 relation: main_file success: 1 - access_level: open_access checksum: 59b49b451a63c5ac06fa31a17640c1a2 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:46:27Z date_updated: 2023-08-03T12:46:27Z file_id: '13641' file_name: Extdata04_GEPHYRIN_xz_n2v.tif file_size: 73174939 relation: main_file success: 1 - access_level: open_access checksum: 1ee1feea85c8319ebc6c49147502e412 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:46:26Z date_updated: 2023-08-03T12:46:26Z file_id: '13642' file_name: Extdata04_GEPHYRIN_xz.tif file_size: 36614327 relation: main_file success: 1 - access_level: open_access checksum: 64d9d868ef89c5cfc65cb199aff831b4 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:52:23Z date_updated: 2023-08-03T12:52:23Z file_id: '13643' file_name: Extdata06_a-b_n2v.tif file_size: 2195652677 relation: main_file success: 1 - access_level: open_access checksum: df41d97987798715b1f66e6e72be169b content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:51:41Z date_updated: 2023-08-03T12:51:41Z file_id: '13644' file_name: Extdata06_a-b.tif file_size: 1097875840 relation: main_file success: 1 - access_level: open_access checksum: 95a3eaa3b70e964f6871a5765a53659b content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:52:57Z date_updated: 2023-08-03T12:52:57Z file_id: '13645' file_name: Extdata07_01_bottom.tif file_size: 3564577 relation: main_file success: 1 - access_level: open_access checksum: 80b41ad0de73fd61eb67a35262627fac content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:52:57Z date_updated: 2023-08-03T12:52:57Z file_id: '13646' file_name: Extdata07_01_top.tif file_size: 11958844 relation: main_file success: 1 - access_level: open_access checksum: f694a0f11e2f782702cb4c411941873a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:54:27Z date_updated: 2023-08-03T12:54:27Z file_id: '13647' file_name: Extdata07_2_bottom.tif file_size: 3564581 relation: main_file success: 1 - access_level: open_access checksum: b8b1a1339a25806615c0aa7906a032ff content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:54:27Z date_updated: 2023-08-03T12:54:27Z file_id: '13648' file_name: Extdata07_2_top.tif file_size: 11973592 relation: main_file success: 1 - access_level: open_access checksum: 8a24eb623d65d809fe8afbd527528a77 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:54:27Z date_updated: 2023-08-03T12:54:27Z file_id: '13649' file_name: Extdata07_3_bottom.tif file_size: 1281901 relation: main_file success: 1 - access_level: open_access checksum: 816b35def703bc48d55b0293fcd8212f content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:54:27Z date_updated: 2023-08-03T12:54:27Z file_id: '13650' file_name: Extdata07_3_top.tif file_size: 16569776 relation: main_file success: 1 - access_level: open_access checksum: 7f1375ab8cf28cd136e2e44d1fdfd87d content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:54:27Z date_updated: 2023-08-03T12:54:27Z file_id: '13651' file_name: Extdata07_04_bottom.tif file_size: 3564595 relation: main_file success: 1 - access_level: open_access checksum: b1dbda28e2a010968716c0411568f139 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:54:27Z date_updated: 2023-08-03T12:54:27Z file_id: '13652' file_name: Extdata07_04_top.tif file_size: 5896404 relation: main_file success: 1 - access_level: open_access checksum: d6e96b7c8e6a7084c14eda83a4dd778a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:54:28Z date_updated: 2023-08-03T12:54:28Z file_id: '13653' file_name: Extdata07_5_bottom.tif file_size: 3564609 relation: main_file success: 1 - access_level: open_access checksum: a647f89a3048f71512cc58c9e53ec022 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:54:28Z date_updated: 2023-08-03T12:54:28Z file_id: '13654' file_name: Extdata07_5_top.tif file_size: 15555618 relation: main_file success: 1 - access_level: open_access checksum: 66becb046fe591914df572617d720202 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:54:28Z date_updated: 2023-08-03T12:54:28Z file_id: '13655' file_name: Extdata07_6_bottom.tif file_size: 3564577 relation: main_file success: 1 - access_level: open_access checksum: 5d76b2ad7d7acbb1afa27cf52194b1cb content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:54:28Z date_updated: 2023-08-03T12:54:28Z file_id: '13656' file_name: Extdata07_6_top.tif file_size: 6038186 relation: main_file success: 1 - access_level: open_access checksum: 7f137bdea0f0acb3db75c983ce44ab44 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:54:28Z date_updated: 2023-08-03T12:54:28Z file_id: '13657' file_name: Extdata07_7_bottom.tif file_size: 3560937 relation: main_file success: 1 - access_level: open_access checksum: 479e26106280eb61a2d74e29137a2e43 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:54:28Z date_updated: 2023-08-03T12:54:28Z file_id: '13658' file_name: Extdata07_7_top.tif file_size: 12031850 relation: main_file success: 1 - access_level: open_access checksum: 8426197ad283c1bc83e3193f323d5f5a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:54:28Z date_updated: 2023-08-03T12:54:28Z file_id: '13659' file_name: Extdata07_8_bottom.tif file_size: 3560937 relation: main_file success: 1 - access_level: open_access checksum: b9f75a82b564e1c5c363a495d078f6b7 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:54:28Z date_updated: 2023-08-03T12:54:28Z file_id: '13660' file_name: Extdata07_8_top.tif file_size: 22877176 relation: main_file success: 1 - access_level: open_access checksum: 7f1a9f3bb9611362995ae832b2607f4d content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:54:28Z date_updated: 2023-08-03T12:54:28Z file_id: '13661' file_name: Extdata07_9_bottom.tif file_size: 3564605 relation: main_file success: 1 - access_level: open_access checksum: 40286bcb876b655d7421534d0215e86b content_type: image/tiff creator: jdanzl date_created: 2023-08-03T12:54:28Z date_updated: 2023-08-03T12:54:28Z file_id: '13662' file_name: Extdata07_9_top.tif file_size: 2744190 relation: main_file success: 1 - access_level: open_access checksum: 4af220986cc94d412c2354aa7e6c8cce content_type: image/png creator: jdanzl date_created: 2023-08-03T13:00:03Z date_updated: 2023-08-03T13:00:03Z file_id: '13663' file_name: Extdata08_6_left.png file_size: 7243611 relation: main_file success: 1 - access_level: open_access checksum: af9c2299f1005a3ccc39f41082cea642 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:00:03Z date_updated: 2023-08-03T13:00:03Z file_id: '13664' file_name: Extdata08_6_right.tif file_size: 5562487 relation: main_file success: 1 - access_level: open_access checksum: 63ef28a174215c70e31d2cabf67d90fc content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:00:04Z date_updated: 2023-08-03T13:00:04Z file_id: '13665' file_name: Extdata08_7_left.tif file_size: 34745956 relation: main_file success: 1 - access_level: open_access checksum: 46de918dfe5f3c23e497ee3daa608dd9 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:00:03Z date_updated: 2023-08-03T13:00:03Z file_id: '13666' file_name: Extdata08_7_right.tif file_size: 5562483 relation: main_file success: 1 - access_level: open_access checksum: 8243a7985d2902446183adc35519a0c8 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:00:04Z date_updated: 2023-08-03T13:00:04Z file_id: '13667' file_name: Extdata08_b_1_left.tif file_size: 31506150 relation: main_file success: 1 - access_level: open_access checksum: 857cffa31569efcd5917f9802a106d58 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:00:04Z date_updated: 2023-08-03T13:00:04Z file_id: '13668' file_name: Extdata08_b_1_right.tif file_size: 11117705 relation: main_file success: 1 - access_level: open_access checksum: e34902de9119d2cd9f1910f610627c5f content_type: image/png creator: jdanzl date_created: 2023-08-03T13:00:04Z date_updated: 2023-08-03T13:00:04Z file_id: '13669' file_name: Extdata08_b_2_left.png file_size: 3540493 relation: main_file success: 1 - access_level: open_access checksum: 1247d636ac5af22e8950ffd2ff213fea content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:00:05Z date_updated: 2023-08-03T13:00:05Z file_id: '13670' file_name: Extdata08_b_2_right.tif file_size: 5562553 relation: main_file success: 1 - access_level: open_access checksum: f47c2d3f6824e08853ae2631f6ee7c5f content_type: image/png creator: jdanzl date_created: 2023-08-03T13:00:05Z date_updated: 2023-08-03T13:00:05Z file_id: '13671' file_name: Extdata08_b_3_left.png file_size: 3541547 relation: main_file success: 1 - access_level: open_access checksum: 1247d636ac5af22e8950ffd2ff213fea content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:00:05Z date_updated: 2023-08-03T13:00:05Z file_id: '13672' file_name: Extdata08_b_3_right.tif file_size: 5562553 relation: main_file success: 1 - access_level: open_access checksum: e90a95ec902a683678acd70336852fd9 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:00:05Z date_updated: 2023-08-03T13:00:05Z file_id: '13673' file_name: Extdata08_b_4_left.tif file_size: 25819844 relation: main_file success: 1 - access_level: open_access checksum: 94cd44cd1c8c7a87ffd5861bf88561a1 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:00:05Z date_updated: 2023-08-03T13:00:05Z file_id: '13674' file_name: Extdata08_b_4_right.tif file_size: 5561131 relation: main_file success: 1 - access_level: open_access checksum: fd4ca56dc5c48ad4546df22daef04efc content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:00:06Z date_updated: 2023-08-03T13:00:06Z file_id: '13675' file_name: Extdata08_b_5_left.tif file_size: 38786287 relation: main_file success: 1 - access_level: open_access checksum: 52c04890160c4e0f23d3fe2d3ed0c8e7 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:00:06Z date_updated: 2023-08-03T13:00:06Z file_id: '13676' file_name: Extdata08_b_5_right.tif file_size: 5562487 relation: main_file success: 1 - access_level: open_access checksum: 47ee6f4b083130d5bb720bcf8a832443 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:04:52Z date_updated: 2023-08-03T13:04:52Z file_id: '13677' file_name: Extdata08_a_1-1.png file_size: 2133527 relation: main_file success: 1 - access_level: open_access checksum: 5ca2279c372b3b7dbce3ea5658a68399 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:04:52Z date_updated: 2023-08-03T13:04:52Z file_id: '13678' file_name: Extdata08_a_1-2.png file_size: 1782607 relation: main_file success: 1 - access_level: open_access checksum: 34b7781e3e4abf9f30a0c85db156b6d5 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:04:52Z date_updated: 2023-08-03T13:04:52Z file_id: '13679' file_name: Extdata08_a_2.png file_size: 5117469 relation: main_file success: 1 - access_level: open_access checksum: 25717007393682098d2208bd0676a0f7 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:04:52Z date_updated: 2023-08-03T13:04:52Z file_id: '13680' file_name: Extdata08_a_3.png file_size: 6911658 relation: main_file success: 1 - access_level: open_access checksum: b4b003809acec33c71628066744c7ea9 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:04:53Z date_updated: 2023-08-03T13:04:53Z file_id: '13681' file_name: Extdata08_a_4.png file_size: 8579427 relation: main_file success: 1 - access_level: open_access checksum: 4410976cf867ecacf8f197dbd28cc5a0 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:04:53Z date_updated: 2023-08-03T13:04:53Z file_id: '13682' file_name: Extdata08_a_5.png file_size: 9675065 relation: main_file success: 1 - access_level: open_access checksum: a235dd204f28d3323883e044b031b984 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:04:53Z date_updated: 2023-08-03T13:04:53Z file_id: '13683' file_name: Extdata08_a_6.png file_size: 9769588 relation: main_file success: 1 - access_level: open_access checksum: 0e2b768e4eb7200cf6fe28ba511a5ef6 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:04:53Z date_updated: 2023-08-03T13:04:53Z file_id: '13684' file_name: Extdata08_a_7.png file_size: 9114791 relation: main_file success: 1 - access_level: open_access checksum: df4a01c62233ee8ed601c4b90d7780d0 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:04:57Z date_updated: 2023-08-03T13:04:57Z file_id: '13685' file_name: Extdata08_a_8.png file_size: 124540688 relation: main_file success: 1 - access_level: open_access checksum: 1f407c7915e2717a56fec258708e7b7a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:11:30Z date_updated: 2023-08-03T13:11:30Z file_id: '13686' file_name: Exdata09_c_n2v.tif file_size: 204861336 relation: main_file success: 1 - access_level: open_access checksum: 9089dc7c9914edf9750eebd65819708d content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:11:26Z date_updated: 2023-08-03T13:11:26Z file_id: '13687' file_name: Extdata09_a_zoom.tif file_size: 252149 relation: main_file success: 1 - access_level: open_access checksum: 62d295a62cb8dd36c268b28cf0251322 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:11:26Z date_updated: 2023-08-03T13:11:26Z file_id: '13688' file_name: Extdata09_a.tif file_size: 11117705 relation: main_file success: 1 - access_level: open_access checksum: e874d8ee287f924c1076134b5b06bdb2 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:11:31Z date_updated: 2023-08-03T13:11:31Z file_id: '13689' file_name: Extdata09_b_n2v.tif file_size: 256074660 relation: main_file success: 1 - access_level: open_access checksum: 488068fff7b42bcf5728739e2a06d742 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:12:53Z date_updated: 2023-08-03T13:12:53Z file_id: '13690' file_name: Extdata10_n2v_CLAHE.tif file_size: 127914854 relation: main_file success: 1 - access_level: open_access checksum: 35351f5af21ce854d41577813a7bdb57 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:21:35Z date_updated: 2023-08-03T13:21:35Z file_id: '13691' file_name: Supplfig01_a_1.png file_size: 430878 relation: main_file success: 1 - access_level: open_access checksum: 36204e9e604206366ffc6f61ec91915b content_type: image/png creator: jdanzl date_created: 2023-08-03T13:21:35Z date_updated: 2023-08-03T13:21:35Z file_id: '13692' file_name: Supplfig01_a_2.png file_size: 438843 relation: main_file success: 1 - access_level: open_access checksum: 92ccc934c4603b29f4f7a96573e49c83 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:21:35Z date_updated: 2023-08-03T13:21:35Z file_id: '13693' file_name: Supplfig01_a_3.png file_size: 426713 relation: main_file success: 1 - access_level: open_access checksum: e71faa54934bee8ac3e66ce692f542ab content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:21:35Z date_updated: 2023-08-03T13:21:35Z file_id: '13694' file_name: Supplfig01_a_4.tif file_size: 723221 relation: main_file success: 1 - access_level: open_access checksum: 95dc33563f48b650e5ac020bdfd10c48 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:21:35Z date_updated: 2023-08-03T13:21:35Z file_id: '13695' file_name: Supplfig01_a_5.tif file_size: 723235 relation: main_file success: 1 - access_level: open_access checksum: c62df0a9faf1c47af121d77eb1582edd content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:21:35Z date_updated: 2023-08-03T13:21:35Z file_id: '13696' file_name: Supplfig01_b_1.tif file_size: 1442129 relation: main_file success: 1 - access_level: open_access checksum: 8ae157c5a4a543da1193cb8ca12b1919 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:21:35Z date_updated: 2023-08-03T13:21:35Z file_id: '13697' file_name: Supplfig01_b_2.tif file_size: 725407 relation: main_file success: 1 - access_level: open_access checksum: 388370d954ce842781c0d62edfb448a7 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:21:35Z date_updated: 2023-08-03T13:21:35Z file_id: '13698' file_name: Supplfig01_c_1.tif file_size: 721641 relation: main_file success: 1 - access_level: open_access checksum: 6cae58ba3c98bc8253e1c769e93657a7 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:21:35Z date_updated: 2023-08-03T13:21:35Z file_id: '13699' file_name: Supplfig01_c_2.tif file_size: 6003079 relation: main_file success: 1 - access_level: open_access checksum: 85cf013232c72895aefc07f5411a765a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:21:35Z date_updated: 2023-08-03T13:21:35Z file_id: '13700' file_name: Supplfig01_c_3.tif file_size: 2003311 relation: main_file success: 1 - access_level: open_access checksum: dfb33b91066e3f34d3803f59a4105aba content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:21:35Z date_updated: 2023-08-03T13:21:35Z file_id: '13701' file_name: Supplfig01_c_4.tif file_size: 723271 relation: main_file success: 1 - access_level: open_access checksum: 8b899826fe48d7e7536b0b02a2645e87 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:21:35Z date_updated: 2023-08-03T13:21:35Z file_id: '13702' file_name: Supplfig01_d_1.tif file_size: 721901 relation: main_file success: 1 - access_level: open_access checksum: 67529fa6e0f12c272275e823f6045f6d content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:21:35Z date_updated: 2023-08-03T13:21:35Z file_id: '13703' file_name: Supplfig01_d_2.tif file_size: 721901 relation: main_file success: 1 - access_level: open_access checksum: 111a9231f63c775340d3356109715cb0 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:21:35Z date_updated: 2023-08-03T13:21:35Z file_id: '13704' file_name: Supplfig01_e_1.tif file_size: 723223 relation: main_file success: 1 - access_level: open_access checksum: 7685bf02408dcb095a00854ff22763ed content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:21:35Z date_updated: 2023-08-03T13:21:35Z file_id: '13705' file_name: Supplfig01_e_2.tif file_size: 723223 relation: main_file success: 1 - access_level: open_access checksum: 455f5cb9aa8a87b91586a27aca122610 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:26:00Z date_updated: 2023-08-03T13:26:00Z file_id: '13706' file_name: Supplfig02_b_01.tif file_size: 34821298 relation: main_file success: 1 - access_level: open_access checksum: 311545b39aaa2c72755fd8ae190803a5 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:26:00Z date_updated: 2023-08-03T13:26:00Z file_id: '13707' file_name: Supplfig02_b_02.tif file_size: 32131123 relation: main_file success: 1 - access_level: open_access checksum: 682deb61f57d9ca54716160ddd52a6cf content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:26:01Z date_updated: 2023-08-03T13:26:01Z file_id: '13708' file_name: Supplfig02_b_03.tif file_size: 36872674 relation: main_file success: 1 - access_level: open_access checksum: 4f9579c91b2a3f36ff6e66b592907973 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:26:01Z date_updated: 2023-08-03T13:26:01Z file_id: '13709' file_name: Supplfig02_b_04.tif file_size: 39964115 relation: main_file success: 1 - access_level: open_access checksum: 7ae7053673b53dbed59ffb92618f969a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:26:02Z date_updated: 2023-08-03T13:26:02Z file_id: '13710' file_name: Supplfig02_b_05.tif file_size: 43053091 relation: main_file success: 1 - access_level: open_access checksum: 827b26d3d2b6ddc9bced9d6113023ced content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:26:02Z date_updated: 2023-08-03T13:26:02Z file_id: '13711' file_name: Supplfig02_b_06.tif file_size: 46998147 relation: main_file success: 1 - access_level: open_access checksum: bc2e7e8badb42f8e1facc8b7bc96fdda content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:26:03Z date_updated: 2023-08-03T13:26:03Z file_id: '13712' file_name: Supplfig02_b_07.tif file_size: 45179219 relation: main_file success: 1 - access_level: open_access checksum: c2b78aa0f433928afa10a743c5fb73b8 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:26:03Z date_updated: 2023-08-03T13:26:03Z file_id: '13713' file_name: Supplfig02_b_08.tif file_size: 46978802 relation: main_file success: 1 - access_level: open_access checksum: 9cd1ab61cced2c0981e813aeae930855 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:26:04Z date_updated: 2023-08-03T13:26:04Z file_id: '13714' file_name: Supplfig02_b_09.tif file_size: 48840915 relation: main_file success: 1 - access_level: open_access checksum: 3086126338aee6ec4ebc1d3350551197 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:26:04Z date_updated: 2023-08-03T13:26:04Z file_id: '13715' file_name: Supplfig02_b_10.tif file_size: 45907059 relation: main_file success: 1 - access_level: open_access checksum: 69f52c2b3bb5b5f9fef057860b3386fa content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:26:05Z date_updated: 2023-08-03T13:26:05Z file_id: '13716' file_name: Supplfig02_b_11.tif file_size: 32231538 relation: main_file success: 1 - access_level: open_access checksum: defdbeab1e672456bfeafdd1983e779e content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:26:05Z date_updated: 2023-08-03T13:26:05Z file_id: '13717' file_name: Supplfig02_b_12.tif file_size: 35264963 relation: main_file success: 1 - access_level: open_access checksum: 02c566f781b9ad44f04ce0088a1fa27a content_type: image/png creator: jdanzl date_created: 2023-08-03T13:28:40Z date_updated: 2023-08-03T13:28:40Z file_id: '13718' file_name: Supplfig03_a_std_xy.png file_size: 63326 relation: main_file success: 1 - access_level: open_access checksum: c6c3630ee9a6ed5d207cb68e330da566 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:28:40Z date_updated: 2023-08-03T13:28:40Z file_id: '13719' file_name: Supplfig03_a_std_xz.png file_size: 50211 relation: main_file success: 1 - access_level: open_access checksum: 0dcd4d19e83a7ff259d6aa04d746cd90 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:28:41Z date_updated: 2023-08-03T13:28:41Z file_id: '13720' file_name: Supplfig03_b_std_xy.png file_size: 52629 relation: main_file success: 1 - access_level: open_access checksum: 4785de4a6dcb23b25a06b0da29df5bb5 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:28:41Z date_updated: 2023-08-03T13:28:41Z file_id: '13721' file_name: Supplfig03_b_std_xz.png file_size: 72245 relation: main_file success: 1 - access_level: open_access checksum: 19d0f198bd8a25073e45e7950d7a78c2 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:28:45Z date_updated: 2023-08-03T13:28:45Z file_id: '13722' file_name: Supplfig03_model1.tif file_size: 98570368 relation: main_file success: 1 - access_level: open_access checksum: 51ff687df4a0867f39b69c2c7a4ee3ca content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:28:45Z date_updated: 2023-08-03T13:28:45Z file_id: '13723' file_name: Supplfig03_model2.tif file_size: 98570367 relation: main_file success: 1 - access_level: open_access checksum: ec9d9a041ca85fe632c612baf981fcc5 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:28:49Z date_updated: 2023-08-03T13:28:49Z file_id: '13724' file_name: Supplfig03_model3.tif file_size: 98570365 relation: main_file success: 1 - access_level: open_access checksum: a988b15a9529094f1b5519a72871e98e content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:28:49Z date_updated: 2023-08-03T13:28:49Z file_id: '13725' file_name: Supplfig03_model4.tif file_size: 98570365 relation: main_file success: 1 - access_level: open_access checksum: 4a4fe88fcfd87fcfe118a5a73d81d6b0 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:28:52Z date_updated: 2023-08-03T13:28:52Z file_id: '13726' file_name: Supplfig03_model5.tif file_size: 98570369 relation: main_file success: 1 - access_level: open_access checksum: ce9b774ff5163ebfa4e3fb162f4cfffe content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:34:27Z date_updated: 2023-08-03T13:34:27Z file_id: '13727' file_name: Supplfig04_a_n2v.tif file_size: 1036927887 relation: main_file success: 1 - access_level: open_access checksum: 21f1bb8d2a00c88bdd6febe6285acc2a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:34:13Z date_updated: 2023-08-03T13:34:13Z file_id: '13728' file_name: Supplfig04_a.tif file_size: 518519275 relation: main_file success: 1 - access_level: open_access checksum: 503820214ab994c01b18a241f3b62434 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:34:22Z date_updated: 2023-08-03T13:34:22Z file_id: '13729' file_name: Supplfig04_b.tif file_size: 158440069 relation: main_file success: 1 - access_level: open_access checksum: e0469102a87332b46904b4ba35b8fb2f content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:34:37Z date_updated: 2023-08-03T13:34:37Z file_id: '13730' file_name: Supplfig04_c_n2v.tif file_size: 309407894 relation: main_file success: 1 - access_level: open_access checksum: c30a0d18c43045a8fbc5501a37061bd2 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:34:38Z date_updated: 2023-08-03T13:34:38Z file_id: '13731' file_name: Supplfig04_c.tif file_size: 154728887 relation: main_file success: 1 - access_level: open_access checksum: 69c706710d642b30cda6951494702139 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:34:43Z date_updated: 2023-08-03T13:34:43Z file_id: '13732' file_name: Supplfig04_d_n2v.tif file_size: 106696749 relation: main_file success: 1 - access_level: open_access checksum: 7dbd2e881ebf049352913188fa10224a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:34:41Z date_updated: 2023-08-03T13:34:41Z file_id: '13733' file_name: Supplfig04_d.tif file_size: 53367343 relation: main_file success: 1 - access_level: open_access checksum: fd0d1ec674dabbb499fab383b7eb4d58 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:34:46Z date_updated: 2023-08-03T13:34:46Z file_id: '13734' file_name: Supplfig04_e_n2v.tiff file_size: 127917734 relation: main_file success: 1 - access_level: open_access checksum: 86de309d9cd434afbe371da283d8adb6 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:34:46Z date_updated: 2023-08-03T13:34:46Z file_id: '13735' file_name: Supplfig04_e.tif file_size: 63974204 relation: main_file success: 1 - access_level: open_access checksum: ada99b2b5900cb198d1de3cc9e37ebd1 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:37Z date_updated: 2023-08-03T13:35:37Z file_id: '13736' file_name: Supplfig05_a_xy_1.png file_size: 8403 relation: main_file success: 1 - access_level: open_access checksum: f2e382925a972b98560614016ae3bc55 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:37Z date_updated: 2023-08-03T13:35:37Z file_id: '13737' file_name: Supplfig05_a_xy_2.png file_size: 10087 relation: main_file success: 1 - access_level: open_access checksum: ef22b640f33d677add1a7b5153f95420 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:37Z date_updated: 2023-08-03T13:35:37Z file_id: '13738' file_name: Supplfig05_a_xy_3.png file_size: 24561 relation: main_file success: 1 - access_level: open_access checksum: b854cc4a5224b8a6f5d59c74f5740ccd content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:37Z date_updated: 2023-08-03T13:35:37Z file_id: '13739' file_name: Supplfig05_a_xy_4.png file_size: 8353 relation: main_file success: 1 - access_level: open_access checksum: 446b0362c5ea6e2a5f0e1f8359422358 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:37Z date_updated: 2023-08-03T13:35:37Z file_id: '13740' file_name: Supplfig05_a_xy_5.png file_size: 8337 relation: main_file success: 1 - access_level: open_access checksum: 5585f7b62fa09ed5a63090b679383601 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:37Z date_updated: 2023-08-03T13:35:37Z file_id: '13741' file_name: Supplfig05_a_xz_1.png file_size: 7399 relation: main_file success: 1 - access_level: open_access checksum: 190d88bcacbd11d41f4a0e2bbd140862 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:37Z date_updated: 2023-08-03T13:35:37Z file_id: '13742' file_name: Supplfig05_a_xz_2.png file_size: 10887 relation: main_file success: 1 - access_level: open_access checksum: 0c89010651862f21032a303e159b7a1c content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:37Z date_updated: 2023-08-03T13:35:37Z file_id: '13743' file_name: Supplfig05_a_xz_3.png file_size: 21654 relation: main_file success: 1 - access_level: open_access checksum: 94e61e553aa2280721acce7d407ff24a content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:37Z date_updated: 2023-08-03T13:35:37Z file_id: '13744' file_name: Supplfig05_a_xz_4.png file_size: 7248 relation: main_file success: 1 - access_level: open_access checksum: ef9157274686ff5d7056f5a519d413dd content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:37Z date_updated: 2023-08-03T13:35:37Z file_id: '13745' file_name: Supplfig05_a_xz_5.png file_size: 7214 relation: main_file success: 1 - access_level: open_access checksum: 4b389473cbf769e6e34670dae2224af1 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:37Z date_updated: 2023-08-03T13:35:37Z file_id: '13746' file_name: Supplfig05_b_xy_1.png file_size: 8544 relation: main_file success: 1 - access_level: open_access checksum: b05aa1e201758a5d55e35d719452fafc content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:37Z date_updated: 2023-08-03T13:35:37Z file_id: '13747' file_name: Supplfig05_b_xy_2.png file_size: 11135 relation: main_file success: 1 - access_level: open_access checksum: 890f3516930251a367066c049141d6bb content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:37Z date_updated: 2023-08-03T13:35:37Z file_id: '13748' file_name: Supplfig05_b_xy_3.png file_size: 26762 relation: main_file success: 1 - access_level: open_access checksum: 36345c1d582758ff463072fd04578c0c content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:37Z date_updated: 2023-08-03T13:35:37Z file_id: '13749' file_name: Supplfig05_b_xy_4.png file_size: 8438 relation: main_file success: 1 - access_level: open_access checksum: c9499ad8914c405a07fc4469b19e8987 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:37Z date_updated: 2023-08-03T13:35:37Z file_id: '13750' file_name: Supplfig05_b_xy_5.png file_size: 8434 relation: main_file success: 1 - access_level: open_access checksum: 7e7a7c900ce1fc3187ab648f207f9425 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:37Z date_updated: 2023-08-03T13:35:37Z file_id: '13751' file_name: Supplfig05_b_xz_1.png file_size: 8269 relation: main_file success: 1 - access_level: open_access checksum: b645d1e2422ef3f05344ccd3f955468d content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:37Z date_updated: 2023-08-03T13:35:37Z file_id: '13752' file_name: Supplfig05_b_xz_2.png file_size: 12762 relation: main_file success: 1 - access_level: open_access checksum: ef0b83b49cf47ca7d8ffe3bdc609fe38 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:37Z date_updated: 2023-08-03T13:35:37Z file_id: '13753' file_name: Supplfig05_b_xz_3.png file_size: 24819 relation: main_file success: 1 - access_level: open_access checksum: 68719d4d464a2ffc198cb6ad070c4579 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:37Z date_updated: 2023-08-03T13:35:37Z file_id: '13754' file_name: Supplfig05_b_xz_4.png file_size: 8126 relation: main_file success: 1 - access_level: open_access checksum: 18370f47177ef37a477c6fd7bda3fea0 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:38Z date_updated: 2023-08-03T13:35:38Z file_id: '13755' file_name: Supplfig05_b_xz_5.png file_size: 8114 relation: main_file success: 1 - access_level: open_access checksum: 013d4bd9704ace490810b9ef21b12454 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:38Z date_updated: 2023-08-03T13:35:38Z file_id: '13756' file_name: Supplfig05_c_xy_1.png file_size: 8273 relation: main_file success: 1 - access_level: open_access checksum: bb431f827386e79c54452d6284f501b9 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:38Z date_updated: 2023-08-03T13:35:38Z file_id: '13757' file_name: Supplfig05_c_xy_2.png file_size: 12639 relation: main_file success: 1 - access_level: open_access checksum: 4cd54f58c5afff88832a508655f913bb content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:38Z date_updated: 2023-08-03T13:35:38Z file_id: '13758' file_name: Supplfig05_c_xy_3.png file_size: 25288 relation: main_file success: 1 - access_level: open_access checksum: 07f86f98f6a65eac8608cec8c567309e content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:38Z date_updated: 2023-08-03T13:35:38Z file_id: '13759' file_name: Supplfig05_c_xz_1.png file_size: 6786 relation: main_file success: 1 - access_level: open_access checksum: 492f699b71761214272b17432e3a54fa content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:38Z date_updated: 2023-08-03T13:35:38Z file_id: '13760' file_name: Supplfig05_c_xz_2.png file_size: 9781 relation: main_file success: 1 - access_level: open_access checksum: af617da5638db849bea6ff51a08227c6 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:38Z date_updated: 2023-08-03T13:35:38Z file_id: '13761' file_name: Supplfig05_c_xz_3.png file_size: 20728 relation: main_file success: 1 - access_level: open_access checksum: 5e5d5694af4a22297046d697a01fa4d6 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:38Z date_updated: 2023-08-03T13:35:38Z file_id: '13762' file_name: Supplfig05_d_xy_1.png file_size: 8428 relation: main_file success: 1 - access_level: open_access checksum: 38bf7b75f3dedd0a3722faae05aa0233 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:38Z date_updated: 2023-08-03T13:35:38Z file_id: '13763' file_name: Supplfig05_d_xy_2.png file_size: 10813 relation: main_file success: 1 - access_level: open_access checksum: e4ea966553f158ec2cfbdc696780390e content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:38Z date_updated: 2023-08-03T13:35:38Z file_id: '13764' file_name: Supplfig05_d_xy_3.png file_size: 26552 relation: main_file success: 1 - access_level: open_access checksum: 356f424d9f5f608e9aea962bb63672f1 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:38Z date_updated: 2023-08-03T13:35:38Z file_id: '13765' file_name: Supplfig05_d_xz_1.png file_size: 7876 relation: main_file success: 1 - access_level: open_access checksum: 05068476beee0f394e28b98209686394 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:38Z date_updated: 2023-08-03T13:35:38Z file_id: '13766' file_name: Supplfig05_d_xz_2.png file_size: 11634 relation: main_file success: 1 - access_level: open_access checksum: 78b3a0d93df22383a384a2f3acc80401 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:38Z date_updated: 2023-08-03T13:35:38Z file_id: '13767' file_name: Supplfig05_d_xz_3.png file_size: 25006 relation: main_file success: 1 - access_level: open_access checksum: f5ee6a817f11a42c9db82ad6325f58b9 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:38Z date_updated: 2023-08-03T13:35:38Z file_id: '13768' file_name: Supplfig05_e_xy_1.png file_size: 7895 relation: main_file success: 1 - access_level: open_access checksum: 019ca89e892d6e19589609bc99eab331 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:38Z date_updated: 2023-08-03T13:35:38Z file_id: '13769' file_name: Supplfig05_e_xy_2.png file_size: 6180 relation: main_file success: 1 - access_level: open_access checksum: 0e1a5cbbd70dc245edaecaca70d974cb content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:38Z date_updated: 2023-08-03T13:35:38Z file_id: '13770' file_name: Supplfig05_e_xy_3.png file_size: 18326 relation: main_file success: 1 - access_level: open_access checksum: 4d4d64a5bb7b096aaf8130ece4512bc2 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:38Z date_updated: 2023-08-03T13:35:38Z file_id: '13771' file_name: Supplfig05_e_xz_1.png file_size: 6295 relation: main_file success: 1 - access_level: open_access checksum: 607302aec5ec2a14a271dbffd3465261 content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:38Z date_updated: 2023-08-03T13:35:38Z file_id: '13772' file_name: Supplfig05_e_xz_2.png file_size: 4335 relation: main_file success: 1 - access_level: open_access checksum: a673e17ead1fd2e776b9a5f560a289ab content_type: image/png creator: jdanzl date_created: 2023-08-03T13:35:38Z date_updated: 2023-08-03T13:35:38Z file_id: '13773' file_name: Supplfig05_e_xz_3.png file_size: 23243 relation: main_file success: 1 - access_level: open_access checksum: 4349e511fc86a8bddb790a7be7175c75 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:46:13Z date_updated: 2023-08-03T13:46:13Z file_id: '13774' file_name: Supplfig06_a_1.tif file_size: 4002153 relation: main_file success: 1 - access_level: open_access checksum: cd12977e4c1a472d80193be01f69a895 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:46:13Z date_updated: 2023-08-03T13:46:13Z file_id: '13775' file_name: Supplfig06_a_2.tif file_size: 2252137 relation: main_file success: 1 - access_level: open_access checksum: 575e32b8c25ce658e20f0c86a5f1b9b7 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:46:13Z date_updated: 2023-08-03T13:46:13Z file_id: '13776' file_name: Supplfig06_a_3.tif file_size: 2252137 relation: main_file success: 1 - access_level: open_access checksum: b06f775e0210e7a16cb4b58aed32118c content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:46:13Z date_updated: 2023-08-03T13:46:13Z file_id: '13777' file_name: Supplfig06_a_i.tif file_size: 78329 relation: main_file success: 1 - access_level: open_access checksum: 56854c1a05c721c36877fe7c7454b7d7 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:46:13Z date_updated: 2023-08-03T13:46:13Z file_id: '13778' file_name: Supplfig06_a_ii.tif file_size: 78329 relation: main_file success: 1 - access_level: open_access checksum: 9aff42ea5138931fedb5a00643ae7a22 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:46:13Z date_updated: 2023-08-03T13:46:13Z file_id: '13779' file_name: Supplfig06_a_iii.tif file_size: 78329 relation: main_file success: 1 - access_level: open_access checksum: 9474b7d00d4dee46659afedef75dc095 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:46:13Z date_updated: 2023-08-03T13:46:13Z file_id: '13780' file_name: Supplfig06_d_1.tif file_size: 501149 relation: main_file success: 1 - access_level: open_access checksum: 53df41dd968b04b4657cd2b91870d636 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:46:13Z date_updated: 2023-08-03T13:46:13Z file_id: '13781' file_name: Supplfig06_d_2.tif file_size: 500153 relation: main_file success: 1 - access_level: open_access checksum: 1a39b8310598dd25d97f848b682b8de0 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:46:14Z date_updated: 2023-08-03T13:46:14Z file_id: '13782' file_name: Supplfig06_d_3.tif file_size: 500153 relation: main_file success: 1 - access_level: open_access checksum: 6d9b496be6aecedbb2cb4cbf68f02872 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:46:14Z date_updated: 2023-08-03T13:46:14Z file_id: '13783' file_name: Supplfig06_d_i.tif file_size: 78329 relation: main_file success: 1 - access_level: open_access checksum: bc034b1636c2db8b9d9e7bd131b9780a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:46:14Z date_updated: 2023-08-03T13:46:14Z file_id: '13784' file_name: Supplfig06_d_ii.tif file_size: 78329 relation: main_file success: 1 - access_level: open_access checksum: 54f6e55e30a2aeea6c82eb6dbd376240 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:46:14Z date_updated: 2023-08-03T13:46:14Z file_id: '13785' file_name: Supplfig06_d_iii.tif file_size: 78329 relation: main_file success: 1 - access_level: open_access checksum: 446da3cc16897277890f23f966c2bf52 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:46:14Z date_updated: 2023-08-03T13:46:14Z file_id: '13786' file_name: Supplfig06_g_1.tif file_size: 960011 relation: main_file success: 1 - access_level: open_access checksum: 71192d0ec592a33195f2386a5f95aa86 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:46:14Z date_updated: 2023-08-03T13:46:14Z file_id: '13787' file_name: Supplfig06_g_2.tif file_size: 960011 relation: main_file success: 1 - access_level: open_access checksum: 246782dbe8ff525aea360efc72e65f07 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:46:14Z date_updated: 2023-08-03T13:46:14Z file_id: '13788' file_name: Supplfig06_g_3.tif file_size: 960041 relation: main_file success: 1 - access_level: open_access checksum: d49b12fec5508aa8d72587757cccc0a4 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:46:14Z date_updated: 2023-08-03T13:46:14Z file_id: '13789' file_name: Supplfig06_g_4.tif file_size: 960041 relation: main_file success: 1 - access_level: open_access checksum: 27b11b1d4fc784a49ffd7660624d00b6 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:46:14Z date_updated: 2023-08-03T13:46:14Z file_id: '13790' file_name: Supplfig06_g_5.tif file_size: 963241 relation: main_file success: 1 - access_level: open_access checksum: 9ce944049c1b88fadbf43609385f9e2f content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:38Z date_updated: 2023-08-03T13:51:38Z file_id: '13791' file_name: Suppl08_a_1.tiff file_size: 19286002 relation: main_file success: 1 - access_level: open_access checksum: 06265515f06688843a415362f7b2c485 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:38Z date_updated: 2023-08-03T13:51:38Z file_id: '13792' file_name: Suppl08_a_2.tiff file_size: 19286002 relation: main_file success: 1 - access_level: open_access checksum: 50f0969c6c2c1209ff776bec4861030a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:38Z date_updated: 2023-08-03T13:51:38Z file_id: '13793' file_name: Suppl08_a_3.tif file_size: 617552 relation: main_file success: 1 - access_level: open_access checksum: b90965d20133fea73c99050c32eb7695 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:38Z date_updated: 2023-08-03T13:51:38Z file_id: '13794' file_name: Suppl08_a_4.tif file_size: 617552 relation: main_file success: 1 - access_level: open_access checksum: 568a1e0efaa62527b51e66a7aabfd05c content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:40Z date_updated: 2023-08-03T13:51:40Z file_id: '13795' file_name: Suppl08_a_coCATS_N2V.tif file_size: 19287339 relation: main_file success: 1 - access_level: open_access checksum: 06265515f06688843a415362f7b2c485 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:40Z date_updated: 2023-08-03T13:51:40Z file_id: '13796' file_name: Suppl08_c_1_4_predictedBASSOON.tiff file_size: 19286002 relation: main_file success: 1 - access_level: open_access checksum: 568a1e0efaa62527b51e66a7aabfd05c content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:43Z date_updated: 2023-08-03T13:51:43Z file_id: '13797' file_name: Suppl08_c_1_coCATS.tif file_size: 19287339 relation: main_file success: 1 - access_level: open_access checksum: feae08c38b1d9c540b697977cd7f2666 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T15:36:47Z date_updated: 2023-08-03T15:36:47Z file_id: '13798' file_name: Suppl08_c_2_coCATS.tif file_size: 19287340 relation: main_file success: 1 - access_level: open_access checksum: af2c1199fdcaecfec76189dae86cc12e content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:44Z date_updated: 2023-08-03T13:51:44Z file_id: '13799' file_name: Suppl08_c_2-3_predictedBASSOON.tiff file_size: 19286002 relation: main_file success: 1 - access_level: open_access checksum: 1f92db47605959d0db01f612f7c9c034 content_type: application/octet-stream creator: jdanzl date_created: 2023-08-03T13:51:43Z date_updated: 2023-08-03T13:51:43Z file_id: '13800' file_name: Suppl08_c_3-6_roi.roi file_size: 156 relation: main_file success: 1 - access_level: open_access checksum: 4fc4f8803adcfacd53a41b91f4699dc5 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:45Z date_updated: 2023-08-03T13:51:45Z file_id: '13801' file_name: Suppl08_e_1_3.tiff file_size: 19286002 relation: main_file success: 1 - access_level: open_access checksum: 459551aae114daa4f5ca5d06fcd6b203 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:45Z date_updated: 2023-08-03T13:51:45Z file_id: '13802' file_name: Suppl08_e_1-2.tiff file_size: 19286002 relation: main_file success: 1 - access_level: open_access checksum: 032cbace7ec436f7b62478c0ffd35e5e content_type: application/octet-stream creator: jdanzl date_created: 2023-08-03T13:51:45Z date_updated: 2023-08-03T13:51:45Z file_id: '13803' file_name: Suppl08_e_2-5_roi.roi file_size: 152 relation: main_file success: 1 - access_level: open_access checksum: 7379168be281ef618b8cecd8efd31ed5 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:46Z date_updated: 2023-08-03T13:51:46Z file_id: '13804' file_name: Suppl08_e_4-5_coCATS.tiff file_size: 19286002 relation: main_file success: 1 - access_level: open_access checksum: 5c4c092f608f4c10bb422c9e08b5955b content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:46Z date_updated: 2023-08-03T13:51:46Z file_id: '13805' file_name: Suppl08_e_4.tif file_size: 617552 relation: main_file success: 1 - access_level: open_access checksum: 903e31be124f6e4ec1c2e7ab7db80e6b content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:46Z date_updated: 2023-08-03T13:51:46Z file_id: '13806' file_name: Suppl08_e_5.tif file_size: 617552 relation: main_file success: 1 - access_level: open_access checksum: 173d956392d67b0a7e544629b51881e4 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:48Z date_updated: 2023-08-03T13:51:48Z file_id: '13807' file_name: Suppl08_e_6_8.tiff file_size: 19286002 relation: main_file success: 1 - access_level: open_access checksum: 2a4cea867a253a6af7e9b0d2e100de14 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:48Z date_updated: 2023-08-03T13:51:48Z file_id: '13808' file_name: Suppl08_e_6-7.tiff file_size: 19286002 relation: main_file success: 1 - access_level: open_access checksum: 6b40f99fddfa26f0a9713000769741b7 content_type: application/octet-stream creator: jdanzl date_created: 2023-08-03T13:51:48Z date_updated: 2023-08-03T13:51:48Z file_id: '13809' file_name: Suppl08_e_7-10_roi.roi file_size: 174 relation: main_file success: 1 - access_level: open_access checksum: 82f7013959df99c27366886de9b38ba2 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:49Z date_updated: 2023-08-03T13:51:49Z file_id: '13810' file_name: Suppl08_e_9-10_coCATS.tiff file_size: 19286002 relation: main_file success: 1 - access_level: open_access checksum: 50f0969c6c2c1209ff776bec4861030a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:48Z date_updated: 2023-08-03T13:51:48Z file_id: '13811' file_name: Suppl08_e_9.tif file_size: 617552 relation: main_file success: 1 - access_level: open_access checksum: 569f599d7f2be49d4dcf7cb385f428c4 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:49Z date_updated: 2023-08-03T13:51:49Z file_id: '13812' file_name: Suppl08_e_10.tif file_size: 617552 relation: main_file success: 1 - access_level: open_access checksum: 50f0969c6c2c1209ff776bec4861030a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:49Z date_updated: 2023-08-03T13:51:49Z file_id: '13813' file_name: Suppl08_g_1.tif file_size: 617552 relation: main_file success: 1 - access_level: open_access checksum: 62797fc860176197142a47e831eaf1f6 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:49Z date_updated: 2023-08-03T13:51:49Z file_id: '13814' file_name: Suppl08_g_2.tif file_size: 617552 relation: main_file success: 1 - access_level: open_access checksum: b90965d20133fea73c99050c32eb7695 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:49Z date_updated: 2023-08-03T13:51:49Z file_id: '13815' file_name: Suppl08_g_3.tif file_size: 617552 relation: main_file success: 1 - access_level: open_access checksum: a96dc9f38c6a1d3c959771a649a42748 content_type: application/octet-stream creator: jdanzl date_created: 2023-08-03T13:51:49Z date_updated: 2023-08-03T13:51:49Z file_id: '13816' file_name: Suppl08_i_add_roi.roi file_size: 160 relation: main_file success: 1 - access_level: open_access checksum: f2135207ebbc4bdc014763ba852a5cf0 content_type: application/octet-stream creator: jdanzl date_created: 2023-08-03T13:51:50Z date_updated: 2023-08-03T13:51:50Z file_id: '13817' file_name: Suppl08_i_shape_roi.roi file_size: 160 relation: main_file success: 1 - access_level: open_access checksum: f6f31fe2d87cf7208387f98ce1e37b04 content_type: application/octet-stream creator: jdanzl date_created: 2023-08-03T13:51:50Z date_updated: 2023-08-03T13:51:50Z file_id: '13818' file_name: Suppl08_i_split_roi.roi file_size: 158 relation: main_file success: 1 - access_level: open_access checksum: 71590db0ad391e0c5baf03024981b1d9 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:51Z date_updated: 2023-08-03T13:51:51Z file_id: '13819' file_name: Suppl08_i_1.tiff file_size: 19286002 relation: main_file success: 1 - access_level: open_access checksum: 9ce944049c1b88fadbf43609385f9e2f content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:51Z date_updated: 2023-08-03T13:51:51Z file_id: '13820' file_name: Suppl08_i_2.tiff file_size: 19286002 relation: main_file success: 1 - access_level: open_access checksum: 06265515f06688843a415362f7b2c485 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:52Z date_updated: 2023-08-03T13:51:52Z file_id: '13821' file_name: Suppl08_i_3.tiff file_size: 19286002 relation: main_file success: 1 - access_level: open_access checksum: 16c628c160fb81e40df0ad1eb134e92b content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:52Z date_updated: 2023-08-03T13:51:52Z file_id: '13822' file_name: Suppl08_i_4.tif file_size: 19284766 relation: main_file success: 1 - access_level: open_access checksum: b06e62c3a9834a40002d7aad3eaacc3f content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:53Z date_updated: 2023-08-03T13:51:53Z file_id: '13823' file_name: Suppl08_i_5.tif file_size: 9649818 relation: main_file success: 1 - access_level: open_access checksum: 41ef98c7f01755b43cf6e77fff287732 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:51:53Z date_updated: 2023-08-03T13:51:53Z file_id: '13824' file_name: Suppl08_i_6.tif file_size: 19284766 relation: main_file success: 1 - access_level: open_access checksum: feae08c38b1d9c540b697977cd7f2666 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:53:29Z date_updated: 2023-08-03T13:53:29Z file_id: '13825' file_name: Suppl08_c_2_coCATS.tif file_size: 19287340 relation: main_file success: 1 - access_level: open_access checksum: c01509a1c657fbbbfdbbd484c298b6e3 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:58:08Z date_updated: 2023-08-03T13:58:08Z file_id: '13826' file_name: Supplfig09_b_1_n2v.tiff file_size: 179788642 relation: main_file success: 1 - access_level: open_access checksum: 64a7f270274ff3480b18d690087016e2 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:58:20Z date_updated: 2023-08-03T13:58:20Z file_id: '13827' file_name: Supplfig09_b_2_n2v.tif file_size: 742420240 relation: main_file success: 1 - access_level: open_access checksum: b34a6beaaf13698f421df961e009efeb content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:58:20Z date_updated: 2023-08-03T13:58:20Z file_id: '13828' file_name: Supplfig09_b_3_n2v.tif file_size: 478900363 relation: main_file success: 1 - access_level: open_access checksum: ec04501f234b5e4fd91f9eac0e585395 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:58:25Z date_updated: 2023-08-03T13:58:25Z file_id: '13829' file_name: Supplfig09_b_4_n2v.tif file_size: 191873159 relation: main_file success: 1 - access_level: open_access checksum: 3a1b313298da35c97550abf0d245b4a7 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:59:27Z date_updated: 2023-08-03T13:59:27Z file_id: '13830' file_name: Supplfig11_i.tif file_size: 55286 relation: main_file success: 1 - access_level: open_access checksum: 9cf00c0252f0a2efe1994c83c224389a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:59:27Z date_updated: 2023-08-03T13:59:27Z file_id: '13831' file_name: Supplfig11_ii.tif file_size: 55286 relation: main_file success: 1 - access_level: open_access checksum: 9a6e83acdf6d70bb9a6e76fa7d41a372 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:59:27Z date_updated: 2023-08-03T13:59:27Z file_id: '13832' file_name: Supplfig11_iii.tif file_size: 55257 relation: main_file success: 1 - access_level: open_access checksum: 709fdd13b7e090846a4d8edd2425f675 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T13:59:32Z date_updated: 2023-08-03T13:59:32Z file_id: '13833' file_name: Supplfig11_n2v+prediction.tif file_size: 309457551 relation: main_file success: 1 - access_level: open_access checksum: e60ea3e6bb1bf380460d0d8ccdbd1f07 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:14:32Z date_updated: 2023-08-03T14:14:32Z file_id: '13834' file_name: Supplfig12_a_01_n2v.tif file_size: 119323629 relation: main_file success: 1 - access_level: open_access checksum: 2a4e1771e2f06383894361ba2a8155b4 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:14:29Z date_updated: 2023-08-03T14:14:29Z file_id: '13835' file_name: Supplfig12_a_01.tif file_size: 59680727 relation: main_file success: 1 - access_level: open_access checksum: 993c434069b9d1bcb09bfe70628f5bbe content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:14:34Z date_updated: 2023-08-03T14:14:34Z file_id: '13836' file_name: Supplfig12_a_02_n2v.tif file_size: 106696749 relation: main_file success: 1 - access_level: open_access checksum: e3b6410d68e42004ef3857967707aeb3 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:14:34Z date_updated: 2023-08-03T14:14:34Z file_id: '13837' file_name: Supplfig12_a_02.tif file_size: 53367287 relation: main_file success: 1 - access_level: open_access checksum: 0156e99806fe1539d5f48ea16c78e8c8 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:14:41Z date_updated: 2023-08-03T14:14:41Z file_id: '13838' file_name: Supplfig12_a_03_n2v.tif file_size: 149937979 relation: main_file success: 1 - access_level: open_access checksum: 6cc1533a221526a072a0b09fb44bcf50 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:14:39Z date_updated: 2023-08-03T14:14:39Z file_id: '13839' file_name: Supplfig12_a_03.tif file_size: 74987927 relation: main_file success: 1 - access_level: open_access checksum: f134834bd0d5e8c22e5a35aadf592007 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:14:53Z date_updated: 2023-08-03T14:14:53Z file_id: '13840' file_name: Supplfig12_a_04_n2v.tif file_size: 305581862 relation: main_file success: 1 - access_level: open_access checksum: 212ec76c02552fa1eef91e7bca9f07f7 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:14:50Z date_updated: 2023-08-03T14:14:50Z file_id: '13841' file_name: Supplfig12_a_04.tif file_size: 152821840 relation: main_file success: 1 - access_level: open_access checksum: 7d99807d5b4313b04b4b5e0fbc08ba78 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:14:52Z date_updated: 2023-08-03T14:14:52Z file_id: '13842' file_name: Supplfig12_a_05_n2v.tif file_size: 48082029 relation: main_file success: 1 - access_level: open_access checksum: a6d4024a8c6fa073a532cc0c78323df7 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:14:53Z date_updated: 2023-08-03T14:14:53Z file_id: '13843' file_name: Supplfig12_a_05.tif file_size: 24059983 relation: main_file success: 1 - access_level: open_access checksum: 1c42ad5423636478fe57495a3b506746 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:15:09Z date_updated: 2023-08-03T14:15:09Z file_id: '13844' file_name: Supplfig12_a_06_n2v.tif file_size: 305581860 relation: main_file success: 1 - access_level: open_access checksum: 821f1d31c6dbe68eb2513fb7520b5272 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:15:04Z date_updated: 2023-08-03T14:15:04Z file_id: '13845' file_name: Supplfig12_a_06.tif file_size: 152821840 relation: main_file success: 1 - access_level: open_access checksum: 86a4dc1e4948c4bc9c71e6d55b4fd104 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:15:08Z date_updated: 2023-08-03T14:15:08Z file_id: '13846' file_name: Supplfig12_a_07_n2v.tif file_size: 66855793 relation: main_file success: 1 - access_level: open_access checksum: fd5d45b1135800124fec635c4667dafe content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:15:09Z date_updated: 2023-08-03T14:15:09Z file_id: '13847' file_name: Supplfig12_a_07.tif file_size: 33446807 relation: main_file success: 1 - access_level: open_access checksum: 5683760cc119a09f0b7de8fea98cda9c content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:15:19Z date_updated: 2023-08-03T14:15:19Z file_id: '13848' file_name: Supplfig12_a_08_n2v.tif file_size: 231476260 relation: main_file success: 1 - access_level: open_access checksum: 0c336d554bcd8524f11bd25c2188b56f content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:15:15Z date_updated: 2023-08-03T14:15:15Z file_id: '13849' file_name: Supplfig12_a_08.tif file_size: 115769040 relation: main_file success: 1 - access_level: open_access checksum: fcaea6c95c363bd864a524fca8ed8e9b content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:15:31Z date_updated: 2023-08-03T14:15:31Z file_id: '13850' file_name: Supplfig12_a_09_n2v.tif file_size: 305581869 relation: main_file success: 1 - access_level: open_access checksum: f401f1875f072c345d106a1e419f9d13 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:15:28Z date_updated: 2023-08-03T14:15:28Z file_id: '13851' file_name: Supplfig12_a_09.tif file_size: 152821840 relation: main_file success: 1 - access_level: open_access checksum: 7ad7d5b1ac81da1ec3d5003d00ee870a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:15:42Z date_updated: 2023-08-03T14:15:42Z file_id: '13852' file_name: Supplfig12_a_10_n2v.tif file_size: 266386255 relation: main_file success: 1 - access_level: open_access checksum: 77b93d082debd5248348c0a1e886eab9 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:15:40Z date_updated: 2023-08-03T14:15:40Z file_id: '13853' file_name: Supplfig12_a_10.tif file_size: 133239040 relation: main_file success: 1 - access_level: open_access checksum: 5ece1d503f05133d07d5b867f666d7a8 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:15:49Z date_updated: 2023-08-03T14:15:49Z file_id: '13854' file_name: Supplfig12_a_11_n2v.tif file_size: 191866269 relation: main_file success: 1 - access_level: open_access checksum: a72ee7ab433097752ff00a63421d4b61 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:15:48Z date_updated: 2023-08-03T14:15:48Z file_id: '13855' file_name: Supplfig12_a_11.tif file_size: 95955040 relation: main_file success: 1 - access_level: open_access checksum: c9c6e4692e0e7f305a43058b201b50d3 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:16:49Z date_updated: 2023-08-03T14:16:49Z file_id: '13856' file_name: Supplfig13_i.tif file_size: 55281 relation: main_file success: 1 - access_level: open_access checksum: 345d11dbd70123d9d2723b547cbfc4fc content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:16:49Z date_updated: 2023-08-03T14:16:49Z file_id: '13857' file_name: Supplfig13_ii.tif file_size: 55193 relation: main_file success: 1 - access_level: open_access checksum: b4c74c08077cfd3e11bfd6ea9ee1c5b2 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:16:49Z date_updated: 2023-08-03T14:16:49Z file_id: '13858' file_name: Supplfig13_n2v+predict.tif file_size: 539037 relation: main_file success: 1 - access_level: open_access checksum: 15f5b44257d075f9e45811304dfd5f85 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:18:10Z date_updated: 2023-08-03T14:18:10Z file_id: '13859' file_name: Supplfig14_a_n2v.tif file_size: 854898609 relation: main_file success: 1 - access_level: open_access checksum: a9ca03e3e5696988d06fc6ab1c103440 content_type: image/png creator: jdanzl date_created: 2023-08-03T14:19:58Z date_updated: 2023-08-03T14:19:58Z file_id: '13860' file_name: Supplfig15_a_1.png file_size: 7514502 relation: main_file success: 1 - access_level: open_access checksum: 4be3451e203a0fc5d9eb14279ff68a7a content_type: image/png creator: jdanzl date_created: 2023-08-03T14:19:58Z date_updated: 2023-08-03T14:19:58Z file_id: '13861' file_name: Supplfig15_a_2.png file_size: 1784041 relation: main_file success: 1 - access_level: open_access checksum: 43068c31eecddb798dbf2f51bda9b6c9 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:19:58Z date_updated: 2023-08-03T14:19:58Z file_id: '13862' file_name: Supplfig15_b_1.tif file_size: 6030878 relation: main_file success: 1 - access_level: open_access checksum: ded4c0797f1a9152dc3128f1bb8c32a5 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:19:58Z date_updated: 2023-08-03T14:19:58Z file_id: '13863' file_name: Supplfig15_b_2.tif file_size: 723293 relation: main_file success: 1 - access_level: open_access checksum: 705394732d94bd8463479aee83c2d36e content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:19:58Z date_updated: 2023-08-03T14:19:58Z file_id: '13864' file_name: Supplfig15_c_i.tif file_size: 723409 relation: main_file success: 1 - access_level: open_access checksum: e08efe220bec6a93d583cab17754dd19 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:19:58Z date_updated: 2023-08-03T14:19:58Z file_id: '13865' file_name: Supplfig15_c_ii.tif file_size: 723409 relation: main_file success: 1 - access_level: open_access checksum: 0e08e5d965815240b0a8195e0f899aab content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:19:59Z date_updated: 2023-08-03T14:19:59Z file_id: '13866' file_name: Supplfig15_c.tif file_size: 31572914 relation: main_file success: 1 - access_level: open_access checksum: 594696a77d4a9be512046be5e2d602f0 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:19:59Z date_updated: 2023-08-03T14:19:59Z file_id: '13867' file_name: Supplfig15_d_1.tif file_size: 6030752 relation: main_file success: 1 - access_level: open_access checksum: ffe6733eb77858008c4ca07b5f8c432b content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:19:59Z date_updated: 2023-08-03T14:19:59Z file_id: '13868' file_name: Supplfig15_d_2.tif file_size: 8005495 relation: main_file success: 1 - access_level: open_access checksum: 663bf013cf1e5019e1e7ddd2d12fa492 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:20:56Z date_updated: 2023-08-03T14:20:56Z file_id: '13869' file_name: Supplfig16_a.tif file_size: 11117709 relation: main_file success: 1 - access_level: open_access checksum: 80aee233dc2a1f26ed8cc323270cf3a9 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:20:56Z date_updated: 2023-08-03T14:20:56Z file_id: '13870' file_name: Supplfig16_b.tif file_size: 113709 relation: main_file success: 1 - access_level: open_access checksum: 3b408e9345df2f16a942ad4ea61739b7 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:20:56Z date_updated: 2023-08-03T14:20:56Z file_id: '13871' file_name: Supplfig16_c.tif file_size: 113709 relation: main_file success: 1 - access_level: open_access checksum: fbf688ef1f907149f92e9e936d02df72 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:25:47Z date_updated: 2023-08-03T14:25:47Z file_id: '13872' file_name: Supplfig17_a_1.tif file_size: 6003131 relation: main_file success: 1 - access_level: open_access checksum: 9a56470f251f14b43903036fab338f76 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:25:47Z date_updated: 2023-08-03T14:25:47Z file_id: '13873' file_name: Supplfig17_a_2.tif file_size: 8004085 relation: main_file success: 1 - access_level: open_access checksum: 4578c020ba5d0a6ffe2a8a1c22e52c75 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:25:47Z date_updated: 2023-08-03T14:25:47Z file_id: '13874' file_name: Supplfig17_a_3.tif file_size: 6003123 relation: main_file success: 1 - access_level: open_access checksum: a681d32f515da3bff8e803946f1d8b50 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:25:47Z date_updated: 2023-08-03T14:25:47Z file_id: '13875' file_name: Supplfig17_a_4.tif file_size: 6003131 relation: main_file success: 1 - access_level: open_access checksum: b89d366c39e25d17dc5d8ceee9145c8b content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:25:47Z date_updated: 2023-08-03T14:25:47Z file_id: '13876' file_name: Supplfig17_a_5.tif file_size: 6003131 relation: main_file success: 1 - access_level: open_access checksum: 0b9d60f0aba79525a97c122d972f0b22 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:25:47Z date_updated: 2023-08-03T14:25:47Z file_id: '13877' file_name: Supplfig17_a_6.tif file_size: 6003079 relation: main_file success: 1 - access_level: open_access checksum: 169aad3cea521cc2a0ce4c3e41473e0c content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:25:47Z date_updated: 2023-08-03T14:25:47Z file_id: '13878' file_name: Supplfig17_a_7.tif file_size: 6003115 relation: main_file success: 1 - access_level: open_access checksum: 39a44d77d9047bfa10da8d9c9bd7b391 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:25:47Z date_updated: 2023-08-03T14:25:47Z file_id: '13879' file_name: Supplfig17_a_8.tif file_size: 4002129 relation: main_file success: 1 - access_level: open_access checksum: f4ecb2bd44f2cea3d71587670344ac40 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:25:48Z date_updated: 2023-08-03T14:25:48Z file_id: '13880' file_name: Supplfig17_b.tif file_size: 8214335 relation: main_file success: 1 - access_level: open_access checksum: 44a20d2621680c90227416bf32b5a566 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:27:06Z date_updated: 2023-08-03T14:27:06Z file_id: '13881' file_name: Supplfig18_a.tif file_size: 7471479 relation: main_file success: 1 - access_level: open_access checksum: 5a5f7b616785f9213064e8c77f9d38c4 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:27:06Z date_updated: 2023-08-03T14:27:06Z file_id: '13882' file_name: Supplfig18_b.tif file_size: 290625 relation: main_file success: 1 - access_level: open_access checksum: 8f621722a636e808a03d85f9597ad1a2 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:27:07Z date_updated: 2023-08-03T14:27:07Z file_id: '13883' file_name: Supplfig18_c.tif file_size: 411767 relation: main_file success: 1 - access_level: open_access checksum: 3c8356f9170fe345e2ef725cd7d1b167 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:27:07Z date_updated: 2023-08-03T14:27:07Z file_id: '13884' file_name: Supplfig18_d.tif file_size: 11117685 relation: main_file success: 1 - access_level: open_access checksum: 5c8443e97724b54f359f7355483b890e content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:27:10Z date_updated: 2023-08-03T14:27:10Z file_id: '13885' file_name: Supplfig18_e_n2v.tif file_size: 259509773 relation: main_file success: 1 - access_level: open_access checksum: 413e3105c1bcd2ac2c569fa2b06253f2 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:29:25Z date_updated: 2023-08-03T14:29:25Z file_id: '13886' file_name: Supplfig19_n2v.tif file_size: 1430939360 relation: main_file success: 1 - access_level: open_access checksum: a864dc5b54f469c723e86286d538bb52 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:29:16Z date_updated: 2023-08-03T14:29:16Z file_id: '13887' file_name: Supplfig19.tif file_size: 715524468 relation: main_file success: 1 - access_level: open_access checksum: 8a78ce49446d207c0bf31196b788fa93 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:32:54Z date_updated: 2023-08-03T14:32:54Z file_id: '13888' file_name: Supplfig20_a_left.tif file_size: 8004743 relation: main_file success: 1 - access_level: open_access checksum: 48fa3abfd16a00c7a3757d6452a482ec content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:32:54Z date_updated: 2023-08-03T14:32:54Z file_id: '13889' file_name: Supplfig20_a_right.tif file_size: 5561081 relation: main_file success: 1 - access_level: open_access checksum: 85d82cd94dd3202f04b5987bc4466573 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:32:54Z date_updated: 2023-08-03T14:32:54Z file_id: '13890' file_name: Supplfig20_b_1.tif file_size: 8456797 relation: main_file success: 1 - access_level: open_access checksum: e16f04d5d4d40f6ec33456d0cf02e1eb content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:32:54Z date_updated: 2023-08-03T14:32:54Z file_id: '13891' file_name: Supplfig20_b_2.tif file_size: 8456795 relation: main_file success: 1 - access_level: open_access checksum: ff190edb269c28b25d27bffaeb7d25cf content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:32:54Z date_updated: 2023-08-03T14:32:54Z file_id: '13892' file_name: Supplfig20_b_3.tif file_size: 8456796 relation: main_file success: 1 - access_level: open_access checksum: deb10b81bae62d9e20e681411fb75fcc content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:32:54Z date_updated: 2023-08-03T14:32:54Z file_id: '13893' file_name: Supplfig20_b_4.tif file_size: 8538887 relation: main_file success: 1 - access_level: open_access checksum: 5c64bb94e76030d7a9d8624bac4b0f57 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:32:54Z date_updated: 2023-08-03T14:32:54Z file_id: '13894' file_name: Supplfig20_b_5.tif file_size: 8538851 relation: main_file success: 1 - access_level: open_access checksum: d6c20232c4bd36e213b4c456c5009644 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:32:54Z date_updated: 2023-08-03T14:32:54Z file_id: '13895' file_name: Supplfig20_c_1.tif file_size: 11077737 relation: main_file success: 1 - access_level: open_access checksum: 49c3396b8960af3f6fd8f6b078971d51 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:32:54Z date_updated: 2023-08-03T14:32:54Z file_id: '13896' file_name: Supplfig20_c_2.tif file_size: 11077737 relation: main_file success: 1 - access_level: open_access checksum: 73471528f691fb337839b84c31014da4 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:32:55Z date_updated: 2023-08-03T14:32:55Z file_id: '13897' file_name: Supplfig20_c_3.tif file_size: 11077737 relation: main_file success: 1 - access_level: open_access checksum: 47a0fd1a36d7e7907ce18007bdaaa145 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:32:55Z date_updated: 2023-08-03T14:32:55Z file_id: '13898' file_name: Supplfig20_c_4.tif file_size: 11077737 relation: main_file success: 1 - access_level: open_access checksum: 0c74b07f13fb08a91e61669368f38c9a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:32:55Z date_updated: 2023-08-03T14:32:55Z file_id: '13899' file_name: Supplfig20_c_5.tif file_size: 11077737 relation: main_file success: 1 - access_level: open_access checksum: fe3b76446ec8bd0d5cdba94a128a84b8 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:32:55Z date_updated: 2023-08-03T14:32:55Z file_id: '13900' file_name: Supplfig20_d_1.tif file_size: 4002133 relation: main_file success: 1 - access_level: open_access checksum: 0570bab9a471af3d0d1d8bf9a3cb17e7 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:32:55Z date_updated: 2023-08-03T14:32:55Z file_id: '13901' file_name: Supplfig20_d_2.tif file_size: 4002133 relation: main_file success: 1 - access_level: open_access checksum: 59f330990b5c95f98a768761a009940c content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:32:55Z date_updated: 2023-08-03T14:32:55Z file_id: '13902' file_name: Supplfig20_d_3.tif file_size: 4002199 relation: main_file success: 1 - access_level: open_access checksum: f0da06f2a278dff4bbd1aeace11700bf content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:32:55Z date_updated: 2023-08-03T14:32:55Z file_id: '13903' file_name: Supplfig20_d_4.tif file_size: 4002133 relation: main_file success: 1 - access_level: open_access checksum: e61d49dcc0952af3623cc26a78cc6495 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:32:55Z date_updated: 2023-08-03T14:32:55Z file_id: '13904' file_name: Supplfig20_d_5.tif file_size: 4002133 relation: main_file success: 1 - access_level: open_access checksum: bcf8294487abaf1a75033f388fba06ec content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:42:01Z date_updated: 2023-08-03T14:42:01Z file_id: '13905' file_name: Supplfig22_b_1.tif file_size: 12627576 relation: main_file success: 1 - access_level: open_access checksum: 14097feb4a73e7bb1e1694cef0115cab content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:42:01Z date_updated: 2023-08-03T14:42:01Z file_id: '13906' file_name: Supplfig22_b_2.tif file_size: 8543366 relation: main_file success: 1 - access_level: open_access checksum: 7e74b8cff2ada56d47d135a6a9e71e76 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:42:04Z date_updated: 2023-08-03T14:42:04Z file_id: '13907' file_name: Supplfig22_b_3.tif file_size: 8394010 relation: main_file success: 1 - access_level: open_access checksum: f6e6e0f0e3854fedd201ab8ff08a7651 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T15:35:39Z date_updated: 2023-08-03T15:35:39Z file_id: '13908' file_name: Supplfig22_b_4.tif file_size: 8682992 relation: main_file success: 1 - access_level: open_access checksum: 6ddeb84249768b46b9c2072bf85bdc8b content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:42:04Z date_updated: 2023-08-03T14:42:04Z file_id: '13909' file_name: Supplfig22_b_5.tif file_size: 8503466 relation: main_file success: 1 - access_level: open_access checksum: 40648b8a4ef375b8352f11a6772ea1a6 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:42:04Z date_updated: 2023-08-03T14:42:04Z file_id: '13910' file_name: Supplfig22_b_6.tif file_size: 8543342 relation: main_file success: 1 - access_level: open_access checksum: 78f601de4d88f6ccb97861eaf4a995f8 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:42:06Z date_updated: 2023-08-03T14:42:06Z file_id: '13911' file_name: Supplfig22_b_7.tif file_size: 33588990 relation: main_file success: 1 - access_level: open_access checksum: 2873c488b7c8ad4d111726025086e9ea content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:42:41Z date_updated: 2023-08-03T14:42:41Z file_id: '13912' file_name: Supplfig22_c.tif file_size: 1453171518 relation: main_file success: 1 - access_level: open_access checksum: c1d0e5e61ac0d0ddf08704769f80ac78 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:47:43Z date_updated: 2023-08-03T14:47:43Z file_id: '13913' file_name: Supplfig23_a.tif file_size: 1325919782 relation: main_file success: 1 - access_level: open_access checksum: f97632984b6a73e06cc0c8c947cdcc71 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:47:25Z date_updated: 2023-08-03T14:47:25Z file_id: '13914' file_name: Supplfig23_b.tif file_size: 31366288 relation: main_file success: 1 - access_level: open_access checksum: 16f4c17835a79d7c06e2a97b1603baf1 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:47:26Z date_updated: 2023-08-03T14:47:26Z file_id: '13915' file_name: Supplfig23_c.tif file_size: 31366288 relation: main_file success: 1 - access_level: open_access checksum: 00f35ca77165642ca9b3bc3608bd04c1 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:47:27Z date_updated: 2023-08-03T14:47:27Z file_id: '13916' file_name: Supplfig23_d.tif file_size: 31366428 relation: main_file success: 1 - access_level: open_access checksum: 1aff850f47ae8c8f05ca48ff9faa38b1 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:47:27Z date_updated: 2023-08-03T14:47:27Z file_id: '13917' file_name: Supplfig23_e.tif file_size: 31500832 relation: main_file success: 1 - access_level: open_access checksum: f644de697d142c83461ed5ad1d72a043 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:48:38Z date_updated: 2023-08-03T14:48:38Z file_id: '13918' file_name: Supplfig24_a_i.tif file_size: 44179078 relation: main_file success: 1 - access_level: open_access checksum: eccb84925a6699b396d4b07efcbc7349 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:48:38Z date_updated: 2023-08-03T14:48:38Z file_id: '13919' file_name: Supplfig24_a_ii.tif file_size: 44125924 relation: main_file success: 1 - access_level: open_access checksum: afe7253e70ec79144e59b28c3c66703a content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:48:54Z date_updated: 2023-08-03T14:48:54Z file_id: '13920' file_name: Supplfig24_a.tif file_size: 1061835435 relation: main_file success: 1 - access_level: open_access checksum: 94a03b022aa84ea6e8515450a481ad82 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:48:39Z date_updated: 2023-08-03T14:48:39Z file_id: '13921' file_name: Supplfig24_b_iii.tif file_size: 3977824 relation: main_file success: 1 - access_level: open_access checksum: 166832c173fcda88ec6e35decdf0d197 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:48:39Z date_updated: 2023-08-03T14:48:39Z file_id: '13922' file_name: Supplfig24_b_iv.tif file_size: 3977825 relation: main_file success: 1 - access_level: open_access checksum: 53175073b83ab569241ae64ef7f180b3 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:51:27Z date_updated: 2023-08-03T14:51:27Z file_id: '13923' file_name: Supplfig25_a_1.tif file_size: 37641738 relation: main_file success: 1 - access_level: open_access checksum: 70e6a1780daeae6a5bef2c27c996c442 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:51:26Z date_updated: 2023-08-03T14:51:26Z file_id: '13924' file_name: Supplfig25_a_2.tif file_size: 4932897 relation: main_file success: 1 - access_level: open_access checksum: 1748266d7b8a2ae1f6292b9c265c2068 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:51:31Z date_updated: 2023-08-03T14:51:31Z file_id: '13925' file_name: Supplfig25_b_1.tif file_size: 357433570 relation: main_file success: 1 - access_level: open_access checksum: 8490f44160a482ea06d858eb3bc25a11 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:51:27Z date_updated: 2023-08-03T14:51:27Z file_id: '13926' file_name: Supplfig25_b_2.tif file_size: 27734506 relation: main_file success: 1 - access_level: open_access checksum: e5e9c550cc934a7725dc209c79951847 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:53:43Z date_updated: 2023-08-03T14:53:43Z file_id: '13927' file_name: Suppfig26_h.tif file_size: 35082394 relation: main_file success: 1 - access_level: open_access checksum: 39ae411d1e950e78bdc12937fb36f661 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:53:42Z date_updated: 2023-08-03T14:53:42Z file_id: '13928' file_name: Supplfig26_a_1.tif file_size: 16676477 relation: main_file success: 1 - access_level: open_access checksum: 450f5d0e8091639e27eb7a7991524e88 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:53:42Z date_updated: 2023-08-03T14:53:42Z file_id: '13929' file_name: Supplfig26_a_2.tif file_size: 170493 relation: main_file success: 1 - access_level: open_access checksum: 8e5a71801fa1fcb7f679d1af23344662 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:53:43Z date_updated: 2023-08-03T14:53:43Z file_id: '13930' file_name: Supplfig26_b_1.tif file_size: 11117737 relation: main_file success: 1 - access_level: open_access checksum: 519fb0326a0f0774b3edc1dafffcdd08 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:53:43Z date_updated: 2023-08-03T14:53:43Z file_id: '13931' file_name: Supplfig26_b_2.tif file_size: 113753 relation: main_file success: 1 - access_level: open_access checksum: d051c7d717eeb6f2ca59d8727ea62200 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:53:52Z date_updated: 2023-08-03T14:53:52Z file_id: '13932' file_name: Supplfig26_c.tif file_size: 495452386 relation: main_file success: 1 - access_level: open_access checksum: 5437b53e708572e2e9ad1432c260a04f content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:53:46Z date_updated: 2023-08-03T14:53:46Z file_id: '13933' file_name: Supplfig26_d.tif file_size: 132167170 relation: main_file success: 1 - access_level: open_access checksum: 0baab38829a8587ded5e39f85068124b content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:53:46Z date_updated: 2023-08-03T14:53:46Z file_id: '13934' file_name: Supplfig26_e.tif file_size: 11431214 relation: main_file success: 1 - access_level: open_access checksum: afa57f254c9dd987d90d5e43db3fb9e6 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:53:48Z date_updated: 2023-08-03T14:53:48Z file_id: '13935' file_name: Supplfig26_f.tif file_size: 64005702 relation: main_file success: 1 - access_level: open_access checksum: c35ba67ab92c410cb4370f91f3dea819 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:53:52Z date_updated: 2023-08-03T14:53:52Z file_id: '13936' file_name: Supplfig26_g.tif file_size: 246421054 relation: main_file success: 1 - access_level: open_access checksum: 3fd6186d73cbce1be79cf14a94a7f3bd content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:56:43Z date_updated: 2023-08-03T14:56:43Z file_id: '13937' file_name: Supplfig27_a.tif file_size: 166614932 relation: main_file success: 1 - access_level: open_access checksum: d1fc4c88e8e258e4e536a26e196d09b0 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:56:42Z date_updated: 2023-08-03T14:56:42Z file_id: '13938' file_name: Supplfig27_b.tif file_size: 143583446 relation: main_file success: 1 - access_level: open_access checksum: 8d6985530e86f38548e89e6380d73771 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:56:47Z date_updated: 2023-08-03T14:56:47Z file_id: '13939' file_name: Supplfig27_c.tif file_size: 172528188 relation: main_file success: 1 - access_level: open_access checksum: d0b1309d2120892ede84e04fdf0dbfbf content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:56:46Z date_updated: 2023-08-03T14:56:46Z file_id: '13940' file_name: Supplfig27_d.tif file_size: 113699256 relation: main_file success: 1 - access_level: open_access checksum: 4789b5254d0415ce314fc9e39cc52121 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:56:47Z date_updated: 2023-08-03T14:56:47Z file_id: '13941' file_name: Supplfig27_e.tif file_size: 88664548 relation: main_file success: 1 - access_level: open_access checksum: 7ff2d06534f062b0f17dab181f6c1f4e content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:56:47Z date_updated: 2023-08-03T14:56:47Z file_id: '13942' file_name: Supplfig27_f.tif file_size: 2298356 relation: main_file success: 1 - access_level: open_access checksum: 46de66d457b0def90f753c11927536b7 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:56:47Z date_updated: 2023-08-03T14:56:47Z file_id: '13943' file_name: Supplfig27_g_1.tif file_size: 499618 relation: main_file success: 1 - access_level: open_access checksum: 9ef5fba064a73a79dbc74b5e166d08ec content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:56:50Z date_updated: 2023-08-03T14:56:50Z file_id: '13944' file_name: Supplfig27_g_2.tif file_size: 202079026 relation: main_file success: 1 - access_level: open_access checksum: bf956c2b58d3da2baa869db5206d8d49 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T14:56:48Z date_updated: 2023-08-03T14:56:48Z file_id: '13945' file_name: Supplfig27_g_3.tif file_size: 14639269 relation: main_file success: 1 - access_level: open_access checksum: 327dca11f42d5375d7f47f4cbd5b36c0 content_type: application/octet-stream creator: jdanzl date_created: 2023-08-03T15:21:01Z date_updated: 2023-08-03T15:21:01Z file_id: '13946' file_name: model.p file_size: 279467712 relation: main_file success: 1 file_date_updated: 2023-08-04T13:19:47Z has_accepted_license: '1' license: https://creativecommons.org/licenses/by-nc-sa/4.0/ month: '08' oa: 1 oa_version: Published Version project: - _id: 265CB4D0-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03600 name: Optical control of synaptic function via adhesion molecules - _id: 26AA4EF2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize - _id: 23889792-32DE-11EA-91FC-C7463DDC885E name: High content imaging to decode human immune cell interactions in health and allergic disease - _id: 25444568-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715508' name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9 call_identifier: H2020 grant_number: '101026635' name: Synaptic computations of the hippocampal CA3 circuitry publisher: Institute of Science and Technology Austria related_material: link: - 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. ' relation: research_data url: https://pub.ista.ac.at/group_danzl/data/CATS/ record: - id: '14257' relation: used_in_publication status: public status: public title: Research data for the publication "Imaging brain tissue architecture across millimeter to nanometer scales" tmp: image: /images/cc_by_nc_sa.png legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) short: CC BY-NC-SA (4.0) type: research_data user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2023' ... --- _id: '14257' 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. acknowledged_ssus: - _id: ScienComp - _id: Bio - _id: PreCl - _id: LifeSc - _id: M-Shop - _id: E-Lib 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.).' article_processing_charge: Yes (in subscription journal) article_type: original author: - first_name: Julia M full_name: Michalska, Julia M id: 443DB6DE-F248-11E8-B48F-1D18A9856A87 last_name: Michalska orcid: 0000-0003-3862-1235 - first_name: Julia full_name: Lyudchik, Julia id: 46E28B80-F248-11E8-B48F-1D18A9856A87 last_name: Lyudchik - first_name: Philipp full_name: Velicky, Philipp id: 39BDC62C-F248-11E8-B48F-1D18A9856A87 last_name: Velicky orcid: 0000-0002-2340-7431 - first_name: Hana full_name: Korinkova, Hana id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed last_name: Korinkova - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Alban full_name: Cenameri, Alban id: 9ac8f577-2357-11eb-997a-e566c5550886 last_name: Cenameri - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Alessandro full_name: Venturino, Alessandro id: 41CB84B2-F248-11E8-B48F-1D18A9856A87 last_name: Venturino orcid: 0000-0003-2356-9403 - first_name: Karl full_name: Roessler, Karl last_name: Roessler - first_name: Thomas full_name: Czech, Thomas last_name: Czech - first_name: Romana full_name: Höftberger, Romana last_name: Höftberger - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 citation: 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 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 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. ieee: J. M. Michalska et al., “Imaging brain tissue architecture across millimeter to nanometer scales,” Nature Biotechnology. Springer Nature, 2023. 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. 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. 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). date_created: 2023-09-03T22:01:15Z date_published: 2023-08-31T00:00:00Z date_updated: 2024-02-21T12:18:18Z day: '31' department: - _id: SaSi - _id: GaNo - _id: PeJo - _id: JoDa - _id: Bio - _id: RySh doi: 10.1038/s41587-023-01911-8 ec_funded: 1 external_id: isi: - '001065254200001' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1038/s41587-023-01911-8 month: '08' oa: 1 oa_version: Published Version project: - _id: 265CB4D0-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03600 name: Optical control of synaptic function via adhesion molecules - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize - _id: 23889792-32DE-11EA-91FC-C7463DDC885E name: High content imaging to decode human immune cell interactions in health and allergic disease - _id: 25444568-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715508' name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9 call_identifier: H2020 grant_number: '101026635' name: Synaptic computations of the hippocampal CA3 circuitry publication: Nature Biotechnology publication_identifier: eissn: - 1546-1696 issn: - 1087-0156 publication_status: epub_ahead publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: software url: https://github.com/danzllab/CATS record: - id: '13126' relation: research_data status: public scopus_import: '1' status: public title: Imaging brain tissue architecture across millimeter to nanometer scales type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2023' ... --- _id: '10763' abstract: - lang: eng text: "AMPA-type glutamate receptors (AMPARs) mediate rapid signal transmission at excitatory\r\nsynapses in the brain. Glutamate binding to the receptor’s ligand-binding domains (LBDs)\r\nleads to ion channel activation and desensitization. Gating kinetics shape synaptic transmission\r\nand are strongly modulated by transmembrane AMPAR regulatory proteins (TARPs)\r\nthrough currently incompletely resolved mechanisms. Here, electron cryo-microscopy\r\nstructures of the GluA1/2 TARP-γ8 complex, in both open and desensitized states\r\n(at 3.5 Å), reveal state-selective engagement of the LBDs by the large TARP-γ8 loop (‘β1’),\r\nelucidating how this TARP stabilizes specific gating states. We further show how TARPs alter\r\nchannel rectification, by interacting with the pore helix of the selectivity filter. Lastly, we\r\nreveal that the Q/R-editing site couples the channel constriction at the filter entrance to the\r\ngate, and forms the major cation binding site in the conduction path. Our results provide a\r\nmechanistic framework of how TARPs modulate AMPAR gating and conductance." acknowledgement: "We thank Ondrej Cais for critical reading of the manuscript. We are grateful to LMB\r\nscientific computing and the EM facility for support, Paul Emsley for help with model\r\nbuilding and Takanori Nakane for helpful comments with Relion 3.1. This work was\r\nsupported by grants from the Medical Research Council (MC_U105174197) and BBSRC\r\n(BB/N002113/1) to I.H.G, and grants from the MCIN/AEI/ 10.13039/501100011033 and\r\n“ESF Investing in your future” to B.H (PID2019-106284GA-I00 and RYC2018-025720-I)." article_number: '734' article_processing_charge: No article_type: original author: - first_name: Beatriz full_name: Herguedas, Beatriz last_name: Herguedas - first_name: Bianka K. full_name: Kohegyi, Bianka K. last_name: Kohegyi - first_name: Jan Niklas full_name: Dohrke, Jan Niklas last_name: Dohrke - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Danyang full_name: Zhang, Danyang last_name: Zhang - first_name: Hinze full_name: Ho, Hinze last_name: Ho - first_name: Saher A. full_name: Shaikh, Saher A. last_name: Shaikh - first_name: Remigijus full_name: Lape, Remigijus last_name: Lape - first_name: James M. full_name: Krieger, James M. last_name: Krieger - first_name: Ingo H. full_name: Greger, Ingo H. last_name: Greger citation: ama: Herguedas B, Kohegyi BK, Dohrke JN, et al. Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor. Nature Communications. 2022;13. doi:10.1038/s41467-022-28404-7 apa: Herguedas, B., Kohegyi, B. K., Dohrke, J. N., Watson, J., Zhang, D., Ho, H., … Greger, I. H. (2022). Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-28404-7 chicago: Herguedas, Beatriz, Bianka K. Kohegyi, Jan Niklas Dohrke, Jake Watson, Danyang Zhang, Hinze Ho, Saher A. Shaikh, Remigijus Lape, James M. Krieger, and Ingo H. Greger. “Mechanisms Underlying TARP Modulation of the GluA1/2-Γ8 AMPA Receptor.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-28404-7. ieee: B. Herguedas et al., “Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor,” Nature Communications, vol. 13. Springer Nature, 2022. ista: Herguedas B, Kohegyi BK, Dohrke JN, Watson J, Zhang D, Ho H, Shaikh SA, Lape R, Krieger JM, Greger IH. 2022. Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor. Nature Communications. 13, 734. mla: Herguedas, Beatriz, et al. “Mechanisms Underlying TARP Modulation of the GluA1/2-Γ8 AMPA Receptor.” Nature Communications, vol. 13, 734, Springer Nature, 2022, doi:10.1038/s41467-022-28404-7. short: B. Herguedas, B.K. Kohegyi, J.N. Dohrke, J. Watson, D. Zhang, H. Ho, S.A. Shaikh, R. Lape, J.M. Krieger, I.H. Greger, Nature Communications 13 (2022). date_created: 2022-02-20T23:01:30Z date_published: 2022-02-08T00:00:00Z date_updated: 2023-08-02T14:25:33Z day: '08' ddc: - '570' department: - _id: PeJo doi: 10.1038/s41467-022-28404-7 external_id: isi: - '000757297200008' pmid: - '35136046' file: - access_level: open_access checksum: d86ee8eabe8b794730729ffbb1a8832e content_type: application/pdf creator: dernst date_created: 2022-02-21T07:59:32Z date_updated: 2022-02-21T07:59:32Z file_id: '10778' file_name: 2022_NatureCommunications_Herguedas.pdf file_size: 2625540 relation: main_file success: 1 file_date_updated: 2022-02-21T07:59:32Z has_accepted_license: '1' intvolume: ' 13' isi: 1 language: - iso: eng month: '02' oa: 1 oa_version: Published Version pmid: 1 publication: Nature Communications publication_identifier: eissn: - '20411723' publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 13 year: '2022' ... --- _id: '11951' abstract: - lang: eng 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. acknowledged_ssus: - _id: Bio - _id: SSU 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.). article_number: '4826' article_processing_charge: No article_type: original author: - first_name: Yoav full_name: Ben Simon, Yoav id: 43DF3136-F248-11E8-B48F-1D18A9856A87 last_name: Ben Simon - first_name: Karola full_name: Käfer, Karola id: 2DAA49AA-F248-11E8-B48F-1D18A9856A87 last_name: Käfer - first_name: Philipp full_name: Velicky, Philipp id: 39BDC62C-F248-11E8-B48F-1D18A9856A87 last_name: Velicky orcid: 0000-0002-2340-7431 - first_name: Jozsef L full_name: Csicsvari, Jozsef L id: 3FA14672-F248-11E8-B48F-1D18A9856A87 last_name: Csicsvari orcid: 0000-0002-5193-4036 - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: 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 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. 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. 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. 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. short: Y. Ben Simon, K. Käfer, P. Velicky, J.L. Csicsvari, J.G. Danzl, P.M. Jonas, Nature Communications 13 (2022). date_created: 2022-08-24T08:25:50Z date_published: 2022-08-16T00:00:00Z date_updated: 2023-08-03T13:01:19Z day: '16' ddc: - '570' department: - _id: JoCs - _id: PeJo - _id: JoDa doi: 10.1038/s41467-022-32559-8 ec_funded: 1 external_id: isi: - '000841396400008' file: - access_level: open_access checksum: 405936d9e4d33625d80c093c9713a91f content_type: application/pdf creator: dernst date_created: 2022-08-26T11:51:40Z date_updated: 2022-08-26T11:51:40Z file_id: '11990' file_name: 2022_NatureCommunications_BenSimon.pdf file_size: 5910357 relation: main_file success: 1 file_date_updated: 2022-08-26T11:51:40Z has_accepted_license: '1' intvolume: ' 13' isi: 1 keyword: - General Physics and Astronomy - General Biochemistry - Genetics and Molecular Biology - General Chemistry - Multidisciplinary language: - iso: eng month: '08' oa: 1 oa_version: Published Version project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 265CB4D0-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03600 name: Optical control of synaptic function via adhesion molecules - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize publication: Nature Communications publication_identifier: issn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' status: public title: A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 13 year: '2022' ... --- _id: '12288' 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. acknowledged_ssus: - _id: Bio - _id: PreCl 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). article_number: '79848' article_processing_charge: No article_type: original author: - first_name: Anton L full_name: Sumser, Anton L id: 3320A096-F248-11E8-B48F-1D18A9856A87 last_name: Sumser orcid: 0000-0002-4792-1881 - first_name: Maximilian A full_name: Jösch, Maximilian A id: 2BD278E6-F248-11E8-B48F-1D18A9856A87 last_name: Jösch orcid: 0000-0002-3937-1330 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 - first_name: Yoav full_name: Ben Simon, Yoav id: 43DF3136-F248-11E8-B48F-1D18A9856A87 last_name: Ben Simon citation: 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. 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. 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. short: A.L. Sumser, M.A. Jösch, P.M. Jonas, Y. Ben Simon, ELife 11 (2022). date_created: 2023-01-16T10:04:15Z date_published: 2022-09-15T00:00:00Z date_updated: 2023-08-04T10:29:48Z day: '15' ddc: - '570' department: - _id: MaJö - _id: PeJo doi: 10.7554/elife.79848 ec_funded: 1 external_id: isi: - '000892204300001' pmid: - '36040301' file: - access_level: open_access checksum: 5a2a65e3e7225090c3d8199f3bbd7b7b content_type: application/pdf creator: dernst date_created: 2023-01-30T11:50:53Z date_updated: 2023-01-30T11:50:53Z file_id: '12463' file_name: 2022_eLife_Sumser.pdf file_size: 8506811 relation: main_file success: 1 file_date_updated: 2023-01-30T11:50:53Z has_accepted_license: '1' intvolume: ' 11' isi: 1 keyword: - General Immunology and Microbiology - General Biochemistry - Genetics and Molecular Biology - General Medicine - General Neuroscience language: - iso: eng month: '09' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 2634E9D2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '756502' name: Circuits of Visual Attention - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize - _id: 266D407A-B435-11E9-9278-68D0E5697425 grant_number: LT000256 name: Neuronal networks of salience and spatial detection in the murine superior colliculus - _id: 264FEA02-B435-11E9-9278-68D0E5697425 grant_number: ALTF 1098-2017 name: Connecting sensory with motor processing in the superior colliculus publication: eLife publication_identifier: eissn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 11 year: '2022' ... --- _id: '11196' abstract: - lang: eng text: "One of the fundamental questions in Neuroscience is how the structure of synapses and their physiological properties are related. While synaptic transmission remains a dynamic process, electron microscopy provides images with comparably low temporal resolution (Studer et al., 2014). The current work overcomes this challenge and describes an improved “Flash and Freeze” technique (Watanabe et al., 2013a; Watanabe et al., 2013b) to study synaptic transmission at the hippocampal mossy fiber-CA3 pyramidal neuron synapses, using mouse acute brain slices and organotypic slices culture. The improved method allowed for selective stimulation of presynaptic mossy fiber boutons and the observation of synaptic vesicle pool dynamics at the active zones. Our results uncovered several intriguing morphological features of mossy fiber boutons. First, the docked vesicle pool was largely depleted (more than 70%) after stimulation, implying that the docked synaptic vesicles pool and readily releasable pool are vastly overlapping in mossy fiber boutons. Second, the synaptic vesicles are skewed towards larger diameters, displaying a wide range of sizes. An increase in the mean diameter of synaptic vesicles, after single and repetitive stimulation, suggests that smaller vesicles have a higher release probability. Third, we observed putative endocytotic structures after moderate light stimulation, matching the timing of previously described ultrafast endocytosis (Watanabe et al., 2013a; Delvendahl et al., 2016). \r\n\tIn addition, synaptic transmission depends on a sophisticated system of protein machinery and calcium channels (Südhof, 2013b), which amplifies the challenge in studying synaptic communication as these interactions can be potentially modified during synaptic plasticity. And although recent study elucidated the potential correlation between physiological and morphological properties of synapses during synaptic plasticity (Vandael et al., 2020), the molecular underpinning of it remains unknown. Thus, the presented work tries to overcome this challenge and aims to pinpoint changes in the molecular architecture at hippocampal mossy fiber bouton synapses during short- and long-term potentiation (STP and LTP), we combined chemical potentiation, with the application of a cyclic adenosine monophosphate agonist (i.e. forskolin) and freeze-fracture replica immunolabelling. This method allowed the localization of membrane-bound proteins with nanometer precision within the active zone, in particular, P/Q-type calcium channels and synaptic vesicle priming proteins Munc13-1/2. First, we found that the number of clusters of Munc13-1 in the mossy fiber bouton active zone increased significantly during STP, but decreased to lower than the control value during LTP. Secondly, although the distance between the calcium channels and Munc13-1s did not change after induction of STP, it shortened during the LTP phase. Additionally, forskolin did not affect Munc13-2 distribution during STP and LTP. These results indicate the existence of two distinct mechanisms that govern STP and LTP at mossy fiber bouton synapses: an increase in the readily realizable pool in the case of STP and a potential increase in release probability during LTP. “Flash and freeze” and functional electron microscopy, are versatile methods that can be successfully applied to intact brain circuits to study synaptic transmission even at the molecular level.\r\n" acknowledged_ssus: - _id: EM-Fac - _id: PreCl alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Olena full_name: Kim, Olena id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87 last_name: Kim citation: ama: Kim O. Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses. 2022. doi:10.15479/at:ista:11196 apa: Kim, O. (2022). Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:11196 chicago: Kim, Olena. “Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:11196. ieee: O. Kim, “Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses,” Institute of Science and Technology Austria, 2022. ista: Kim O. 2022. Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses. Institute of Science and Technology Austria. mla: Kim, Olena. Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:11196. short: O. Kim, Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses, Institute of Science and Technology Austria, 2022. date_created: 2022-04-20T09:47:12Z date_published: 2022-04-20T00:00:00Z date_updated: 2023-08-18T06:31:52Z day: '20' ddc: - '570' degree_awarded: PhD department: - _id: PeJo - _id: GradSch doi: 10.15479/at:ista:11196 ec_funded: 1 file: - access_level: open_access checksum: 1616a8bf6f13a57c892dac873dcd0936 content_type: application/pdf creator: okim date_created: 2022-04-20T14:21:56Z date_updated: 2023-04-20T22:30:03Z embargo: 2023-04-19 file_id: '11220' file_name: Olena_KIM_thesis_final.pdf file_size: 21273537 relation: main_file - access_level: closed checksum: 1acb433f98dc42abb0b4b0cbb0c4b918 content_type: application/x-zip-compressed creator: okim date_created: 2022-04-20T14:22:56Z date_updated: 2023-04-20T22:30:03Z embargo_to: open_access file_id: '11221' file_name: KIM_thesis_final.zip file_size: 59248569 relation: source_file file_date_updated: 2023-04-20T22:30:03Z has_accepted_license: '1' language: - iso: eng month: '04' oa: 1 oa_version: Published Version page: '132' project: - _id: 25BAF7B2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '708497' name: Presynaptic calcium channels distribution and impact on coupling at the hippocampal mossy fiber synapse - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 25C3DBB6-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W01205 name: Zellkommunikation in Gesundheit und Krankheit - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '11222' relation: part_of_dissertation status: public - id: '7473' relation: part_of_dissertation status: public status: public supervisor: - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 title: Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: dissertation user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 year: '2022' ... --- _id: '11943' abstract: - lang: eng text: Complex wiring between neurons underlies the information-processing network enabling all brain functions, including cognition and memory. For understanding how the network is structured, processes information, and changes over time, comprehensive visualization of the architecture of living brain tissue with its cellular and molecular components would open up major opportunities. However, electron microscopy (EM) provides nanometre-scale resolution required for full in-silico reconstruction1–5, yet is limited to fixed specimens and static representations. Light microscopy allows live observation, with super-resolution approaches6–12 facilitating nanoscale visualization, but comprehensive 3D-reconstruction of living brain tissue has been hindered by tissue photo-burden, photobleaching, insufficient 3D-resolution, and inadequate signal-to-noise ratio (SNR). Here we demonstrate saturated reconstruction of living brain tissue. We developed an integrated imaging and analysis technology, adapting stimulated emission depletion (STED) microscopy6,13 in extracellularly labelled tissue14 for high SNR and near-isotropic resolution. Centrally, a two-stage deep-learning approach leveraged previously obtained information on sample structure to drastically reduce photo-burden and enable automated volumetric reconstruction down to single synapse level. Live reconstruction provides unbiased analysis of tissue architecture across time in relation to functional activity and targeted activation, and contextual understanding of molecular labelling. This adoptable technology will facilitate novel insights into the dynamic functional architecture of living brain tissue. article_processing_charge: No author: - first_name: Philipp full_name: Velicky, Philipp id: 39BDC62C-F248-11E8-B48F-1D18A9856A87 last_name: Velicky orcid: 0000-0002-2340-7431 - first_name: Eder full_name: Miguel Villalba, Eder id: 3FB91342-F248-11E8-B48F-1D18A9856A87 last_name: Miguel Villalba orcid: 0000-0001-5665-0430 - first_name: Julia M full_name: Michalska, Julia M id: 443DB6DE-F248-11E8-B48F-1D18A9856A87 last_name: Michalska orcid: 0000-0003-3862-1235 - first_name: Donglai full_name: Wei, Donglai last_name: Wei - first_name: Zudi full_name: Lin, Zudi last_name: Lin - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Jakob full_name: Troidl, Jakob last_name: Troidl - first_name: Johanna full_name: Beyer, Johanna last_name: Beyer - first_name: Yoav full_name: Ben Simon, Yoav id: 43DF3136-F248-11E8-B48F-1D18A9856A87 last_name: Ben Simon - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Wiebke full_name: Jahr, Wiebke id: 425C1CE8-F248-11E8-B48F-1D18A9856A87 last_name: Jahr - first_name: Alban full_name: Cenameri, Alban id: 9ac8f577-2357-11eb-997a-e566c5550886 last_name: Cenameri - first_name: Johannes full_name: Broichhagen, Johannes last_name: Broichhagen - first_name: Seth G. N. full_name: Grant, Seth G. N. last_name: Grant - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Hanspeter full_name: Pfister, Hanspeter last_name: Pfister - first_name: Bernd full_name: Bickel, Bernd id: 49876194-F248-11E8-B48F-1D18A9856A87 last_name: Bickel orcid: 0000-0001-6511-9385 - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 citation: ama: Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction of living brain tissue. bioRxiv. doi:10.1101/2022.03.16.484431 apa: Velicky, P., Miguel Villalba, E., Michalska, J. M., Wei, D., Lin, Z., Watson, J., … Danzl, J. G. (n.d.). Saturated reconstruction of living brain tissue. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.03.16.484431 chicago: Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Donglai Wei, Zudi Lin, Jake Watson, Jakob Troidl, et al. “Saturated Reconstruction of Living Brain Tissue.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2022.03.16.484431. ieee: P. Velicky et al., “Saturated reconstruction of living brain tissue,” bioRxiv. Cold Spring Harbor Laboratory. ista: Velicky P, Miguel Villalba E, Michalska JM, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. Saturated reconstruction of living brain tissue. bioRxiv, 10.1101/2022.03.16.484431. mla: Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.03.16.484431. short: P. Velicky, E. Miguel Villalba, J.M. Michalska, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, BioRxiv (n.d.). date_created: 2022-08-23T11:07:59Z date_published: 2022-05-09T00:00:00Z date_updated: 2024-03-27T23:30:20Z day: '09' department: - _id: PeJo - _id: GaNo - _id: BeBi - _id: JoDa doi: 10.1101/2022.03.16.484431 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2022.03.16.484431 month: '05' oa: 1 oa_version: Preprint publication: bioRxiv publication_status: submitted publisher: Cold Spring Harbor Laboratory related_material: record: - id: '12470' relation: dissertation_contains status: public status: public title: Saturated reconstruction of living brain tissue type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2022' ... --- _id: '11950' 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 nanoscopic synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS leverages fixation-compatible extracellular labeling and advanced optical readout, in particular stimulated-emission depletion and expansion microscopy, to comprehensively delineate cellular structures. It enables 3D-reconstructing single synapses and mapping synaptic connectivity by identification and tailored analysis of putative synaptic cleft regions. Applying CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal the system’s molecularly informed ultrastructure across spatial scales and assess local connectivity by reconstructing and quantifying the synaptic input and output structure of identified neurons. article_processing_charge: No author: - first_name: Julia M full_name: Michalska, Julia M id: 443DB6DE-F248-11E8-B48F-1D18A9856A87 last_name: Michalska orcid: 0000-0003-3862-1235 - first_name: Julia full_name: Lyudchik, Julia id: 46E28B80-F248-11E8-B48F-1D18A9856A87 last_name: Lyudchik - first_name: Philipp full_name: Velicky, Philipp id: 39BDC62C-F248-11E8-B48F-1D18A9856A87 last_name: Velicky orcid: 0000-0002-2340-7431 - first_name: Hana full_name: Korinkova, Hana id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed last_name: Korinkova - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Alban full_name: Cenameri, Alban id: 9ac8f577-2357-11eb-997a-e566c5550886 last_name: Cenameri - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Alessandro full_name: Venturino, Alessandro id: 41CB84B2-F248-11E8-B48F-1D18A9856A87 last_name: Venturino orcid: 0000-0003-2356-9403 - first_name: Karl full_name: Roessler, Karl last_name: Roessler - first_name: Thomas full_name: Czech, Thomas last_name: Czech - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 citation: ama: Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv. doi:10.1101/2022.08.17.504272 apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.08.17.504272 chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2022.08.17.504272. ieee: J. M. Michalska et al., “Uncovering brain tissue architecture across scales with super-resolution light microscopy,” bioRxiv. Cold Spring Harbor Laboratory. ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv, 10.1101/2022.08.17.504272. mla: Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.08.17.504272. short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, BioRxiv (n.d.). date_created: 2022-08-24T08:24:52Z date_published: 2022-08-18T00:00:00Z date_updated: 2024-03-27T23:30:20Z day: '18' department: - _id: SaSi - _id: GaNo - _id: PeJo - _id: JoDa doi: 10.1101/2022.08.17.504272 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2022.08.17.504272 month: '08' oa: 1 oa_version: Preprint publication: bioRxiv publication_status: submitted publisher: Cold Spring Harbor Laboratory related_material: record: - id: '12470' relation: dissertation_contains status: public status: public title: Uncovering brain tissue architecture across scales with super-resolution light microscopy type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2022' ... --- _id: '9097' abstract: - lang: eng text: Psoriasis is a chronic inflammatory skin disease clinically characterized by the appearance of red colored, well-demarcated plaques with thickened skin and with silvery scales. Recent studies have established the involvement of a complex signalling network of interactions between cytokines, immune cells and skin cells called keratinocytes. Keratinocytes form the cells of the outermost layer of the skin (epidermis). Visible plaques in psoriasis are developed due to the fast proliferation and unusual differentiation of keratinocyte cells. Despite that, the exact mechanism of the appearance of these plaques in the cytokine-immune cell network is not clear. A mathematical model embodying interactions between key immune cells believed to be involved in psoriasis, keratinocytes and relevant cytokines has been developed. The complex network formed of these interactions poses several challenges. Here, we choose to study subnetworks of this complex network and initially focus on interactions involving TNFα, IL-23/IL-17, and IL-15. These are chosen based on known evidence of their therapeutic efficacy. In addition, we explore the role of IL-15 in the pathogenesis of psoriasis and its potential as a future drug target for a novel treatment option. We perform steady state analyses for these subnetworks and demonstrate that the interactions between cells, driven by cytokines could cause the emergence of a psoriasis state (hyper-proliferation of keratinocytes) when levels of TNFα, IL-23/IL-17 or IL-15 are increased. The model results explain and support the clinical potentiality of anti-cytokine treatments. Interestingly, our results suggest different dynamic scenarios underpin the pathogenesis of psoriasis, depending upon the dominant cytokines of subnetworks. We observed that the increase in the level of IL-23/IL-17 and IL-15 could lead to psoriasis via a bistable route, whereas an increase in the level of TNFα would lead to a monotonic and gradual disease progression. Further, we demonstrate how this insight, bistability, could be exploited to improve the current therapies and develop novel treatment strategies for psoriasis. acknowledgement: RP acknowledges the Department of Science and Technology, India for the support through the DST-INSPIRE Faculty Award (DST/INSPIRE/04/2015/001939). This work was supported by the Engineering and Physical Sciences Research Council (EPSRC), United Kingdom (Grant numbers EP/J018295/1, EP/J018392/1, EP/N014391/1). The contribution of RP was also supported by the later Grant. This work was generously supported by the Welcome Trust Institutional Strategic Support Award (204909/Z/16/Z) too. The contribution of MG was supported by the EPSRC via EP/N014391/1 and a Wellcome Trust Institutional Strategic Support Award (WT105618MA). The contribution of YA was generously supported by the Wellcome Trust Institutional Strategic Support Award (WT105618MA). article_number: '2204' article_processing_charge: No article_type: original author: - first_name: Rakesh full_name: Pandey, Rakesh last_name: Pandey - first_name: Yusur full_name: Al-Nuaimi, Yusur last_name: Al-Nuaimi - first_name: Rajiv Kumar full_name: Mishra, Rajiv Kumar id: 46CB58F2-F248-11E8-B48F-1D18A9856A87 last_name: Mishra - first_name: Sarah K. full_name: Spurgeon, Sarah K. last_name: Spurgeon - first_name: Marc full_name: Goodfellow, Marc last_name: Goodfellow citation: ama: Pandey R, Al-Nuaimi Y, Mishra RK, Spurgeon SK, Goodfellow M. Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis. Scientific Reports. 2021;11. doi:10.1038/s41598-020-80507-7 apa: Pandey, R., Al-Nuaimi, Y., Mishra, R. K., Spurgeon, S. K., & Goodfellow, M. (2021). Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis. Scientific Reports. Springer Nature. https://doi.org/10.1038/s41598-020-80507-7 chicago: Pandey, Rakesh, Yusur Al-Nuaimi, Rajiv Kumar Mishra, Sarah K. Spurgeon, and Marc Goodfellow. “Role of Subnetworks Mediated by TNF α, IL-23/IL-17 and IL-15 in a Network Involved in the Pathogenesis of Psoriasis.” Scientific Reports. Springer Nature, 2021. https://doi.org/10.1038/s41598-020-80507-7. ieee: R. Pandey, Y. Al-Nuaimi, R. K. Mishra, S. K. Spurgeon, and M. Goodfellow, “Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis,” Scientific Reports, vol. 11. Springer Nature, 2021. ista: Pandey R, Al-Nuaimi Y, Mishra RK, Spurgeon SK, Goodfellow M. 2021. Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis. Scientific Reports. 11, 2204. mla: Pandey, Rakesh, et al. “Role of Subnetworks Mediated by TNF α, IL-23/IL-17 and IL-15 in a Network Involved in the Pathogenesis of Psoriasis.” Scientific Reports, vol. 11, 2204, Springer Nature, 2021, doi:10.1038/s41598-020-80507-7. short: R. Pandey, Y. Al-Nuaimi, R.K. Mishra, S.K. Spurgeon, M. Goodfellow, Scientific Reports 11 (2021). date_created: 2021-02-07T23:01:12Z date_published: 2021-01-26T00:00:00Z date_updated: 2022-08-19T07:22:23Z day: '26' ddc: - '570' department: - _id: PeJo doi: 10.1038/s41598-020-80507-7 file: - access_level: open_access checksum: e8a68df48750712671f5c47b0228e531 content_type: application/pdf creator: dernst date_created: 2021-02-09T07:33:23Z date_updated: 2021-02-09T07:33:23Z file_id: '9106' file_name: 2021_ScientificReports_Pandey.pdf file_size: 2885056 relation: main_file success: 1 file_date_updated: 2021-02-09T07:33:23Z has_accepted_license: '1' intvolume: ' 11' language: - iso: eng month: '01' oa: 1 oa_version: Published Version publication: Scientific Reports publication_identifier: eissn: - '20452322' publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 11 year: '2021' ... --- _id: '9329' abstract: - lang: eng text: "Background: To understand information coding in single neurons, it is necessary to analyze subthreshold synaptic events, action potentials (APs), and their interrelation in different behavioral states. However, detecting excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) in behaving animals remains challenging, because of unfavorable signal-to-noise ratio, high frequency, fluctuating amplitude, and variable time course of synaptic events.\r\nNew method: We developed a method for synaptic event detection, termed MOD (Machine-learning Optimal-filtering Detection-procedure), which combines concepts of supervised machine learning and optimal Wiener filtering. Experts were asked to manually score short epochs of data. The algorithm was trained to obtain the optimal filter coefficients of a Wiener filter and the optimal detection threshold. Scored and unscored data were then processed with the optimal filter, and events were detected as peaks above threshold.\r\nResults: We challenged MOD with EPSP traces in vivo in mice during spatial navigation and EPSC traces in vitro in slices under conditions of enhanced transmitter release. The area under the curve (AUC) of the receiver operating characteristics (ROC) curve was, on average, 0.894 for in vivo and 0.969 for in vitro data sets, indicating high detection accuracy and efficiency.\r\nComparison with existing methods: When benchmarked using a (1 − AUC)−1 metric, MOD outperformed previous methods (template-fit, deconvolution, and Bayesian methods) by an average factor of 3.13 for in vivo data sets, but showed comparable (template-fit, deconvolution) or higher (Bayesian) computational efficacy.\r\nConclusions: MOD may become an important new tool for large-scale, real-time analysis of synaptic activity." acknowledged_ssus: - _id: SSU acknowledgement: This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement number 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award to P.J.). We thank Drs. Jozsef Csicsvari, Christoph Lampert, and Federico Stella for critically reading previous manuscript versions. We are also grateful to Drs. Josh Merel and Ben Shababo for their help with applying the Bayesian detection method to our data. We also thank Florian Marr for technical assistance, Eleftheria Kralli-Beller for manuscript editing, and the Scientific Service Units of IST Austria for efficient support. article_number: '109125' article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Xiaomin full_name: Zhang, Xiaomin id: 423EC9C2-F248-11E8-B48F-1D18A9856A87 last_name: Zhang - first_name: Alois full_name: Schlögl, Alois id: 45BF87EE-F248-11E8-B48F-1D18A9856A87 last_name: Schlögl orcid: 0000-0002-5621-8100 - first_name: David H full_name: Vandael, David H id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87 last_name: Vandael orcid: 0000-0001-7577-1676 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: 'Zhang X, Schlögl A, Vandael DH, Jonas PM. MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo. Journal of Neuroscience Methods. 2021;357(6). doi:10.1016/j.jneumeth.2021.109125' apa: 'Zhang, X., Schlögl, A., Vandael, D. H., & Jonas, P. M. (2021). MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo. Journal of Neuroscience Methods. Elsevier. https://doi.org/10.1016/j.jneumeth.2021.109125' chicago: 'Zhang, Xiaomin, Alois Schlögl, David H Vandael, and Peter M Jonas. “MOD: A Novel Machine-Learning Optimal-Filtering Method for Accurate and Efficient Detection of Subthreshold Synaptic Events in Vivo.” Journal of Neuroscience Methods. Elsevier, 2021. https://doi.org/10.1016/j.jneumeth.2021.109125.' ieee: 'X. Zhang, A. Schlögl, D. H. Vandael, and P. M. Jonas, “MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo,” Journal of Neuroscience Methods, vol. 357, no. 6. Elsevier, 2021.' ista: 'Zhang X, Schlögl A, Vandael DH, Jonas PM. 2021. MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo. Journal of Neuroscience Methods. 357(6), 109125.' mla: 'Zhang, Xiaomin, et al. “MOD: A Novel Machine-Learning Optimal-Filtering Method for Accurate and Efficient Detection of Subthreshold Synaptic Events in Vivo.” Journal of Neuroscience Methods, vol. 357, no. 6, 109125, Elsevier, 2021, doi:10.1016/j.jneumeth.2021.109125.' short: X. Zhang, A. Schlögl, D.H. Vandael, P.M. Jonas, Journal of Neuroscience Methods 357 (2021). date_created: 2021-04-18T22:01:39Z date_published: 2021-03-09T00:00:00Z date_updated: 2023-08-07T14:36:14Z day: '09' ddc: - '570' department: - _id: PeJo - _id: ScienComp doi: 10.1016/j.jneumeth.2021.109125 ec_funded: 1 external_id: isi: - '000661088500005' file: - access_level: open_access checksum: 2a5800d91b96d08b525e17319dcd5e44 content_type: application/pdf creator: dernst date_created: 2021-04-19T08:30:22Z date_updated: 2021-04-19T08:30:22Z file_id: '9339' file_name: 2021_JourNeuroscienceMeth_Zhang.pdf file_size: 6924738 relation: main_file success: 1 file_date_updated: 2021-04-19T08:30:22Z has_accepted_license: '1' intvolume: ' 357' isi: 1 issue: '6' language: - iso: eng month: '03' oa: 1 oa_version: Published Version project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize publication: Journal of Neuroscience Methods publication_identifier: eissn: - 1872-678X issn: - 0165-0270 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: 'MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo' tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 357 year: '2021' ...