[{"language":[{"iso":"eng"}],"doi":"10.1016/j.neuron.2019.12.022","project":[{"call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"grant_number":"708497","_id":"25BAF7B2-B435-11E9-9278-68D0E5697425","name":"Presynaptic calcium channels distribution and impact on coupling at the hippocampal mossy fiber synapse","call_identifier":"H2020"},{"name":"The Wittgenstein Prize","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"},{"_id":"25C3DBB6-B435-11E9-9278-68D0E5697425","grant_number":"W01205","call_identifier":"FWF","name":"Zellkommunikation in Gesundheit und Krankheit"}],"isi":1,"quality_controlled":"1","external_id":{"pmid":["31928842"],"isi":["000520854700008"]},"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"oa":1,"publication_identifier":{"issn":["0896-6273"]},"month":"03","volume":105,"date_updated":"2024-03-28T23:30:07Z","date_created":"2020-02-10T15:59:45Z","related_material":{"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/flash-and-freeze-reveals-dynamics-of-nerve-connections/"}],"record":[{"id":"11196","status":"public","relation":"dissertation_contains"}]},"author":[{"full_name":"Borges Merjane, Carolina","id":"4305C450-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0005-401X","first_name":"Carolina","last_name":"Borges Merjane"},{"full_name":"Kim, Olena","first_name":"Olena","last_name":"Kim","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Jonas, Peter M","last_name":"Jonas","first_name":"Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"department":[{"_id":"PeJo"}],"publisher":"Elsevier","publication_status":"published","pmid":1,"acknowledgement":"This project has received funding from the European Research Council (ERC) and European Commission (EC), under the European Union’s Horizon 2020 research and innovation programme (ERC grant agreement No. 692692 and Marie Sklodowska-Curie 708497) and from Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27 Wittgenstein award and DK W1205-B09). We thank Johann Danzl and Ryuichi Shigemoto for critically reading the manuscript; Walter Kaufmann, Daniel Gutl, and Vanessa Zheden for extensive EM training, advice, and experimental assistance; Benjamin Suter for substantial help with light stimulation, ImageJ plugins for analysis, and manuscript editing; Florian Marr and Christina Altmutter for technical support; Eleftheria Kralli-Beller for manuscript editing; Julia König and Paul Wurzinger (Leica Microsystems) for helpful technical discussions; and Taija Makinen for providing the Prox1-CreERT2 mouse line.","year":"2020","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","ec_funded":1,"file_date_updated":"2020-11-20T08:58:53Z","date_published":"2020-03-18T00:00:00Z","page":"992-1006","article_type":"original","citation":{"chicago":"Borges Merjane, Carolina, Olena Kim, and Peter M Jonas. “Functional Electron Microscopy (‘Flash and Freeze’) of Identified Cortical Synapses in Acute Brain Slices.” Neuron. Elsevier, 2020. https://doi.org/10.1016/j.neuron.2019.12.022.","short":"C. Borges Merjane, O. Kim, P.M. Jonas, Neuron 105 (2020) 992–1006.","mla":"Borges Merjane, Carolina, et al. “Functional Electron Microscopy (‘Flash and Freeze’) of Identified Cortical Synapses in Acute Brain Slices.” Neuron, vol. 105, Elsevier, 2020, pp. 992–1006, doi:10.1016/j.neuron.2019.12.022.","ieee":"C. Borges Merjane, O. Kim, and P. M. Jonas, “Functional electron microscopy (‘Flash and Freeze’) of identified cortical synapses in acute brain slices,” Neuron, vol. 105. Elsevier, pp. 992–1006, 2020.","apa":"Borges Merjane, C., Kim, O., & Jonas, P. M. (2020). Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2019.12.022","ista":"Borges Merjane C, Kim O, Jonas PM. 2020. Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. Neuron. 105, 992–1006.","ama":"Borges Merjane C, Kim O, Jonas PM. Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. Neuron. 2020;105:992-1006. doi:10.1016/j.neuron.2019.12.022"},"publication":"Neuron","has_accepted_license":"1","article_processing_charge":"No","day":"18","scopus_import":"1","oa_version":"Published Version","file":[{"date_created":"2020-11-20T08:58:53Z","date_updated":"2020-11-20T08:58:53Z","checksum":"3582664addf26859e86ac5bec3e01416","success":1,"relation":"main_file","file_id":"8778","file_size":9712957,"content_type":"application/pdf","creator":"dernst","file_name":"2020_Neuron_BorgesMerjane.pdf","access_level":"open_access"}],"intvolume":" 105","title":"Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices","status":"public","ddc":["570"],"_id":"7473","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","abstract":[{"text":"How structural and functional properties of synapses relate to each other is a fundamental question in neuroscience. Electrophysiology has elucidated mechanisms of synaptic transmission, and electron microscopy (EM) has provided insight into morphological properties of synapses. Here we describe an enhanced method for functional EM (“flash and freeze”), combining optogenetic stimulation with high-pressure freezing. We demonstrate that the improved method can be applied to intact networks in acute brain slices and organotypic slice cultures from mice. As a proof of concept, we probed vesicle pool changes during synaptic transmission at the hippocampal mossy fiber-CA3 pyramidal neuron synapse. Our findings show overlap of the docked vesicle pool and the functionally defined readily releasable pool and provide evidence of fast endocytosis at this synapse. Functional EM with acute slices and slice cultures has the potential to reveal the structural and functional mechanisms of transmission in intact, genetically perturbed, and disease-affected synapses.","lang":"eng"}],"type":"journal_article"},{"language":[{"iso":"eng"}],"doi":"10.1038/s41467-020-17734-z","isi":1,"quality_controlled":"1","project":[{"call_identifier":"FWF","name":"Revealing the mechanisms underlying drug interactions","grant_number":"P27201-B22","_id":"25E9AF9E-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","name":"Biophysics of information processing in gene regulation","grant_number":"P28844-B27","_id":"254E9036-B435-11E9-9278-68D0E5697425"}],"oa":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"},"external_id":{"isi":["000562769300008"]},"month":"08","publication_identifier":{"issn":["2041-1723"]},"date_updated":"2024-03-28T23:30:08Z","date_created":"2020-08-12T09:13:50Z","volume":11,"author":[{"full_name":"Kavcic, Bor","last_name":"Kavcic","first_name":"Bor","orcid":"0000-0001-6041-254X","id":"350F91D2-F248-11E8-B48F-1D18A9856A87"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","first_name":"Gašper","last_name":"Tkačik","full_name":"Tkačik, Gašper"},{"full_name":"Bollenbach, Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4398-476X","first_name":"Tobias","last_name":"Bollenbach"}],"related_material":{"record":[{"id":"8657","status":"public","relation":"dissertation_contains"}]},"publication_status":"published","department":[{"_id":"GaTk"}],"publisher":"Springer Nature","year":"2020","acknowledgement":"We thank M. Hennessey-Wesen, I. Tomanek, K. Jain, A. Staron, K. Tomasek, M. Scott,\r\nK.C. Huang, and Z. Gitai for reading the manuscript and constructive comments. B.K. is\r\nindebted to C. Guet for additional guidance and generous support, which rendered this\r\nwork possible. B.K. thanks all members of Guet group for many helpful discussions and\r\nsharing of resources. B.K. additionally acknowledges the tremendous support from A.\r\nAngermayr and K. Mitosch with experimental work. We further thank E. Brown for\r\nhelpful comments regarding lamotrigine, and A. Buskirk for valuable suggestions\r\nregarding the ribosome footprint size. This work was supported in part by Austrian\r\nScience Fund (FWF) standalone grants P 27201-B22 (to T.B.) and P 28844 (to G.T.),\r\nHFSP program Grant RGP0042/2013 (to T.B.), German Research Foundation (DFG)\r\nstandalone grant BO 3502/2-1 (to T.B.), and German Research Foundation (DFG)\r\nCollaborative Research Centre (SFB) 1310 (to T.B.). Open access funding provided by\r\nProjekt DEAL.","license":"https://creativecommons.org/licenses/by/4.0/","file_date_updated":"2020-08-17T07:36:57Z","article_number":"4013","date_published":"2020-08-11T00:00:00Z","article_type":"original","publication":"Nature Communications","citation":{"mla":"Kavcic, Bor, et al. “Mechanisms of Drug Interactions between Translation-Inhibiting Antibiotics.” Nature Communications, vol. 11, 4013, Springer Nature, 2020, doi:10.1038/s41467-020-17734-z.","short":"B. Kavcic, G. Tkačik, M.T. Bollenbach, Nature Communications 11 (2020).","chicago":"Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “Mechanisms of Drug Interactions between Translation-Inhibiting Antibiotics.” Nature Communications. Springer Nature, 2020. https://doi.org/10.1038/s41467-020-17734-z.","ama":"Kavcic B, Tkačik G, Bollenbach MT. Mechanisms of drug interactions between translation-inhibiting antibiotics. Nature Communications. 2020;11. doi:10.1038/s41467-020-17734-z","ista":"Kavcic B, Tkačik G, Bollenbach MT. 2020. Mechanisms of drug interactions between translation-inhibiting antibiotics. Nature Communications. 11, 4013.","apa":"Kavcic, B., Tkačik, G., & Bollenbach, M. T. (2020). Mechanisms of drug interactions between translation-inhibiting antibiotics. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-020-17734-z","ieee":"B. Kavcic, G. Tkačik, and M. T. Bollenbach, “Mechanisms of drug interactions between translation-inhibiting antibiotics,” Nature Communications, vol. 11. Springer Nature, 2020."},"day":"11","has_accepted_license":"1","article_processing_charge":"No","file":[{"relation":"main_file","file_id":"8275","checksum":"986bebb308850a55850028d3d2b5b664","success":1,"date_updated":"2020-08-17T07:36:57Z","date_created":"2020-08-17T07:36:57Z","access_level":"open_access","file_name":"2020_NatureComm_Kavcic.pdf","file_size":1965672,"content_type":"application/pdf","creator":"dernst"}],"oa_version":"Published Version","status":"public","ddc":["570"],"title":"Mechanisms of drug interactions between translation-inhibiting antibiotics","intvolume":" 11","_id":"8250","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","abstract":[{"lang":"eng","text":"Antibiotics that interfere with translation, when combined, interact in diverse and difficult-to-predict ways. Here, we explain these interactions by “translation bottlenecks”: points in the translation cycle where antibiotics block ribosomal progression. To elucidate the underlying mechanisms of drug interactions between translation inhibitors, we generate translation bottlenecks genetically using inducible control of translation factors that regulate well-defined translation cycle steps. These perturbations accurately mimic antibiotic action and drug interactions, supporting that the interplay of different translation bottlenecks causes these interactions. We further show that growth laws, combined with drug uptake and binding kinetics, enable the direct prediction of a large fraction of observed interactions, yet fail to predict suppression. However, varying two translation bottlenecks simultaneously supports that dense traffic of ribosomes and competition for translation factors account for the previously unexplained suppression. These results highlight the importance of “continuous epistasis” in bacterial physiology."}],"type":"journal_article"},{"status":"public","title":"A minimal biophysical model of combined antibiotic action","publication_status":"published","publisher":"Cold Spring Harbor Laboratory","department":[{"_id":"GaTk"}],"year":"2020","_id":"7673","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2020-04-22T08:27:56Z","date_updated":"2024-03-28T23:30:08Z","oa_version":"Preprint","author":[{"full_name":"Kavcic, Bor","first_name":"Bor","last_name":"Kavcic","id":"350F91D2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6041-254X"},{"full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkačik","first_name":"Gašper"},{"full_name":"Bollenbach, Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4398-476X","first_name":"Tobias","last_name":"Bollenbach"}],"related_material":{"record":[{"id":"8997","relation":"later_version","status":"public"},{"relation":"dissertation_contains","status":"public","id":"8657"}]},"type":"preprint","abstract":[{"text":"Combining drugs can improve the efficacy of treatments. However, predicting the effect of drug combinations is still challenging. The combined potency of drugs determines the drug interaction, which is classified as synergistic, additive, antagonistic, or suppressive. While probabilistic, non-mechanistic models exist, there is currently no biophysical model that can predict antibiotic interactions. Here, we present a physiologically relevant model of the combined action of antibiotics that inhibit protein synthesis by targeting the ribosome. This model captures the kinetics of antibiotic binding and transport, and uses bacterial growth laws to predict growth in the presence of antibiotic combinations. We find that this biophysical model can produce all drug interaction types except suppression. We show analytically that antibiotics which cannot bind to the ribosome simultaneously generally act as substitutes for one another, leading to additive drug interactions. Previously proposed null expectations for higher-order drug interactions follow as a limiting case of our model. We further extend the model to include the effects of direct physical or allosteric interactions between individual drugs on the ribosome. Notably, such direct interactions profoundly change the combined drug effect, depending on the kinetic parameters of the drugs used. The model makes additional predictions for the effects of resistance genes on drug interactions and for interactions between ribosome-targeting antibiotics and antibiotics with other targets. These findings enhance our understanding of the interplay between drug action and cell physiology and are a key step toward a general framework for predicting drug interactions.","lang":"eng"}],"project":[{"name":"Revealing the mechanisms underlying drug interactions","call_identifier":"FWF","grant_number":"P27201-B22","_id":"25E9AF9E-B435-11E9-9278-68D0E5697425"},{"_id":"254E9036-B435-11E9-9278-68D0E5697425","grant_number":"P28844-B27","call_identifier":"FWF","name":"Biophysics of information processing in gene regulation"}],"publication":"bioRxiv","main_file_link":[{"url":"https://doi.org/10.1101/2020.04.18.047886 ","open_access":"1"}],"citation":{"short":"B. Kavcic, G. Tkačik, M.T. Bollenbach, BioRxiv (2020).","mla":"Kavcic, Bor, et al. “A Minimal Biophysical Model of Combined Antibiotic Action.” BioRxiv, Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.04.18.047886.","chicago":"Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “A Minimal Biophysical Model of Combined Antibiotic Action.” BioRxiv. Cold Spring Harbor Laboratory, 2020. https://doi.org/10.1101/2020.04.18.047886.","ama":"Kavcic B, Tkačik G, Bollenbach MT. A minimal biophysical model of combined antibiotic action. bioRxiv. 2020. doi:10.1101/2020.04.18.047886","apa":"Kavcic, B., Tkačik, G., & Bollenbach, M. T. (2020). A minimal biophysical model of combined antibiotic action. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.04.18.047886","ieee":"B. Kavcic, G. Tkačik, and M. T. Bollenbach, “A minimal biophysical model of combined antibiotic action,” bioRxiv. Cold Spring Harbor Laboratory, 2020.","ista":"Kavcic B, Tkačik G, Bollenbach MT. 2020. A minimal biophysical model of combined antibiotic action. bioRxiv, 10.1101/2020.04.18.047886."},"oa":1,"language":[{"iso":"eng"}],"doi":"10.1101/2020.04.18.047886","date_published":"2020-04-18T00:00:00Z","day":"18","month":"04","article_processing_charge":"No"},{"publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"month":"06","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"doi":"10.1073/pnas.2003346117","project":[{"call_identifier":"H2020","name":"Tracing Evolution of Auxin Transport and Polarity in Plants","grant_number":"742985","_id":"261099A6-B435-11E9-9278-68D0E5697425"},{"grant_number":"P29988","_id":"262EF96E-B435-11E9-9278-68D0E5697425","name":"RNA-directed DNA methylation in plant development","call_identifier":"FWF"}],"quality_controlled":"1","isi":1,"external_id":{"isi":["000565729700033"],"pmid":["32541049"]},"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"oa":1,"ec_funded":1,"file_date_updated":"2020-07-14T12:48:07Z","article_number":"202003346","volume":117,"date_updated":"2024-03-28T23:30:10Z","date_created":"2020-06-22T13:33:52Z","related_material":{"link":[{"url":"https://ist.ac.at/en/news/how-wounded-plants-coordinate-their-healing/","description":"News on IST Homepage","relation":"press_release"}],"record":[{"id":"9992","status":"public","relation":"dissertation_contains"}]},"author":[{"first_name":"Lukas","last_name":"Hörmayer","id":"2EEE7A2A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8295-2926","full_name":"Hörmayer, Lukas"},{"full_name":"Montesinos López, Juan C","orcid":"0000-0001-9179-6099","id":"310A8E3E-F248-11E8-B48F-1D18A9856A87","last_name":"Montesinos López","first_name":"Juan C"},{"id":"44E59624-F248-11E8-B48F-1D18A9856A87","last_name":"Marhavá","first_name":"Petra","full_name":"Marhavá, Petra"},{"full_name":"Benková, Eva","orcid":"0000-0002-8510-9739","id":"38F4F166-F248-11E8-B48F-1D18A9856A87","last_name":"Benková","first_name":"Eva"},{"id":"2E46069C-F248-11E8-B48F-1D18A9856A87","last_name":"Yoshida","first_name":"Saiko","full_name":"Yoshida, Saiko"},{"orcid":"0000-0002-8302-7596","id":"4159519E-F248-11E8-B48F-1D18A9856A87","last_name":"Friml","first_name":"Jiří","full_name":"Friml, Jiří"}],"department":[{"_id":"JiFr"},{"_id":"EvBe"}],"publisher":"Proceedings of the National Academy of Sciences","publication_status":"published","pmid":1,"year":"2020","article_processing_charge":"No","has_accepted_license":"1","day":"30","scopus_import":"1","date_published":"2020-06-30T00:00:00Z","article_type":"original","citation":{"ista":"Hörmayer L, Montesinos López JC, Marhavá P, Benková E, Yoshida S, Friml J. 2020. Wounding-induced changes in cellular pressure and localized auxin signalling spatially coordinate restorative divisions in roots. Proceedings of the National Academy of Sciences. 117(26), 202003346.","ieee":"L. Hörmayer, J. C. Montesinos López, P. Marhavá, E. Benková, S. Yoshida, and J. Friml, “Wounding-induced changes in cellular pressure and localized auxin signalling spatially coordinate restorative divisions in roots,” Proceedings of the National Academy of Sciences, vol. 117, no. 26. Proceedings of the National Academy of Sciences, 2020.","apa":"Hörmayer, L., Montesinos López, J. C., Marhavá, P., Benková, E., Yoshida, S., & Friml, J. (2020). Wounding-induced changes in cellular pressure and localized auxin signalling spatially coordinate restorative divisions in roots. Proceedings of the National Academy of Sciences. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2003346117","ama":"Hörmayer L, Montesinos López JC, Marhavá P, Benková E, Yoshida S, Friml J. Wounding-induced changes in cellular pressure and localized auxin signalling spatially coordinate restorative divisions in roots. Proceedings of the National Academy of Sciences. 2020;117(26). doi:10.1073/pnas.2003346117","chicago":"Hörmayer, Lukas, Juan C Montesinos López, Petra Marhavá, Eva Benková, Saiko Yoshida, and Jiří Friml. “Wounding-Induced Changes in Cellular Pressure and Localized Auxin Signalling Spatially Coordinate Restorative Divisions in Roots.” Proceedings of the National Academy of Sciences. Proceedings of the National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.2003346117.","mla":"Hörmayer, Lukas, et al. “Wounding-Induced Changes in Cellular Pressure and Localized Auxin Signalling Spatially Coordinate Restorative Divisions in Roots.” Proceedings of the National Academy of Sciences, vol. 117, no. 26, 202003346, Proceedings of the National Academy of Sciences, 2020, doi:10.1073/pnas.2003346117.","short":"L. Hörmayer, J.C. Montesinos López, P. Marhavá, E. Benková, S. Yoshida, J. Friml, Proceedings of the National Academy of Sciences 117 (2020)."},"publication":"Proceedings of the National Academy of Sciences","issue":"26","abstract":[{"text":"Wound healing in plant tissues, consisting of rigid cell wall-encapsulated cells, represents a considerable challenge and occurs through largely unknown mechanisms distinct from those in animals. Owing to their inability to migrate, plant cells rely on targeted cell division and expansion to regenerate wounds. Strict coordination of these wound-induced responses is essential to ensure efficient, spatially restricted wound healing. Single-cell tracking by live imaging allowed us to gain mechanistic insight into the wound perception and coordination of wound responses after laser-based wounding in Arabidopsis root. We revealed a crucial contribution of the collapse of damaged cells in wound perception and detected an auxin increase specific to cells immediately adjacent to the wound. This localized auxin increase balances wound-induced cell expansion and restorative division rates in a dose-dependent manner, leading to tumorous overproliferation when the canonical TIR1 auxin signaling is disrupted. Auxin and wound-induced turgor pressure changes together also spatially define the activation of key components of regeneration, such as the transcription regulator ERF115. Our observations suggest that the wound signaling involves the sensing of collapse of damaged cells and a local auxin signaling activation to coordinate the downstream transcriptional responses in the immediate wound vicinity.","lang":"eng"}],"type":"journal_article","oa_version":"None","file":[{"checksum":"908b09437680181de9990915f2113aca","date_updated":"2020-07-14T12:48:07Z","date_created":"2020-06-23T11:30:53Z","file_id":"8009","relation":"main_file","creator":"dernst","file_size":2407102,"content_type":"application/pdf","access_level":"open_access","file_name":"2020_PNAS_Hoermayer.pdf"}],"intvolume":" 117","status":"public","title":"Wounding-induced changes in cellular pressure and localized auxin signalling spatially coordinate restorative divisions in roots","ddc":["580"],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"8002"},{"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"1028"}]},"author":[{"full_name":"Kainrath, Stephanie","first_name":"Stephanie","last_name":"Kainrath","id":"32CFBA64-F248-11E8-B48F-1D18A9856A87"}],"date_updated":"2023-09-22T09:20:10Z","date_created":"2020-04-24T16:00:51Z","year":"2020","publisher":"Institute of Science and Technology Austria","department":[{"_id":"CaGu"}],"publication_status":"published","file_date_updated":"2021-10-31T23:30:05Z","doi":"10.15479/AT:ISTA:7680","language":[{"iso":"eng"}],"supervisor":[{"first_name":"Harald L","last_name":"Janovjak","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8023-9315","full_name":"Janovjak, Harald L"}],"degree_awarded":"PhD","oa":1,"publication_identifier":{"eissn":["2663-337X"]},"month":"04","oa_version":"None","file":[{"access_level":"open_access","file_name":"Thesis_without-signatures_PDFA.pdf","file_size":3268017,"content_type":"application/pdf","creator":"stgingl","relation":"main_file","embargo":"2021-10-30","file_id":"7692","checksum":"fb9a4468eb27be92690728e35c823796","date_created":"2020-04-28T11:19:21Z","date_updated":"2021-10-31T23:30:05Z"},{"date_updated":"2021-10-31T23:30:05Z","date_created":"2020-04-28T11:19:24Z","checksum":"f6c80ca97104a631a328cb79a2c53493","file_id":"7693","relation":"source_file","creator":"stgingl","content_type":"application/octet-stream","file_size":5167703,"file_name":"Thesis_without signatures.docx","embargo_to":"open_access","access_level":"closed"}],"_id":"7680","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","ddc":["570"],"title":"Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals","status":"public","abstract":[{"text":"Proteins and their complex dynamic interactions regulate cellular mechanisms from sensing and transducing extracellular signals, to mediating genetic responses, and sustaining or changing cell morphology. To manipulate these protein-protein interactions (PPIs) that govern the behavior and fate of cells, synthetically constructed, genetically encoded tools provide the means to precisely target proteins of interest (POIs), and control their subcellular localization and activity in vitro and in vivo. Ideal synthetic tools react to an orthogonal cue, i.e. a trigger that does not activate any other endogenous process, thereby allowing manipulation of the POI alone.\r\nIn optogenetics, naturally occurring photosensory domain from plants, algae and bacteria are re-purposed and genetically fused to POIs. Illumination with light of a specific wavelength triggers a conformational change that can mediate PPIs, such as dimerization or oligomerization. By using light as a trigger, these tools can be activated with high spatial and temporal precision, on subcellular and millisecond scales. Chemogenetic tools consist of protein domains that recognize and bind small molecules. By genetic fusion to POIs, these domains can mediate PPIs upon addition of their specific ligands, which are often synthetically designed to provide highly specific interactions and exhibit good bioavailability.\r\nMost optogenetic tools to mediate PPIs are based on well-studied photoreceptors responding to red, blue or near-UV light, leaving a striking gap in the green band of the visible light spectrum. Among both optogenetic and chemogenetic tools, there is an abundance of methods to induce PPIs, but tools to disrupt them require UV illumination, rely on covalent linkage and subsequent enzymatic cleavage or initially result in protein clustering of unknown stoichiometry.\r\nThis work describes how the recently structurally and photochemically characterized green-light responsive cobalamin-binding domains (CBDs) from bacterial transcription factors were re-purposed to function as a green-light responsive optogenetic tool. In contrast to previously engineered optogenetic tools, CBDs do not induce PPI, but rather confer a PPI already upon expression, which can be rapidly disrupted by illumination. This was employed to mimic inhibition of constitutive activity of a growth factor receptor, and successfully implement for cell signalling in mammalian cells and in vivo to rescue development in zebrafish. This work further describes the development and application of a chemically induced de-dimerizer (CDD) based on a recently identified and structurally described bacterial oxyreductase. CDD forms a dimer upon expression in absence of its cofactor, the flavin derivative F420. Safety and of domain expression and ligand exposure are demonstrated in vitro and in vivo in zebrafish. The system is further applied to inhibit cell signalling output from a chimeric receptor upon F420 treatment.\r\nCBDs and CDD expand the repertoire of synthetic tools by providing novel mechanisms of mediating PPIs, and by recognizing previously not utilized cues. In the future, they can readily be combined with existing synthetic tools to functionally manipulate PPIs in vitro and in vivo.","lang":"eng"}],"type":"dissertation","alternative_title":["ISTA Thesis"],"date_published":"2020-04-24T00:00:00Z","citation":{"short":"S. Kainrath, Synthetic Tools for Optogenetic and Chemogenetic Inhibition of Cellular Signals, Institute of Science and Technology Austria, 2020.","mla":"Kainrath, Stephanie. Synthetic Tools for Optogenetic and Chemogenetic Inhibition of Cellular Signals. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7680.","chicago":"Kainrath, Stephanie. “Synthetic Tools for Optogenetic and Chemogenetic Inhibition of Cellular Signals.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7680.","ama":"Kainrath S. Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals. 2020. doi:10.15479/AT:ISTA:7680","ieee":"S. Kainrath, “Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals,” Institute of Science and Technology Austria, 2020.","apa":"Kainrath, S. (2020). Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7680","ista":"Kainrath S. 2020. Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals. Institute of Science and Technology Austria."},"page":"98","has_accepted_license":"1","article_processing_charge":"No","day":"24"},{"month":"10","publication_identifier":{"issn":["2663-337X"]},"project":[{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24","call_identifier":"FWF","name":"Molecular Drug Targets"},{"name":"Neural stem cells in autism and epilepsy","grant_number":"F07807","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E"}],"oa":1,"degree_awarded":"PhD","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"supervisor":[{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia"}],"language":[{"iso":"eng"}],"doi":"10.15479/AT:ISTA:8620","file_date_updated":"2021-10-16T22:30:04Z","publication_status":"published","department":[{"_id":"GaNo"}],"publisher":"Institute of Science and Technology Austria","acknowledgement":"I would like to especially thank Armel Nicolas from the Proteomics and Christoph Sommer from the Bioimaging Facilities for the data analysis, and to thank the team of the Preclinical Facility, especially Sabina Deixler, Angela Schlerka, Anita Lepold, Mihalea Mihai and Michael Schun for taking care of the mouse line maintenance and their great support.","year":"2020","date_created":"2020-10-07T14:53:13Z","date_updated":"2023-09-07T13:22:14Z","author":[{"full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin","last_name":"Morandell"}],"related_material":{"record":[{"id":"7800","relation":"part_of_dissertation","status":"public"},{"relation":"part_of_dissertation","status":"public","id":"8131"}]},"day":"12","article_processing_charge":"No","has_accepted_license":"1","page":"138","citation":{"chicago":"Morandell, Jasmin. “Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8620.","short":"J. Morandell, Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis, Institute of Science and Technology Austria, 2020.","mla":"Morandell, Jasmin. Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8620.","ieee":"J. Morandell, “Illuminating the role of Cul3 in autism spectrum disorder pathogenesis,” Institute of Science and Technology Austria, 2020.","apa":"Morandell, J. (2020). Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8620","ista":"Morandell J. 2020. Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. Institute of Science and Technology Austria.","ama":"Morandell J. Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. 2020. doi:10.15479/AT:ISTA:8620"},"date_published":"2020-10-12T00:00:00Z","alternative_title":["ISTA Thesis"],"type":"dissertation","abstract":[{"text":"The development of the human brain occurs through a tightly regulated series of dynamic and adaptive processes during prenatal and postnatal life. A disruption of this strictly orchestrated series of events can lead to a number of neurodevelopmental conditions, including Autism Spectrum Disorders (ASDs). ASDs are a very common, etiologically and phenotypically heterogeneous group of disorders sharing the core symptoms of social interaction and communication deficits and restrictive and repetitive interests and behaviors. They are estimated to affect one in 59 individuals in the U.S. and, over the last three decades, mutations in more than a hundred genetic loci have been convincingly linked to ASD pathogenesis. Yet, for the vast majority of these ASD-risk genes their role during brain development and precise molecular function still remain elusive.\r\nDe novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin 3 (CUL3) lead to ASD. In the study described here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 heterozygous knockout mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3+/-, Cul3+/fl Emx1-Cre and Cul3fl/fl Emx1-Cre mutant brains display cortical lamination abnormalities due to defective migration of post-mitotic excitatory neurons, as well as reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal cortical organization, Cul3 heterozygous deletion is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level we show that Cul3 regulates cytoskeletal and adhesion protein abundance in the mouse embryonic cortex. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neural cells results in atypical organization of the actin mesh at the cell leading edge. Of note, heterozygous deletion of Cul3 in adult mice does not induce the majority of the behavioral defects observed in constitutive Cul3 haploinsufficient animals, pointing to a critical time-window for Cul3 deficiency.\r\nIn conclusion, our data indicate that Cul3 plays a critical role in the regulation of cytoskeletal proteins and neuronal migration. ASD-associated defects and behavioral abnormalities are primarily due to dosage sensitive Cul3 functions at early brain developmental stages.","lang":"eng"}],"ddc":["610"],"status":"public","title":"Illuminating the role of Cul3 in autism spectrum disorder pathogenesis","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"8620","file":[{"checksum":"7ee83e42de3e5ce2fedb44dff472f75f","date_created":"2020-10-07T14:41:49Z","date_updated":"2021-10-16T22:30:04Z","embargo":"2021-10-15","file_id":"8621","relation":"main_file","creator":"jmorande","content_type":"application/pdf","file_size":16155786,"access_level":"open_access","file_name":"Jasmin_Morandell_Thesis-2020_final.pdf"},{"file_id":"8622","relation":"source_file","date_updated":"2021-10-16T22:30:04Z","date_created":"2020-10-07T14:45:07Z","checksum":"5e0464af453734210ce7aab7b4a92e3a","file_name":"Jasmin_Morandell_Thesis-2020_final.zip","embargo_to":"open_access","access_level":"closed","creator":"jmorande","file_size":24344152,"content_type":"application/x-zip-compressed"}],"oa_version":"Published Version"},{"article_processing_charge":"No","has_accepted_license":"1","day":"09","page":"242","citation":{"chicago":"Kampjut, Domen. “Molecular Mechanisms of Mitochondrial Redox-Coupled Proton Pumping Enzymes.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8340.","short":"D. Kampjut, Molecular Mechanisms of Mitochondrial Redox-Coupled Proton Pumping Enzymes, Institute of Science and Technology Austria, 2020.","mla":"Kampjut, Domen. Molecular Mechanisms of Mitochondrial Redox-Coupled Proton Pumping Enzymes. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8340.","apa":"Kampjut, D. (2020). Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8340","ieee":"D. Kampjut, “Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes,” Institute of Science and Technology Austria, 2020.","ista":"Kampjut D. 2020. Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes. Institute of Science and Technology Austria.","ama":"Kampjut D. Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes. 2020. doi:10.15479/AT:ISTA:8340"},"date_published":"2020-09-09T00:00:00Z","alternative_title":["ISTA Thesis"],"type":"dissertation","abstract":[{"lang":"eng","text":"Mitochondria are sites of oxidative phosphorylation in eukaryotic cells. Oxidative phosphorylation operates by a chemiosmotic mechanism made possible by redox-driven proton pumping machines which establish a proton motive force across the inner mitochondrial membrane. This electrochemical proton gradient is used to drive ATP synthesis, which powers the majority of cellular processes such as protein synthesis, locomotion and signalling. In this thesis I investigate the structures and molecular mechanisms of two inner mitochondrial proton pumping enzymes, respiratory complex I and transhydrogenase. I present the first high-resolution structure of the full transhydrogenase from any species, and a significantly improved structure of complex I. Improving the resolution from 3.3 Å available previously to up to 2.3 Å in this thesis allowed us to model bound water molecules, crucial in the proton pumping mechanism. For both enzymes, up to five cryo-EM datasets with different substrates and inhibitors bound were solved to delineate the catalytic cycle and understand the proton pumping mechanism. In transhydrogenase, the proton channel is gated by reversible detachment of the NADP(H)-binding domain which opens the proton channel to the opposite sites of the membrane. In complex I, the proton channels are gated by reversible protonation of key glutamate and lysine residues and breaking of the water wire connecting the proton pumps with the quinone reduction site. The tight coupling between the redox and the proton pumping reactions in transhydrogenase is achieved by controlling the NADP(H) exchange which can only happen when the NADP(H)-binding domain interacts with the membrane domain. In complex I, coupling is achieved by cycling of the whole complex between the closed state, in which quinone can get reduced, and the open state, in which NADH can induce quinol ejection from the binding pocket. On the basis of these results I propose detailed mechanisms for catalytic cycles of transhydrogenase and complex I that are consistent with a large amount of previous work. In both enzymes, conformational and electrostatic mechanisms contribute to the overall catalytic process. Results presented here could be used for better understanding of the human pathologies arising from deficiencies of complex I or transhydrogenase and could be used to develop novel therapies."}],"ddc":["572"],"status":"public","title":"Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes","_id":"8340","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"None","file":[{"file_id":"8345","relation":"source_file","checksum":"dd270baf82121eb4472ad19d77bf227c","date_updated":"2021-09-11T22:30:04Z","date_created":"2020-09-08T13:32:06Z","access_level":"closed","file_name":"ThesisFull20200908.docx","embargo_to":"open_access","creator":"dkampjut","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":166146359},{"creator":"dernst","content_type":"application/pdf","file_size":13873769,"access_level":"open_access","file_name":"2020_Thesis_Kampjut.pdf","checksum":"82fce6f95ffa47ecc4ebca67ea2cc38c","date_created":"2020-09-14T15:02:20Z","date_updated":"2021-09-11T22:30:04Z","file_id":"8393","embargo":"2021-09-10","relation":"main_file"}],"publication_identifier":{"isbn":["978-3-99078-008-4"],"issn":["2663-337X"]},"month":"09","project":[{"grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program","call_identifier":"H2020"}],"oa":1,"language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"EM-Fac"}],"supervisor":[{"first_name":"Leonid A","last_name":"Sazanov","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A"}],"degree_awarded":"PhD","doi":"10.15479/AT:ISTA:8340","ec_funded":1,"file_date_updated":"2021-09-11T22:30:04Z","publisher":"Institute of Science and Technology Austria","department":[{"_id":"LeSa"}],"publication_status":"published","year":"2020","acknowledgement":"I acknowledge the support of IST facilities, especially the Electron Miscroscopy facility for providing training and resources. Special thanks also go to cryo-EM specialists who helped me to collect the data present here: Dr Valentin Hodirnau (IST Austria), Dr Tom Heuser (IMBA, Vienna), Dr Rebecca Thompson (Uni. of Leeds) and Dr Jirka Nováček (CEITEC). This work has been supported by iNEXT, project number 653706, funded by the Horizon 2020 programme of the European Union. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 665385.","date_created":"2020-09-07T18:42:23Z","date_updated":"2023-09-07T13:26:17Z","related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"6848"}]},"author":[{"id":"37233050-F248-11E8-B48F-1D18A9856A87","last_name":"Kampjut","first_name":"Domen","full_name":"Kampjut, Domen"}]},{"file_date_updated":"2020-07-14T12:48:03Z","year":"2020","publisher":"Cold Spring Harbor Laboratory","department":[{"_id":"JoDa"},{"_id":"GaNo"},{"_id":"LifeSc"}],"publication_status":"submitted","related_material":{"record":[{"id":"9429","relation":"later_version","status":"public"},{"status":"public","relation":"dissertation_contains","id":"8620"}]},"author":[{"full_name":"Morandell, Jasmin","last_name":"Morandell","first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87"},{"id":"29A8453C-F248-11E8-B48F-1D18A9856A87","last_name":"Schwarz","first_name":"Lena A","full_name":"Schwarz, Lena A"},{"orcid":"0000-0003-1843-3173","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","last_name":"Basilico","first_name":"Bernadette","full_name":"Basilico, Bernadette"},{"full_name":"Tasciyan, Saren","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1671-393X","first_name":"Saren","last_name":"Tasciyan"},{"first_name":"Armel","last_name":"Nicolas","id":"2A103192-F248-11E8-B48F-1D18A9856A87","full_name":"Nicolas, Armel"},{"last_name":"Sommer","first_name":"Christoph M","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M"},{"first_name":"Caroline","last_name":"Kreuzinger","id":"382077BA-F248-11E8-B48F-1D18A9856A87","full_name":"Kreuzinger, Caroline"},{"id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","last_name":"Knaus","first_name":"Lisa","full_name":"Knaus, Lisa"},{"id":"D23090A2-9057-11EA-883A-A8396FC7A38F","first_name":"Zoe","last_name":"Dobler","full_name":"Dobler, Zoe"},{"last_name":"Cacci","first_name":"Emanuele","full_name":"Cacci, Emanuele"},{"orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","first_name":"Johann G","full_name":"Danzl, Johann G"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino"}],"date_created":"2020-05-05T14:31:33Z","date_updated":"2024-03-28T23:30:14Z","month":"01","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"oa":1,"project":[{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF"},{"grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets","call_identifier":"FWF"}],"doi":"10.1101/2020.01.10.902064 ","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"PreCl"}],"type":"preprint","abstract":[{"text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). Here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 haploinsufficient mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3 mutant brain displays cortical lamination abnormalities due to defective neuronal migration and reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal columnar organization, Cul3 haploinsufficiency is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level, employing a quantitative proteomic approach, we show that Cul3 regulates cytoskeletal and adhesion protein abundance in mouse embryos. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neuronal cells results in atypical organization of the actin mesh at the cell leading edge, likely causing the observed migration deficits. In contrast to these important functions early in development, Cul3 deficiency appears less relevant at adult stages. In fact, induction of Cul3 haploinsufficiency in adult mice does not result in the behavioral defects observed in constitutive Cul3 haploinsufficient animals. Taken together, our data indicate that Cul3 has a critical role in the regulation of cytoskeletal proteins and neuronal migration and that ASD-associated defects and behavioral abnormalities are primarily due to Cul3 functions at early developmental stages.","lang":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"7800","ddc":["570"],"title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","status":"public","oa_version":"Preprint","file":[{"creator":"rsix","file_size":2931370,"content_type":"application/pdf","access_level":"open_access","file_name":"2020.01.10.902064v1.full.pdf","checksum":"c6799ab5daba80efe8e2ed63c15f8c81","date_updated":"2020-07-14T12:48:03Z","date_created":"2020-05-05T14:31:19Z","file_id":"7801","relation":"main_file"}],"article_processing_charge":"No","has_accepted_license":"1","day":"11","citation":{"ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv. doi:10.1101/2020.01.10.902064 ","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Nicolas, A., Sommer, C. M., … Novarino, G. (n.d.). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.01.10.902064 ","ieee":"J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” bioRxiv. Cold Spring Harbor Laboratory.","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Nicolas A, Sommer CM, Kreuzinger C, Knaus L, Dobler Z, Cacci E, Danzl JG, Novarino G. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv, 10.1101/2020.01.10.902064 .","short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, A. Nicolas, C.M. Sommer, C. Kreuzinger, L. Knaus, Z. Dobler, E. Cacci, J.G. Danzl, G. Novarino, BioRxiv (n.d.).","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2020.01.10.902064 .","chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Armel Nicolas, Christoph M Sommer, Caroline Kreuzinger, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2020.01.10.902064 ."},"publication":"bioRxiv","date_published":"2020-01-11T00:00:00Z"},{"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"8131","ddc":["570"],"title":"Molecular mechanisms for targeted ASD treatments","status":"public","intvolume":" 65","file":[{"success":1,"date_updated":"2020-07-22T06:47:45Z","date_created":"2020-07-22T06:47:45Z","relation":"main_file","file_id":"8146","file_size":1381545,"content_type":"application/pdf","creator":"dernst","access_level":"open_access","file_name":"2020_CurrentOpGenetics_Basilico.pdf"}],"oa_version":"Published Version","type":"journal_article","abstract":[{"lang":"eng","text":"The possibility to generate construct valid animal models enabled the development and testing of therapeutic strategies targeting the core features of autism spectrum disorders (ASDs). At the same time, these studies highlighted the necessity of identifying sensitive developmental time windows for successful therapeutic interventions. Animal and human studies also uncovered the possibility to stratify the variety of ASDs in molecularly distinct subgroups, potentially facilitating effective treatment design. Here, we focus on the molecular pathways emerging as commonly affected by mutations in diverse ASD-risk genes, on their role during critical windows of brain development and the potential treatments targeting these biological processes."}],"issue":"12","publication":"Current Opinion in Genetics and Development","citation":{"ama":"Basilico B, Morandell J, Novarino G. Molecular mechanisms for targeted ASD treatments. Current Opinion in Genetics and Development. 2020;65(12):126-137. doi:10.1016/j.gde.2020.06.004","ieee":"B. Basilico, J. Morandell, and G. Novarino, “Molecular mechanisms for targeted ASD treatments,” Current Opinion in Genetics and Development, vol. 65, no. 12. Elsevier, pp. 126–137, 2020.","apa":"Basilico, B., Morandell, J., & Novarino, G. (2020). Molecular mechanisms for targeted ASD treatments. Current Opinion in Genetics and Development. Elsevier. https://doi.org/10.1016/j.gde.2020.06.004","ista":"Basilico B, Morandell J, Novarino G. 2020. Molecular mechanisms for targeted ASD treatments. Current Opinion in Genetics and Development. 65(12), 126–137.","short":"B. Basilico, J. Morandell, G. Novarino, Current Opinion in Genetics and Development 65 (2020) 126–137.","mla":"Basilico, Bernadette, et al. “Molecular Mechanisms for Targeted ASD Treatments.” Current Opinion in Genetics and Development, vol. 65, no. 12, Elsevier, 2020, pp. 126–37, doi:10.1016/j.gde.2020.06.004.","chicago":"Basilico, Bernadette, Jasmin Morandell, and Gaia Novarino. “Molecular Mechanisms for Targeted ASD Treatments.” Current Opinion in Genetics and Development. Elsevier, 2020. https://doi.org/10.1016/j.gde.2020.06.004."},"article_type":"original","page":"126-137","date_published":"2020-12-01T00:00:00Z","scopus_import":"1","day":"01","article_processing_charge":"Yes (via OA deal)","has_accepted_license":"1","year":"2020","pmid":1,"publication_status":"published","publisher":"Elsevier","department":[{"_id":"GaNo"}],"author":[{"last_name":"Basilico","first_name":"Bernadette","orcid":"0000-0003-1843-3173","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","full_name":"Basilico, Bernadette"},{"last_name":"Morandell","first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin"},{"first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"8620"}]},"date_updated":"2024-03-28T23:30:14Z","date_created":"2020-07-19T22:00:58Z","volume":65,"file_date_updated":"2020-07-22T06:47:45Z","ec_funded":1,"external_id":{"pmid":["32659636"],"isi":["000598918900019"]},"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"oa":1,"isi":1,"quality_controlled":"1","project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020"},{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24","call_identifier":"FWF","name":"Molecular Drug Targets"},{"name":"Neural stem cells in autism and epilepsy","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E","grant_number":"F07807"}],"doi":"10.1016/j.gde.2020.06.004","language":[{"iso":"eng"}],"month":"12","publication_identifier":{"issn":["0959437X"],"eissn":["18790380"]}},{"oa_version":"Published Version","file":[{"access_level":"open_access","file_name":"2020_JournalCellScience_Dimchev.pdf","creator":"dernst","content_type":"application/pdf","file_size":13493302,"embargo":"2020-10-10","file_id":"8435","relation":"main_file","checksum":"ba917e551acc4ece2884b751434df9ae","date_updated":"2020-10-11T22:30:02Z","date_created":"2020-09-17T14:07:51Z"}],"_id":"8434","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","ddc":["570"],"status":"public","title":"Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation","intvolume":" 133","abstract":[{"text":"Efficient migration on adhesive surfaces involves the protrusion of lamellipodial actin networks and their subsequent stabilization by nascent adhesions. The actin-binding protein lamellipodin (Lpd) is thought to play a critical role in lamellipodium protrusion, by delivering Ena/VASP proteins onto the growing plus ends of actin filaments and by interacting with the WAVE regulatory complex, an activator of the Arp2/3 complex, at the leading edge. Using B16-F1 melanoma cell lines, we demonstrate that genetic ablation of Lpd compromises protrusion efficiency and coincident cell migration without altering essential parameters of lamellipodia, including their maximal rate of forward advancement and actin polymerization. We also confirmed lamellipodia and migration phenotypes with CRISPR/Cas9-mediated Lpd knockout Rat2 fibroblasts, excluding cell type-specific effects. Moreover, computer-aided analysis of cell-edge morphodynamics on B16-F1 cell lamellipodia revealed that loss of Lpd correlates with reduced temporal protrusion maintenance as a prerequisite of nascent adhesion formation. We conclude that Lpd optimizes protrusion and nascent adhesion formation by counteracting frequent, chaotic retraction and membrane ruffling.This article has an associated First Person interview with the first author of the paper. ","lang":"eng"}],"issue":"7","type":"journal_article","date_published":"2020-04-09T00:00:00Z","publication":"Journal of Cell Science","citation":{"chicago":"Dimchev, Georgi A, Behnam Amiri, Ashley C. Humphries, Matthias Schaks, Vanessa Dimchev, Theresia E. B. Stradal, Jan Faix, et al. “Lamellipodin Tunes Cell Migration by Stabilizing Protrusions and Promoting Adhesion Formation.” Journal of Cell Science. The Company of Biologists, 2020. https://doi.org/10.1242/jcs.239020.","mla":"Dimchev, Georgi A., et al. “Lamellipodin Tunes Cell Migration by Stabilizing Protrusions and Promoting Adhesion Formation.” Journal of Cell Science, vol. 133, no. 7, jcs239020, The Company of Biologists, 2020, doi:10.1242/jcs.239020.","short":"G.A. Dimchev, B. Amiri, A.C. Humphries, M. Schaks, V. Dimchev, T.E.B. Stradal, J. Faix, M. Krause, M. Way, M. Falcke, K. Rottner, Journal of Cell Science 133 (2020).","ista":"Dimchev GA, Amiri B, Humphries AC, Schaks M, Dimchev V, Stradal TEB, Faix J, Krause M, Way M, Falcke M, Rottner K. 2020. Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation. Journal of Cell Science. 133(7), jcs239020.","ieee":"G. A. Dimchev et al., “Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation,” Journal of Cell Science, vol. 133, no. 7. The Company of Biologists, 2020.","apa":"Dimchev, G. A., Amiri, B., Humphries, A. C., Schaks, M., Dimchev, V., Stradal, T. E. B., … Rottner, K. (2020). Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation. Journal of Cell Science. The Company of Biologists. https://doi.org/10.1242/jcs.239020","ama":"Dimchev GA, Amiri B, Humphries AC, et al. Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation. Journal of Cell Science. 2020;133(7). doi:10.1242/jcs.239020"},"article_type":"original","day":"09","has_accepted_license":"1","article_processing_charge":"No","keyword":["Cell Biology"],"author":[{"full_name":"Dimchev, Georgi A","first_name":"Georgi A","last_name":"Dimchev","id":"38C393BE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8370-6161"},{"last_name":"Amiri","first_name":"Behnam","full_name":"Amiri, Behnam"},{"full_name":"Humphries, Ashley C.","first_name":"Ashley C.","last_name":"Humphries"},{"first_name":"Matthias","last_name":"Schaks","full_name":"Schaks, Matthias"},{"full_name":"Dimchev, Vanessa","first_name":"Vanessa","last_name":"Dimchev"},{"last_name":"Stradal","first_name":"Theresia E. B.","full_name":"Stradal, Theresia E. B."},{"full_name":"Faix, Jan","last_name":"Faix","first_name":"Jan"},{"last_name":"Krause","first_name":"Matthias","full_name":"Krause, Matthias"},{"full_name":"Way, Michael","last_name":"Way","first_name":"Michael"},{"first_name":"Martin","last_name":"Falcke","full_name":"Falcke, Martin"},{"full_name":"Rottner, Klemens","first_name":"Klemens","last_name":"Rottner"}],"date_updated":"2023-09-05T15:41:48Z","date_created":"2020-09-17T14:00:33Z","volume":133,"acknowledgement":"This work was supported in part by Deutsche Forschungsgemeinschaft (DFG)[GRK2223/1, RO2414/5-1 (to K.R.), FA350/11-1 (to M.F.) and FA330/11-1 (to J.F.)],as well as by intramural funding from the Helmholtz Association (to T.E.B.S. andK.R.). G.D. was additionally funded by the Austrian Science Fund (FWF) LiseMeitner Program [M-2495]. A.C.H. and M.W. are supported by the Francis CrickInstitute, which receives its core funding from Cancer Research UK [FC001209], theMedical Research Council [FC001209] and the Wellcome Trust [FC001209]. M.K. issupported by the Biotechnology and Biological Sciences Research Council [BB/F011431/1, BB/J000590/1, BB/N000226/1]. Deposited in PMC for release after 6months.","year":"2020","pmid":1,"publication_status":"published","department":[{"_id":"FlSc"}],"publisher":"The Company of Biologists","file_date_updated":"2020-10-11T22:30:02Z","article_number":"jcs239020","doi":"10.1242/jcs.239020","language":[{"iso":"eng"}],"oa":1,"external_id":{"pmid":[" 32094266"],"isi":["000534387800005"]},"quality_controlled":"1","isi":1,"project":[{"_id":"2674F658-B435-11E9-9278-68D0E5697425","grant_number":"M02495","call_identifier":"FWF","name":"Protein structure and function in filopodia across scales"}],"month":"04","publication_identifier":{"eissn":["1477-9137"],"issn":["0021-9533"]}},{"date_published":"2020-04-27T00:00:00Z","publication":"Nature Biotechnology","citation":{"ista":"Mitiouchkina T, Mishin AS, Gonzalez Somermeyer L, Markina NM, Chepurnyh TV, Guglya EB, Karataeva TA, Palkina KA, Shakhova ES, Fakhranurova LI, Chekova SV, Tsarkova AS, Golubev YV, Negrebetsky VV, Dolgushin SA, Shalaev PV, Shlykov D, Melnik OA, Shipunova VO, Deyev SM, Bubyrev AI, Pushin AS, Choob VV, Dolgov SV, Kondrashov F, Yampolsky IV, Sarkisyan KS. 2020. Plants with genetically encoded autoluminescence. Nature Biotechnology. 38, 944–946.","ieee":"T. Mitiouchkina et al., “Plants with genetically encoded autoluminescence,” Nature Biotechnology, vol. 38. Springer Nature, pp. 944–946, 2020.","apa":"Mitiouchkina, T., Mishin, A. S., Gonzalez Somermeyer, L., Markina, N. M., Chepurnyh, T. V., Guglya, E. B., … Sarkisyan, K. S. (2020). Plants with genetically encoded autoluminescence. Nature Biotechnology. Springer Nature. https://doi.org/10.1038/s41587-020-0500-9","ama":"Mitiouchkina T, Mishin AS, Gonzalez Somermeyer L, et al. Plants with genetically encoded autoluminescence. Nature Biotechnology. 2020;38:944-946. doi:10.1038/s41587-020-0500-9","chicago":"Mitiouchkina, Tatiana, Alexander S. Mishin, Louisa Gonzalez Somermeyer, Nadezhda M. Markina, Tatiana V. Chepurnyh, Elena B. Guglya, Tatiana A. Karataeva, et al. “Plants with Genetically Encoded Autoluminescence.” Nature Biotechnology. Springer Nature, 2020. https://doi.org/10.1038/s41587-020-0500-9.","mla":"Mitiouchkina, Tatiana, et al. “Plants with Genetically Encoded Autoluminescence.” Nature Biotechnology, vol. 38, Springer Nature, 2020, pp. 944–46, doi:10.1038/s41587-020-0500-9.","short":"T. Mitiouchkina, A.S. Mishin, L. Gonzalez Somermeyer, N.M. Markina, T.V. Chepurnyh, E.B. Guglya, T.A. Karataeva, K.A. Palkina, E.S. Shakhova, L.I. Fakhranurova, S.V. Chekova, A.S. Tsarkova, Y.V. Golubev, V.V. Negrebetsky, S.A. Dolgushin, P.V. Shalaev, D. Shlykov, O.A. Melnik, V.O. Shipunova, S.M. Deyev, A.I. Bubyrev, A.S. Pushin, V.V. Choob, S.V. Dolgov, F. Kondrashov, I.V. Yampolsky, K.S. Sarkisyan, Nature Biotechnology 38 (2020) 944–946."},"article_type":"original","page":"944-946","day":"27","has_accepted_license":"1","article_processing_charge":"No","scopus_import":"1","file":[{"relation":"main_file","embargo":"2021-03-01","file_id":"8316","date_updated":"2021-03-02T23:30:03Z","date_created":"2020-08-28T08:57:07Z","checksum":"1b30467500ec6277229a875b06e196d0","file_name":"2020_NatureBiotech_Mitiouchkina.pdf","access_level":"open_access","file_size":1180086,"content_type":"application/pdf","creator":"dernst"}],"oa_version":"Submitted Version","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"7889","title":"Plants with genetically encoded autoluminescence","status":"public","ddc":["570"],"intvolume":" 38","abstract":[{"lang":"eng","text":"Autoluminescent plants engineered to express a bacterial bioluminescence gene cluster in plastids have not been widely adopted because of low light output. We engineered tobacco plants with a fungal bioluminescence system that converts caffeic acid (present in all plants) into luciferin and report self-sustained luminescence that is visible to the naked eye. Our findings could underpin development of a suite of imaging tools for plants."}],"type":"journal_article","doi":"10.1038/s41587-020-0500-9","language":[{"iso":"eng"}],"external_id":{"isi":["000529298800003"],"pmid":["32341562"]},"oa":1,"quality_controlled":"1","isi":1,"project":[{"grant_number":"771209","_id":"26580278-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Characterizing the fitness landscape on population and global scales"}],"month":"04","publication_identifier":{"issn":["1087-0156"],"eissn":["1546-1696"]},"author":[{"first_name":"Tatiana","last_name":"Mitiouchkina","full_name":"Mitiouchkina, Tatiana"},{"full_name":"Mishin, Alexander S.","last_name":"Mishin","first_name":"Alexander S."},{"full_name":"Gonzalez Somermeyer, Louisa","first_name":"Louisa","last_name":"Gonzalez Somermeyer","id":"4720D23C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9139-5383"},{"full_name":"Markina, Nadezhda M.","first_name":"Nadezhda M.","last_name":"Markina"},{"last_name":"Chepurnyh","first_name":"Tatiana V.","full_name":"Chepurnyh, Tatiana V."},{"last_name":"Guglya","first_name":"Elena B.","full_name":"Guglya, Elena B."},{"full_name":"Karataeva, Tatiana A.","last_name":"Karataeva","first_name":"Tatiana A."},{"full_name":"Palkina, Kseniia A.","first_name":"Kseniia A.","last_name":"Palkina"},{"full_name":"Shakhova, Ekaterina S.","first_name":"Ekaterina S.","last_name":"Shakhova"},{"full_name":"Fakhranurova, Liliia I.","last_name":"Fakhranurova","first_name":"Liliia I."},{"full_name":"Chekova, Sofia V.","first_name":"Sofia V.","last_name":"Chekova"},{"full_name":"Tsarkova, Aleksandra S.","last_name":"Tsarkova","first_name":"Aleksandra S."},{"full_name":"Golubev, Yaroslav V.","first_name":"Yaroslav V.","last_name":"Golubev"},{"last_name":"Negrebetsky","first_name":"Vadim V.","full_name":"Negrebetsky, Vadim V."},{"full_name":"Dolgushin, Sergey A.","first_name":"Sergey A.","last_name":"Dolgushin"},{"first_name":"Pavel V.","last_name":"Shalaev","full_name":"Shalaev, Pavel V."},{"first_name":"Dmitry","last_name":"Shlykov","full_name":"Shlykov, Dmitry"},{"first_name":"Olesya A.","last_name":"Melnik","full_name":"Melnik, Olesya A."},{"full_name":"Shipunova, Victoria O.","first_name":"Victoria O.","last_name":"Shipunova"},{"full_name":"Deyev, Sergey M.","first_name":"Sergey M.","last_name":"Deyev"},{"last_name":"Bubyrev","first_name":"Andrey I.","full_name":"Bubyrev, Andrey I."},{"full_name":"Pushin, Alexander S.","last_name":"Pushin","first_name":"Alexander S."},{"first_name":"Vladimir V.","last_name":"Choob","full_name":"Choob, Vladimir V."},{"first_name":"Sergey V.","last_name":"Dolgov","full_name":"Dolgov, Sergey V."},{"last_name":"Kondrashov","first_name":"Fyodor","orcid":"0000-0001-8243-4694","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","full_name":"Kondrashov, Fyodor"},{"last_name":"Yampolsky","first_name":"Ilia V.","full_name":"Yampolsky, Ilia V."},{"full_name":"Sarkisyan, Karen S.","last_name":"Sarkisyan","first_name":"Karen S."}],"related_material":{"link":[{"url":"https://doi.org/10.1038/s41587-020-0578-0","relation":"erratum"}]},"date_updated":"2023-09-05T15:30:34Z","date_created":"2020-05-25T15:02:00Z","volume":38,"year":"2020","acknowledgement":"This study was designed, performed and funded by Planta LLC. We thank K. Wood for assisting in manuscript development. Planta acknowledges support from the Skolkovo Innovation Centre. We thank D. Bolotin and the Milaboratory (milaboratory.com) for access to computing and storage infrastructure. We thank S. Shakhov for providing\r\nphotography equipment. The Synthetic Biology Group is funded by the MRC London Institute of Medical Sciences (UKRI MC-A658-5QEA0, K.S.S.). K.S.S. is supported by an Imperial College Research Fellowship. Experiments were partially carried out using equipment provided by the Institute of Bioorganic Chemistry of the Russian Academy\r\nof Sciences Сore Facility (CKP IBCH; supported by the Russian Ministry of Education and Science Grant RFMEFI62117X0018). The F.A.K. lab is supported by ERC grant agreement 771209—CharFL. This project received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Marie Skłodowska-Curie\r\nGrant Agreement 665385. K.S.S. acknowledges support by President’s Grant 075-15-2019-411. Design and assembly of some of the plasmids was supported by Russian Science Foundation grant 19-74-10102. Imaging experiments were partially supported by Russian Science Foundation grant 17-14-01169p. LC-MS/MS analyses of extracts were\r\nsupported by Russian Science Foundation grant 16-14-00052p. Design and assembly of plasmids was partially supported by grant 075-15-2019-1789 from the Ministry of Science and Higher Education of the Russian Federation allocated to the Center for Precision Genome Editing and Genetic Technologies for Biomedicine. The authors\r\nwould like to acknowledge the work of Genomics Core Facility of the Skolkovo Institute of Science and Technology, which performed the sequencing and bioinformatic analysis.","pmid":1,"publication_status":"published","publisher":"Springer Nature","department":[{"_id":"FyKo"}],"file_date_updated":"2021-03-02T23:30:03Z","ec_funded":1},{"type":"preprint","ec_funded":1,"abstract":[{"text":"Tension of the actomyosin cell cortex plays a key role in determining cell-cell contact growth and size. The level of cortical tension outside of the cell-cell contact, when pulling at the contact edge, scales with the total size to which a cell-cell contact can grow1,2. Here we show in zebrafish primary germ layer progenitor cells that this monotonic relationship only applies to a narrow range of cortical tension increase, and that above a critical threshold, contact size inversely scales with cortical tension. This switch from cortical tension increasing to decreasing progenitor cell-cell contact size is caused by cortical tension promoting E-cadherin anchoring to the actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin at the contact. Once tension-mediated E-cadherin stabilization at the contact exceeds a critical threshold level, the rate by which the contact expands in response to pulling forces from the cortex sharply drops, leading to smaller contacts at physiologically relevant timescales of contact formation. Thus, the activity of cortical tension in expanding cell-cell contact size is limited by tension stabilizing E-cadherin-actin complexes at the contact.","lang":"eng"}],"publisher":"Cold Spring Harbor Laboratory","department":[{"_id":"CaHe"},{"_id":"EM-Fac"},{"_id":"Bio"}],"status":"public","title":"Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion","publication_status":"published","_id":"9750","year":"2020","acknowledgement":"We would like to thank Edouard Hannezo for discussions, Shayan Shami Pour and Daniel Capek for help with data analysis, Vanessa Barone and other members of the Heisenberg laboratory for thoughtful discussions and comments on the manuscript. We also thank Jack Merrin for preparing the microwells, and the Scientific Service Units at IST Austria, specifically Bioimaging and Electron Microscopy, and the Zebrafish Facility for continuous support. We acknowledge Hitoshi Morita for the kind gift of VinculinB-GFP plasmid. This research was supported by an ERC Advanced Grant (MECSPEC) to C.-P.H, EMBO Long Term grant (ALTF 187-2013) to M.S and IST Fellow Marie-Curie COFUND No. P_IST_EU01 to J.S.","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","oa_version":"Preprint","date_created":"2021-07-29T11:29:50Z","date_updated":"2024-03-28T23:30:19Z","related_material":{"record":[{"id":"10766","status":"public","relation":"later_version"},{"id":"9623","relation":"dissertation_contains","status":"public"}]},"author":[{"full_name":"Slovakova, Jana","first_name":"Jana","last_name":"Slovakova","id":"30F3F2F0-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sikora, Mateusz K","first_name":"Mateusz K","last_name":"Sikora","id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Silvia","last_name":"Caballero Mancebo","id":"2F1E1758-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5223-3346","full_name":"Caballero Mancebo, Silvia"},{"first_name":"Gabriel","last_name":"Krens","id":"2B819732-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4761-5996","full_name":"Krens, Gabriel"},{"full_name":"Kaufmann, Walter","first_name":"Walter","last_name":"Kaufmann","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315"},{"id":"44C6F6A6-F248-11E8-B48F-1D18A9856A87","last_name":"Huljev","first_name":"Karla","full_name":"Huljev, Karla"},{"id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566","first_name":"Carl-Philipp J","last_name":"Heisenberg","full_name":"Heisenberg, Carl-Philipp J"}],"article_processing_charge":"No","month":"11","day":"20","project":[{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"},{"call_identifier":"H2020","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","grant_number":"742573","_id":"260F1432-B435-11E9-9278-68D0E5697425"},{"name":"Modulation of adhesion function in cell-cell contact formation by cortical tension","grant_number":"187-2013","_id":"2521E28E-B435-11E9-9278-68D0E5697425"}],"page":"41","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2020.11.20.391284"}],"citation":{"short":"J. Slovakova, M.K. Sikora, S. Caballero Mancebo, G. Krens, W. Kaufmann, K. Huljev, C.-P.J. Heisenberg, BioRxiv (2020).","mla":"Slovakova, Jana, et al. “Tension-Dependent Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion.” BioRxiv, Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.11.20.391284.","chicago":"Slovakova, Jana, Mateusz K Sikora, Silvia Caballero Mancebo, Gabriel Krens, Walter Kaufmann, Karla Huljev, and Carl-Philipp J Heisenberg. “Tension-Dependent Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion.” BioRxiv. Cold Spring Harbor Laboratory, 2020. https://doi.org/10.1101/2020.11.20.391284.","ama":"Slovakova J, Sikora MK, Caballero Mancebo S, et al. Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion. bioRxiv. 2020. doi:10.1101/2020.11.20.391284","ieee":"J. Slovakova et al., “Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion,” bioRxiv. Cold Spring Harbor Laboratory, 2020.","apa":"Slovakova, J., Sikora, M. K., Caballero Mancebo, S., Krens, G., Kaufmann, W., Huljev, K., & Heisenberg, C.-P. J. (2020). Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.11.20.391284","ista":"Slovakova J, Sikora MK, Caballero Mancebo S, Krens G, Kaufmann W, Huljev K, Heisenberg C-PJ. 2020. Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion. bioRxiv, 10.1101/2020.11.20.391284."},"oa":1,"publication":"bioRxiv","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"SSU"}],"date_published":"2020-11-20T00:00:00Z","doi":"10.1101/2020.11.20.391284"},{"related_material":{"record":[{"id":"14697","status":"public","relation":"dissertation_contains"},{"id":"12401","relation":"dissertation_contains","status":"public"}],"link":[{"url":"https://ist.ac.at/en/news/off-road-mode-enables-mobile-cells-to-move-freely/","relation":"press_release","description":"News on IST Homepage"}]},"author":[{"last_name":"Reversat","first_name":"Anne","orcid":"0000-0003-0666-8928","id":"35B76592-F248-11E8-B48F-1D18A9856A87","full_name":"Reversat, Anne"},{"full_name":"Gärtner, Florian R","orcid":"0000-0001-6120-3723","id":"397A88EE-F248-11E8-B48F-1D18A9856A87","last_name":"Gärtner","first_name":"Florian R"},{"full_name":"Merrin, Jack","last_name":"Merrin","first_name":"Jack","orcid":"0000-0001-5145-4609","id":"4515C308-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Stopp","first_name":"Julian A","id":"489E3F00-F248-11E8-B48F-1D18A9856A87","full_name":"Stopp, Julian A"},{"full_name":"Tasciyan, Saren","first_name":"Saren","last_name":"Tasciyan","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1671-393X"},{"last_name":"Aguilera Servin","first_name":"Juan L","orcid":"0000-0002-2862-8372","id":"2A67C376-F248-11E8-B48F-1D18A9856A87","full_name":"Aguilera Servin, Juan L"},{"full_name":"De Vries, Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","first_name":"Ingrid","last_name":"De Vries"},{"full_name":"Hauschild, Robert","last_name":"Hauschild","first_name":"Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-6625-3348","id":"4167FE56-F248-11E8-B48F-1D18A9856A87","last_name":"Hons","first_name":"Miroslav","full_name":"Hons, Miroslav"},{"last_name":"Piel","first_name":"Matthieu","full_name":"Piel, Matthieu"},{"full_name":"Callan-Jones, Andrew","last_name":"Callan-Jones","first_name":"Andrew"},{"last_name":"Voituriez","first_name":"Raphael","full_name":"Voituriez, Raphael"},{"orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K"}],"volume":582,"date_updated":"2024-03-28T23:30:24Z","date_created":"2020-05-24T22:01:01Z","year":"2020","acknowledgement":"We thank A. Leithner and J. Renkawitz for discussion and critical reading of the manuscript; J. Schwarz and M. Mehling for establishing the microfluidic setups; the Bioimaging Facility of IST Austria for excellent support, as well as the Life Science Facility and the Miba Machine Shop of IST Austria; and F. N. Arslan, L. E. Burnett and L. Li for their work during their rotation in the IST PhD programme. This work was supported by the European Research Council (ERC StG 281556 and CoG 724373) to M.S. and grants from the Austrian Science Fund (FWF P29911) and the WWTF to M.S. M.H. was supported by the European Regional Development Fund Project (CZ.02.1.01/0.0/0.0/15_003/0000476). F.G. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 747687.","publisher":"Springer Nature","department":[{"_id":"NanoFab"},{"_id":"Bio"},{"_id":"MiSi"}],"publication_status":"published","ec_funded":1,"doi":"10.1038/s41586-020-2283-z","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"external_id":{"isi":["000532688300008"]},"project":[{"call_identifier":"FP7","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","_id":"25A603A2-B435-11E9-9278-68D0E5697425","grant_number":"281556"},{"call_identifier":"H2020","name":"Cellular navigation along spatial gradients","grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425"},{"_id":"26018E70-B435-11E9-9278-68D0E5697425","grant_number":"P29911","name":"Mechanical adaptation of lamellipodial actin","call_identifier":"FWF"},{"_id":"260AA4E2-B435-11E9-9278-68D0E5697425","grant_number":"747687","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells","call_identifier":"H2020"}],"quality_controlled":"1","isi":1,"publication_identifier":{"issn":["00280836"],"eissn":["14764687"]},"month":"06","oa_version":"None","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"7885","intvolume":" 582","title":"Cellular locomotion using environmental topography","status":"public","abstract":[{"text":"Eukaryotic cells migrate by coupling the intracellular force of the actin cytoskeleton to the environment. While force coupling is usually mediated by transmembrane adhesion receptors, especially those of the integrin family, amoeboid cells such as leukocytes can migrate extremely fast despite very low adhesive forces1. Here we show that leukocytes cannot only migrate under low adhesion but can also transmit forces in the complete absence of transmembrane force coupling. When confined within three-dimensional environments, they use the topographical features of the substrate to propel themselves. Here the retrograde flow of the actin cytoskeleton follows the texture of the substrate, creating retrograde shear forces that are sufficient to drive the cell body forwards. Notably, adhesion-dependent and adhesion-independent migration are not mutually exclusive, but rather are variants of the same principle of coupling retrograde actin flow to the environment and thus can potentially operate interchangeably and simultaneously. As adhesion-free migration is independent of the chemical composition of the environment, it renders cells completely autonomous in their locomotive behaviour.","lang":"eng"}],"type":"journal_article","date_published":"2020-06-25T00:00:00Z","citation":{"chicago":"Reversat, Anne, Florian R Gärtner, Jack Merrin, Julian A Stopp, Saren Tasciyan, Juan L Aguilera Servin, Ingrid de Vries, et al. “Cellular Locomotion Using Environmental Topography.” Nature. Springer Nature, 2020. https://doi.org/10.1038/s41586-020-2283-z.","mla":"Reversat, Anne, et al. “Cellular Locomotion Using Environmental Topography.” Nature, vol. 582, Springer Nature, 2020, pp. 582–585, doi:10.1038/s41586-020-2283-z.","short":"A. Reversat, F.R. Gärtner, J. Merrin, J.A. Stopp, S. Tasciyan, J.L. Aguilera Servin, I. de Vries, R. Hauschild, M. Hons, M. Piel, A. Callan-Jones, R. Voituriez, M.K. Sixt, Nature 582 (2020) 582–585.","ista":"Reversat A, Gärtner FR, Merrin J, Stopp JA, Tasciyan S, Aguilera Servin JL, de Vries I, Hauschild R, Hons M, Piel M, Callan-Jones A, Voituriez R, Sixt MK. 2020. Cellular locomotion using environmental topography. Nature. 582, 582–585.","apa":"Reversat, A., Gärtner, F. R., Merrin, J., Stopp, J. A., Tasciyan, S., Aguilera Servin, J. L., … Sixt, M. K. (2020). Cellular locomotion using environmental topography. Nature. Springer Nature. https://doi.org/10.1038/s41586-020-2283-z","ieee":"A. Reversat et al., “Cellular locomotion using environmental topography,” Nature, vol. 582. Springer Nature, pp. 582–585, 2020.","ama":"Reversat A, Gärtner FR, Merrin J, et al. Cellular locomotion using environmental topography. Nature. 2020;582:582–585. doi:10.1038/s41586-020-2283-z"},"publication":"Nature","page":"582–585","article_type":"original","article_processing_charge":"No","day":"25","scopus_import":"1"},{"month":"05","publication_identifier":{"issn":["1751-570X"]},"quality_controlled":"1","isi":1,"project":[{"_id":"25863FF4-B435-11E9-9278-68D0E5697425","grant_number":"S11407","name":"Game Theory","call_identifier":"FWF"},{"name":"The Wittgenstein Prize","call_identifier":"FWF","grant_number":"Z211","_id":"25F42A32-B435-11E9-9278-68D0E5697425"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"oa":1,"external_id":{"isi":["000528828600003"]},"language":[{"iso":"eng"}],"doi":"10.1016/j.nahs.2020.100856","article_number":"100856","file_date_updated":"2022-05-16T22:30:04Z","publication_status":"published","department":[{"_id":"ToHe"}],"publisher":"Elsevier","year":"2020","date_updated":"2023-08-17T14:32:54Z","date_created":"2020-02-02T23:00:59Z","volume":36,"author":[{"id":"4B3207F6-F248-11E8-B48F-1D18A9856A87","orcid":"0000−0003−2936−5719","first_name":"Miriam","last_name":"Garcia Soto","full_name":"Garcia Soto, Miriam"},{"first_name":"Pavithra","last_name":"Prabhakar","full_name":"Prabhakar, Pavithra"}],"scopus_import":"1","day":"01","article_processing_charge":"No","has_accepted_license":"1","article_type":"original","publication":"Nonlinear Analysis: Hybrid Systems","citation":{"ama":"Garcia Soto M, Prabhakar P. Abstraction based verification of stability of polyhedral switched systems. Nonlinear Analysis: Hybrid Systems. 2020;36(5). doi:10.1016/j.nahs.2020.100856","apa":"Garcia Soto, M., & Prabhakar, P. (2020). Abstraction based verification of stability of polyhedral switched systems. Nonlinear Analysis: Hybrid Systems. Elsevier. https://doi.org/10.1016/j.nahs.2020.100856","ieee":"M. Garcia Soto and P. Prabhakar, “Abstraction based verification of stability of polyhedral switched systems,” Nonlinear Analysis: Hybrid Systems, vol. 36, no. 5. Elsevier, 2020.","ista":"Garcia Soto M, Prabhakar P. 2020. Abstraction based verification of stability of polyhedral switched systems. Nonlinear Analysis: Hybrid Systems. 36(5), 100856.","short":"M. Garcia Soto, P. Prabhakar, Nonlinear Analysis: Hybrid Systems 36 (2020).","mla":"Garcia Soto, Miriam, and Pavithra Prabhakar. “Abstraction Based Verification of Stability of Polyhedral Switched Systems.” Nonlinear Analysis: Hybrid Systems, vol. 36, no. 5, 100856, Elsevier, 2020, doi:10.1016/j.nahs.2020.100856.","chicago":"Garcia Soto, Miriam, and Pavithra Prabhakar. “Abstraction Based Verification of Stability of Polyhedral Switched Systems.” Nonlinear Analysis: Hybrid Systems. Elsevier, 2020. https://doi.org/10.1016/j.nahs.2020.100856."},"date_published":"2020-05-01T00:00:00Z","type":"journal_article","abstract":[{"text":"This paper presents a novel abstraction technique for analyzing Lyapunov and asymptotic stability of polyhedral switched systems. A polyhedral switched system is a hybrid system in which the continuous dynamics is specified by polyhedral differential inclusions, the invariants and guards are specified by polyhedral sets and the switching between the modes do not involve reset of variables. A finite state weighted graph abstracting the polyhedral switched system is constructed from a finite partition of the state–space, such that the satisfaction of certain graph conditions, such as the absence of cycles with product of weights on the edges greater than (or equal) to 1, implies the stability of the system. However, the graph is in general conservative and hence, the violation of the graph conditions does not imply instability. If the analysis fails to establish stability due to the conservativeness in the approximation, a counterexample (cycle with product of edge weights greater than or equal to 1) indicating a potential reason for the failure is returned. Further, a more precise approximation of the switched system can be constructed by considering a finer partition of the state–space in the construction of the finite weighted graph. We present experimental results on analyzing stability of switched systems using the above method.","lang":"eng"}],"issue":"5","title":"Abstraction based verification of stability of polyhedral switched systems","ddc":["000"],"status":"public","intvolume":" 36","_id":"7426","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"Submitted Version","file":[{"checksum":"560abfddb53f9fe921b6744f59f2cfaa","date_created":"2020-10-21T13:16:45Z","date_updated":"2022-05-16T22:30:04Z","relation":"main_file","file_id":"8688","embargo":"2022-05-15","file_size":818774,"content_type":"application/pdf","creator":"dernst","access_level":"open_access","file_name":"2020_NAHS_GarciaSoto.pdf"}]},{"month":"12","publication_identifier":{"issn":["2663-337X"]},"doi":"10.15479/AT:ISTA:8983","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"E-Lib"},{"_id":"CampIT"}],"degree_awarded":"PhD","supervisor":[{"last_name":"Siekhaus","first_name":"Daria E","orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","full_name":"Siekhaus, Daria E"}],"language":[{"iso":"eng"}],"oa":1,"file_date_updated":"2021-12-31T23:30:04Z","author":[{"full_name":"Emtenani, Shamsi","first_name":"Shamsi","last_name":"Emtenani","id":"49D32318-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6981-6938"}],"related_material":{"record":[{"id":"8557","relation":"part_of_dissertation","status":"public"},{"relation":"part_of_dissertation","status":"public","id":"6187"}]},"date_created":"2020-12-30T15:41:26Z","date_updated":"2023-09-07T13:24:17Z","year":"2020","acknowledgement":"Also, I would like to express my appreciation and thanks to the Bioimaging facility, LSF, GSO, library, and IT people at IST Austria.","publication_status":"published","department":[{"_id":"DaSi"}],"publisher":"Institute of Science and Technology Austria","day":"30","article_processing_charge":"No","has_accepted_license":"1","date_published":"2020-12-30T00:00:00Z","citation":{"short":"S. Emtenani, Metabolic Regulation of Drosophila Macrophage Tissue Invasion, Institute of Science and Technology Austria, 2020.","mla":"Emtenani, Shamsi. Metabolic Regulation of Drosophila Macrophage Tissue Invasion. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8983.","chicago":"Emtenani, Shamsi. “Metabolic Regulation of Drosophila Macrophage Tissue Invasion.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8983.","ama":"Emtenani S. Metabolic regulation of Drosophila macrophage tissue invasion. 2020. doi:10.15479/AT:ISTA:8983","apa":"Emtenani, S. (2020). Metabolic regulation of Drosophila macrophage tissue invasion. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8983","ieee":"S. Emtenani, “Metabolic regulation of Drosophila macrophage tissue invasion,” Institute of Science and Technology Austria, 2020.","ista":"Emtenani S. 2020. Metabolic regulation of Drosophila macrophage tissue invasion. Institute of Science and Technology Austria."},"page":"141","abstract":[{"lang":"eng","text":"Metabolic adaptation is a critical feature of migrating cells. It tunes the metabolic programs of migrating cells to allow them to efficiently exert their crucial roles in development, inflammatory responses and tumor metastasis. Cell migration through physically challenging contexts requires energy. However, how the metabolic reprogramming that underlies in vivo cell invasion is controlled is still unanswered. In my PhD project, I identify a novel conserved metabolic shift in Drosophila melanogaster immune cells that by modulating their bioenergetic potential controls developmentally programmed tissue invasion. We show that this regulation requires a novel conserved nuclear protein, named Atossa. Atossa enhances the transcription of a set of proteins, including an RNA helicase Porthos and two metabolic enzymes, each of which increases the tissue invasion of leading Drosophila macrophages and can rescue the atossa mutant phenotype. Porthos selectively regulates the translational efficiency of a subset of mRNAs containing a 5’-UTR cis-regulatory TOP-like sequence. These 5’TOPL mRNA targets encode mitochondrial-related proteins, including subunits of mitochondrial oxidative phosphorylation (OXPHOS) components III and V and other metabolic-related proteins. Porthos powers up mitochondrial OXPHOS to engender a sufficient ATP supply, which is required for tissue invasion of leading macrophages. Atossa’s two vertebrate orthologs rescue the invasion defect. In my PhD project, I elucidate that Atossa displays a conserved developmental metabolic control to modulate metabolic capacities and the cellular energy state, through altered transcription and translation, to aid the tissue infiltration of leading cells into energy demanding barriers."}],"type":"dissertation","alternative_title":["ISTA Thesis"],"file":[{"file_id":"8984","embargo":"2021-12-30","relation":"main_file","checksum":"ec2797ab7a6f253b35df0572b36d1b43","date_updated":"2021-12-31T23:30:04Z","date_created":"2020-12-30T15:34:01Z","access_level":"open_access","file_name":"Thesis_Shamsi_Emtenani_pdfA.pdf","creator":"semtenan","content_type":"application/pdf","file_size":10848175},{"relation":"source_file","file_id":"8985","checksum":"cc30e6608a9815414024cf548dff3b3a","date_created":"2020-12-30T15:37:36Z","date_updated":"2021-12-31T23:30:04Z","access_level":"closed","embargo_to":"open_access","file_name":"Thesis_Shamsi_Emtenani_source file.pdf","file_size":10073648,"content_type":"application/pdf","creator":"semtenan"}],"oa_version":"Published Version","_id":"8983","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","ddc":["570"],"status":"public","title":"Metabolic regulation of Drosophila macrophage tissue invasion"},{"oa_version":"Preprint","date_created":"2020-09-23T09:36:47Z","date_updated":"2024-03-28T23:30:25Z","related_material":{"record":[{"id":"10614","status":"public","relation":"later_version"},{"id":"8983","status":"public","relation":"dissertation_contains"}]},"author":[{"full_name":"Belyaeva, Vera","last_name":"Belyaeva","first_name":"Vera","id":"47F080FE-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Wachner, Stephanie","id":"2A95E7B0-F248-11E8-B48F-1D18A9856A87","last_name":"Wachner","first_name":"Stephanie"},{"first_name":"Igor","last_name":"Gridchyn","id":"4B60654C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1807-1929","full_name":"Gridchyn, Igor"},{"last_name":"Linder","first_name":"Markus","full_name":"Linder, Markus"},{"last_name":"Emtenani","first_name":"Shamsi","orcid":"0000-0001-6981-6938","id":"49D32318-F248-11E8-B48F-1D18A9856A87","full_name":"Emtenani, Shamsi"},{"id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1819-198X","first_name":"Attila","last_name":"György","full_name":"György, Attila"},{"full_name":"Sibilia, Maria","last_name":"Sibilia","first_name":"Maria"},{"full_name":"Siekhaus, Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353","first_name":"Daria E","last_name":"Siekhaus"}],"department":[{"_id":"DaSi"},{"_id":"JoCs"}],"status":"public","publication_status":"submitted","title":"Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"8557","acknowledgement":"We thank the following for their contributions: The Drosophila Genomics Resource Center supported by NIH grant 2P40OD010949-10A1 for plasmids, K. Brueckner. B. Stramer, M. Uhlirova, O. Schuldiner, the Bloomington Drosophila Stock Center supported by NIH grant P40OD018537 and the Vienna Drosophila Resource Center for fly stocks, FlyBase (Thurmond et al., 2019) for essential genomic information, and the BDGP in situ database for data (Tomancak et al., 2002, 2007). 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. A.G. was supported by the Austrian Science Fund (FWF) grant DASI_FWF01_P29638S, D.E.S. by Marie Curie CIG 334077/IRTIM. M.S. is supported by the FWF, PhD program W1212 915 and the European Research Council (ERC) Advanced grant (ERC-2015-AdG TNT-Tumors 694883). S.W. is supported by an OEAW, DOC fellowship.","year":"2020","ec_funded":1,"abstract":[{"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. Cortical F-actin levels are critical as expressing a dominant active form of Diaphanous, a actin polymerizing Formin, can rescue the Dfos Dominant Negative macrophage invasion defect. In vivo imaging shows that Dfos is required to enhance 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 mechanical properties of the macrophage nucleus from affecting tissue entry. We thus identify tuning the cortical actin cytoskeleton through Dfos as a key process allowing efficient forward movement of an immune cell into surrounding tissues.","lang":"eng"}],"type":"preprint","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"LifeSc"}],"doi":"10.1101/2020.09.18.301481","date_published":"2020-09-18T00:00:00Z","project":[{"grant_number":"P29638","_id":"253B6E48-B435-11E9-9278-68D0E5697425","name":"Drosophila TNFa´s Funktion in Immunzellen","call_identifier":"FWF"},{"grant_number":"334077","_id":"2536F660-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Investigating the role of transporters in invasive migration through junctions"},{"_id":"26199CA4-B435-11E9-9278-68D0E5697425","grant_number":"24800","name":"Tissue barrier penetration is crucial for immunity and metastasis"}],"citation":{"chicago":"Belyaeva, Vera, Stephanie Wachner, Igor Gridchyn, Markus Linder, Shamsi Emtenani, Attila György, Maria Sibilia, and Daria E Siekhaus. “Cortical Actin Properties Controlled by Drosophila Fos Aid Macrophage Infiltration against Surrounding Tissue Resistance.” BioRxiv, n.d. https://doi.org/10.1101/2020.09.18.301481.","short":"V. Belyaeva, S. Wachner, I. Gridchyn, M. Linder, S. Emtenani, A. György, M. Sibilia, D.E. Siekhaus, BioRxiv (n.d.).","mla":"Belyaeva, Vera, et al. “Cortical Actin Properties Controlled by Drosophila Fos Aid Macrophage Infiltration against Surrounding Tissue Resistance.” BioRxiv, doi:10.1101/2020.09.18.301481.","apa":"Belyaeva, V., Wachner, S., Gridchyn, I., Linder, M., Emtenani, S., György, A., … Siekhaus, D. E. (n.d.). Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance. bioRxiv. https://doi.org/10.1101/2020.09.18.301481","ieee":"V. Belyaeva et al., “Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance,” bioRxiv. .","ista":"Belyaeva V, Wachner S, Gridchyn I, Linder M, Emtenani S, György A, Sibilia M, Siekhaus DE. Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance. bioRxiv, 10.1101/2020.09.18.301481.","ama":"Belyaeva V, Wachner S, Gridchyn I, et al. Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance. bioRxiv. doi:10.1101/2020.09.18.301481"},"main_file_link":[{"url":"https://doi.org/10.1101/2020.09.18.301481","open_access":"1"}],"oa":1,"publication":"bioRxiv","article_processing_charge":"No","month":"09","day":"18"},{"file_date_updated":"2020-12-02T10:42:31Z","ec_funded":1,"article_number":"2012.00322","author":[{"full_name":"Aggarwal, Kushagra","id":"b22ab905-3539-11eb-84c3-fc159dcd79cb","orcid":"0000-0001-9985-9293","first_name":"Kushagra","last_name":"Aggarwal"},{"full_name":"Hofmann, Andrea C","first_name":"Andrea C","last_name":"Hofmann","id":"340F461A-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Jirovec, Daniel","orcid":"0000-0002-7197-4801","id":"4C473F58-F248-11E8-B48F-1D18A9856A87","last_name":"Jirovec","first_name":"Daniel"},{"full_name":"Prieto Gonzalez, Ivan","first_name":"Ivan","last_name":"Prieto Gonzalez","id":"2A307FE2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7370-5357"},{"first_name":"Amir","last_name":"Sammak","full_name":"Sammak, Amir"},{"full_name":"Botifoll, Marc","first_name":"Marc","last_name":"Botifoll"},{"last_name":"Marti-Sanchez","first_name":"Sara","full_name":"Marti-Sanchez, Sara"},{"full_name":"Veldhorst, Menno","first_name":"Menno","last_name":"Veldhorst"},{"full_name":"Arbiol, Jordi","first_name":"Jordi","last_name":"Arbiol"},{"full_name":"Scappucci, Giordano","last_name":"Scappucci","first_name":"Giordano"},{"last_name":"Katsaros","first_name":"Georgios","orcid":"0000-0001-8342-202X","id":"38DB5788-F248-11E8-B48F-1D18A9856A87","full_name":"Katsaros, Georgios"}],"related_material":{"record":[{"status":"public","relation":"later_version","id":"10559"},{"status":"public","relation":"research_data","id":"8834"},{"id":"10058","relation":"dissertation_contains","status":"public"}]},"date_created":"2020-12-02T10:42:53Z","date_updated":"2024-03-28T23:30:27Z","acknowledgement":"This research and related results were made possible with the support of the NOMIS Foundation. This research was supported by the Scientific Service Units of IST Austria through resources provided by the MIBA Machine Shop and the nanofabrication facility, the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement #844511 and the Grant Agreement #862046. ICN2 acknowledge funding from Generalitat de Catalunya 2017 SGR 327. ICN2 is supported by the Severo Ochoa\r\nprogram from Spanish MINECO (Grant No. SEV2017-0706) and is funded by the CERCA Programme / Generalitat de Catalunya. Part of the present work has been performed in the framework of Universitat Aut`onoma de Barcelona Materials Science PhD program. The HAADF-STEM microscopy was conducted in the Laboratorio de Microscopias Avanzadas at Instituto de Nanociencia de Aragon-Universidad de Zaragoza. Authors acknowledge the LMA-INA for offering access to their instruments and expertise. We acknowledge support from CSIC Research Platform on Quantum Technologies PTI-001. This project has received funding from\r\nthe European Union’s Horizon 2020 research and innovation programme under grant agreement No 823717 – ESTEEM3. M.B. acknowledges support from SUR Generalitat de Catalunya and the EU Social Fund; project ref. 2020 FI 00103. GS and MV acknowledge support through a projectruimte grant associated with the Netherlands Organization of Scientific Research (NWO).","year":"2020","publication_status":"submitted","department":[{"_id":"GeKa"}],"month":"12","acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"NanoFab"}],"language":[{"iso":"eng"}],"external_id":{"arxiv":["2012.00322"]},"oa":1,"project":[{"name":"Hybrid Semiconductor - Superconductor Quantum Devices","_id":"262116AA-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","name":"Majorana bound states in Ge/SiGe heterostructures","grant_number":"844511","_id":"26A151DA-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","name":"TOPOLOGICALLY PROTECTED AND SCALABLE QUANTUM BITS","grant_number":"862046","_id":"237E5020-32DE-11EA-91FC-C7463DDC885E"}],"abstract":[{"text":"Holes in planar Ge have high mobilities, strong spin-orbit interaction and electrically tunable g-factors, and are therefore emerging as a promising candidate for hybrid superconductorsemiconductor devices. This is further motivated by the observation of supercurrent transport in planar Ge Josephson Field effect transistors (JoFETs). A key challenge towards hybrid germanium quantum technology is the design of high quality interfaces and superconducting contacts that are robust against magnetic fields. By combining the assets of Al, which has a long superconducting coherence, and Nb, which has a significant superconducting gap, we form low-disordered JoFETs with large ICRN products that are capable of withstanding high magnetic fields. We furthermore demonstrate the ability of phase-biasing individual JoFETs opening up an avenue to explore topological superconductivity in planar Ge. The persistence of superconductivity in the reported hybrid devices beyond 1.8 T paves the way towards integrating spin qubits and proximity-induced superconductivity on the same chip.","lang":"eng"}],"type":"preprint","file":[{"access_level":"open_access","file_name":"Superconducting_2D_Ge.pdf","creator":"gkatsaro","file_size":1697939,"content_type":"application/pdf","file_id":"8832","relation":"main_file","checksum":"22a612e206232fa94b138b2c2f957582","date_created":"2020-12-02T10:42:31Z","date_updated":"2020-12-02T10:42:31Z"}],"oa_version":"Submitted Version","_id":"8831","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","ddc":["530"],"title":"Enhancement of proximity induced superconductivity in planar Germanium","day":"02","has_accepted_license":"1","article_processing_charge":"No","date_published":"2020-12-02T00:00:00Z","publication":"arXiv","citation":{"mla":"Aggarwal, Kushagra, et al. “Enhancement of Proximity Induced Superconductivity in Planar Germanium.” ArXiv, 2012.00322.","short":"K. Aggarwal, A.C. Hofmann, D. Jirovec, I. Prieto Gonzalez, A. Sammak, M. Botifoll, S. Marti-Sanchez, M. Veldhorst, J. Arbiol, G. Scappucci, G. Katsaros, ArXiv (n.d.).","chicago":"Aggarwal, Kushagra, Andrea C Hofmann, Daniel Jirovec, Ivan Prieto Gonzalez, Amir Sammak, Marc Botifoll, Sara Marti-Sanchez, et al. “Enhancement of Proximity Induced Superconductivity in Planar Germanium.” ArXiv, n.d.","ama":"Aggarwal K, Hofmann AC, Jirovec D, et al. Enhancement of proximity induced superconductivity in planar Germanium. arXiv.","ista":"Aggarwal K, Hofmann AC, Jirovec D, Prieto Gonzalez I, Sammak A, Botifoll M, Marti-Sanchez S, Veldhorst M, Arbiol J, Scappucci G, Katsaros G. Enhancement of proximity induced superconductivity in planar Germanium. arXiv, 2012.00322.","apa":"Aggarwal, K., Hofmann, A. C., Jirovec, D., Prieto Gonzalez, I., Sammak, A., Botifoll, M., … Katsaros, G. (n.d.). Enhancement of proximity induced superconductivity in planar Germanium. arXiv.","ieee":"K. Aggarwal et al., “Enhancement of proximity induced superconductivity in planar Germanium,” arXiv. ."}},{"month":"09","publication_identifier":{"issn":["16616596"],"eissn":["14220067"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"isi":["000579945300001"]},"quality_controlled":"1","isi":1,"project":[{"_id":"25CA28EA-B435-11E9-9278-68D0E5697425","grant_number":"694539","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","call_identifier":"H2020"},{"name":"Mechanism of formation and maintenance of input side-dependent asymmetry in the hippocampus","_id":"25D32BC0-B435-11E9-9278-68D0E5697425"},{"_id":"26436750-B435-11E9-9278-68D0E5697425","grant_number":"785907","call_identifier":"H2020","name":"Human Brain Project Specific Grant Agreement 2 (HBP SGA 2)"}],"doi":"10.3390/ijms21186737","language":[{"iso":"eng"}],"article_number":"6737","file_date_updated":"2020-09-21T14:08:58Z","ec_funded":1,"acknowledgement":"This research was funded by Austrian Academy of Sciences, DOC fellowship to D.K., European Research\r\nCouncil Advanced Grant 694539 and European Union Human Brain Project (HBP) SGA2 785907 to R.S.\r\nWe acknowledge Elena Hollergschwandtner for technical support.","year":"2020","publication_status":"published","department":[{"_id":"RySh"}],"publisher":"MDPI","author":[{"full_name":"Kleindienst, David","id":"42E121A4-F248-11E8-B48F-1D18A9856A87","last_name":"Kleindienst","first_name":"David"},{"full_name":"Montanaro-Punzengruber, Jacqueline-Claire","first_name":"Jacqueline-Claire","last_name":"Montanaro-Punzengruber","id":"3786AB44-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-0863-4481","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","last_name":"Bhandari","first_name":"Pradeep","full_name":"Bhandari, Pradeep"},{"full_name":"Case, Matthew J","first_name":"Matthew J","last_name":"Case","id":"44B7CA5A-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Fukazawa","first_name":"Yugo","full_name":"Fukazawa, Yugo"},{"full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444"}],"related_material":{"record":[{"id":"9562","status":"public","relation":"dissertation_contains"}]},"date_updated":"2024-03-28T23:30:31Z","date_created":"2020-09-20T22:01:35Z","volume":21,"scopus_import":"1","day":"14","has_accepted_license":"1","article_processing_charge":"No","publication":"International Journal of Molecular Sciences","citation":{"ama":"Kleindienst D, Montanaro-Punzengruber J-C, Bhandari P, Case MJ, Fukazawa Y, Shigemoto R. Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses. International Journal of Molecular Sciences. 2020;21(18). doi:10.3390/ijms21186737","ista":"Kleindienst D, Montanaro-Punzengruber J-C, Bhandari P, Case MJ, Fukazawa Y, Shigemoto R. 2020. Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses. International Journal of Molecular Sciences. 21(18), 6737.","apa":"Kleindienst, D., Montanaro-Punzengruber, J.-C., Bhandari, P., Case, M. J., Fukazawa, Y., & Shigemoto, R. (2020). Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses. International Journal of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms21186737","ieee":"D. Kleindienst, J.-C. Montanaro-Punzengruber, P. Bhandari, M. J. Case, Y. Fukazawa, and R. Shigemoto, “Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses,” International Journal of Molecular Sciences, vol. 21, no. 18. MDPI, 2020.","mla":"Kleindienst, David, et al. “Deep Learning-Assisted High-Throughput Analysis of Freeze-Fracture Replica Images Applied to Glutamate Receptors and Calcium Channels at Hippocampal Synapses.” International Journal of Molecular Sciences, vol. 21, no. 18, 6737, MDPI, 2020, doi:10.3390/ijms21186737.","short":"D. Kleindienst, J.-C. Montanaro-Punzengruber, P. Bhandari, M.J. Case, Y. Fukazawa, R. Shigemoto, International Journal of Molecular Sciences 21 (2020).","chicago":"Kleindienst, David, Jacqueline-Claire Montanaro-Punzengruber, Pradeep Bhandari, Matthew J Case, Yugo Fukazawa, and Ryuichi Shigemoto. “Deep Learning-Assisted High-Throughput Analysis of Freeze-Fracture Replica Images Applied to Glutamate Receptors and Calcium Channels at Hippocampal Synapses.” International Journal of Molecular Sciences. MDPI, 2020. https://doi.org/10.3390/ijms21186737."},"article_type":"original","date_published":"2020-09-14T00:00:00Z","type":"journal_article","abstract":[{"lang":"eng","text":"The molecular anatomy of synapses defines their characteristics in transmission and plasticity. Precise measurements of the number and distribution of synaptic proteins are important for our understanding of synapse heterogeneity within and between brain regions. Freeze–fracture replica immunogold electron microscopy enables us to analyze them quantitatively on a two-dimensional membrane surface. Here, we introduce Darea software, which utilizes deep learning for analysis of replica images and demonstrate its usefulness for quick measurements of the pre- and postsynaptic areas, density and distribution of gold particles at synapses in a reproducible manner. We used Darea for comparing glutamate receptor and calcium channel distributions between hippocampal CA3-CA1 spine synapses on apical and basal dendrites, which differ in signaling pathways involved in synaptic plasticity. We found that apical synapses express a higher density of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and a stronger increase of AMPA receptors with synaptic size, while basal synapses show a larger increase in N-methyl-D-aspartate (NMDA) receptors with size. Interestingly, AMPA and NMDA receptors are segregated within postsynaptic sites and negatively correlated in density among both apical and basal synapses. In the presynaptic sites, Cav2.1 voltage-gated calcium channels show similar densities in apical and basal synapses with distributions consistent with an exclusion zone model of calcium channel-release site topography."}],"issue":"18","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"8532","ddc":["570"],"status":"public","title":"Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses","intvolume":" 21","file":[{"checksum":"2e4f62f3cfe945b7391fc3070e5a289f","success":1,"date_updated":"2020-09-21T14:08:58Z","date_created":"2020-09-21T14:08:58Z","relation":"main_file","file_id":"8551","content_type":"application/pdf","file_size":5748456,"creator":"dernst","access_level":"open_access","file_name":"2020_JournMolecSciences_Kleindienst.pdf"}],"oa_version":"Published Version"},{"month":"04","publication_identifier":{"issn":["03029743"],"isbn":["9783030449131"],"eissn":["16113349"]},"conference":{"start_date":"2020-04-25","location":"Dublin, Ireland","end_date":"2020-04-30","name":"ESOP: Programming Languages and Systems"},"doi":"10.1007/978-3-030-44914-8_5","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"isi":["000681656800005"]},"isi":1,"quality_controlled":"1","project":[{"grant_number":"S 11407_N23","_id":"25832EC2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Rigorous Systems Engineering"},{"name":"Efficient Algorithms for Computer Aided Verification","_id":"25892FC0-B435-11E9-9278-68D0E5697425","grant_number":"ICT15-003"},{"_id":"266EEEC0-B435-11E9-9278-68D0E5697425","name":"Quantitative Game-theoretic Analysis of Blockchain Applications and Smart Contracts"},{"name":"Quantitative Analysis of Probablistic Systems with a focus on Crypto-currencies","_id":"267066CE-B435-11E9-9278-68D0E5697425"}],"file_date_updated":"2020-07-14T12:48:03Z","author":[{"last_name":"Chatterjee","first_name":"Krishnendu","orcid":"0000-0002-4561-241X","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87","full_name":"Chatterjee, Krishnendu"},{"full_name":"Goharshady, Amir Kafshdar","last_name":"Goharshady","first_name":"Amir Kafshdar","orcid":"0000-0003-1702-6584","id":"391365CE-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Ibsen-Jensen","first_name":"Rasmus","orcid":"0000-0003-4783-0389","id":"3B699956-F248-11E8-B48F-1D18A9856A87","full_name":"Ibsen-Jensen, Rasmus"},{"full_name":"Pavlogiannis, Andreas","last_name":"Pavlogiannis","first_name":"Andreas","orcid":"0000-0002-8943-0722","id":"49704004-F248-11E8-B48F-1D18A9856A87"}],"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"8934"}]},"date_updated":"2024-03-28T23:30:34Z","date_created":"2020-05-10T22:00:50Z","volume":12075,"year":"2020","publication_status":"published","publisher":"Springer Nature","department":[{"_id":"KrCh"}],"day":"18","has_accepted_license":"1","article_processing_charge":"No","scopus_import":"1","date_published":"2020-04-18T00:00:00Z","publication":"European Symposium on Programming","citation":{"ista":"Chatterjee K, Goharshady AK, Ibsen-Jensen R, Pavlogiannis A. 2020. Optimal and perfectly parallel algorithms for on-demand data-flow analysis. European Symposium on Programming. ESOP: Programming Languages and Systems, LNCS, vol. 12075, 112–140.","ieee":"K. Chatterjee, A. K. Goharshady, R. Ibsen-Jensen, and A. Pavlogiannis, “Optimal and perfectly parallel algorithms for on-demand data-flow analysis,” in European Symposium on Programming, Dublin, Ireland, 2020, vol. 12075, pp. 112–140.","apa":"Chatterjee, K., Goharshady, A. K., Ibsen-Jensen, R., & Pavlogiannis, A. (2020). Optimal and perfectly parallel algorithms for on-demand data-flow analysis. In European Symposium on Programming (Vol. 12075, pp. 112–140). Dublin, Ireland: Springer Nature. https://doi.org/10.1007/978-3-030-44914-8_5","ama":"Chatterjee K, Goharshady AK, Ibsen-Jensen R, Pavlogiannis A. Optimal and perfectly parallel algorithms for on-demand data-flow analysis. In: European Symposium on Programming. Vol 12075. Springer Nature; 2020:112-140. doi:10.1007/978-3-030-44914-8_5","chicago":"Chatterjee, Krishnendu, Amir Kafshdar Goharshady, Rasmus Ibsen-Jensen, and Andreas Pavlogiannis. “Optimal and Perfectly Parallel Algorithms for On-Demand Data-Flow Analysis.” In European Symposium on Programming, 12075:112–40. Springer Nature, 2020. https://doi.org/10.1007/978-3-030-44914-8_5.","mla":"Chatterjee, Krishnendu, et al. “Optimal and Perfectly Parallel Algorithms for On-Demand Data-Flow Analysis.” European Symposium on Programming, vol. 12075, Springer Nature, 2020, pp. 112–40, doi:10.1007/978-3-030-44914-8_5.","short":"K. Chatterjee, A.K. Goharshady, R. Ibsen-Jensen, A. Pavlogiannis, in:, European Symposium on Programming, Springer Nature, 2020, pp. 112–140."},"page":"112-140","abstract":[{"text":"Interprocedural data-flow analyses form an expressive and useful paradigm of numerous static analysis applications, such as live variables analysis, alias analysis and null pointers analysis. The most widely-used framework for interprocedural data-flow analysis is IFDS, which encompasses distributive data-flow functions over a finite domain. On-demand data-flow analyses restrict the focus of the analysis on specific program locations and data facts. This setting provides a natural split between (i) an offline (or preprocessing) phase, where the program is partially analyzed and analysis summaries are created, and (ii) an online (or query) phase, where analysis queries arrive on demand and the summaries are used to speed up answering queries.\r\nIn this work, we consider on-demand IFDS analyses where the queries concern program locations of the same procedure (aka same-context queries). We exploit the fact that flow graphs of programs have low treewidth to develop faster algorithms that are space and time optimal for many common data-flow analyses, in both the preprocessing and the query phase. We also use treewidth to develop query solutions that are embarrassingly parallelizable, i.e. the total work for answering each query is split to a number of threads such that each thread performs only a constant amount of work. Finally, we implement a static analyzer based on our algorithms, and perform a series of on-demand analysis experiments on standard benchmarks. Our experimental results show a drastic speed-up of the queries after only a lightweight preprocessing phase, which significantly outperforms existing techniques.","lang":"eng"}],"type":"conference","alternative_title":["LNCS"],"oa_version":"Published Version","file":[{"access_level":"open_access","file_name":"2020_LNCS_Chatterjee.pdf","creator":"dernst","content_type":"application/pdf","file_size":651250,"file_id":"7895","relation":"main_file","checksum":"8618b80f4cf7b39a60e61a6445ad9807","date_updated":"2020-07-14T12:48:03Z","date_created":"2020-05-26T13:34:48Z"}],"_id":"7810","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","title":"Optimal and perfectly parallel algorithms for on-demand data-flow analysis","status":"public","ddc":["000"],"intvolume":" 12075"},{"file_date_updated":"2020-11-06T07:41:03Z","year":"2020","publication_status":"published","department":[{"_id":"KrCh"}],"publisher":"Springer Nature","author":[{"full_name":"Asadi, Ali","last_name":"Asadi","first_name":"Ali"},{"first_name":"Krishnendu","last_name":"Chatterjee","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4561-241X","full_name":"Chatterjee, Krishnendu"},{"last_name":"Goharshady","first_name":"Amir Kafshdar","orcid":"0000-0003-1702-6584","id":"391365CE-F248-11E8-B48F-1D18A9856A87","full_name":"Goharshady, Amir Kafshdar"},{"full_name":"Mohammadi, Kiarash","first_name":"Kiarash","last_name":"Mohammadi"},{"full_name":"Pavlogiannis, Andreas","id":"49704004-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8943-0722","first_name":"Andreas","last_name":"Pavlogiannis"}],"related_material":{"record":[{"id":"8934","status":"public","relation":"dissertation_contains"}]},"date_created":"2020-11-06T07:30:05Z","date_updated":"2024-03-28T23:30:34Z","volume":12302,"month":"10","publication_identifier":{"issn":["0302-9743"],"eisbn":["9783030591526"],"eissn":["1611-3349"],"isbn":["9783030591519"]},"external_id":{"isi":["000723555700014"]},"oa":1,"quality_controlled":"1","isi":1,"project":[{"name":"Rigorous Systems Engineering","call_identifier":"FWF","_id":"25832EC2-B435-11E9-9278-68D0E5697425","grant_number":"S 11407_N23"},{"grant_number":"ICT15-003","_id":"25892FC0-B435-11E9-9278-68D0E5697425","name":"Efficient Algorithms for Computer Aided Verification"},{"_id":"267066CE-B435-11E9-9278-68D0E5697425","name":"Quantitative Analysis of Probablistic Systems with a focus on Crypto-currencies"}],"conference":{"end_date":"2020-10-23","location":"Hanoi, Vietnam","start_date":"2020-10-19","name":"ATVA: Automated Technology for Verification and Analysis"},"doi":"10.1007/978-3-030-59152-6_14","language":[{"iso":"eng"}],"type":"conference","alternative_title":["LNCS"],"abstract":[{"text":"Discrete-time Markov Chains (MCs) and Markov Decision Processes (MDPs) are two standard formalisms in system analysis. Their main associated quantitative objectives are hitting probabilities, discounted sum, and mean payoff. Although there are many techniques for computing these objectives in general MCs/MDPs, they have not been thoroughly studied in terms of parameterized algorithms, particularly when treewidth is used as the parameter. This is in sharp contrast to qualitative objectives for MCs, MDPs and graph games, for which treewidth-based algorithms yield significant complexity improvements. In this work, we show that treewidth can also be used to obtain faster algorithms for the quantitative problems. For an MC with n states and m transitions, we show that each of the classical quantitative objectives can be computed in O((n+m)⋅t2) time, given a tree decomposition of the MC with width t. Our results also imply a bound of O(κ⋅(n+m)⋅t2) for each objective on MDPs, where κ is the number of strategy-iteration refinements required for the given input and objective. Finally, we make an experimental evaluation of our new algorithms on low-treewidth MCs and MDPs obtained from the DaCapo benchmark suite. Our experiments show that on low-treewidth MCs and MDPs, our algorithms outperform existing well-established methods by one or more orders of magnitude.","lang":"eng"}],"_id":"8728","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","ddc":["000"],"status":"public","title":"Faster algorithms for quantitative analysis of MCs and MDPs with small treewidth","intvolume":" 12302","file":[{"file_name":"2020_LNCS_ATVA_Asadi_accepted.pdf","access_level":"open_access","creator":"dernst","content_type":"application/pdf","file_size":726648,"file_id":"8729","relation":"main_file","date_created":"2020-11-06T07:41:03Z","date_updated":"2020-11-06T07:41:03Z","success":1,"checksum":"ae83f27e5b189d5abc2e7514f1b7e1b5"}],"oa_version":"Submitted Version","scopus_import":"1","day":"12","article_processing_charge":"No","has_accepted_license":"1","publication":"Automated Technology for Verification and Analysis","citation":{"ama":"Asadi A, Chatterjee K, Goharshady AK, Mohammadi K, Pavlogiannis A. Faster algorithms for quantitative analysis of MCs and MDPs with small treewidth. In: Automated Technology for Verification and Analysis. Vol 12302. Springer Nature; 2020:253-270. doi:10.1007/978-3-030-59152-6_14","ista":"Asadi A, Chatterjee K, Goharshady AK, Mohammadi K, Pavlogiannis A. 2020. Faster algorithms for quantitative analysis of MCs and MDPs with small treewidth. Automated Technology for Verification and Analysis. ATVA: Automated Technology for Verification and Analysis, LNCS, vol. 12302, 253–270.","ieee":"A. Asadi, K. Chatterjee, A. K. Goharshady, K. Mohammadi, and A. Pavlogiannis, “Faster algorithms for quantitative analysis of MCs and MDPs with small treewidth,” in Automated Technology for Verification and Analysis, Hanoi, Vietnam, 2020, vol. 12302, pp. 253–270.","apa":"Asadi, A., Chatterjee, K., Goharshady, A. K., Mohammadi, K., & Pavlogiannis, A. (2020). Faster algorithms for quantitative analysis of MCs and MDPs with small treewidth. In Automated Technology for Verification and Analysis (Vol. 12302, pp. 253–270). Hanoi, Vietnam: Springer Nature. https://doi.org/10.1007/978-3-030-59152-6_14","mla":"Asadi, Ali, et al. “Faster Algorithms for Quantitative Analysis of MCs and MDPs with Small Treewidth.” Automated Technology for Verification and Analysis, vol. 12302, Springer Nature, 2020, pp. 253–70, doi:10.1007/978-3-030-59152-6_14.","short":"A. Asadi, K. Chatterjee, A.K. Goharshady, K. Mohammadi, A. Pavlogiannis, in:, Automated Technology for Verification and Analysis, Springer Nature, 2020, pp. 253–270.","chicago":"Asadi, Ali, Krishnendu Chatterjee, Amir Kafshdar Goharshady, Kiarash Mohammadi, and Andreas Pavlogiannis. “Faster Algorithms for Quantitative Analysis of MCs and MDPs with Small Treewidth.” In Automated Technology for Verification and Analysis, 12302:253–70. Springer Nature, 2020. https://doi.org/10.1007/978-3-030-59152-6_14."},"page":"253-270","date_published":"2020-10-12T00:00:00Z"}]