[{"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"has_accepted_license":"1","date_published":"2022-04-20T00:00:00Z","ddc":["570"],"corr_author":"1","author":[{"first_name":"Olena","last_name":"Kim","full_name":"Kim, Olena","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2344-1039"}],"day":"20","year":"2022","file":[{"embargo":"2023-04-19","file_name":"Olena_KIM_thesis_final.pdf","file_id":"11220","creator":"okim","content_type":"application/pdf","date_updated":"2023-04-20T22:30:03Z","file_size":21273537,"relation":"main_file","date_created":"2022-04-20T14:21:56Z","checksum":"1616a8bf6f13a57c892dac873dcd0936","access_level":"open_access"},{"file_name":"KIM_thesis_final.zip","file_id":"11221","creator":"okim","content_type":"application/x-zip-compressed","date_updated":"2023-04-20T22:30:03Z","embargo_to":"open_access","file_size":59248569,"checksum":"1acb433f98dc42abb0b4b0cbb0c4b918","date_created":"2022-04-20T14:22:56Z","relation":"source_file","access_level":"closed"}],"status":"public","publication_status":"published","publisher":"Institute of Science and Technology Austria","date_updated":"2026-06-18T10:49:27Z","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"}],"project":[{"name":"Presynaptic calcium channels distribution and impact on coupling at the hippocampal mossy fiber synapse","call_identifier":"H2020","_id":"25BAF7B2-B435-11E9-9278-68D0E5697425","grant_number":"708497"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"_id":"25C3DBB6-B435-11E9-9278-68D0E5697425","grant_number":"W01205","name":"Zellkommunikation in Gesundheit und Krankheit","call_identifier":"FWF"},{"call_identifier":"FWF","name":"Synaptic communication in neuronal microcircuits","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425"}],"page":"132","article_processing_charge":"No","supervisor":[{"orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","last_name":"Jonas"}],"file_date_updated":"2023-04-20T22:30:03Z","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"}],"ec_funded":1,"alternative_title":["ISTA Thesis"],"title":"Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses","language":[{"iso":"eng"}],"OA_place":"publisher","department":[{"_id":"PeJo"},{"_id":"GradSch"}],"oa":1,"oa_version":"Published Version","doi":"10.15479/at:ista:11196","date_created":"2022-04-20T09:47:12Z","publication_identifier":{"issn":["2663-337X"]},"_id":"11196","related_material":{"record":[{"id":"7473","relation":"part_of_dissertation","status":"public"},{"relation":"part_of_dissertation","status":"public","id":"11222"}]},"degree_awarded":"PhD","citation":{"ista":"Kim O. 2022. Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses. Institute of Science and Technology Austria.","apa":"Kim, O. (2022). <i>Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:11196\">https://doi.org/10.15479/at:ista:11196</a>","ieee":"O. Kim, “Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses,” Institute of Science and Technology Austria, 2022.","mla":"Kim, Olena. <i>Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:11196\">10.15479/at:ista:11196</a>.","short":"O. Kim, Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses, Institute of Science and Technology Austria, 2022.","chicago":"Kim, Olena. “Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:11196\">https://doi.org/10.15479/at:ista:11196</a>.","ama":"Kim O. Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:11196\">10.15479/at:ista:11196</a>"},"month":"04","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","type":"dissertation"},{"has_accepted_license":"1","keyword":["high ambient temperature","auxin","PINs","Zinc-Finger proteins","thermomorphogenesis","stress"],"date_published":"2022-08-17T00:00:00Z","ddc":["580"],"corr_author":"1","author":[{"first_name":"Christina","last_name":"Artner","full_name":"Artner, Christina","id":"45DF286A-F248-11E8-B48F-1D18A9856A87"}],"day":"17","year":"2022","file":[{"file_id":"11907","file_name":"ChristinaArtner_PhD_Thesis_2022.pdf","embargo":"2023-09-08","access_level":"open_access","relation":"main_file","checksum":"a2c2fdc28002538840490bfa6a08b2cb","date_created":"2022-08-17T12:08:49Z","file_size":11113608,"date_updated":"2023-09-09T22:30:03Z","content_type":"application/pdf","creator":"cartner"},{"file_name":"ChristinaArtner_PhD_Thesis_2022.7z","file_id":"11908","creator":"cartner","embargo_to":"open_access","file_size":19097730,"content_type":"application/octet-stream","date_updated":"2023-09-09T22:30:03Z","relation":"source_file","checksum":"66b461c074b815fbe63481b3f46a9f43","date_created":"2022-08-17T12:08:59Z","access_level":"closed"}],"publication_status":"published","status":"public","publisher":"Institute of Science and Technology Austria","date_updated":"2026-04-07T14:30:39Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"SSU"}],"project":[{"name":"Hormonal regulation of plant adaptive responses to environmental signals","_id":"2685A872-B435-11E9-9278-68D0E5697425"}],"supervisor":[{"orcid":"0000-0002-8510-9739","id":"38F4F166-F248-11E8-B48F-1D18A9856A87","full_name":"Benková, Eva","last_name":"Benková","first_name":"Eva"}],"article_processing_charge":"No","page":"128","file_date_updated":"2023-09-09T22:30:03Z","alternative_title":["ISTA Thesis"],"abstract":[{"lang":"eng","text":"As the overall global mean surface temperature is increasing due to climate change, plant\r\nadaptation to those stressful conditions is of utmost importance for their survival. Plants are\r\nsessile organisms, thus to compensate for their lack of mobility, they evolved a variety of\r\nmechanisms enabling them to flexibly adjust their physiological, growth and developmental\r\nprocesses to fluctuating temperatures and to survive in harsh environments. While these unique\r\nadaptation abilities provide an important evolutionary advantage, overall modulation of plant\r\ngrowth and developmental program due to non-optimal temperature negatively affects biomass\r\nproduction, crop productivity or sensitivity to pathogens. Thus, understanding molecular\r\nprocesses underlying plant adaptation to increased temperature can provide important\r\nresources for breeding strategies to ensure sufficient agricultural food production.\r\nAn increase in ambient temperature by a few degrees leads to profound changes in organ growth\r\nincluding enhanced hypocotyl elongation, expansion of petioles, hyponastic growth of leaves and\r\ncotyledons, collectively named thermomorphogenesis (Casal & Balasubramanian, 2019). Auxin,\r\none of the best-studied growth hormones, plays an essential role in this process by direct\r\nactivation of transcriptional and non-transcriptional processes resulting in elongation growth\r\n(Majda & Robert, 2018).To modulate hypocotyl growth in response to high ambient temperature\r\n(hAT), auxin needs to be redistributed accordingly. PINs, auxin efflux transporters, are key\r\ncomponents of the polar auxin transport (PAT) machinery, which controls the amount and\r\ndirection of auxin translocated in the plant tissues and organs(Adamowski & Friml, 2015). Hence,\r\nPIN-mediated transport is tightly linked with thermo-morphogenesis, and interference with PAT\r\nthrough either chemical or genetic means dramatically affecting the adaptive responses to hAT.\r\nIntriguingly, despite the key role of PIN mediated transport in growth response to hAT, whether\r\nand how PINs at the level of expression adapt to fluctuation in temperature is scarcely\r\nunderstood.\r\nWith genetic, molecular and advanced bio-imaging approaches, we demonstrate the role of PIN\r\nauxin transporters in the regulation of hypocotyl growth in response to hAT. We show that via\r\nadjustment of PIN3, PIN4 and PIN7 expression in cotyledons and hypocotyls, auxin distribution is modulated thereby determining elongation pattern of epidermal cells at hAT. Furthermore, we\r\nidentified three Zinc-Finger (ZF) transcription factors as novel molecular components of the\r\nthermo-regulatory network, which through negative regulation of PIN transcription adjust the\r\ntransport of auxin at hAT. Our results suggest that the ZF-PIN module might be a part of the\r\nnegative feedback loop attenuating the activity of the thermo-sensing pathway to restrain\r\nexaggerated growth and developmental responses to hAT."}],"title":"Modulation of auxin transport via ZF proteins adjust plant response to high ambient temperature","language":[{"iso":"eng"}],"OA_place":"publisher","department":[{"_id":"GradSch"},{"_id":"EvBe"}],"oa":1,"oa_version":"Published Version","publication_identifier":{"isbn":["978-3-99078-022-0"],"issn":["2663-337X"]},"_id":"11879","date_created":"2022-08-17T07:58:53Z","doi":"10.15479/at:ista:11879","acknowledgement":"I would like to acknowledge ISTA and all the people from the Scientific Service Units and at ISTA, in particular Dorota Jaworska for excellent technical and scientific support as well as ÖAW for funding my research for over 3 years (DOC ÖAW Fellowship PR1022OEAW02).","citation":{"ama":"Artner C. Modulation of auxin transport via ZF proteins adjust plant response to high ambient temperature. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:11879\">10.15479/at:ista:11879</a>","chicago":"Artner, Christina. “Modulation of Auxin Transport via ZF Proteins Adjust Plant Response to High Ambient Temperature.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:11879\">https://doi.org/10.15479/at:ista:11879</a>.","short":"C. Artner, Modulation of Auxin Transport via ZF Proteins Adjust Plant Response to High Ambient Temperature, Institute of Science and Technology Austria, 2022.","mla":"Artner, Christina. <i>Modulation of Auxin Transport via ZF Proteins Adjust Plant Response to High Ambient Temperature</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:11879\">10.15479/at:ista:11879</a>.","ieee":"C. Artner, “Modulation of auxin transport via ZF proteins adjust plant response to high ambient temperature,” Institute of Science and Technology Austria, 2022.","apa":"Artner, C. (2022). <i>Modulation of auxin transport via ZF proteins adjust plant response to high ambient temperature</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:11879\">https://doi.org/10.15479/at:ista:11879</a>","ista":"Artner C. 2022. Modulation of auxin transport via ZF proteins adjust plant response to high ambient temperature. Institute of Science and Technology Austria."},"degree_awarded":"PhD","type":"dissertation","month":"08","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd"},{"type":"dissertation","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","month":"05","citation":{"apa":"Jevtic, M. (2022). <i>Contextual fear learning induced changes in AMPA receptor subtypes along the proximodistal axis in dorsal hippocampus</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:11393\">https://doi.org/10.15479/at:ista:11393</a>","ista":"Jevtic M. 2022. Contextual fear learning induced changes in AMPA receptor subtypes along the proximodistal axis in dorsal hippocampus. Institute of Science and Technology Austria.","chicago":"Jevtic, Marijo. “Contextual Fear Learning Induced Changes in AMPA Receptor Subtypes along the Proximodistal Axis in Dorsal Hippocampus.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:11393\">https://doi.org/10.15479/at:ista:11393</a>.","ama":"Jevtic M. Contextual fear learning induced changes in AMPA receptor subtypes along the proximodistal axis in dorsal hippocampus. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:11393\">10.15479/at:ista:11393</a>","ieee":"M. Jevtic, “Contextual fear learning induced changes in AMPA receptor subtypes along the proximodistal axis in dorsal hippocampus,” Institute of Science and Technology Austria, 2022.","mla":"Jevtic, Marijo. <i>Contextual Fear Learning Induced Changes in AMPA Receptor Subtypes along the Proximodistal Axis in Dorsal Hippocampus</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:11393\">10.15479/at:ista:11393</a>.","short":"M. Jevtic, Contextual Fear Learning Induced Changes in AMPA Receptor Subtypes along the Proximodistal Axis in Dorsal Hippocampus, Institute of Science and Technology Austria, 2022."},"degree_awarded":"PhD","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"7391"}]},"_id":"11393","publication_identifier":{"issn":["2663-337X"]},"date_created":"2022-05-17T08:57:41Z","doi":"10.15479/at:ista:11393","oa_version":"Published Version","oa":1,"department":[{"_id":"GradSch"},{"_id":"RySh"}],"OA_place":"publisher","language":[{"iso":"eng"}],"title":"Contextual fear learning induced changes in AMPA receptor subtypes along the proximodistal axis in dorsal hippocampus","alternative_title":["ISTA Thesis"],"abstract":[{"lang":"eng","text":"AMPA receptors (AMPARs) mediate fast excitatory neurotransmission and their role is\r\nimplicated in complex processes such as learning and memory and various neurological\r\ndiseases. These receptors are composed of different subunits and the subunit composition can\r\naffect channel properties, receptor trafficking and interaction with other associated proteins.\r\nUsing the high sensitivity SDS-digested freeze-fracture replica labeling (SDS-FRL) for\r\nelectron microscopy I investigated the number, density, and localization of AMPAR subunits,\r\nGluA1, GluA2, GluA3, and GluA1-3 (panAMPA) in pyramidal cells in the CA1 area of mouse\r\nhippocampus. I have found that the immunogold labeling for all of these subunits in the\r\npostsynaptic sites was highest in stratum radiatum and lowest in stratum lacunosummoleculare. The labeling density for the all subunits in the extrasynaptic sites showed a gradual\r\nincrease from the pyramidal cell soma towards the distal part of stratum radiatum. The densities\r\nof extrasynaptic GluA1, GluA2 and panAMPA labeling reached 10-15% of synaptic densities,\r\nwhile the ratio of extrasynaptic labeling for GluA3 was significantly lower compared than those\r\nfor other subunits. The labeling patterns for GluA1, GluA2 and GluA1-3 are similar and their\r\ndensities were higher in the periphery than center of synapses. In contrast, the GluA3-\r\ncontaining receptors were more centrally localized compared to the GluA1- and GluA2-\r\ncontaining receptors.\r\nThe hippocampus plays a central role in learning and memory. Contextual learning has been\r\nshown to require the delivery of AMPA receptors to CA1 synapses in the dorsal hippocampus.\r\nHowever, proximodistal heterogeneity of this plasticity and particular contribution of different\r\nAMPA receptor subunits are not fully understood. By combining inhibitory avoidance task, a\r\nhippocampus-dependent contextual fear-learning paradigm, with SDS-FRL, I have revealed an\r\nincrease in synaptic density specific to GluA1-containing AMPA receptors in the CA1 area.\r\nThe intrasynaptic distribution of GluA1 also changed from the periphery to center-preferred\r\npattern. Furthermore, this synaptic plasticity was evident selectively in stratum radiatum but\r\nnot stratum oriens, and in the CA1 subregion proximal but not distal to CA2. These findings\r\nfurther contribute to our understanding of how specific hippocampal subregions and AMPA\r\nreceptor subunits are involved in physiological learning.\r\nAlthough the immunolabeling results above shed light on subunit-specific plasticity in\r\nAMPAR distribution, no tools to visualize and study the subunit composition at the single\r\nchannel level in situ have been available. Electron microscopy with conventional immunogold\r\nlabeling approaches has limitations in the single channel analysis because of the large size of\r\nantibodies and steric hindrance hampering multiple subunit labeling of single channels. I\r\nmanaged to develop a new chemical labeling system using a short peptide tag and small\r\nsynthetic probes, which form specific covalent bond with a cysteine residue in the tag fused to\r\nproteins of interest (reactive tag system). I additionally made substantial progress into adapting\r\nthis system for AMPA receptor subunits."}],"file_date_updated":"2023-05-17T22:30:03Z","supervisor":[{"orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi","last_name":"Shigemoto"}],"page":"108","article_processing_charge":"No","acknowledged_ssus":[{"_id":"EM-Fac"}],"date_updated":"2026-04-07T14:31:19Z","publisher":"Institute of Science and Technology Austria","publication_status":"published","status":"public","file":[{"file_id":"11395","file_name":"MJ thesis.docx","access_level":"closed","checksum":"8fc695d88020d70d231dad0e9f10b138","date_created":"2022-05-17T09:08:06Z","relation":"source_file","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_updated":"2023-05-17T22:30:03Z","file_size":56427603,"embargo_to":"open_access","creator":"cchlebak"},{"access_level":"open_access","date_created":"2022-05-17T12:09:25Z","checksum":"c1dd20a1aece521b3500607b00e463d6","relation":"main_file","file_size":4351981,"date_updated":"2023-05-17T22:30:03Z","content_type":"application/pdf","creator":"cchlebak","file_id":"11397","file_name":"MJ_thesis_PDFA.pdf","embargo":"2023-05-16"}],"year":"2022","day":"16","author":[{"id":"4BE3BC94-F248-11E8-B48F-1D18A9856A87","full_name":"Jevtic, Marijo","last_name":"Jevtic","first_name":"Marijo"}],"corr_author":"1","date_published":"2022-05-16T00:00:00Z","ddc":["570"],"has_accepted_license":"1"},{"type":"journal_article","month":"01","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"apa":"Belyaeva, V., Wachner, S., György, A., Emtenani, S., Gridchyn, I., Akhmanova, M., … Siekhaus, D. E. (2022). Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila. <i>PLoS Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pbio.3001494\">https://doi.org/10.1371/journal.pbio.3001494</a>","ista":"Belyaeva V, Wachner S, György A, Emtenani S, Gridchyn I, Akhmanova M, Linder M, Roblek M, Sibilia M, Siekhaus DE. 2022. Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila. PLoS Biology. 20(1), e3001494.","chicago":"Belyaeva, Vera, Stephanie Wachner, Attila György, Shamsi Emtenani, Igor Gridchyn, Maria Akhmanova, M Linder, Marko Roblek, M Sibilia, and Daria E Siekhaus. “Fos Regulates Macrophage Infiltration against Surrounding Tissue Resistance by a Cortical Actin-Based Mechanism in Drosophila.” <i>PLoS Biology</i>. Public Library of Science, 2022. <a href=\"https://doi.org/10.1371/journal.pbio.3001494\">https://doi.org/10.1371/journal.pbio.3001494</a>.","ama":"Belyaeva V, Wachner S, György A, et al. Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila. <i>PLoS Biology</i>. 2022;20(1):e3001494. doi:<a href=\"https://doi.org/10.1371/journal.pbio.3001494\">10.1371/journal.pbio.3001494</a>","ieee":"V. Belyaeva <i>et al.</i>, “Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila,” <i>PLoS Biology</i>, vol. 20, no. 1. Public Library of Science, p. e3001494, 2022.","mla":"Belyaeva, Vera, et al. “Fos Regulates Macrophage Infiltration against Surrounding Tissue Resistance by a Cortical Actin-Based Mechanism in Drosophila.” <i>PLoS Biology</i>, vol. 20, no. 1, Public Library of Science, 2022, p. e3001494, doi:<a href=\"https://doi.org/10.1371/journal.pbio.3001494\">10.1371/journal.pbio.3001494</a>.","short":"V. Belyaeva, S. Wachner, A. György, S. Emtenani, I. Gridchyn, M. Akhmanova, M. Linder, M. Roblek, M. Sibilia, D.E. Siekhaus, PLoS Biology 20 (2022) e3001494."},"scopus_import":"1","acknowledgement":"We thank the following for their contributions: Plasmids were supplied by the Drosophila Genomics Resource Center (NIH 2P40OD010949-10A1); fly stocks were provided by K. Brueckner, B. Stramer, M. Uhlirova, O. Schuldiner, the Bloomington Drosophila Stock Center (NIH P40OD018537) and the Vienna Drosophila Resource Center, FlyBase for essential genomic information, and the BDGP in situ database for data. For antibodies, we thank the Developmental Studies Hybridoma Bank, which was created by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the NIH and is maintained at the University of Iowa, as well as J. Zeitlinger for her generous gift of Dfos antibody. We thank the Vienna BioCenter Core Facilities for RNA sequencing and analysis and the Life Scientific Service Units at IST Austria for technical support and assistance with microscopy and FACS analysis. We thank C. P. Heisenberg, P. Martin, M. Sixt, and Siekhaus group members for discussions and T. Hurd, A. Ratheesh, and P. Rangan for comments on the manuscript.","_id":"10614","related_material":{"record":[{"relation":"earlier_version","status":"public","id":"8557"},{"relation":"dissertation_contains","status":"public","id":"11193"}],"link":[{"relation":"earlier_version","url":"https://www.biorxiv.org/content/10.1101/2020.09.18.301481"},{"description":"News on the ISTA Website","relation":"press_release","url":"https://ista.ac.at/en/news/resisting-the-pressure/"}]},"publication_identifier":{"issn":["1544-9173"],"eissn":["1545-7885"]},"doi":"10.1371/journal.pbio.3001494","date_created":"2022-01-12T10:18:17Z","oa_version":"Published Version","oa":1,"department":[{"_id":"DaSi"},{"_id":"JoCs"}],"quality_controlled":"1","language":[{"iso":"eng"}],"issue":"1","title":"Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila","volume":20,"ec_funded":1,"publication":"PLoS Biology","abstract":[{"lang":"eng","text":"The infiltration of immune cells into tissues underlies the establishment of tissue-resident macrophages and responses to infections and tumors. Yet the mechanisms immune cells utilize to negotiate tissue barriers in living organisms are not well understood, and a role for cortical actin has not been examined. Here, we find that the tissue invasion of Drosophila macrophages, also known as plasmatocytes or hemocytes, utilizes enhanced cortical F-actin levels stimulated by the Drosophila member of the fos proto oncogene transcription factor family (Dfos, Kayak). RNA sequencing analysis and live imaging show that Dfos enhances F-actin levels around the entire macrophage surface by increasing mRNA levels of the membrane spanning molecular scaffold tetraspanin TM4SF, and the actin cross-linking filamin Cheerio, which are themselves required for invasion. Both the filamin and the tetraspanin enhance the cortical activity of Rho1 and the formin Diaphanous and thus the assembly of cortical actin, which is a critical function since expressing a dominant active form of Diaphanous can rescue the Dfos macrophage invasion defect. In vivo imaging shows that Dfos enhances the efficiency of the initial phases of macrophage tissue entry. Genetic evidence argues that this Dfos-induced program in macrophages counteracts the constraint produced by the tension of surrounding tissues and buffers the properties of the macrophage nucleus from affecting tissue entry. We thus identify strengthening the cortical actin cytoskeleton through Dfos as a key process allowing efficient forward movement of an immune cell into surrounding tissues. "}],"file_date_updated":"2022-01-12T13:50:04Z","article_processing_charge":"No","external_id":{"isi":["000971223700001"],"pmid":["34990456"]},"page":"e3001494","project":[{"grant_number":"P29638","_id":"253B6E48-B435-11E9-9278-68D0E5697425","name":"The role of Drosophila TNF alpha in immune cell invasion","call_identifier":"FWF"},{"_id":"26199CA4-B435-11E9-9278-68D0E5697425","grant_number":"24800","name":"Implications of a TGFβ/Dpp-activated subpopulation for Drosophila macrophage migration"},{"call_identifier":"FP7","name":"Investigating the role of transporters in invasive migration through junctions","_id":"2536F660-B435-11E9-9278-68D0E5697425","grant_number":"334077"}],"acknowledged_ssus":[{"_id":"LifeSc"}],"date_updated":"2026-06-27T22:30:05Z","publisher":"Public Library of Science","article_type":"original","pmid":1,"publication_status":"published","status":"public","file":[{"access_level":"open_access","relation":"main_file","checksum":"f454212a5522a7818ba4b2892315c478","date_created":"2022-01-12T13:50:04Z","file_size":5426932,"content_type":"application/pdf","date_updated":"2022-01-12T13:50:04Z","creator":"cchlebak","file_id":"10615","file_name":"2022_PLOSBio_Belyaeva.pdf","success":1}],"year":"2022","day":"06","author":[{"last_name":"Belyaeva","first_name":"Vera","id":"47F080FE-F248-11E8-B48F-1D18A9856A87","full_name":"Belyaeva, Vera"},{"full_name":"Wachner, Stephanie","id":"2A95E7B0-F248-11E8-B48F-1D18A9856A87","first_name":"Stephanie","last_name":"Wachner"},{"id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","full_name":"György, Attila","orcid":"0000-0002-1819-198X","last_name":"György","first_name":"Attila"},{"first_name":"Shamsi","last_name":"Emtenani","full_name":"Emtenani, Shamsi","id":"49D32318-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6981-6938"},{"last_name":"Gridchyn","first_name":"Igor","id":"4B60654C-F248-11E8-B48F-1D18A9856A87","full_name":"Gridchyn, Igor","orcid":"0000-0002-1807-1929"},{"first_name":"Maria","last_name":"Akhmanova","orcid":"0000-0003-1522-3162","full_name":"Akhmanova, Maria","id":"3425EC26-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Linder","first_name":"M","full_name":"Linder, M"},{"first_name":"Marko","last_name":"Roblek","orcid":"0000-0001-9588-1389","full_name":"Roblek, Marko","id":"3047D808-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sibilia, M","first_name":"M","last_name":"Sibilia"},{"last_name":"Siekhaus","first_name":"Daria E","orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","full_name":"Siekhaus, Daria E"}],"corr_author":"1","date_published":"2022-01-06T00:00:00Z","ddc":["570"],"has_accepted_license":"1","intvolume":"        20","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"isi":1},{"author":[{"last_name":"Villa","first_name":"Carlo Emanuele","full_name":"Villa, Carlo Emanuele"},{"last_name":"Cheroni","first_name":"Cristina","full_name":"Cheroni, Cristina"},{"last_name":"Dotter","first_name":"Christoph","orcid":"0000-0002-9033-9096","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","full_name":"Dotter, Christoph"},{"full_name":"López-Tóbon, Alejandro","first_name":"Alejandro","last_name":"López-Tóbon"},{"first_name":"Bárbara","last_name":"Oliveira","full_name":"Oliveira, Bárbara","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87"},{"id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","full_name":"Sacco, Roberto","last_name":"Sacco","first_name":"Roberto"},{"last_name":"Yahya","first_name":"Aysan Çerağ","id":"365A65F8-F248-11E8-B48F-1D18A9856A87","full_name":"Yahya, Aysan Çerağ"},{"last_name":"Morandell","first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin"},{"last_name":"Gabriele","first_name":"Michele","full_name":"Gabriele, Michele"},{"id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","full_name":"Tavakoli, Mojtaba","orcid":"0000-0002-7667-6854","last_name":"Tavakoli","first_name":"Mojtaba"},{"first_name":"Julia","last_name":"Lyudchik","full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Sommer","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105"},{"full_name":"Gabitto, Mariano","first_name":"Mariano","last_name":"Gabitto"},{"first_name":"Johann G","last_name":"Danzl","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973"},{"first_name":"Giuseppe","last_name":"Testa","full_name":"Testa, Giuseppe"},{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"}],"corr_author":"1","date_published":"2022-04-05T00:00:00Z","ddc":["570"],"keyword":["General Biochemistry","Genetics and Molecular Biology"],"has_accepted_license":"1","intvolume":"        39","isi":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"date_updated":"2026-06-27T22:30:04Z","article_type":"original","publisher":"Elsevier","status":"public","publication_status":"published","pmid":1,"file":[{"creator":"dernst","content_type":"application/pdf","date_updated":"2022-04-15T09:06:25Z","file_size":"7808644","checksum":"b4e8d68f0268dec499af333e6fd5d8e1","date_created":"2022-04-15T09:06:25Z","relation":"main_file","access_level":"open_access","success":1,"file_name":"2022_CellReports_Villa.pdf","file_id":"11164"}],"year":"2022","day":"05","article_number":"110615","title":"CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories","abstract":[{"lang":"eng","text":"Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency affects neurodevelopmental is unclear. Here, employing human cerebral organoids, we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories with an accelerated and delayed generation of, respectively, inhibitory and excitatory neurons that yields, at days 60 and 120, symmetrically opposite expansions in their proportions. This imbalance is consistent with an enlargement of cerebral organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic design of patient-specific mutations and mosaic organoids, we define genotype-phenotype relationships and uncover their cell-autonomous nature. Our results define cell-type-specific CHD8-dependent molecular defects related to an abnormal program of proliferation and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations, our study uncovers reproducible developmental alterations that may be employed for neurodevelopmental disease modeling."}],"publication":"Cell Reports","ec_funded":1,"volume":39,"file_date_updated":"2022-04-15T09:06:25Z","external_id":{"isi":["000785983900003"],"pmid":["35385734"]},"article_processing_charge":"Yes","project":[{"call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508"},{"name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","call_identifier":"FWF","_id":"2690FEAC-B435-11E9-9278-68D0E5697425","grant_number":"I04205"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","month":"04","type":"journal_article","scopus_import":"1","citation":{"short":"C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco, A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer, M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022).","mla":"Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>, vol. 39, no. 1, 110615, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">10.1016/j.celrep.2022.110615</a>.","ieee":"C. E. Villa <i>et al.</i>, “CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories,” <i>Cell Reports</i>, vol. 39, no. 1. Elsevier, 2022.","ama":"Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>. 2022;39(1). doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">10.1016/j.celrep.2022.110615</a>","chicago":"Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon, Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">https://doi.org/10.1016/j.celrep.2022.110615</a>.","ista":"Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ, Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG, Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615.","apa":"Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco, R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">https://doi.org/10.1016/j.celrep.2022.110615</a>"},"acknowledgement":"We thank Farnaz Freeman for technical assistance. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facility (BIF) and the Life Science Facility (LSF). This work supported by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 to G.N. (REVERSEAUTISM) and grant 825759 to G.T. (ENDpoiNTs); the Fondazione Cariplo 2017-0886 to A.L.T.; E-Rare-3 JTC 2018 IMPACT to M. Gabriele; and the Austrian Science Fund FWF I 4205-B to G.N. Graphical abstract and figures were created using BioRender.com.","doi":"10.1016/j.celrep.2022.110615","date_created":"2022-04-15T09:03:10Z","_id":"11160","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"18681"},{"id":"18674","status":"public","relation":"dissertation_contains"},{"id":"12364","status":"public","relation":"dissertation_contains"}]},"publication_identifier":{"issn":["2211-1247"]},"oa_version":"Published Version","oa":1,"department":[{"_id":"JoDa"},{"_id":"GaNo"}],"issue":"1","quality_controlled":"1","language":[{"iso":"eng"}]},{"project":[{"grant_number":"401299","_id":"254BA948-B435-11E9-9278-68D0E5697425","name":"Probing development and reversibility of autism spectrum disorders"},{"name":"Critical windows and reversibility of ASD associated with mutations in chromatin remodelers","_id":"9B91375C-BA93-11EA-9121-9846C619BF3A","grant_number":"707964"},{"_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020"},{"call_identifier":"FWF","name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","grant_number":"I04205","_id":"2690FEAC-B435-11E9-9278-68D0E5697425"}],"article_processing_charge":"No","page":"152","supervisor":[{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino","first_name":"Gaia"}],"file_date_updated":"2023-09-20T22:30:03Z","abstract":[{"text":"Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders character\u0002ized by behavioral symptoms such as problems in social communication and interaction, as\r\nwell as repetitive, restricted behaviors and interests. These disorders show a high degree\r\nof heritability and hundreds of risk genes have been identifed using high throughput\r\nsequencing technologies. This genetic heterogeneity has hampered eforts in understanding\r\nthe pathogenesis of ASD but at the same time given rise to the concept of convergent\r\nmechanisms. Previous studies have identifed that risk genes for ASD broadly converge\r\nonto specifc functional categories with transcriptional regulation being one of the biggest\r\ngroups. In this thesis, I focus on this subgroup of genes and investigate the gene regulatory\r\nconsequences of some of them in the context of neurodevelopment.\r\nFirst, we showed that mutations in the ASD and intellectual disability risk gene Setd5 lead\r\nto perturbations of gene regulatory programs in early cell fate specifcation. In addition,\r\nadult animals display abnormal learning behavior which is mirrored at the transcriptional\r\nlevel by altered activity dependent regulation of postsynaptic gene expression. Lastly,\r\nwe link the regulatory function of Setd5 to its interaction with the Paf1 and the NCoR\r\ncomplex.\r\nSecond, by modeling the heterozygous loss of the top ASD gene CHD8 in human cerebral\r\norganoids we demonstrate profound changes in the developmental trajectories of both\r\ninhibitory and excitatory neurons using single cell RNA-sequencing. While the former\r\nwere generated earlier in CHD8+/- organoids, the generation of the latter was shifted to\r\nlater times in favor of a prolonged progenitor expansion phase and ultimately increased\r\norganoid size.\r\nFinally, by modeling heterozygous mutations for four ASD associated chromatin modifers,\r\nASH1L, KDM6B, KMT5B, and SETD5 in human cortical spheroids we show evidence of\r\nregulatory convergence across three of those genes. We observe a shift from dorsal cortical\r\nexcitatory neuron fates towards partially ventralized cell types resembling cells from the\r\nlateral ganglionic eminence. As this project is still ongoing at the time of writing, future\r\nexperiments will aim at elucidating the regulatory mechanisms underlying this shift with\r\nthe aim of linking these three ASD risk genes through biological convergence.","lang":"eng"}],"alternative_title":["ISTA Thesis"],"ec_funded":1,"title":"Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder","language":[{"iso":"eng"}],"OA_place":"publisher","department":[{"_id":"GradSch"},{"_id":"GaNo"}],"oa":1,"oa_version":"Published Version","date_created":"2023-01-24T13:09:57Z","doi":"10.15479/at:ista:12094","related_material":{"record":[{"id":"11160","status":"public","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","status":"public","id":"3"}]},"_id":"12364","publication_identifier":{"issn":["2663-337X"]},"degree_awarded":"PhD","citation":{"ieee":"C. Dotter, “Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder,” Institute of Science and Technology Austria, 2022.","mla":"Dotter, Christoph. <i>Transcriptional Consequences of Mutations in Genes Associated with Autism Spectrum Disorder</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:12094\">10.15479/at:ista:12094</a>.","short":"C. Dotter, Transcriptional Consequences of Mutations in Genes Associated with Autism Spectrum Disorder, Institute of Science and Technology Austria, 2022.","chicago":"Dotter, Christoph. “Transcriptional Consequences of Mutations in Genes Associated with Autism Spectrum Disorder.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:12094\">https://doi.org/10.15479/at:ista:12094</a>.","ama":"Dotter C. Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:12094\">10.15479/at:ista:12094</a>","ista":"Dotter C. 2022. Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder. Institute of Science and Technology Austria.","apa":"Dotter, C. (2022). <i>Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:12094\">https://doi.org/10.15479/at:ista:12094</a>"},"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","month":"09","type":"dissertation","has_accepted_license":"1","date_published":"2022-09-19T00:00:00Z","ddc":["570"],"corr_author":"1","author":[{"first_name":"Christoph","last_name":"Dotter","orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87"}],"day":"19","year":"2022","file":[{"file_id":"12365","file_name":"220923_Thesis_CDotter_Final.pdf","embargo":"2023-09-19","access_level":"open_access","checksum":"896f4cac9adb6d3f26a6605772f4e1a3","date_created":"2023-01-24T13:15:45Z","relation":"main_file","content_type":"application/pdf","date_updated":"2023-09-20T22:30:03Z","file_size":20457465,"creator":"cchlebak"},{"file_name":"latex_source_CDotter_Thesis_2022.zip","file_id":"12482","creator":"cchlebak","embargo_to":"open_access","file_size":22433512,"content_type":"application/x-zip-compressed","date_updated":"2023-09-20T22:30:03Z","date_created":"2023-02-02T09:15:35Z","relation":"source_file","checksum":"ad01bb20da163be6893b7af832e58419","access_level":"closed"}],"status":"public","publication_status":"published","publisher":"Institute of Science and Technology Austria","date_updated":"2026-04-07T14:30:57Z"},{"title":"Controllable states of superconducting Qubit ensembles","file_date_updated":"2023-01-26T23:30:44Z","abstract":[{"text":"Recent substantial advances in the feld of superconducting circuits have shown its\r\npotential as a leading platform for future quantum computing. In contrast to classical\r\ncomputers based on bits that are represented by a single binary value, 0 or 1, quantum\r\nbits (or qubits) can be in a superposition of both. Thus, quantum computers can store\r\nand handle more information at the same time and a quantum advantage has already\r\nbeen demonstrated for two types of computational tasks. Rapid progress in academic\r\nand industry labs accelerates the development of superconducting processors which may\r\nsoon fnd applications in complex computations, chemical simulations, cryptography, and\r\noptimization. Now that these machines are scaled up to tackle such problems the questions\r\nof qubit interconnects and networks becomes very relevant. How to route signals on-chip\r\nbetween diferent processor components? What is the most efcient way to entangle\r\nqubits? And how to then send and process entangled signals between distant cryostats\r\nhosting superconducting processors?\r\nIn this thesis, we are looking for solutions to these problems by studying the collective\r\nbehavior of superconducting qubit ensembles. We frst demonstrate on-demand tunable\r\ndirectional scattering of microwave photons from a pair of qubits in a waveguide. Such a\r\ndevice can route microwave photons on-chip with a high diode efciency. Then we focus\r\non studying ultra-strong coupling regimes between light (microwave photons) and matter\r\n(superconducting qubits), a regime that could be promising for extremely fast multi-qubit\r\nentanglement generation. Finally, we show coherent pulse storage and periodic revivals\r\nin a fve qubit ensemble strongly coupled to a resonator. Such a reconfgurable storage\r\ndevice could be used as part of a quantum repeater that is needed for longer-distance\r\nquantum communication.\r\nThe achieved high degree of control over multi-qubit ensembles highlights not only the\r\nbeautiful physics of circuit quantum electrodynamics, it also represents the frst step\r\ntoward new quantum simulation and communication methods, and certain techniques\r\nmay also fnd applications in future superconducting quantum computing hardware.\r\n","lang":"eng"}],"alternative_title":["ISTA Thesis"],"ec_funded":1,"project":[{"call_identifier":"H2020","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385"},{"call_identifier":"H2020","name":"A Fiber Optic Transceiver for Superconducting Qubits","grant_number":"758053","_id":"26336814-B435-11E9-9278-68D0E5697425"},{"_id":"237CBA6C-32DE-11EA-91FC-C7463DDC885E","grant_number":"862644","call_identifier":"H2020","name":"Quantum readout techniques and technologies"}],"article_processing_charge":"No","page":"168","supervisor":[{"last_name":"Fink","first_name":"Johannes M","id":"4B591CBA-F248-11E8-B48F-1D18A9856A87","full_name":"Fink, Johannes M","orcid":"0000-0001-8112-028X"}],"acknowledged_ssus":[{"_id":"NanoFab"},{"_id":"M-Shop"},{"_id":"EM-Fac"}],"degree_awarded":"PhD","citation":{"ama":"Redchenko E. Controllable states of superconducting Qubit ensembles. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:12132\">10.15479/at:ista:12132</a>","chicago":"Redchenko, Elena. “Controllable States of Superconducting Qubit Ensembles.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:12132\">https://doi.org/10.15479/at:ista:12132</a>.","short":"E. Redchenko, Controllable States of Superconducting Qubit Ensembles, Institute of Science and Technology Austria, 2022.","mla":"Redchenko, Elena. <i>Controllable States of Superconducting Qubit Ensembles</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:12132\">10.15479/at:ista:12132</a>.","ieee":"E. Redchenko, “Controllable states of superconducting Qubit ensembles,” Institute of Science and Technology Austria, 2022.","apa":"Redchenko, E. (2022). <i>Controllable states of superconducting Qubit ensembles</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:12132\">https://doi.org/10.15479/at:ista:12132</a>","ista":"Redchenko E. 2022. Controllable states of superconducting Qubit ensembles. Institute of Science and Technology Austria."},"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","month":"09","type":"dissertation","doi":"10.15479/at:ista:12132","date_created":"2023-01-25T09:17:02Z","publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-024-4"]},"_id":"12366","department":[{"_id":"GradSch"},{"_id":"JoFi"}],"oa_version":"Published Version","oa":1,"language":[{"iso":"eng"}],"OA_place":"publisher","author":[{"first_name":"Elena","last_name":"Redchenko","full_name":"Redchenko, Elena","id":"2C21D6E8-F248-11E8-B48F-1D18A9856A87"}],"date_published":"2022-09-26T00:00:00Z","ddc":["530"],"corr_author":"1","has_accepted_license":"1","publisher":"Institute of Science and Technology Austria","date_updated":"2026-04-07T14:22:39Z","status":"public","publication_status":"published","file":[{"access_level":"open_access","checksum":"39eabb1e006b41335f17f3b29af09648","date_created":"2023-01-25T09:41:49Z","relation":"main_file","date_updated":"2023-01-26T23:30:44Z","content_type":"application/pdf","file_size":56076868,"creator":"cchlebak","file_id":"12367","file_name":"Final_Thesis_ES_Redchenko.pdf","embargo":"2022-12-28"}],"day":"26","year":"2022"},{"oa":1,"oa_version":"Published Version","department":[{"_id":"GradSch"},{"_id":"DaSi"}],"OA_place":"publisher","language":[{"iso":"eng"}],"type":"dissertation","month":"04","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","citation":{"ista":"Wachner S. 2022. Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells. Institute of Science and Technology Austria.","apa":"Wachner, S. (2022). <i>Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:11193\">https://doi.org/10.15479/at:ista:11193</a>","ieee":"S. Wachner, “Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells,” Institute of Science and Technology Austria, 2022.","mla":"Wachner, Stephanie. <i>Transcriptional Regulation by Dfos and BMP-Signaling Support Tissue Invasion of Drosophila Immune Cells</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:11193\">10.15479/at:ista:11193</a>.","short":"S. Wachner, Transcriptional Regulation by Dfos and BMP-Signaling Support Tissue Invasion of Drosophila Immune Cells, Institute of Science and Technology Austria, 2022.","chicago":"Wachner, Stephanie. “Transcriptional Regulation by Dfos and BMP-Signaling Support Tissue Invasion of Drosophila Immune Cells.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:11193\">https://doi.org/10.15479/at:ista:11193</a>.","ama":"Wachner S. Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:11193\">10.15479/at:ista:11193</a>"},"degree_awarded":"PhD","publication_identifier":{"issn":["2663-337X"]},"_id":"11193","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"10614"},{"id":"544","relation":"part_of_dissertation","status":"public"}]},"doi":"10.15479/at:ista:11193","date_created":"2022-04-20T08:59:07Z","supervisor":[{"last_name":"Siekhaus","first_name":"Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353"}],"article_processing_charge":"No","page":"170","project":[{"_id":"26199CA4-B435-11E9-9278-68D0E5697425","grant_number":"24800","name":"Implications of a TGFβ/Dpp-activated subpopulation for Drosophila macrophage migration"}],"acknowledged_ssus":[{"_id":"LifeSc"}],"title":"Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells","alternative_title":["ISTA Thesis"],"abstract":[{"lang":"eng","text":"The infiltration of immune cells into tissues underlies the establishment of tissue-resident\r\nmacrophages and responses to infections and tumors. However, the mechanisms immune\r\ncells utilize to collectively migrate through tissue barriers in vivo are not yet well understood.\r\nIn this thesis, I describe two mechanisms that Drosophila immune cells (hemocytes) use to\r\novercome the tissue barrier of the germband in the embryo. One strategy is the strengthening\r\nof the actin cortex through developmentally controlled transcriptional regulation induced by\r\nthe Drosophila proto-oncogene family member Dfos, which I show in Chapter 2. Dfos induces\r\nexpression of the tetraspanin TM4SF and the filamin Cher leading to higher levels of the\r\nactivated formin Dia at the cortex and increased cortical F-actin. This enhanced cortical\r\nstrength allows hemocytes to overcome the physical resistance of the surrounding tissue and\r\ntranslocate their nucleus to move forward. This mechanism affects the speed of migration\r\nwhen hemocytes face a confined environment in vivo.\r\nAnother aspect of the invasion process is the initial step of the leading hemocytes entering\r\nthe tissue, which potentially guides the follower cells. In Chapter 3, I describe a novel\r\nsubpopulation of hemocytes activated by BMP signaling prior to tissue invasion that leads\r\npenetration into the germband. Hemocytes that are deficient in BMP signaling activation\r\nshow impaired persistence at the tissue entry, while their migration speed remains\r\nunaffected.\r\nThis suggests that there might be different mechanisms controlling immune cell migration\r\nwithin the confined environment in vivo, one of these being the general ability to overcome\r\nthe resistance of the surrounding tissue and another affecting the order of hemocytes that\r\ncollectively invade the tissue in a stream of individual cells.\r\nTogether, my findings provide deeper insights into transcriptional changes in immune\r\ncells that enable efficient tissue invasion and pave the way for future studies investigating the\r\nearly colonization of tissues by macrophages in higher organisms. Moreover, they extend the\r\ncurrent view of Drosophila immune cell heterogeneity and point toward a potentially\r\nconserved role for canonical BMP signaling in specifying immune cells that lead the migration\r\nof tissue resident macrophages during embryogenesis."}],"file_date_updated":"2023-04-21T22:30:03Z","file":[{"date_created":"2022-04-20T09:03:57Z","checksum":"999ab16884c4522486136ebc5ae8dbff","relation":"main_file","access_level":"open_access","creator":"cchlebak","file_size":8820951,"date_updated":"2023-04-21T22:30:03Z","content_type":"application/pdf","file_name":"Thesis_Stephanie_Wachner_20200414_formatted.pdf","file_id":"11195","embargo":"2023-04-20"},{"date_created":"2022-04-22T12:41:00Z","relation":"source_file","checksum":"fd92b1e38d53bdf8b458213882d41383","access_level":"closed","creator":"cchlebak","date_updated":"2023-04-21T22:30:03Z","content_type":"application/x-zip-compressed","embargo_to":"open_access","file_size":65864612,"file_name":"Thesis_Stephanie_Wachner_20200414.zip","file_id":"11329"}],"year":"2022","day":"20","date_updated":"2026-04-07T14:24:19Z","publisher":"Institute of Science and Technology Austria","publication_status":"published","status":"public","has_accepted_license":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"author":[{"full_name":"Wachner, Stephanie","id":"2A95E7B0-F248-11E8-B48F-1D18A9856A87","first_name":"Stephanie","last_name":"Wachner"}],"corr_author":"1","date_published":"2022-04-20T00:00:00Z","ddc":["570"]},{"publication_identifier":{"isbn":["978-3-99078-018-3"]},"_id":"11388","related_material":{"record":[{"id":"6713","status":"public","relation":"part_of_dissertation"}]},"date_created":"2022-05-16T16:49:18Z","doi":"10.15479/at:ista:11388","citation":{"ista":"Belohlavy S. 2022. The genetic basis of complex traits studied via analysis of evolve and resequence experiments. Institute of Science and Technology Austria.","apa":"Belohlavy, S. (2022). <i>The genetic basis of complex traits studied via analysis of evolve and resequence experiments</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:11388\">https://doi.org/10.15479/at:ista:11388</a>","ieee":"S. Belohlavy, “The genetic basis of complex traits studied via analysis of evolve and resequence experiments,” Institute of Science and Technology Austria, 2022.","mla":"Belohlavy, Stefanie. <i>The Genetic Basis of Complex Traits Studied via Analysis of Evolve and Resequence Experiments</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:11388\">10.15479/at:ista:11388</a>.","short":"S. Belohlavy, The Genetic Basis of Complex Traits Studied via Analysis of Evolve and Resequence Experiments, Institute of Science and Technology Austria, 2022.","chicago":"Belohlavy, Stefanie. “The Genetic Basis of Complex Traits Studied via Analysis of Evolve and Resequence Experiments.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:11388\">https://doi.org/10.15479/at:ista:11388</a>.","ama":"Belohlavy S. The genetic basis of complex traits studied via analysis of evolve and resequence experiments. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:11388\">10.15479/at:ista:11388</a>"},"degree_awarded":"PhD","type":"dissertation","month":"05","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","language":[{"iso":"eng"}],"OA_place":"publisher","department":[{"_id":"GradSch"},{"_id":"NiBa"}],"oa_version":"Published Version","oa":1,"file_date_updated":"2023-05-20T22:30:03Z","alternative_title":["ISTA Thesis"],"abstract":[{"lang":"eng","text":"In evolve and resequence experiments, a population is sequenced, subjected to selection and\r\nthen sequenced again, so that genetic changes before and after selection can be observed at\r\nthe genetic level. Here, I use these studies to better understand the genetic basis of complex\r\ntraits - traits which depend on more than a few genes.\r\nIn the first chapter, I discuss the first evolve and resequence experiment, in which a population\r\nof mice, the so-called \"Longshanks\" mice, were selected for tibia length while their body mass\r\nwas kept constant. The full pedigree is known. We observed a selection response on all\r\nchromosomes and used the infinitesimal model with linkage, a model which assumes an infinite\r\nnumber of genes with infinitesimally small effect sizes, as a null model. Results implied a very\r\npolygenic basis with a few loci of major effect standing out and changing in parallel. There\r\nwas large variability between the different chromosomes in this study, probably due to LD.\r\nIn chapter two, I go on to discuss the impact of LD, on the variability in an allele-frequency\r\nbased summary statistic, giving an equation based on the initial allele frequencies, average\r\npairwise LD, and the first four moments of the haplotype block copy number distribution. I\r\ndescribe this distribution by referring back to the founder generation. I then demonstrate\r\nhow to infer selection via a maximum likelihood scheme on the example of a single locus and\r\ndiscuss how to extend this to more realistic scenarios.\r\nIn chapter three, I discuss the second evolve and resequence experiment, in which a small\r\npopulation of Drosophila melanogaster was selected for increased pupal case size over 6\r\ngenerations. The experiment was highly replicated with 27 lines selected within family and a\r\nknown pedigree. We observed a phenotypic selection response of over one standard deviation.\r\nI describe the patterns in allele frequency data, including allele frequency changes and patterns\r\nof heterozygosity, and give ideas for future work."}],"title":"The genetic basis of complex traits studied via analysis of evolve and resequence experiments","supervisor":[{"id":"4880FE40-F248-11E8-B48F-1D18A9856A87","full_name":"Barton, Nicholas H","orcid":"0000-0002-8548-5240","last_name":"Barton","first_name":"Nicholas H"}],"page":"98","article_processing_charge":"No","publication_status":"published","status":"public","publisher":"Institute of Science and Technology Austria","date_updated":"2026-04-07T14:29:57Z","day":"18","year":"2022","file":[{"file_size":8247240,"content_type":"application/pdf","date_updated":"2023-05-20T22:30:03Z","creator":"sbelohla","access_level":"open_access","checksum":"4d75e6a619df7e8a9d6e840aee182380","relation":"main_file","date_created":"2022-05-19T13:03:13Z","embargo":"2023-05-19","file_id":"11398","file_name":"thesis_sb_final_pdfa.pdf"},{"file_name":"thesis_sb_final.zip","file_id":"11399","date_created":"2022-05-19T13:07:47Z","checksum":"7a5d8b6dd0ca00784f860075b0a7d8f0","relation":"source_file","access_level":"closed","creator":"sbelohla","date_updated":"2023-05-20T22:30:03Z","content_type":"application/x-zip-compressed","file_size":7094,"embargo_to":"open_access"}],"ddc":["576"],"date_published":"2022-05-18T00:00:00Z","corr_author":"1","author":[{"first_name":"Stefanie","last_name":"Belohlavy","orcid":"0000-0002-9849-498X","full_name":"Belohlavy, Stefanie","id":"43FE426A-F248-11E8-B48F-1D18A9856A87"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"has_accepted_license":"1"},{"has_accepted_license":"1","keyword":["General Neuroscience"],"intvolume":"        25","isi":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"author":[{"orcid":"0000-0001-9434-8902","full_name":"Colombo, Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","first_name":"Gloria","last_name":"Colombo"},{"first_name":"Ryan J","last_name":"Cubero","orcid":"0000-0003-0002-1867","full_name":"Cubero, Ryan J","id":"850B2E12-9CD4-11E9-837F-E719E6697425"},{"full_name":"Kanari, Lida","first_name":"Lida","last_name":"Kanari"},{"first_name":"Alessandro","last_name":"Venturino","orcid":"0000-0003-2356-9403","full_name":"Venturino, Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-5297-733X","full_name":"Schulz, Rouven","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","first_name":"Rouven","last_name":"Schulz"},{"full_name":"Scolamiero, Martina","last_name":"Scolamiero","first_name":"Martina"},{"full_name":"Agerberg, Jens","first_name":"Jens","last_name":"Agerberg"},{"full_name":"Mathys, Hansruedi","first_name":"Hansruedi","last_name":"Mathys"},{"last_name":"Tsai","first_name":"Li-Huei","full_name":"Tsai, Li-Huei"},{"last_name":"Chachólski","first_name":"Wojciech","full_name":"Chachólski, Wojciech"},{"full_name":"Hess, Kathryn","first_name":"Kathryn","last_name":"Hess"},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877","last_name":"Siegert","first_name":"Sandra"}],"corr_author":"1","ddc":["570"],"date_published":"2022-10-01T00:00:00Z","file":[{"success":1,"file_id":"12437","file_name":"2022_NatureNeuroscience_Colombo.pdf","file_size":23789835,"date_updated":"2023-01-30T08:06:56Z","content_type":"application/pdf","creator":"dernst","access_level":"open_access","checksum":"28431146873096f52e0107b534f178c9","date_created":"2023-01-30T08:06:56Z","relation":"main_file"}],"year":"2022","day":"01","date_updated":"2026-06-27T22:30:07Z","article_type":"original","publisher":"Springer Nature","publication_status":"published","pmid":1,"status":"public","external_id":{"isi":["000862214700001"],"pmid":["36180790"]},"article_processing_charge":"No","page":"1379-1393","project":[{"name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411"},{"call_identifier":"H2020","name":"Microglia action towards neuronal circuit formation and function in health and disease","grant_number":"715571","_id":"25D4A630-B435-11E9-9278-68D0E5697425"}],"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"ScienComp"}],"title":"A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes","volume":25,"ec_funded":1,"publication":"Nature Neuroscience","abstract":[{"lang":"eng","text":"Environmental cues influence the highly dynamic morphology of microglia. Strategies to characterize these changes usually involve user-selected morphometric features, which preclude the identification of a spectrum of context-dependent morphological phenotypes. Here we develop MorphOMICs, a topological data analysis approach, which enables semiautomatic mapping of microglial morphology into an atlas of cue-dependent phenotypes and overcomes feature-selection biases and biological variability. We extract spatially heterogeneous and sexually dimorphic morphological phenotypes for seven adult mouse brain regions. This sex-specific phenotype declines with maturation but increases over the disease trajectories in two neurodegeneration mouse models, with females showing a faster morphological shift in affected brain regions. Remarkably, microglia morphologies reflect an adaptation upon repeated exposure to ketamine anesthesia and do not recover to control morphologies. Finally, we demonstrate that both long primary processes and short terminal processes provide distinct insights to morphological phenotypes. MorphOMICs opens a new perspective to characterize microglial morphology."}],"file_date_updated":"2023-01-30T08:06:56Z","oa_version":"Published Version","oa":1,"department":[{"_id":"SaSi"}],"quality_controlled":"1","language":[{"iso":"eng"}],"issue":"10","type":"journal_article","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","month":"10","citation":{"ista":"Colombo G, Cubero RJ, Kanari L, Venturino A, Schulz R, Scolamiero M, Agerberg J, Mathys H, Tsai L-H, Chachólski W, Hess K, Siegert S. 2022. A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes. Nature Neuroscience. 25(10), 1379–1393.","apa":"Colombo, G., Cubero, R. J., Kanari, L., Venturino, A., Schulz, R., Scolamiero, M., … Siegert, S. (2022). A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes. <i>Nature Neuroscience</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41593-022-01167-6\">https://doi.org/10.1038/s41593-022-01167-6</a>","short":"G. Colombo, R.J. Cubero, L. Kanari, A. Venturino, R. Schulz, M. Scolamiero, J. Agerberg, H. Mathys, L.-H. Tsai, W. Chachólski, K. Hess, S. Siegert, Nature Neuroscience 25 (2022) 1379–1393.","mla":"Colombo, Gloria, et al. “A Tool for Mapping Microglial Morphology, MorphOMICs, Reveals Brain-Region and Sex-Dependent Phenotypes.” <i>Nature Neuroscience</i>, vol. 25, no. 10, Springer Nature, 2022, pp. 1379–93, doi:<a href=\"https://doi.org/10.1038/s41593-022-01167-6\">10.1038/s41593-022-01167-6</a>.","ieee":"G. Colombo <i>et al.</i>, “A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes,” <i>Nature Neuroscience</i>, vol. 25, no. 10. Springer Nature, pp. 1379–1393, 2022.","ama":"Colombo G, Cubero RJ, Kanari L, et al. A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes. <i>Nature Neuroscience</i>. 2022;25(10):1379-1393. doi:<a href=\"https://doi.org/10.1038/s41593-022-01167-6\">10.1038/s41593-022-01167-6</a>","chicago":"Colombo, Gloria, Ryan J Cubero, Lida Kanari, Alessandro Venturino, Rouven Schulz, Martina Scolamiero, Jens Agerberg, et al. “A Tool for Mapping Microglial Morphology, MorphOMICs, Reveals Brain-Region and Sex-Dependent Phenotypes.” <i>Nature Neuroscience</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41593-022-01167-6\">https://doi.org/10.1038/s41593-022-01167-6</a>."},"scopus_import":"1","acknowledgement":"We thank the scientific service units at ISTA, in particular M. Schunn’s team at the preclinical facility, and especially our colony manager S. Haslinger, for excellent support. We are also grateful to the ISTA Imaging & Optics Facility, and in particular C. Sommer for helping with the data file conversions. We thank R. Erhart from the ISTA Scientific Computing Unit for improving the script performance. We thank M. Maes, B. Nagy, S. Oakeley and M. Benevento and all members of the Siegert group for constant feedback on the project and on the manuscript. This research was supported by the European Union Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Actions program (754411 to R.J.A.C.), and by the European Research Council (grant no. 715571 to S.S.). L.K. was supported by funding to the Blue Brain Project, a research center of the École polytechnique fédérale de Lausanne, from the Swiss government’s ETH Board of the Swiss Federal Institutes of Technology. L.-H.T. was supported by NIH (grant no. R37NS051874) and by the JPB Foundation. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.","publication_identifier":{"issn":["1097-6256"],"eissn":["1546-1726"]},"_id":"12244","related_material":{"record":[{"id":"12378","status":"public","relation":"dissertation_contains"}],"link":[{"relation":"press_release","url":"https://ista.ac.at/en/news/morphomics-revealing-the-hidden-meaning-of-microglia-shape/","description":"News on ISTA website"}]},"date_created":"2023-01-16T09:53:07Z","doi":"10.1038/s41593-022-01167-6"},{"month":"08","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","type":"dissertation","degree_awarded":"PhD","citation":{"ista":"Nardin M. 2022. On the encoding, transfer, and consolidation of spatial memories. Institute of Science and Technology Austria.","apa":"Nardin, M. (2022). <i>On the encoding, transfer, and consolidation of spatial memories</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:11932\">https://doi.org/10.15479/at:ista:11932</a>","short":"M. Nardin, On the Encoding, Transfer, and Consolidation of Spatial Memories, Institute of Science and Technology Austria, 2022.","mla":"Nardin, Michele. <i>On the Encoding, Transfer, and Consolidation of Spatial Memories</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:11932\">10.15479/at:ista:11932</a>.","ieee":"M. Nardin, “On the encoding, transfer, and consolidation of spatial memories,” Institute of Science and Technology Austria, 2022.","ama":"Nardin M. On the encoding, transfer, and consolidation of spatial memories. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:11932\">10.15479/at:ista:11932</a>","chicago":"Nardin, Michele. “On the Encoding, Transfer, and Consolidation of Spatial Memories.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:11932\">https://doi.org/10.15479/at:ista:11932</a>."},"acknowledgement":"I acknowledge the support from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant Agreement No. 665385.","doi":"10.15479/at:ista:11932","date_created":"2022-08-19T08:52:30Z","related_material":{"record":[{"id":"6194","status":"public","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","status":"public","id":"10077"}]},"_id":"11932","publication_identifier":{"issn":["2663-337X"]},"oa":1,"oa_version":"Published Version","department":[{"_id":"GradSch"},{"_id":"JoCs"}],"OA_place":"publisher","language":[{"iso":"eng"}],"title":"On the encoding, transfer, and consolidation of spatial memories","abstract":[{"text":"The ability to form and retrieve memories is central to survival. In mammals, the hippocampus\r\nis a brain region essential to the acquisition and consolidation of new memories. It is also\r\ninvolved in keeping track of one’s position in space and aids navigation. Although this\r\nspace-memory has been a source of contradiction, evidence supports the view that the role of\r\nthe hippocampus in navigation is memory, thanks to the formation of cognitive maps. First\r\nintroduced by Tolman in 1948, cognitive maps are generally used to organize experiences in\r\nmemory; however, the detailed mechanisms by which these maps are formed and stored are not\r\nyet agreed upon. Some influential theories describe this process as involving three fundamental\r\nsteps: initial encoding by the hippocampus, interactions between the hippocampus and other\r\ncortical areas, and long-term extra-hippocampal consolidation. In this thesis, I will show how\r\nthe investigation of cognitive maps of space helped to shed light on each of these three memory\r\nprocesses.\r\nThe first study included in this thesis deals with the initial encoding of spatial memories in\r\nthe hippocampus. Much is known about encoding at the level of single cells, but less about\r\ntheir co-activity or joint contribution to the encoding of novel spatial information. I will\r\ndescribe the structure of an interaction network that allows for efficient encoding of noisy\r\nspatial information during the first exploration of a novel environment.\r\nThe second study describes the interactions between the hippocampus and the prefrontal\r\ncortex (PFC), two areas directly and indirectly connected. It is known that the PFC, in concert\r\nwith the hippocampus, is involved in various processes, including memory storage and spatial\r\nnavigation. Nonetheless, the detailed mechanisms by which PFC receives information from the\r\nhippocampus are not clear. I will show how a transient improvement in theta phase locking of\r\nPFC cells enables interactions of cell pairs across the two regions.\r\nThe third study describes the learning of behaviorally-relevant spatial locations in the hippocampus and the medial entorhinal cortex. I will show how the accumulation of firing around\r\ngoal locations, a correlate of learning, can shed light on the transition from short- to long-term\r\nspatial memories and the speed of consolidation in different brain areas.\r\nThe studies included in this thesis represent the main scientific contributions of my Ph.D. They\r\ninvolve statistical analyses and models of neural responses of cells in different brain areas of\r\nrats executing spatial tasks. I will conclude the thesis by discussing the impact of the findings\r\non principles of memory formation and retention, including the mechanisms, the speed, and\r\nthe duration of these processes.","lang":"eng"}],"alternative_title":["ISTA Thesis"],"ec_funded":1,"file_date_updated":"2023-06-20T22:30:04Z","page":"136","article_processing_charge":"No","supervisor":[{"id":"3FA14672-F248-11E8-B48F-1D18A9856A87","full_name":"Csicsvari, Jozsef L","orcid":"0000-0002-5193-4036","last_name":"Csicsvari","first_name":"Jozsef L"}],"project":[{"call_identifier":"H2020","name":"International IST Doctoral Program","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"}],"date_updated":"2026-04-07T14:22:58Z","publisher":"Institute of Science and Technology Austria","status":"public","publication_status":"published","file":[{"file_id":"11935","file_name":"Michele Nardin, Ph.D. Thesis - ISTA (1).zip","content_type":"application/zip","date_updated":"2023-06-20T22:30:04Z","embargo_to":"open_access","file_size":13515457,"creator":"mnardin","access_level":"closed","relation":"source_file","date_created":"2022-08-19T16:31:34Z","checksum":"2dbb70c74aaa3b64c1f463e943baf09c"},{"creator":"mnardin","file_size":9906458,"content_type":"application/pdf","date_updated":"2023-06-20T22:30:04Z","checksum":"0ec94035ea35a47a9f589ed168e60b48","relation":"main_file","date_created":"2022-08-22T09:43:50Z","access_level":"open_access","embargo":"2023-06-19","file_name":"Michele_Nardin_Phd_Thesis_PDFA.pdf","file_id":"11941"}],"year":"2022","day":"19","author":[{"last_name":"Nardin","first_name":"Michele","orcid":"0000-0001-8849-6570","id":"30BD0376-F248-11E8-B48F-1D18A9856A87","full_name":"Nardin, Michele"}],"corr_author":"1","ddc":["573"],"date_published":"2022-08-19T00:00:00Z","has_accepted_license":"1"},{"date_updated":"2026-04-07T14:29:41Z","publisher":"Institute of Science and Technology Austria","publication_status":"published","status":"public","file":[{"access_level":"closed","checksum":"8cd3ddfe9b53381dcf086023d8d8893a","date_created":"2023-01-25T14:31:32Z","relation":"source_file","file_size":23890382,"embargo_to":"open_access","date_updated":"2023-04-12T22:30:03Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","creator":"cchlebak","file_id":"12379","file_name":"Gloria_Colombo_Thesis.docx"},{"relation":"main_file","checksum":"8af4319c18b516e8758e9a6cb02b103b","date_created":"2023-01-25T14:31:36Z","access_level":"open_access","creator":"cchlebak","file_size":13802421,"date_updated":"2023-04-12T22:30:03Z","content_type":"application/pdf","file_name":"Gloria_Colombo_Thesis.pdf","file_id":"12380","embargo":"2023-04-11"}],"year":"2022","day":"11","author":[{"full_name":"Colombo, Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9434-8902","first_name":"Gloria","last_name":"Colombo"}],"corr_author":"1","ddc":["570"],"date_published":"2022-11-11T00:00:00Z","has_accepted_license":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"type":"dissertation","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","month":"11","citation":{"ama":"Colombo G. MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:12378\">10.15479/at:ista:12378</a>","chicago":"Colombo, Gloria. “MorphOMICs, a Tool for Mapping Microglial Morphology, Reveals Brain Region- and Sex-Dependent Phenotypes.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:12378\">https://doi.org/10.15479/at:ista:12378</a>.","short":"G. Colombo, MorphOMICs, a Tool for Mapping Microglial Morphology, Reveals Brain Region- and Sex-Dependent Phenotypes, Institute of Science and Technology Austria, 2022.","mla":"Colombo, Gloria. <i>MorphOMICs, a Tool for Mapping Microglial Morphology, Reveals Brain Region- and Sex-Dependent Phenotypes</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:12378\">10.15479/at:ista:12378</a>.","ieee":"G. Colombo, “MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes,” Institute of Science and Technology Austria, 2022.","apa":"Colombo, G. (2022). <i>MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:12378\">https://doi.org/10.15479/at:ista:12378</a>","ista":"Colombo G. 2022. MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes. Institute of Science and Technology Austria."},"degree_awarded":"PhD","related_material":{"record":[{"id":"12244","relation":"part_of_dissertation","status":"public"}]},"_id":"12378","publication_identifier":{"issn":["2663-337X"]},"date_created":"2023-01-25T14:27:43Z","doi":"10.15479/at:ista:12378","oa":1,"oa_version":"Published Version","department":[{"_id":"GradSch"},{"_id":"SaSi"}],"OA_place":"publisher","language":[{"iso":"eng"}],"title":"MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes","alternative_title":["ISTA Thesis"],"ec_funded":1,"abstract":[{"text":"Environmental cues influence the highly dynamic morphology of microglia. Strategies to \r\ncharacterize these changes usually involve user-selected morphometric features, which \r\npreclude the identification of a spectrum of context-dependent morphological phenotypes. \r\nHere, we develop MorphOMICs, a topological data analysis approach, which enables semi\u0002automatic mapping of microglial morphology into an atlas of cue-dependent phenotypes,\r\novercomes feature-selection bias and minimizes biological variability. \r\nFirst, with MorphOMICs we derive the morphological spectrum of microglia across seven \r\nbrain regions during postnatal development and in two distinct Alzheimer’s disease \r\ndegeneration mouse models. We uncover region-specific and sexually dimorphic\r\nmorphological trajectories, with females showing an earlier morphological shift than males in \r\nthe degenerating brain. Overall, we demonstrate that both long primary- and short terminal \r\nprocesses provide distinct insights to morphological phenotypes. Moreover, using machine \r\nlearning to map novel condition on the spectrum, we observe that microglia morphologies \r\nreflect a dose-dependent adaptation upon ketamine anesthesia and do not recover to control \r\nmorphologies.\r\nNext, we took advantage of MorphOMICs to build a high-resolution and layer-specific map of \r\nmicroglial morphological spectrum in the retina, covering postnatal development and rd10 \r\ndegeneration. Here, following photoreceptor death, microglia assume an early development\u0002like morphology. Finally, we map microglial morphology following optic nerve crush on the \r\nretinal spectrum and observe a layer- and sex-dependent response. \r\nOverall, MorphOMICs opens a new perspective to analyze microglial morphology across \r\nmultiple conditions, and provides a novel tool to characterize microglial morphology beyond \r\nthe traditionally dichotomized view of microglia.","lang":"eng"}],"file_date_updated":"2023-04-12T22:30:03Z","supervisor":[{"last_name":"Siegert","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877"}],"article_processing_charge":"No","page":"142","project":[{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","name":"International IST Doctoral Program","call_identifier":"H2020"}],"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"ScienComp"}]},{"file_date_updated":"2023-02-21T23:30:39Z","publication":"Journal of Cell Biology","abstract":[{"text":"Endocytosis is a multistep process involving the sequential recruitment and action of numerous proteins. This process can be divided into two phases: an early phase, in which sites of endocytosis are formed, and a late phase in which clathrin-coated vesicles are formed and internalized into the cytosol, but how these phases link to each other remains unclear. In this study, we demonstrate that anchoring the yeast Eps15-like protein Pan1p to the peroxisome triggers most of the events occurring during the late phase at the peroxisome. At this ectopic location, Pan1p recruits most proteins that function in the late phases—including actin nucleation promoting factors—and then initiates actin polymerization. Pan1p also recruited Prk1 kinase and actin depolymerizing factors, thereby triggering disassembly immediately after actin assembly and inducing dissociation of endocytic proteins from the peroxisome. These observations suggest that Pan1p is a key regulator for initiating, processing, and completing the late phase of endocytosis.","lang":"eng"}],"volume":221,"title":"Eps15/Pan1p is a master regulator of the late stages of the endocytic pathway","article_number":"e202112138","external_id":{"pmid":["35984332"],"isi":["000932770500001"]},"article_processing_charge":"No","date_created":"2022-09-11T22:01:54Z","doi":"10.1083/jcb.202112138","publication_identifier":{"issn":["0021-9525"],"eissn":["1540-8140"]},"_id":"12080","acknowledgement":"This work was supported by JSPS KAKENHI GRANT #18K062291, and the Takeda Science Foundation to J.Y. Toshima, as well as JSPS KAKENHI GRANT #19K065710, the Uehara Memorial Foundation, and Life Science Foundation of JAPAN to J. Toshima.","scopus_import":"1","citation":{"ieee":"M. Enshoji <i>et al.</i>, “Eps15/Pan1p is a master regulator of the late stages of the endocytic pathway,” <i>Journal of Cell Biology</i>, vol. 221, no. 10. Rockefeller University Press, 2022.","mla":"Enshoji, Mariko, et al. “Eps15/Pan1p Is a Master Regulator of the Late Stages of the Endocytic Pathway.” <i>Journal of Cell Biology</i>, vol. 221, no. 10, e202112138, Rockefeller University Press, 2022, doi:<a href=\"https://doi.org/10.1083/jcb.202112138\">10.1083/jcb.202112138</a>.","short":"M. Enshoji, Y. Miyano, N. Yoshida, M. Nagano, M. Watanabe, M. Kunihiro, D.E. Siekhaus, J.Y. Toshima, J. Toshima, Journal of Cell Biology 221 (2022).","chicago":"Enshoji, Mariko, Yoshiko Miyano, Nao Yoshida, Makoto Nagano, Minami Watanabe, Mayumi Kunihiro, Daria E Siekhaus, Junko Y. Toshima, and Jiro Toshima. “Eps15/Pan1p Is a Master Regulator of the Late Stages of the Endocytic Pathway.” <i>Journal of Cell Biology</i>. Rockefeller University Press, 2022. <a href=\"https://doi.org/10.1083/jcb.202112138\">https://doi.org/10.1083/jcb.202112138</a>.","ama":"Enshoji M, Miyano Y, Yoshida N, et al. Eps15/Pan1p is a master regulator of the late stages of the endocytic pathway. <i>Journal of Cell Biology</i>. 2022;221(10). doi:<a href=\"https://doi.org/10.1083/jcb.202112138\">10.1083/jcb.202112138</a>","ista":"Enshoji M, Miyano Y, Yoshida N, Nagano M, Watanabe M, Kunihiro M, Siekhaus DE, Toshima JY, Toshima J. 2022. Eps15/Pan1p is a master regulator of the late stages of the endocytic pathway. Journal of Cell Biology. 221(10), e202112138.","apa":"Enshoji, M., Miyano, Y., Yoshida, N., Nagano, M., Watanabe, M., Kunihiro, M., … Toshima, J. (2022). Eps15/Pan1p is a master regulator of the late stages of the endocytic pathway. <i>Journal of Cell Biology</i>. Rockefeller University Press. <a href=\"https://doi.org/10.1083/jcb.202112138\">https://doi.org/10.1083/jcb.202112138</a>"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","month":"08","type":"journal_article","issue":"10","language":[{"iso":"eng"}],"quality_controlled":"1","department":[{"_id":"DaSi"}],"oa_version":"Published Version","oa":1,"ddc":["570"],"date_published":"2022-08-19T00:00:00Z","author":[{"full_name":"Enshoji, Mariko","last_name":"Enshoji","first_name":"Mariko"},{"full_name":"Miyano, Yoshiko","last_name":"Miyano","first_name":"Yoshiko"},{"full_name":"Yoshida, Nao","first_name":"Nao","last_name":"Yoshida"},{"last_name":"Nagano","first_name":"Makoto","full_name":"Nagano, Makoto"},{"last_name":"Watanabe","first_name":"Minami","full_name":"Watanabe, Minami"},{"last_name":"Kunihiro","first_name":"Mayumi","full_name":"Kunihiro, Mayumi"},{"orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","full_name":"Siekhaus, Daria E","last_name":"Siekhaus","first_name":"Daria E"},{"first_name":"Junko Y.","last_name":"Toshima","full_name":"Toshima, Junko Y."},{"full_name":"Toshima, Jiro","first_name":"Jiro","last_name":"Toshima"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","short":"CC BY-NC-SA (4.0)","image":"/images/cc_by_nc_sa.png","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)"},"isi":1,"intvolume":"       221","has_accepted_license":"1","status":"public","publication_status":"published","pmid":1,"publisher":"Rockefeller University Press","article_type":"original","date_updated":"2023-08-03T13:49:07Z","day":"19","year":"2022","file":[{"file_size":7816875,"content_type":"application/pdf","date_updated":"2023-02-21T23:30:39Z","creator":"dernst","access_level":"open_access","date_created":"2023-01-20T09:32:53Z","relation":"main_file","checksum":"f2e581e66b5cdab9df81b56e850b3eaa","embargo":"2023-02-20","file_id":"12321","file_name":"2022_JCB_Enshoji.pdf"}]},{"year":"2022","day":"05","file":[{"description":"The folder contains the following datasets (fasta files, and text files):\nSup. Dataset 1: Genome assemblies: A. sinica male high quality assembly, A. sp. Kazakhstan\nmale draft assembly\nSup. Dataset 2: Male transcriptome assemblies for A. sinica and A. franciscana\nSup. Dataset 3: Male and female coverage for A. sinica, A. sp. Kazakhstan, A. urmiana, and\nA. parthenogenetica females and rare male.\nSup. Dataset 4: Artemia sinica Male:female FST per 1Kb window\nSup. Dataset 5: FASTA file with candidate W scaffolds\nSup. Dataset 6: Candidate W-derived transcripts and alignments\nSup. Dataset 7: Gene expression with genomic location\nSup. Dataset 8: VCF for asexual female and rare male\nSup. Dataset 9: FST between backcrossed asexual and control females (pooled analysis)\nSup. Dataset 10: VCF of backcrossed asexual and control females (individual analysis using\nA. sp. Kazakhstan as the reference), and inferred ancestry\nSup. Dataset 11: GO and DE annotations of all the Artemia sinica transcripts and their\nlocations in the Artemia sinica male genome.\n","access_level":"open_access","checksum":"5f1d7c6d7ab5375ed2564521432bed0c","relation":"main_file","date_created":"2022-07-26T12:37:52Z","date_updated":"2022-08-08T22:30:04Z","content_type":"application/x-zip-compressed","title":"Supplementary Datasets","file_size":2209382998,"creator":"melkrewi","file_id":"11655","file_name":"Data.zip","embargo":"2022-08-07"}],"oa_version":"Published Version","oa":1,"department":[{"_id":"GradSch"},{"_id":"BeVi"}],"related_material":{"record":[{"id":"12248","status":"public","relation":"used_in_publication"}]},"_id":"11653","date_created":"2022-07-26T11:01:47Z","doi":"10.15479/AT:ISTA:11653","status":"public","type":"research_data","month":"08","date_updated":"2025-04-15T08:34:17Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Institute of Science and Technology Austria","citation":{"ista":"Elkrewi MN. 2022. Data from Elkrewi, Khauratovich, Toups et al. 2022, ‘ZW sex-chromosome evolution and contagious parthenogenesis in Artemia brine shrimp’, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:11653\">10.15479/AT:ISTA:11653</a>.","apa":"Elkrewi, M. N. (2022). Data from Elkrewi, Khauratovich, Toups et al. 2022, “ZW sex-chromosome evolution and contagious parthenogenesis in Artemia brine shrimp.” Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:11653\">https://doi.org/10.15479/AT:ISTA:11653</a>","short":"M.N. Elkrewi, (2022).","mla":"Elkrewi, Marwan N. <i>Data from Elkrewi, Khauratovich, Toups et Al. 2022, “ZW Sex-Chromosome Evolution and Contagious Parthenogenesis in Artemia Brine Shrimp.”</i> Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:11653\">10.15479/AT:ISTA:11653</a>.","ieee":"M. N. Elkrewi, “Data from Elkrewi, Khauratovich, Toups et al. 2022, ‘ZW sex-chromosome evolution and contagious parthenogenesis in Artemia brine shrimp.’” Institute of Science and Technology Austria, 2022.","ama":"Elkrewi MN. Data from Elkrewi, Khauratovich, Toups et al. 2022, “ZW sex-chromosome evolution and contagious parthenogenesis in Artemia brine shrimp.” 2022. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:11653\">10.15479/AT:ISTA:11653</a>","chicago":"Elkrewi, Marwan N. “Data from Elkrewi, Khauratovich, Toups et Al. 2022, ‘ZW Sex-Chromosome Evolution and Contagious Parthenogenesis in Artemia Brine Shrimp.’” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/AT:ISTA:11653\">https://doi.org/10.15479/AT:ISTA:11653</a>."},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"article_processing_charge":"No","has_accepted_license":"1","contributor":[{"id":"0B46FACA-A8E1-11E9-9BD3-79D1E5697425","orcid":"0000-0002-5328-7231","first_name":"Marwan N","last_name":"Elkrewi"},{"last_name":"Khauratovich","first_name":"Uladzislava"},{"id":"4E099E4E-F248-11E8-B48F-1D18A9856A87","last_name":"Toups","first_name":"Melissa A"},{"id":"57854184-AAE0-11E9-8D04-98D6E5697425","last_name":"Bett","first_name":"Vincent K"},{"id":"353FAC84-AE61-11E9-8BFC-00D3E5697425","last_name":"Mrnjavac","first_name":"Andrea"},{"id":"2A0848E2-F248-11E8-B48F-1D18A9856A87","first_name":"Ariana","last_name":"Macon"},{"first_name":"Christelle","last_name":"Fraisse","orcid":"0000-0001-8441-5075","id":"32DF5794-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Luca","last_name":"Sax"},{"id":"4C0A3874-F248-11E8-B48F-1D18A9856A87","first_name":"Ann K","last_name":"Huylmans"},{"first_name":"Francisco","last_name":"Hontoria "},{"id":"49E1C5C6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4579-8306","last_name":"Vicoso","first_name":"Beatriz"}],"corr_author":"1","abstract":[{"text":"Eurasian brine shrimp (genus Artemia) have closely related sexual and asexual lineages of parthenogenetic females, which produce rare males at low frequencies. Although they are known to have ZW chromosomes, these are not well characterized, and it is unclear whether they are shared across the clade. Furthermore, the underlying genetic architecture of the transmission of asexuality, which can occur when rare males mate with closely related sexual females, is not well understood. We produced a chromosome-level assembly for the sexual Eurasian species A. sinica and characterized in detail the pair of sex chromosomes of this species. We combined this new assembly with short-read genomic data for the sexual species A. sp. Kazakhstan and several asexual lineages of A. parthenogenetica, allowing us to perform an in-depth characterization of sex-chromosome evolution across the genus. We identified a small differentiated region of the ZW pair that is shared by all sexual and asexual lineages, supporting the shared ancestry of the sex chromosomes. We also inferred that recombination suppression has spread to larger sections of the chromosome independently in the American and Eurasian lineages. Finally, we took advantage of a rare male, which we backcrossed to sexual females, to explore the genetic basis of asexuality. Our results suggest that parthenogenesis is likely partly controlled by a locus on the Z chromosome, highlighting the interplay between sex determination and asexuality.","lang":"eng"}],"date_published":"2022-08-05T00:00:00Z","ddc":["570"],"file_date_updated":"2022-08-08T22:30:04Z","title":"Data from Elkrewi, Khauratovich, Toups et al. 2022, \"ZW sex-chromosome evolution and contagious parthenogenesis in Artemia brine shrimp\"","author":[{"id":"0B46FACA-A8E1-11E9-9BD3-79D1E5697425","full_name":"Elkrewi, Marwan N","orcid":"0000-0002-5328-7231","last_name":"Elkrewi","first_name":"Marwan N"}]},{"title":"Saturated reconstruction of living brain tissue","author":[{"last_name":"Velicky","first_name":"Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431"},{"orcid":"0000-0001-5665-0430","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","full_name":"Miguel Villalba, Eder","last_name":"Miguel Villalba","first_name":"Eder"},{"orcid":"0000-0003-3862-1235","full_name":"Michalska, Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M","last_name":"Michalska"},{"last_name":"Wei","first_name":"Donglai","full_name":"Wei, Donglai"},{"full_name":"Lin, Zudi","last_name":"Lin","first_name":"Zudi"},{"last_name":"Watson","first_name":"Jake","orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E","full_name":"Watson, Jake"},{"full_name":"Troidl, Jakob","first_name":"Jakob","last_name":"Troidl"},{"full_name":"Beyer, Johanna","first_name":"Johanna","last_name":"Beyer"},{"last_name":"Ben Simon","first_name":"Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","full_name":"Ben Simon, Yoav"},{"orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","last_name":"Sommer","first_name":"Christoph M"},{"first_name":"Wiebke","last_name":"Jahr","full_name":"Jahr, Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0201-2315"},{"last_name":"Cenameri","first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban"},{"first_name":"Johannes","last_name":"Broichhagen","full_name":"Broichhagen, Johannes"},{"first_name":"Seth G. N.","last_name":"Grant","full_name":"Grant, Seth G. N."},{"orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","last_name":"Jonas","first_name":"Peter M"},{"first_name":"Gaia","last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Pfister, Hanspeter","last_name":"Pfister","first_name":"Hanspeter"},{"orcid":"0000-0001-6511-9385","id":"49876194-F248-11E8-B48F-1D18A9856A87","full_name":"Bickel, Bernd","last_name":"Bickel","first_name":"Bernd"},{"last_name":"Danzl","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973"}],"corr_author":"1","abstract":[{"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 <jats:italic>in-silico</jats:italic> reconstruction<jats:sup>1–5</jats:sup>, yet is limited to fixed specimens and static representations. Light microscopy allows live observation, with super-resolution approaches<jats:sup>6–12</jats:sup> 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) microscopy<jats:sup>6,13</jats:sup> in extracellularly labelled tissue<jats:sup>14</jats:sup> 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.","lang":"eng"}],"publication":"bioRxiv","date_published":"2022-05-09T00:00:00Z","article_processing_charge":"No","type":"preprint","date_updated":"2026-06-27T22:30:09Z","month":"05","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Cold Spring Harbor Laboratory","citation":{"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.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2022.03.16.484431\">https://doi.org/10.1101/2022.03.16.484431</a>.","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction of living brain tissue. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>","mla":"Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>.","ieee":"P. Velicky <i>et al.</i>, “Saturated reconstruction of living brain tissue,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","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.).","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. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2022.03.16.484431\">https://doi.org/10.1101/2022.03.16.484431</a>","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, <a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>."},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2022.03.16.484431"}],"related_material":{"record":[{"relation":"later_version","status":"public","id":"13267"},{"relation":"dissertation_contains","status":"public","id":"12470"}]},"_id":"11943","publication_status":"draft","status":"public","doi":"10.1101/2022.03.16.484431","date_created":"2022-08-23T11:07:59Z","oa":1,"oa_version":"Preprint","department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"}],"year":"2022","OA_place":"repository","language":[{"iso":"eng"}],"day":"09"},{"year":"2022","language":[{"iso":"eng"}],"day":"18","oa":1,"oa_version":"Preprint","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"}],"main_file_link":[{"url":"https://doi.org/10.1101/2022.08.17.504272","open_access":"1"}],"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"12470"}]},"_id":"11950","publication_status":"draft","status":"public","date_created":"2022-08-24T08:24:52Z","doi":"10.1101/2022.08.17.504272","type":"preprint","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"08","date_updated":"2026-06-27T22:30:09Z","publisher":"Cold Spring Harbor Laboratory","citation":{"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, <a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>.","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. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2022.08.17.504272\">https://doi.org/10.1101/2022.08.17.504272</a>","mla":"Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>.","ieee":"J. M. Michalska <i>et al.</i>, “Uncovering brain tissue architecture across scales with super-resolution light microscopy,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","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.).","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.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2022.08.17.504272\">https://doi.org/10.1101/2022.08.17.504272</a>.","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture across scales with super-resolution light microscopy. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>"},"article_processing_charge":"No","corr_author":"1","publication":"bioRxiv","abstract":[{"text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to 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.","lang":"eng"}],"date_published":"2022-08-18T00:00:00Z","title":"Uncovering brain tissue architecture across scales with super-resolution light microscopy","author":[{"last_name":"Michalska","first_name":"Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235"},{"first_name":"Julia","last_name":"Lyudchik","full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Velicky","first_name":"Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431"},{"id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","full_name":"Korinkova, Hana","last_name":"Korinkova","first_name":"Hana"},{"first_name":"Jake","last_name":"Watson","full_name":"Watson, Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823"},{"last_name":"Cenameri","first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban"},{"orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","last_name":"Sommer"},{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403","last_name":"Venturino","first_name":"Alessandro"},{"last_name":"Roessler","first_name":"Karl","full_name":"Roessler, Karl"},{"last_name":"Czech","first_name":"Thomas","full_name":"Czech, Thomas"},{"first_name":"Sandra","last_name":"Siegert","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Novarino","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178"},{"orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","last_name":"Jonas"},{"full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","first_name":"Johann G","last_name":"Danzl"}]},{"publication":"Developmental Cell","abstract":[{"text":"When crawling through the body, leukocytes often traverse tissues that are densely packed with extracellular matrix and other cells, and this raises the question: How do leukocytes overcome compressive mechanical loads? Here, we show that the actin cortex of leukocytes is mechanoresponsive and that this responsiveness requires neither force sensing via the nucleus nor adhesive interactions with a substrate. Upon global compression of the cell body as well as local indentation of the plasma membrane, Wiskott-Aldrich syndrome protein (WASp) assembles into dot-like structures, providing activation platforms for Arp2/3 nucleated actin patches. These patches locally push against the external load, which can be obstructing collagen fibers or other cells, and thereby create space to facilitate forward locomotion. We show in vitro and in vivo that this WASp function is rate limiting for ameboid leukocyte migration in dense but not in loose environments and is required for trafficking through diverse tissues such as skin and lymph nodes.","lang":"eng"}],"volume":57,"ec_funded":1,"title":"WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"EM-Fac"}],"project":[{"grant_number":"747687","_id":"260AA4E2-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells"},{"name":"Cellular Navigation Along Spatial Gradients","call_identifier":"H2020","_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373"}],"external_id":{"pmid":["34919802"],"isi":["000768933800005"]},"page":"47-62.e9","article_processing_charge":"No","doi":"10.1016/j.devcel.2021.11.024","date_created":"2022-01-30T23:01:33Z","publication_identifier":{"issn":["1534-5807"],"eissn":["1878-1551"]},"_id":"10703","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"20149"},{"status":"public","relation":"dissertation_contains","id":"12726"},{"relation":"dissertation_contains","status":"public","id":"14530"},{"id":"12401","relation":"dissertation_contains","status":"public"}]},"main_file_link":[{"open_access":"1","url":"https://www.sciencedirect.com/science/article/pii/S1534580721009497"}],"acknowledgement":"We thank N. Darwish-Miranda, F. Leite, F.P. Assen, and A. Eichner for advice and help with experiments. We thank J. Renkawitz, E. Kiermaier, A. Juanes Garcia, and M. Avellaneda for critical reading of the manuscript. We thank M. Driscoll for advice on fluorescent labeling of collagen gels. This research was supported by the Scientific Service Units (SSUs) of IST Austria through resources provided by Molecular Biology Services/Lab Support Facility (LSF)/Bioimaging Facility/Electron Microscopy Facility. This work was funded by grants from the European Research Council ( CoG 724373 ) and the Austrian Science Foundation (FWF) to M.S. F.G. received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 747687.","scopus_import":"1","citation":{"apa":"Gaertner, F., Dos Reis Rodrigues, P., de Vries, I., Hons, M., Aguilera, J., Riedl, M., … Sixt, M. K. (2022). WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. <i>Developmental Cell</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.devcel.2021.11.024\">https://doi.org/10.1016/j.devcel.2021.11.024</a>","ista":"Gaertner F, Dos Reis Rodrigues P, de Vries I, Hons M, Aguilera J, Riedl M, Leithner AF, Tasciyan S, Kopf A, Merrin J, Zheden V, Kaufmann W, Hauschild R, Sixt MK. 2022. WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. Developmental Cell. 57(1), 47–62.e9.","chicago":"Gaertner, Florian, Patricia Dos Reis Rodrigues, Ingrid de Vries, Miroslav Hons, Juan Aguilera, Michael Riedl, Alexander F Leithner, et al. “WASp Triggers Mechanosensitive Actin Patches to Facilitate Immune Cell Migration in Dense Tissues.” <i>Developmental Cell</i>. Cell Press, 2022. <a href=\"https://doi.org/10.1016/j.devcel.2021.11.024\">https://doi.org/10.1016/j.devcel.2021.11.024</a>.","ama":"Gaertner F, Dos Reis Rodrigues P, de Vries I, et al. WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. <i>Developmental Cell</i>. 2022;57(1):47-62.e9. doi:<a href=\"https://doi.org/10.1016/j.devcel.2021.11.024\">10.1016/j.devcel.2021.11.024</a>","mla":"Gaertner, Florian, et al. “WASp Triggers Mechanosensitive Actin Patches to Facilitate Immune Cell Migration in Dense Tissues.” <i>Developmental Cell</i>, vol. 57, no. 1, Cell Press, 2022, p. 47–62.e9, doi:<a href=\"https://doi.org/10.1016/j.devcel.2021.11.024\">10.1016/j.devcel.2021.11.024</a>.","ieee":"F. Gaertner <i>et al.</i>, “WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues,” <i>Developmental Cell</i>, vol. 57, no. 1. Cell Press, p. 47–62.e9, 2022.","short":"F. Gaertner, P. Dos Reis Rodrigues, I. de Vries, M. Hons, J. Aguilera, M. Riedl, A.F. Leithner, S. Tasciyan, A. Kopf, J. Merrin, V. Zheden, W. Kaufmann, R. Hauschild, M.K. Sixt, Developmental Cell 57 (2022) 47–62.e9."},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","month":"01","type":"journal_article","issue":"1","quality_controlled":"1","language":[{"iso":"eng"}],"department":[{"_id":"MiSi"},{"_id":"EM-Fac"},{"_id":"NanoFab"},{"_id":"BjHo"}],"oa_version":"Published Version","oa":1,"date_published":"2022-01-10T00:00:00Z","ddc":["570"],"corr_author":"1","author":[{"full_name":"Gaertner, Florian","last_name":"Gaertner","first_name":"Florian"},{"orcid":"0000-0003-1681-508X","full_name":"Dos Reis Rodrigues, Patricia","id":"26E95904-5160-11E9-9C0B-C5B0DC97E90F","first_name":"Patricia","last_name":"Dos Reis Rodrigues"},{"full_name":"De Vries, Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","first_name":"Ingrid","last_name":"De Vries"},{"full_name":"Hons, Miroslav","id":"4167FE56-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6625-3348","first_name":"Miroslav","last_name":"Hons"},{"full_name":"Aguilera, Juan","last_name":"Aguilera","first_name":"Juan"},{"last_name":"Riedl","first_name":"Michael","id":"3BE60946-F248-11E8-B48F-1D18A9856A87","full_name":"Riedl, Michael","orcid":"0000-0003-4844-6311"},{"id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","full_name":"Leithner, Alexander F","orcid":"0000-0002-1073-744X","last_name":"Leithner","first_name":"Alexander F"},{"first_name":"Saren","last_name":"Tasciyan","orcid":"0000-0003-1671-393X","full_name":"Tasciyan, Saren","id":"4323B49C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Aglaja","last_name":"Kopf","orcid":"0000-0002-2187-6656","full_name":"Kopf, Aglaja","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jack","last_name":"Merrin","full_name":"Merrin, Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5145-4609"},{"first_name":"Vanessa","last_name":"Zheden","full_name":"Zheden, Vanessa","id":"39C5A68A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9438-4783"},{"orcid":"0000-0001-9735-5315","full_name":"Kaufmann, Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","first_name":"Walter","last_name":"Kaufmann"},{"first_name":"Robert","last_name":"Hauschild","orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Sixt","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"isi":1,"intvolume":"        57","status":"public","pmid":1,"publication_status":"published","article_type":"original","publisher":"Cell Press","date_updated":"2026-06-27T22:30:11Z","day":"10","year":"2022"},{"has_accepted_license":"1","corr_author":"1","date_published":"2022-12-22T00:00:00Z","ddc":["610"],"author":[{"last_name":"Tasciyan","first_name":"Saren","orcid":"0000-0003-1671-393X","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","full_name":"Tasciyan, Saren"}],"year":"2022","day":"22","file":[{"file_id":"12402","file_name":"PhD-Thesis_Saren Tasciyan_formatted_aftercrash_fixed_600dpi_95pc_final_PDFA3b.pdf","embargo":"2023-12-20","access_level":"open_access","checksum":"cc4a2b4a7e3c4ee8ef7f2dbf909b12bd","date_created":"2023-01-26T11:58:14Z","relation":"main_file","file_size":42059787,"content_type":"application/pdf","date_updated":"2023-12-21T23:30:03Z","creator":"cchlebak"},{"creator":"cchlebak","file_size":261256696,"embargo_to":"open_access","content_type":"application/x-zip-compressed","date_updated":"2023-12-21T23:30:03Z","date_created":"2023-01-26T12:00:10Z","checksum":"f1b4ca98b8ab0cb043b1830971e9bd9c","relation":"source_file","access_level":"closed","file_name":"Source Files - Saren Tasciyan - PhD Thesis.zip","file_id":"12403"}],"publication_status":"published","status":"public","date_updated":"2026-04-14T09:07:14Z","publisher":"Institute of Science and Technology Austria","supervisor":[{"last_name":"Sixt","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179"}],"article_processing_charge":"No","page":"105","alternative_title":["ISTA Thesis"],"abstract":[{"lang":"eng","text":"Detachment of the cancer cells from the bulk of the tumor is the first step of metastasis, which\r\nis the primary cause of cancer related deaths. It is unclear, which factors contribute to this step.\r\nRecent studies indicate a crucial role of the tumor microenvironment in malignant\r\ntransformation and metastasis. Studying cancer cell invasion and detachments quantitatively in\r\nthe context of its physiological microenvironment is technically challenging. Especially, precise\r\ncontrol of microenvironmental properties in vivo is currently not possible. Here, I studied the\r\nrole of microenvironment geometry in the invasion and detachment of cancer cells from the\r\nbulk with a simplistic and reductionist approach. In this approach, I engineered microfluidic\r\ndevices to mimic a pseudo 3D extracellular matrix environment, where I was able to\r\nquantitatively tune the geometrical configuration of the microenvironment and follow tumor\r\ncells with fluorescence live imaging. To aid quantitative analysis I developed a widely applicable\r\nsoftware application to automatically analyze and visualize particle tracking data.\r\nQuantitative analysis of tumor cell invasion in isotropic and anisotropic microenvironments\r\nshowed that heterogeneity in the microenvironment promotes faster invasion and more\r\nfrequent detachment of cells. These observations correlated with overall higher speed of cells at\r\nthe edge of the bulk of the cells. In heterogeneous microenvironments cells preferentially\r\npassed through larger pores, thus invading areas of least resistance and generating finger-like\r\ninvasive structures. The detachments occurred mostly at the tips of these structures.\r\nTo investigate the potential mechanism, we established a two dimensional model to simulate\r\nactive Brownian particles representing the cell nuclei dynamics. These simulations backed our in\r\nvitro observations without the need of precise fitting the simulation parameters. Our model\r\nsuggests the importance of the pore heterogeneity in the direction perpendicular to the\r\norientation of bias field (lateral heterogeneity), which causes the interface roughening."}],"file_date_updated":"2023-12-21T23:30:03Z","title":"Role of microenvironment heterogeneity in cancer cell invasion","OA_place":"publisher","language":[{"iso":"eng"}],"oa_version":"Published Version","oa":1,"department":[{"_id":"GradSch"},{"_id":"MiSi"}],"_id":"12401","publication_identifier":{"issn":["2663-337X"]},"related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"7885"},{"relation":"part_of_dissertation","status":"public","id":"10703"},{"id":"679","relation":"part_of_dissertation","status":"public"},{"status":"public","relation":"part_of_dissertation","id":"9429"}]},"doi":"10.15479/at:ista:12401","date_created":"2023-01-26T11:55:16Z","type":"dissertation","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","month":"12","citation":{"ista":"Tasciyan S. 2022. Role of microenvironment heterogeneity in cancer cell invasion. Institute of Science and Technology Austria.","apa":"Tasciyan, S. (2022). <i>Role of microenvironment heterogeneity in cancer cell invasion</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:12401\">https://doi.org/10.15479/at:ista:12401</a>","short":"S. Tasciyan, Role of Microenvironment Heterogeneity in Cancer Cell Invasion, Institute of Science and Technology Austria, 2022.","ieee":"S. Tasciyan, “Role of microenvironment heterogeneity in cancer cell invasion,” Institute of Science and Technology Austria, 2022.","mla":"Tasciyan, Saren. <i>Role of Microenvironment Heterogeneity in Cancer Cell Invasion</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:12401\">10.15479/at:ista:12401</a>.","ama":"Tasciyan S. Role of microenvironment heterogeneity in cancer cell invasion. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:12401\">10.15479/at:ista:12401</a>","chicago":"Tasciyan, Saren. “Role of Microenvironment Heterogeneity in Cancer Cell Invasion.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:12401\">https://doi.org/10.15479/at:ista:12401</a>."},"degree_awarded":"PhD"},{"file_date_updated":"2023-05-30T17:07:05Z","volume":609,"ec_funded":1,"publication":"Nature","abstract":[{"text":"Complex I is the first enzyme in the respiratory chain, which is responsible for energy production in mitochondria and bacteria1. Complex I couples the transfer of two electrons from NADH to quinone and the translocation of four protons across the membrane2, but the coupling mechanism remains contentious. Here we present cryo-electron microscopy structures of Escherichia coli complex I (EcCI) in different redox states, including catalytic turnover. EcCI exists mostly in the open state, in which the quinone cavity is exposed to the cytosol, allowing access for water molecules, which enable quinone movements. Unlike the mammalian paralogues3, EcCI can convert to the closed state only during turnover, showing that closed and open states are genuine turnover intermediates. The open-to-closed transition results in the tightly engulfed quinone cavity being connected to the central axis of the membrane arm, a source of substrate protons. Consistently, the proportion of the closed state increases with increasing pH. We propose a detailed but straightforward and robust mechanism comprising a ‘domino effect’ series of proton transfers and electrostatic interactions: the forward wave (‘dominoes stacking’) primes the pump, and the reverse wave (‘dominoes falling’) results in the ejection of all pumped protons from the distal subunit NuoL. This mechanism explains why protons exit exclusively from the NuoL subunit and is supported by our mutagenesis data. We contend that this is a universal coupling mechanism of complex I and related enzymes.","lang":"eng"}],"title":"A universal coupling mechanism of respiratory complex I","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"},{"_id":"ScienComp"}],"project":[{"_id":"238A0A5A-32DE-11EA-91FC-C7463DDC885E","grant_number":"25541","name":"Structural characterization of E. coli complex I: an important mechanistic model"},{"grant_number":"101020697","_id":"627abdeb-2b32-11ec-9570-ec31a97243d3","name":"Structure and mechanism of respiratory chain molecular machines","call_identifier":"H2020"}],"external_id":{"isi":["000854788200001"],"pmid":["36104567"]},"page":"808-814","article_processing_charge":"No","_id":"12138","related_material":{"link":[{"url":"https://doi.org/10.1038/s41586-022-05457-8","relation":"erratum"},{"description":"News on ISTA website","relation":"press_release","url":"https://ista.ac.at/en/news/proton-dominos-kick-off-life/"}],"record":[{"status":"public","relation":"dissertation_contains","id":"12781"}]},"publication_identifier":{"issn":["0028-0836"],"eissn":["1476-4687"]},"doi":"10.1038/s41586-022-05199-7","date_created":"2023-01-12T12:04:33Z","acknowledgement":"This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Electron Microscopy Facility (EMF), the Life Science Facility (LSF) and the IST high-performance computing cluster. We thank V.-V. Hodirnau from IST Austria EMF, M. Babiak from CEITEC for assistance with collecting cryo-EM data and A. Charnagalov for the assistance with protein purification. V.K. was a recipient of a DOC Fellowship of the Austrian Academy of Sciences at the Institute of Science and Technology, Austria. V.K. and O.P. are funded by the ERC Advanced Grant 101020697 RESPICHAIN to L.S. This work was also supported by the Medical Research Council (UK).","citation":{"ista":"Kravchuk V, Petrova O, Kampjut D, Wojciechowska-Bason A, Breese Z, Sazanov LA. 2022. A universal coupling mechanism of respiratory complex I. Nature. 609(7928), 808–814.","apa":"Kravchuk, V., Petrova, O., Kampjut, D., Wojciechowska-Bason, A., Breese, Z., &#38; Sazanov, L. A. (2022). A universal coupling mechanism of respiratory complex I. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-022-05199-7\">https://doi.org/10.1038/s41586-022-05199-7</a>","ieee":"V. Kravchuk, O. Petrova, D. Kampjut, A. Wojciechowska-Bason, Z. Breese, and L. A. Sazanov, “A universal coupling mechanism of respiratory complex I,” <i>Nature</i>, vol. 609, no. 7928. Springer Nature, pp. 808–814, 2022.","mla":"Kravchuk, Vladyslav, et al. “A Universal Coupling Mechanism of Respiratory Complex I.” <i>Nature</i>, vol. 609, no. 7928, Springer Nature, 2022, pp. 808–14, doi:<a href=\"https://doi.org/10.1038/s41586-022-05199-7\">10.1038/s41586-022-05199-7</a>.","short":"V. Kravchuk, O. Petrova, D. Kampjut, A. Wojciechowska-Bason, Z. Breese, L.A. Sazanov, Nature 609 (2022) 808–814.","chicago":"Kravchuk, Vladyslav, Olga Petrova, Domen Kampjut, Anna Wojciechowska-Bason, Zara Breese, and Leonid A Sazanov. “A Universal Coupling Mechanism of Respiratory Complex I.” <i>Nature</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41586-022-05199-7\">https://doi.org/10.1038/s41586-022-05199-7</a>.","ama":"Kravchuk V, Petrova O, Kampjut D, Wojciechowska-Bason A, Breese Z, Sazanov LA. A universal coupling mechanism of respiratory complex I. <i>Nature</i>. 2022;609(7928):808-814. doi:<a href=\"https://doi.org/10.1038/s41586-022-05199-7\">10.1038/s41586-022-05199-7</a>"},"scopus_import":"1","type":"journal_article","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","month":"09","quality_controlled":"1","language":[{"iso":"eng"}],"issue":"7928","department":[{"_id":"LeSa"}],"oa_version":"Submitted Version","oa":1,"date_published":"2022-09-22T00:00:00Z","ddc":["572"],"corr_author":"1","author":[{"last_name":"Kravchuk","first_name":"Vladyslav","id":"4D62F2A6-F248-11E8-B48F-1D18A9856A87","full_name":"Kravchuk, Vladyslav","orcid":"0000-0001-9523-9089"},{"first_name":"Olga","last_name":"Petrova","full_name":"Petrova, Olga","id":"5D8C9660-5D49-11EA-8188-567B3DDC885E"},{"last_name":"Kampjut","first_name":"Domen","orcid":"0000-0002-6018-3422","id":"37233050-F248-11E8-B48F-1D18A9856A87","full_name":"Kampjut, 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4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"keyword":["Bacterial cell division","in vitro reconstitution","FtsZ","FtsN","FtsA"],"contributor":[{"id":"462D4284-F248-11E8-B48F-1D18A9856A87","contributor_type":"supervisor","orcid":"0000-0001-7309-9724","last_name":"Loose","first_name":"Martin"},{"contributor_type":"researcher","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","last_name":"Sommer"},{"contributor_type":"researcher","first_name":"Paulo","last_name":"Caldas"},{"last_name":"Michalik","first_name":"David","contributor_type":"researcher","id":"B9577E20-AA38-11E9-AC9A-0930E6697425"},{"first_name":"Natalia","last_name":"Baranova","contributor_type":"researcher"}],"has_accepted_license":"1","corr_author":"1","ddc":["572"],"date_published":"2022-04-05T00:00:00Z","author":[{"first_name":"Philipp","last_name":"Radler","orcid":" 0000-0001-9198-2182 ","full_name":"Radler, Philipp","id":"40136C2A-F248-11E8-B48F-1D18A9856A87"}],"oa_version":"Submitted Version","oa":1,"department":[{"_id":"GradSch"},{"_id":"MaLo"}],"acknowledgement":"We acknowledge members of the Loose laboratory at IST Austria for helpful discussions—in particular L. Lindorfer for his assistance with cloning and purifications. We thank J. Löwe and T. Nierhaus (MRC-LMB Cambridge, UK) for sharing unpublished work and helpful discussions, as well as D. Vavylonis and D. Rutkowski (Lehigh University, Bethlehem, PA, USA) as well as S. Martin (University of Lausanne, Switzerland) for sharing their code for FRAP analysis. We are also thankful for the support by the Scientific Service Units (SSU) of IST Austria through resources provided by the Imaging and Optics Facility (IOF) and the Lab Support Facility (LSF). This work was supported by the European Research Council through grant ERC 2015-StG-679239 and by the Austrian Science Fund (FWF) StandAlone P34607 to M.L. and HFSP LT 000824/2016-L4 to N.B. For the purpose of open access, we have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.","date_created":"2022-03-31T11:32:32Z","doi":"10.15479/AT:ISTA:10934","related_material":{"link":[{"relation":"software","url":"https://doi.org/10.5281/zenodo.6400639","description":"A custom written code (FRAPdiff) to quantify the Off binding rate and Diffusion coefficient of membrane bound proteins. Written by Christoph Sommer."}],"record":[{"id":"11373","status":"public","relation":"used_in_publication"},{"id":"14280","relation":"used_in_publication","status":"public"}]},"_id":"10934","month":"04","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","type":"research_data","citation":{"chicago":"Radler, Philipp. “In Vitro Reconstitution of Escherichia Coli Divisome Activation.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/AT:ISTA:10934\">https://doi.org/10.15479/AT:ISTA:10934</a>.","ama":"Radler P. In vitro reconstitution of Escherichia coli divisome activation. 2022. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:10934\">10.15479/AT:ISTA:10934</a>","mla":"Radler, Philipp. <i>In Vitro Reconstitution of Escherichia Coli Divisome Activation</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:10934\">10.15479/AT:ISTA:10934</a>.","ieee":"P. Radler, “In vitro reconstitution of Escherichia coli divisome activation.” Institute of Science and Technology Austria, 2022.","short":"P. Radler, (2022).","apa":"Radler, P. (2022). In vitro reconstitution of Escherichia coli divisome activation. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:10934\">https://doi.org/10.15479/AT:ISTA:10934</a>","ista":"Radler P. 2022. In vitro reconstitution of Escherichia coli divisome activation, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:10934\">10.15479/AT:ISTA:10934</a>."},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"article_processing_charge":"No","project":[{"call_identifier":"H2020","name":"Self-Organization of the Bacterial Cell","grant_number":"679239","_id":"2595697A-B435-11E9-9278-68D0E5697425"},{"_id":"fc38323b-9c52-11eb-aca3-ff8afb4a011d","grant_number":"P34607","name":"In vitro reconstitution of bacterial cell division"}],"abstract":[{"text":"FtsA is crucial for assembly of the E. coli divisome, as it dynamically links cytoplasmic FtsZ filaments with transmembrane cell division proteins. FtsA allegedly initiates cell division by switching from an inactive polymeric to an active monomeric confirmation, which recruits downstream proteins and stabilizes FtsZ filaments. Here, we use biochemical reconstitution experiments combined with quantitative fluorescence microscopy to study divisome activation in vitro. We compare wildtype-FtsA with FtsA-R286W, a constantly active gain-of-function mutant and find that R286W outperforms the wildtype protein in replicating FtsZ treadmilling dynamics, stabilizing FtsZ filaments and recruiting FtsN. We attribute these differences to a faster membrane exchange of FtsA-R286W and its higher packing density below FtsZ filaments.  Using FRET microscopy, we find that FtsN binding does not compete with, but promotes FtsA self-interaction. Our findings suggest a model where FtsA always forms dynamic polymers on the membrane, which re-organize during assembly and activation of the divisome. ","lang":"eng"}],"ec_funded":1,"file_date_updated":"2022-04-22T10:15:19Z","title":"In vitro reconstitution of Escherichia coli divisome activation"}]