[{"article_processing_charge":"No","author":[{"first_name":"Tatiana","full_name":"Mitiouchkina, Tatiana","last_name":"Mitiouchkina"},{"first_name":"Alexander S.","last_name":"Mishin","full_name":"Mishin, Alexander S."},{"full_name":"Gonzalez Somermeyer, Louisa","last_name":"Gonzalez Somermeyer","first_name":"Louisa","id":"4720D23C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9139-5383"},{"full_name":"Markina, Nadezhda M.","last_name":"Markina","first_name":"Nadezhda M."},{"first_name":"Tatiana V.","full_name":"Chepurnyh, Tatiana V.","last_name":"Chepurnyh"},{"first_name":"Elena B.","last_name":"Guglya","full_name":"Guglya, Elena B."},{"full_name":"Karataeva, Tatiana A.","last_name":"Karataeva","first_name":"Tatiana A."},{"last_name":"Palkina","full_name":"Palkina, Kseniia A.","first_name":"Kseniia A."},{"last_name":"Shakhova","full_name":"Shakhova, Ekaterina S.","first_name":"Ekaterina S."},{"first_name":"Liliia I.","last_name":"Fakhranurova","full_name":"Fakhranurova, Liliia I."},{"full_name":"Chekova, Sofia V.","last_name":"Chekova","first_name":"Sofia V."},{"full_name":"Tsarkova, Aleksandra S.","last_name":"Tsarkova","first_name":"Aleksandra S."},{"first_name":"Yaroslav V.","full_name":"Golubev, Yaroslav V.","last_name":"Golubev"},{"full_name":"Negrebetsky, Vadim V.","last_name":"Negrebetsky","first_name":"Vadim V."},{"full_name":"Dolgushin, Sergey A.","last_name":"Dolgushin","first_name":"Sergey A."},{"full_name":"Shalaev, Pavel V.","last_name":"Shalaev","first_name":"Pavel V."},{"last_name":"Shlykov","full_name":"Shlykov, Dmitry","first_name":"Dmitry"},{"first_name":"Olesya A.","last_name":"Melnik","full_name":"Melnik, Olesya A."},{"full_name":"Shipunova, Victoria O.","last_name":"Shipunova","first_name":"Victoria O."},{"last_name":"Deyev","full_name":"Deyev, Sergey M.","first_name":"Sergey M."},{"first_name":"Andrey I.","full_name":"Bubyrev, Andrey I.","last_name":"Bubyrev"},{"last_name":"Pushin","full_name":"Pushin, Alexander S.","first_name":"Alexander S."},{"full_name":"Choob, Vladimir V.","last_name":"Choob","first_name":"Vladimir V."},{"first_name":"Sergey V.","last_name":"Dolgov","full_name":"Dolgov, Sergey V."},{"last_name":"Kondrashov","full_name":"Kondrashov, Fyodor","orcid":"0000-0001-8243-4694","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","first_name":"Fyodor"},{"last_name":"Yampolsky","full_name":"Yampolsky, Ilia V.","first_name":"Ilia V."},{"full_name":"Sarkisyan, Karen S.","last_name":"Sarkisyan","first_name":"Karen S."}],"department":[{"_id":"FyKo"}],"date_updated":"2025-04-14T07:49:47Z","status":"public","isi":1,"type":"journal_article","oa_version":"Submitted Version","publication_status":"published","doi":"10.1038/s41587-020-0500-9","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","month":"04","publication_identifier":{"eissn":["1546-1696"],"issn":["1087-0156"]},"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.","file":[{"date_updated":"2021-03-02T23:30:03Z","file_name":"2020_NatureBiotech_Mitiouchkina.pdf","checksum":"1b30467500ec6277229a875b06e196d0","embargo":"2021-03-01","relation":"main_file","file_size":1180086,"file_id":"8316","date_created":"2020-08-28T08:57:07Z","access_level":"open_access","creator":"dernst","content_type":"application/pdf"}],"related_material":{"link":[{"relation":"erratum","url":"https://doi.org/10.1038/s41587-020-0578-0"}]},"page":"944-946","external_id":{"pmid":["32341562"],"isi":["000529298800003"]},"language":[{"iso":"eng"}],"citation":{"ama":"Mitiouchkina T, Mishin AS, Gonzalez Somermeyer L, et al. Plants with genetically encoded autoluminescence. <i>Nature Biotechnology</i>. 2020;38:944-946. doi:<a href=\"https://doi.org/10.1038/s41587-020-0500-9\">10.1038/s41587-020-0500-9</a>","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. <i>Nature Biotechnology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41587-020-0500-9\">https://doi.org/10.1038/s41587-020-0500-9</a>","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.” <i>Nature Biotechnology</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1038/s41587-020-0500-9\">https://doi.org/10.1038/s41587-020-0500-9</a>.","ieee":"T. Mitiouchkina <i>et al.</i>, “Plants with genetically encoded autoluminescence,” <i>Nature Biotechnology</i>, vol. 38. Springer Nature, pp. 944–946, 2020.","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.","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.","mla":"Mitiouchkina, Tatiana, et al. “Plants with Genetically Encoded Autoluminescence.” <i>Nature Biotechnology</i>, vol. 38, Springer Nature, 2020, pp. 944–46, doi:<a href=\"https://doi.org/10.1038/s41587-020-0500-9\">10.1038/s41587-020-0500-9</a>."},"has_accepted_license":"1","project":[{"call_identifier":"H2020","name":"Characterizing the fitness landscape on population and global scales","_id":"26580278-B435-11E9-9278-68D0E5697425","grant_number":"771209"}],"file_date_updated":"2021-03-02T23:30:03Z","scopus_import":"1","oa":1,"year":"2020","date_published":"2020-04-27T00:00:00Z","quality_controlled":"1","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."}],"date_created":"2020-05-25T15:02:00Z","intvolume":"        38","ec_funded":1,"article_type":"original","title":"Plants with genetically encoded autoluminescence","volume":38,"publication":"Nature Biotechnology","pmid":1,"ddc":["570"],"publisher":"Springer Nature","day":"27","_id":"7889"},{"_id":"7888","day":"06","publisher":"eLife Sciences Publications","ddc":["570"],"pmid":1,"publication":"eLife","volume":9,"title":"Zebrafish embryonic explants undergo genetically encoded self-assembly","article_type":"original","ec_funded":1,"date_created":"2020-05-25T15:01:40Z","abstract":[{"text":"Embryonic stem cell cultures are thought to self-organize into embryoid bodies, able to undergo symmetry-breaking, germ layer specification and even morphogenesis. Yet, it is unclear how to reconcile this remarkable self-organization capacity with classical experiments demonstrating key roles for extrinsic biases by maternal factors and/or extraembryonic tissues in embryogenesis. Here, we show that zebrafish embryonic tissue explants, prepared prior to germ layer induction and lacking extraembryonic tissues, can specify all germ layers and form a seemingly complete mesendoderm anlage. Importantly, explant organization requires polarized inheritance of maternal factors from dorsal-marginal regions of the blastoderm. Moreover, induction of endoderm and head-mesoderm, which require peak Nodal-signaling levels, is highly variable in explants, reminiscent of embryos with reduced Nodal signals from the extraembryonic tissues. Together, these data suggest that zebrafish explants do not undergo bona fide self-organization, but rather display features of genetically encoded self-assembly, where intrinsic genetic programs control the emergence of order.","lang":"eng"}],"intvolume":"         9","quality_controlled":"1","date_published":"2020-04-06T00:00:00Z","year":"2020","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"oa":1,"scopus_import":"1","project":[{"_id":"260F1432-B435-11E9-9278-68D0E5697425","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","call_identifier":"H2020","grant_number":"742573"},{"name":"Mesendoderm specification in zebrafish: The role of extraembryonic tissues","_id":"26B1E39C-B435-11E9-9278-68D0E5697425","grant_number":"25239"},{"grant_number":"ALTF 850-2017","name":"Coordination of mesendoderm cell fate specification and internalization during zebrafish gastrulation","_id":"26520D1E-B435-11E9-9278-68D0E5697425"},{"name":"Coordination of mesendoderm fate specification and internalization during zebrafish gastrulation","_id":"266BC5CE-B435-11E9-9278-68D0E5697425","grant_number":"LT000429"}],"file_date_updated":"2020-07-14T12:48:04Z","corr_author":"1","article_number":"e55190","has_accepted_license":"1","citation":{"ama":"Schauer A, Nunes Pinheiro DC, Hauschild R, Heisenberg C-PJ. Zebrafish embryonic explants undergo genetically encoded self-assembly. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/elife.55190\">10.7554/elife.55190</a>","apa":"Schauer, A., Nunes Pinheiro, D. C., Hauschild, R., &#38; Heisenberg, C.-P. J. (2020). Zebrafish embryonic explants undergo genetically encoded self-assembly. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.55190\">https://doi.org/10.7554/elife.55190</a>","chicago":"Schauer, Alexandra, Diana C Nunes Pinheiro, Robert Hauschild, and Carl-Philipp J Heisenberg. “Zebrafish Embryonic Explants Undergo Genetically Encoded Self-Assembly.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/elife.55190\">https://doi.org/10.7554/elife.55190</a>.","ieee":"A. Schauer, D. C. Nunes Pinheiro, R. Hauschild, and C.-P. J. Heisenberg, “Zebrafish embryonic explants undergo genetically encoded self-assembly,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020.","short":"A. Schauer, D.C. Nunes Pinheiro, R. Hauschild, C.-P.J. Heisenberg, ELife 9 (2020).","ista":"Schauer A, Nunes Pinheiro DC, Hauschild R, Heisenberg C-PJ. 2020. Zebrafish embryonic explants undergo genetically encoded self-assembly. eLife. 9, e55190.","mla":"Schauer, Alexandra, et al. “Zebrafish Embryonic Explants Undergo Genetically Encoded Self-Assembly.” <i>ELife</i>, vol. 9, e55190, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/elife.55190\">10.7554/elife.55190</a>."},"language":[{"iso":"eng"}],"external_id":{"pmid":["32250246"],"isi":["000531544400001"]},"related_material":{"record":[{"id":"12891","status":"public","relation":"dissertation_contains"}]},"file":[{"creator":"dernst","content_type":"application/pdf","file_id":"7890","access_level":"open_access","date_created":"2020-05-25T15:15:43Z","relation":"main_file","checksum":"f6aad884cf706846ae9357fcd728f8b5","file_size":7744848,"file_name":"2020_eLife_Schauer.pdf","date_updated":"2020-07-14T12:48:04Z"}],"publication_identifier":{"issn":["2050-084X"]},"month":"04","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","doi":"10.7554/elife.55190","publication_status":"published","oa_version":"Published Version","type":"journal_article","isi":1,"status":"public","date_updated":"2026-05-13T22:30:13Z","department":[{"_id":"CaHe"},{"_id":"Bio"}],"author":[{"orcid":"0000-0001-7659-9142","id":"30A536BA-F248-11E8-B48F-1D18A9856A87","first_name":"Alexandra","full_name":"Schauer, Alexandra","last_name":"Schauer"},{"full_name":"Nunes Pinheiro, Diana C","last_name":"Nunes Pinheiro","first_name":"Diana C","orcid":"0000-0003-4333-7503","id":"2E839F16-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild","full_name":"Hauschild, Robert"},{"orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87","first_name":"Carl-Philipp J","last_name":"Heisenberg","full_name":"Heisenberg, Carl-Philipp J"}],"article_processing_charge":"No"},{"oa_version":"Published Version","type":"conference","publication_status":"published","status":"public","department":[{"_id":"TiVo"}],"date_updated":"2026-05-13T22:30:17Z","author":[{"id":"C7610134-B532-11EA-BD9F-F5753DDC885E","first_name":"Basile J","full_name":"Confavreux, Basile J","last_name":"Confavreux"},{"last_name":"Zenke","full_name":"Zenke, Friedemann","first_name":"Friedemann"},{"first_name":"Everton J.","last_name":"Agnes","full_name":"Agnes, Everton J."},{"last_name":"Lillicrap","full_name":"Lillicrap, Timothy","first_name":"Timothy"},{"first_name":"Tim P","orcid":"0000-0003-3295-6181","id":"CB6FF8D2-008F-11EA-8E08-2637E6697425","last_name":"Vogels","full_name":"Vogels, Tim P"}],"article_processing_charge":"No","project":[{"grant_number":"819603","_id":"0aacfa84-070f-11eb-9043-d7eb2c709234","name":"Learning the shape of synaptic plasticity rules for neuronal architectures and function through machine learning.","call_identifier":"H2020"},{"grant_number":"214316/Z/18/Z","_id":"c084a126-5a5b-11eb-8a69-d75314a70a87","name":"What’s in a memory? Spatiotemporal dynamics in strongly coupled recurrent neuronal networks."}],"scopus_import":"1","language":[{"iso":"eng"}],"citation":{"ama":"Confavreux BJ, Zenke F, Agnes EJ, Lillicrap T, Vogels TP. A meta-learning approach to (re)discover plasticity rules that carve a desired function into a neural network. In: <i>Advances in Neural Information Processing Systems</i>. Vol 33. ; 2020:16398-16408.","chicago":"Confavreux, Basile J, Friedemann Zenke, Everton J. Agnes, Timothy Lillicrap, and Tim P Vogels. “A Meta-Learning Approach to (Re)Discover Plasticity Rules That Carve a Desired Function into a Neural Network.” In <i>Advances in Neural Information Processing Systems</i>, 33:16398–408, 2020.","apa":"Confavreux, B. J., Zenke, F., Agnes, E. J., Lillicrap, T., &#38; Vogels, T. P. (2020). A meta-learning approach to (re)discover plasticity rules that carve a desired function into a neural network. In <i>Advances in Neural Information Processing Systems</i> (Vol. 33, pp. 16398–16408). Vancouver, Canada.","mla":"Confavreux, Basile J., et al. “A Meta-Learning Approach to (Re)Discover Plasticity Rules That Carve a Desired Function into a Neural Network.” <i>Advances in Neural Information Processing Systems</i>, vol. 33, 2020, pp. 16398–408.","ista":"Confavreux BJ, Zenke F, Agnes EJ, Lillicrap T, Vogels TP. 2020. A meta-learning approach to (re)discover plasticity rules that carve a desired function into a neural network. Advances in Neural Information Processing Systems. NeurIPS: Conference on Neural Information Processing Systems vol. 33, 16398–16408.","ieee":"B. J. Confavreux, F. Zenke, E. J. Agnes, T. Lillicrap, and T. P. Vogels, “A meta-learning approach to (re)discover plasticity rules that carve a desired function into a neural network,” in <i>Advances in Neural Information Processing Systems</i>, Vancouver, Canada, 2020, vol. 33, pp. 16398–16408.","short":"B.J. Confavreux, F. Zenke, E.J. Agnes, T. Lillicrap, T.P. Vogels, in:, Advances in Neural Information Processing Systems, 2020, pp. 16398–16408."},"publication_identifier":{"issn":["1049-5258"]},"page":"16398-16408","related_material":{"record":[{"id":"14422","relation":"dissertation_contains","status":"public"}],"link":[{"url":"https://doi.org/10.1101/2020.10.24.353409","relation":"is_continued_by"}]},"acknowledgement":"We would like to thank Chaitanya Chintaluri, Georgia Christodoulou, Bill Podlaski and Merima Šabanovic for useful discussions and comments. This work was supported by a Wellcome Trust ´ Senior Research Fellowship (214316/Z/18/Z), a BBSRC grant (BB/N019512/1), an ERC consolidator Grant (SYNAPSEEK), a Leverhulme Trust Project Grant (RPG-2016-446), and funding from École Polytechnique, Paris.","conference":{"location":"Vancouver, Canada","start_date":"2020-12-06","name":"NeurIPS: Conference on Neural Information Processing Systems","end_date":"2020-12-12"},"month":"12","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","quality_controlled":"1","main_file_link":[{"open_access":"1","url":"https://proceedings.neurips.cc/paper/2020/hash/bdbd5ebfde4934142c8a88e7a3796cd5-Abstract.html"}],"intvolume":"        33","date_created":"2021-07-04T22:01:27Z","abstract":[{"text":"The search for biologically faithful synaptic plasticity rules has resulted in a large body of models. They are usually inspired by – and fitted to – experimental data, but they rarely produce neural dynamics that serve complex functions. These failures suggest that current plasticity models are still under-constrained by existing data. Here, we present an alternative approach that uses meta-learning to discover plausible synaptic plasticity rules. Instead of experimental data, the rules are constrained by the functions they implement and the structure they are meant to produce. Briefly, we parameterize synaptic plasticity rules by a Volterra expansion and then use supervised learning methods (gradient descent or evolutionary strategies) to minimize a problem-dependent loss function that quantifies how effectively a candidate plasticity rule transforms an initially random network into one with the desired function. We first validate our approach by re-discovering previously described plasticity rules, starting at the single-neuron level and “Oja’s rule”, a simple Hebbian plasticity rule that captures the direction of most variability of inputs to a neuron (i.e., the first principal component). We expand the problem to the network level and ask the framework to find Oja’s rule together with an anti-Hebbian rule such that an initially random two-layer firing-rate network will recover several principal components of the input space after learning. Next, we move to networks of integrate-and-fire neurons with plastic inhibitory afferents. We train for rules that achieve a target firing rate by countering tuned excitation. Our algorithm discovers a specific subset of the manifold of rules that can solve this task. Our work is a proof of principle of an automated and unbiased approach to unveil synaptic plasticity rules that obey biological constraints and can solve complex functions.","lang":"eng"}],"year":"2020","date_published":"2020-12-06T00:00:00Z","oa":1,"day":"06","_id":"9633","publication":"Advances in Neural Information Processing Systems","title":"A meta-learning approach to (re)discover plasticity rules that carve a desired function into a neural network","ec_funded":1,"volume":33},{"publication":"Nonlinear Analysis: Hybrid Systems","volume":36,"title":"Abstraction based verification of stability of polyhedral switched systems","article_type":"original","_id":"7426","day":"01","publisher":"Elsevier","ddc":["000"],"date_published":"2020-05-01T00:00:00Z","issue":"5","year":"2020","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"oa":1,"intvolume":"        36","date_created":"2020-02-02T23:00:59Z","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"}],"quality_controlled":"1","external_id":{"isi":["000528828600003"]},"file":[{"checksum":"560abfddb53f9fe921b6744f59f2cfaa","embargo":"2022-05-15","relation":"main_file","file_size":818774,"file_name":"2020_NAHS_GarciaSoto.pdf","date_updated":"2022-05-16T22:30:04Z","creator":"dernst","content_type":"application/pdf","file_id":"8688","date_created":"2020-10-21T13:16:45Z","access_level":"open_access"}],"publication_identifier":{"issn":["1751-570X"]},"month":"05","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","scopus_import":"1","project":[{"_id":"25863FF4-B435-11E9-9278-68D0E5697425","name":"Game Theory","call_identifier":"FWF","grant_number":"S11407"},{"grant_number":"Z211","name":"Formal methods for the design and analysis of complex systems","_id":"25F42A32-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"file_date_updated":"2022-05-16T22:30:04Z","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","corr_author":"1","has_accepted_license":"1","article_number":"100856","citation":{"mla":"Garcia Soto, Miriam, and Pavithra Prabhakar. “Abstraction Based Verification of Stability of Polyhedral Switched Systems.” <i>Nonlinear Analysis: Hybrid Systems</i>, vol. 36, no. 5, 100856, Elsevier, 2020, doi:<a href=\"https://doi.org/10.1016/j.nahs.2020.100856\">10.1016/j.nahs.2020.100856</a>.","ieee":"M. Garcia Soto and P. Prabhakar, “Abstraction based verification of stability of polyhedral switched systems,” <i>Nonlinear Analysis: Hybrid Systems</i>, 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).","ama":"Garcia Soto M, Prabhakar P. Abstraction based verification of stability of polyhedral switched systems. <i>Nonlinear Analysis: Hybrid Systems</i>. 2020;36(5). doi:<a href=\"https://doi.org/10.1016/j.nahs.2020.100856\">10.1016/j.nahs.2020.100856</a>","chicago":"Garcia Soto, Miriam, and Pavithra Prabhakar. “Abstraction Based Verification of Stability of Polyhedral Switched Systems.” <i>Nonlinear Analysis: Hybrid Systems</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.nahs.2020.100856\">https://doi.org/10.1016/j.nahs.2020.100856</a>.","apa":"Garcia Soto, M., &#38; Prabhakar, P. (2020). Abstraction based verification of stability of polyhedral switched systems. <i>Nonlinear Analysis: Hybrid Systems</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.nahs.2020.100856\">https://doi.org/10.1016/j.nahs.2020.100856</a>"},"language":[{"iso":"eng"}],"date_updated":"2025-04-15T06:26:15Z","department":[{"_id":"ToHe"}],"article_processing_charge":"No","author":[{"orcid":"0000−0003−2936−5719","id":"4B3207F6-F248-11E8-B48F-1D18A9856A87","first_name":"Miriam","full_name":"Garcia Soto, Miriam","last_name":"Garcia Soto"},{"first_name":"Pavithra","full_name":"Prabhakar, Pavithra","last_name":"Prabhakar"}],"doi":"10.1016/j.nahs.2020.100856","publication_status":"published","oa_version":"Submitted Version","type":"journal_article","isi":1,"status":"public"},{"file_date_updated":"2021-03-16T23:30:04Z","project":[{"grant_number":"616160","call_identifier":"FP7","name":"Discrete Optimization in Computer Vision: Theory and Practice","_id":"25FBA906-B435-11E9-9278-68D0E5697425"}],"scopus_import":"1","language":[{"iso":"eng"}],"has_accepted_license":"1","citation":{"ieee":"Y. Shehu, A. Gibali, and S. Sagratella, “Inertial projection-type methods for solving quasi-variational inequalities in real Hilbert spaces,” <i>Journal of Optimization Theory and Applications</i>, vol. 184. Springer Nature, pp. 877–894, 2020.","ista":"Shehu Y, Gibali A, Sagratella S. 2020. Inertial projection-type methods for solving quasi-variational inequalities in real Hilbert spaces. Journal of Optimization Theory and Applications. 184, 877–894.","short":"Y. Shehu, A. Gibali, S. Sagratella, Journal of Optimization Theory and Applications 184 (2020) 877–894.","mla":"Shehu, Yekini, et al. “Inertial Projection-Type Methods for Solving Quasi-Variational Inequalities in Real Hilbert Spaces.” <i>Journal of Optimization Theory and Applications</i>, vol. 184, Springer Nature, 2020, pp. 877–894, doi:<a href=\"https://doi.org/10.1007/s10957-019-01616-6\">10.1007/s10957-019-01616-6</a>.","ama":"Shehu Y, Gibali A, Sagratella S. Inertial projection-type methods for solving quasi-variational inequalities in real Hilbert spaces. <i>Journal of Optimization Theory and Applications</i>. 2020;184:877–894. doi:<a href=\"https://doi.org/10.1007/s10957-019-01616-6\">10.1007/s10957-019-01616-6</a>","apa":"Shehu, Y., Gibali, A., &#38; Sagratella, S. (2020). Inertial projection-type methods for solving quasi-variational inequalities in real Hilbert spaces. <i>Journal of Optimization Theory and Applications</i>. Springer Nature. <a href=\"https://doi.org/10.1007/s10957-019-01616-6\">https://doi.org/10.1007/s10957-019-01616-6</a>","chicago":"Shehu, Yekini, Aviv Gibali, and Simone Sagratella. “Inertial Projection-Type Methods for Solving Quasi-Variational Inequalities in Real Hilbert Spaces.” <i>Journal of Optimization Theory and Applications</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1007/s10957-019-01616-6\">https://doi.org/10.1007/s10957-019-01616-6</a>."},"publication_identifier":{"issn":["0022-3239"],"eissn":["1573-2878"]},"external_id":{"isi":["000511805200009"]},"acknowledgement":"We are grateful to the anonymous referees and editor whose insightful comments helped to considerably improve an earlier version of this paper. The research of the first author is supported by an ERC Grant from the Institute of Science and Technology (IST).","file":[{"content_type":"application/pdf","creator":"dernst","access_level":"open_access","date_created":"2020-10-12T10:40:27Z","file_id":"8647","file_size":332641,"embargo":"2021-03-15","relation":"main_file","checksum":"9f6dc6c6bf2b48cb3a2091a9ed5feaf2","file_name":"2020_JourOptimizationTheoryApplic_Shehu.pdf","date_updated":"2021-03-16T23:30:04Z"}],"page":"877–894","month":"03","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"Submitted Version","type":"journal_article","doi":"10.1007/s10957-019-01616-6","publication_status":"published","status":"public","isi":1,"department":[{"_id":"VlKo"}],"date_updated":"2024-11-04T13:52:44Z","article_processing_charge":"No","author":[{"orcid":"0000-0001-9224-7139","id":"3FC7CB58-F248-11E8-B48F-1D18A9856A87","first_name":"Yekini","full_name":"Shehu, Yekini","last_name":"Shehu"},{"full_name":"Gibali, Aviv","last_name":"Gibali","first_name":"Aviv"},{"last_name":"Sagratella","full_name":"Sagratella, Simone","first_name":"Simone"}],"day":"01","publisher":"Springer Nature","_id":"7161","ddc":["518","510","515"],"publication":"Journal of Optimization Theory and Applications","title":"Inertial projection-type methods for solving quasi-variational inequalities in real Hilbert spaces","article_type":"original","ec_funded":1,"volume":184,"quality_controlled":"1","intvolume":"       184","date_created":"2019-12-09T21:33:44Z","abstract":[{"text":"In this paper, we introduce an inertial projection-type method with different updating strategies for solving quasi-variational inequalities with strongly monotone and Lipschitz continuous operators in real Hilbert spaces. Under standard assumptions, we establish different strong convergence results for the proposed algorithm. Primary numerical experiments demonstrate the potential applicability of our scheme compared with some related methods in the literature.","lang":"eng"}],"year":"2020","date_published":"2020-03-01T00:00:00Z","oa":1},{"department":[{"_id":"MiSi"}],"date_updated":"2025-06-12T07:34:40Z","author":[{"full_name":"Sixt, Michael K","last_name":"Sixt","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K"},{"first_name":"Anna","last_name":"Huttenlocher","full_name":"Huttenlocher, Anna"}],"article_processing_charge":"No","oa_version":"Published Version","type":"journal_article","doi":"10.1083/jcb.202007029","publication_status":"published","status":"public","isi":1,"publication_identifier":{"eissn":["1540-8140"]},"external_id":{"isi":["000573631000004"],"pmid":["32699885"]},"file":[{"file_id":"8200","date_created":"2020-08-04T13:11:52Z","access_level":"open_access","creator":"dernst","content_type":"application/pdf","file_name":"2020_JCB_Sixt.pdf","date_updated":"2021-02-02T23:30:03Z","checksum":"30016d778d266b8e17d01094917873b8","relation":"main_file","embargo":"2021-02-01","file_size":830725}],"month":"07","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file_date_updated":"2021-02-02T23:30:03Z","scopus_import":"1","language":[{"iso":"eng"}],"article_number":"e202007029","has_accepted_license":"1","citation":{"mla":"Sixt, Michael K., and Anna Huttenlocher. “Zena Werb (1945-2020): Cell Biology in Context.” <i>The Journal of Cell Biology</i>, vol. 219, no. 8, e202007029, Rockefeller University Press, 2020, doi:<a href=\"https://doi.org/10.1083/jcb.202007029\">10.1083/jcb.202007029</a>.","short":"M.K. Sixt, A. Huttenlocher, The Journal of Cell Biology 219 (2020).","ista":"Sixt MK, Huttenlocher A. 2020. Zena Werb (1945-2020): Cell biology in context. The Journal of Cell Biology. 219(8), e202007029.","ieee":"M. K. Sixt and A. Huttenlocher, “Zena Werb (1945-2020): Cell biology in context,” <i>The Journal of Cell Biology</i>, vol. 219, no. 8. Rockefeller University Press, 2020.","ama":"Sixt MK, Huttenlocher A. Zena Werb (1945-2020): Cell biology in context. <i>The Journal of Cell Biology</i>. 2020;219(8). doi:<a href=\"https://doi.org/10.1083/jcb.202007029\">10.1083/jcb.202007029</a>","chicago":"Sixt, Michael K, and Anna Huttenlocher. “Zena Werb (1945-2020): Cell Biology in Context.” <i>The Journal of Cell Biology</i>. Rockefeller University Press, 2020. <a href=\"https://doi.org/10.1083/jcb.202007029\">https://doi.org/10.1083/jcb.202007029</a>.","apa":"Sixt, M. K., &#38; Huttenlocher, A. (2020). Zena Werb (1945-2020): Cell biology in context. <i>The Journal of Cell Biology</i>. Rockefeller University Press. <a href=\"https://doi.org/10.1083/jcb.202007029\">https://doi.org/10.1083/jcb.202007029</a>"},"issue":"8","year":"2020","date_published":"2020-07-22T00:00:00Z","oa":1,"tmp":{"name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","image":"/images/cc_by_nc_sa.png","short":"CC BY-NC-SA (4.0)"},"intvolume":"       219","date_created":"2020-08-02T22:00:57Z","publication":"The Journal of Cell Biology","title":"Zena Werb (1945-2020): Cell biology in context","article_type":"letter_note","volume":219,"day":"22","publisher":"Rockefeller University Press","_id":"8190","pmid":1,"ddc":["570"]},{"OA_place":"publisher","title":"Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway","keyword":["Cav2.3","medial habenula (MHb)","interpeduncular nucleus (IPN)"],"ddc":["570"],"_id":"7525","supervisor":[{"first_name":"Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi"}],"publisher":"Institute of Science and Technology Austria","day":"28","oa":1,"date_published":"2020-02-28T00:00:00Z","year":"2020","alternative_title":["ISTA Thesis"],"degree_awarded":"PhD","abstract":[{"text":"The medial habenula (MHb) is an evolutionary conserved epithalamic structure important for the modulation of emotional memory. It is involved in regulation of anxiety, compulsive behavior, addiction (nicotinic and opioid), sexual and feeding behavior. MHb receives inputs from septal regions and projects exclusively to the interpeduncular nucleus (IPN). Distinct sub-regions of the septum project to different subnuclei of MHb: the bed nucleus of anterior commissure projects to dorsal MHb and the triangular septum projects to ventral MHb. Furthermore, the dorsal and ventral MHb project to the lateral and rostral/central IPN, respectively. Importantly, these projections have unique features of prominent co-release of different neurotransmitters and requirement of a peculiar type of calcium channel for release. In general, synaptic neurotransmission requires an activity-dependent influx of Ca2+ into the presynaptic terminal through voltage-gated calcium channels. The calcium channel family most commonly involved in neurotransmitter release comprises three members, P/Q-, N- and R-type with Cav2.1, Cav2.2 and Cav2.3 subunits, respectively. In contrast to most CNS synapses that mainly express Cav2.1 and/or Cav2.2, MHb terminals in the IPN exclusively express Cav2.3. In other parts of the brain, such as the hippocampus, Cav2.3 is mostly located to postsynaptic elements. This unusual presynaptic location of Cav2.3 in the MHb-IPN pathway implies unique mechanisms of glutamate release in this pathway. One potential example of such uniqueness is the facilitation of release by GABAB receptor (GBR) activation. Presynaptic GBRs usually inhibit the release of neurotransmitters by inhibiting presynaptic calcium channels. MHb shows the highest expression levels of GBR in the brain. GBRs comprise two subunits, GABAB1 (GB1) and GABAB2 (GB2), and are associated with auxiliary subunits, called potassium channel tetramerization domain containing proteins (KCTD) 8, 12, 12b and 16. Among these four subunits, KCTD12b is exclusively expressed in ventral MHb, and KCTD8 shows the strongest expression in the whole MHb among other brain regions, indicating that KCTD8 and KCTD12b may be involved in the unique mechanisms of neurotransmitter release mediated by Cav2.3 and regulated by GBRs in this pathway. \r\nIn the present study, we first verified that neurotransmission in both dorsal and ventral MHb-IPN pathways is mainly mediated by Cav2.3 using a selective blocker of R-type channels, SNX-482. We next found that baclofen, a GBR agonist, has facilitatory effects on release from ventral MHb terminal in rostral IPN, whereas it has inhibitory effects on release from dorsal MHb terminals in lateral IPN, indicating that KCTD12b expressed exclusively in ventral MHb may have a role in the facilitatory effects of GBR activation. In a heterologous expression system using HEK cells, we found that KCTD8 and KCTD12b but not KCTD12 directly bind with Cav2.3. Pre-embedding immunogold electron microscopy data show that Cav2.3 and KCTD12b are distributed most densely in presynaptic active zone in IPN with KCTD12b being present only in rostral/central but not lateral IPN, whereas GABAB, KCTD8 and KCTD12 are distributed most densely in perisynaptic sites with KCTD12 present more frequently in postsynaptic elements and only in rostral/central IPN. In freeze-fracture replica labelling, Cav2.3, KCTD8 and KCTD12b are co-localized with each other in the same active zone indicating that they may form complexes regulating vesicle release in rostral IPN. \r\nOn electrophysiological studies of wild type (WT) mice, we found that paired-pulse ratio in rostral IPN of KCTD12b knock-out (KO) mice is lower than those of WT and KCTD8 KO mice. Consistent with this finding, in mean variance analysis, release probability in rostral IPN of KCTD12b KO mice is higher than that of WT and KCTD8 KO mice. Although paired-pulse ratios are not different between WT and KCTD8 KO mice, the mean variance analysis revealed significantly lower release probability in rostral IPN of KCTD8 KO than WT mice. These results demonstrate bidirectional regulation of Cav2.3-mediated release by KCTD8 and KCTD12b without GBR activation in rostral IPN. Finally, we examined the baclofen effects in rostral IPN of KCTD8 and KCTD12b KO mice, and found the facilitation of release remained in both KO mice, indicating that the peculiar effects of the GBR activation in this pathway do not depend on the selective expression of these KCTD subunits in ventral MHb. However, we found that presynaptic potentiation of evoked EPSC amplitude by baclofen falls to baseline after washout faster in KCTD12b KO mice than WT, KCTD8 KO and KCTD8/12b double KO mice. This result indicates that KCTD12b is involved in sustained potentiation of vesicle release by GBR activation, whereas KCTD8 is involved in its termination in the absence of KCTD12b. Consistent with these functional findings, replica labelling revealed an increase in density of KCTD8, but not Cav2.3 or GBR at active zone in rostral IPN of KCTD12b KO mice compared with that of WT mice, suggesting that increased association of KCTD8 with Cav2.3 facilitates the release probability and termination of the GBR effect in the absence of KCTD12b.\r\nIn summary, our study provided new insights into the physiological roles of presynaptic Cav2.3, GBRs and their auxiliary subunits KCTDs at an evolutionary conserved neuronal circuit. Future studies will be required to identify the exact molecular mechanism underlying the GBR-mediated presynaptic potentiation on ventral MHb terminals. It remains to be determined whether the prominent presence of presynaptic KCTDs at active zone could exert similar neuromodulatory functions in different pathways of the brain.\r\n","lang":"eng"}],"date_created":"2020-02-26T10:56:37Z","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","month":"02","file":[{"file_name":"Pradeep Bhandari Thesis.pdf","date_updated":"2021-03-01T23:30:04Z","file_size":9646346,"checksum":"4589234fdb12b4ad72273b311723a7b4","title":"Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway","relation":"main_file","embargo":"2021-02-28","date_created":"2020-02-28T08:37:53Z","access_level":"open_access","file_id":"7538","creator":"pbhandari","content_type":"application/pdf"},{"date_created":"2020-02-28T08:47:14Z","access_level":"closed","file_id":"7539","creator":"pbhandari","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_name":"Pradeep Bhandari Thesis.docx","date_updated":"2021-03-01T23:30:04Z","file_size":35252164,"embargo_to":"open_access","checksum":"aa79490553ca0a5c9b6fbcd152e93928","title":"Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway","relation":"source_file"}],"page":"79","acknowledged_ssus":[{"_id":"EM-Fac"}],"publication_identifier":{"issn":["2663-337X"]},"citation":{"ama":"Bhandari P. Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7525\">10.15479/AT:ISTA:7525</a>","chicago":"Bhandari, Pradeep. “Localization and Functional Role of Cav2.3 in the Medial Habenula to Interpeduncular Nucleus Pathway.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:7525\">https://doi.org/10.15479/AT:ISTA:7525</a>.","apa":"Bhandari, P. (2020). <i>Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:7525\">https://doi.org/10.15479/AT:ISTA:7525</a>","mla":"Bhandari, Pradeep. <i>Localization and Functional Role of Cav2.3 in the Medial Habenula to Interpeduncular Nucleus Pathway</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7525\">10.15479/AT:ISTA:7525</a>.","ieee":"P. Bhandari, “Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway,” Institute of Science and Technology Austria, 2020.","ista":"Bhandari P. 2020. Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway. Institute of Science and Technology Austria.","short":"P. Bhandari, Localization and Functional Role of Cav2.3 in the Medial Habenula to Interpeduncular Nucleus Pathway, Institute of Science and Technology Austria, 2020."},"has_accepted_license":"1","language":[{"iso":"eng"}],"corr_author":"1","file_date_updated":"2021-03-01T23:30:04Z","article_processing_charge":"No","author":[{"orcid":"0000-0003-0863-4481","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","first_name":"Pradeep","last_name":"Bhandari","full_name":"Bhandari, Pradeep"}],"date_updated":"2026-04-08T07:27:27Z","department":[{"_id":"RySh"}],"status":"public","publication_status":"published","doi":"10.15479/AT:ISTA:7525","type":"dissertation","oa_version":"Published Version"},{"publication":"Nature Microbiology","volume":5,"ec_funded":1,"title":"Diffusion and capture permits dynamic coupling between treadmilling FtsZ filaments and cell division proteins","article_type":"letter_note","_id":"7387","publisher":"Springer Nature","day":"20","pmid":1,"date_published":"2020-01-20T00:00:00Z","year":"2020","oa":1,"abstract":[{"lang":"eng","text":"Most bacteria accomplish cell division with the help of a dynamic protein complex called the divisome, which spans the cell envelope in the plane of division. Assembly and activation of this machinery are coordinated by the tubulin-related GTPase FtsZ, which was found to form treadmilling filaments on supported bilayers in vitro1, as well as in live cells, in which filaments circle around the cell division site2,3. Treadmilling of FtsZ is thought to actively move proteins around the division septum, thereby distributing peptidoglycan synthesis and coordinating the inward growth of the septum to form the new poles of the daughter cells4. However, the molecular mechanisms underlying this function are largely unknown. Here, to study how FtsZ polymerization dynamics are coupled to downstream proteins, we reconstituted part of the bacterial cell division machinery using its purified components FtsZ, FtsA and truncated transmembrane proteins essential for cell division. We found that the membrane-bound cytosolic peptides of FtsN and FtsQ co-migrated with treadmilling FtsZ–FtsA filaments, but despite their directed collective behaviour, individual peptides showed random motion and transient confinement. Our work suggests that divisome proteins follow treadmilling FtsZ filaments by a diffusion-and-capture mechanism, which can give rise to a moving zone of signalling activity at the division site."}],"date_created":"2020-01-28T16:14:41Z","intvolume":"         5","main_file_link":[{"url":"http://europepmc.org/article/PMC/7048620","open_access":"1"}],"quality_controlled":"1","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"14280"}],"link":[{"relation":"press_release","description":"News on IST Homepage","url":"https://ist.ac.at/en/news/little-cell-big-cover-story/"}]},"acknowledgement":"We acknowledge members of the Loose laboratory at IST Austria for helpful discussions—in particular, P. Caldas for help with the treadmilling analysis, M. Jimenez, A. Raso and N. Ropero for providing Alexa Fluor 488- and Alexa Fluor 647-labelled FtsA for the MST and analytical ultracentrifugation experiments. We thank C. You for providing the DODA-tris-NTA phospholipids, as well as J. Piehler and C. Richter (Department of Biology, University of Osnabruck, Germany) for the SLIMfast single-molecule tracking software and help with the confinement analysis. We thank J. Errington and H. Murray (both at Newcastle University, UK) for critical reading of the manuscript, and J. Brugués (MPI-CBG and MPI-PKS, Dresden, Germany) for help with the MATLAB programming and reading of the manuscript. This work was supported by the European Research Council through grant ERC-2015-StG-679239 to M.L. and grants HFSP LT 000824/2016-L4 and EMBO ALTF 1163-2015 to N.B., a grant from the Ministry of Economy and Competitiveness of the Spanish Government (BFU2016-75471-C2-1-P) to C.A. and G.R., and a Wellcome Trust Senior Investigator award (101824/Z/13/Z) and a grant from the BBSRC (BB/R017409/1) to W.V.","page":"407-417","external_id":{"pmid":["31959972"],"isi":["000508584700007"]},"publication_identifier":{"issn":["2058-5276"]},"month":"01","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","scopus_import":"1","corr_author":"1","project":[{"call_identifier":"H2020","_id":"2595697A-B435-11E9-9278-68D0E5697425","name":"Self-Organization of the Bacterial Cell","grant_number":"679239"},{"grant_number":"LT000824/2016","_id":"259B655A-B435-11E9-9278-68D0E5697425","name":"Reconstitution of bacterial cell wall synthesis"},{"_id":"2596EAB6-B435-11E9-9278-68D0E5697425","name":"Synthesis of bacterial cell wall","grant_number":"ALTF 2015-1163"}],"citation":{"mla":"Baranova, Natalia S., et al. “Diffusion and Capture Permits Dynamic Coupling between Treadmilling FtsZ Filaments and Cell Division Proteins.” <i>Nature Microbiology</i>, vol. 5, Springer Nature, 2020, pp. 407–17, doi:<a href=\"https://doi.org/10.1038/s41564-019-0657-5\">10.1038/s41564-019-0657-5</a>.","short":"N.S. Baranova, P. Radler, V.M. Hernández-Rocamora, C. Alfonso, M.D. Lopez Pelegrin, G. Rivas, W. Vollmer, M. Loose, Nature Microbiology 5 (2020) 407–417.","ieee":"N. S. Baranova <i>et al.</i>, “Diffusion and capture permits dynamic coupling between treadmilling FtsZ filaments and cell division proteins,” <i>Nature Microbiology</i>, vol. 5. Springer Nature, pp. 407–417, 2020.","ista":"Baranova NS, Radler P, Hernández-Rocamora VM, Alfonso C, Lopez Pelegrin MD, Rivas G, Vollmer W, Loose M. 2020. Diffusion and capture permits dynamic coupling between treadmilling FtsZ filaments and cell division proteins. Nature Microbiology. 5, 407–417.","chicago":"Baranova, Natalia S., Philipp Radler, Víctor M. Hernández-Rocamora, Carlos Alfonso, Maria D Lopez Pelegrin, Germán Rivas, Waldemar Vollmer, and Martin Loose. “Diffusion and Capture Permits Dynamic Coupling between Treadmilling FtsZ Filaments and Cell Division Proteins.” <i>Nature Microbiology</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1038/s41564-019-0657-5\">https://doi.org/10.1038/s41564-019-0657-5</a>.","apa":"Baranova, N. S., Radler, P., Hernández-Rocamora, V. M., Alfonso, C., Lopez Pelegrin, M. D., Rivas, G., … Loose, M. (2020). Diffusion and capture permits dynamic coupling between treadmilling FtsZ filaments and cell division proteins. <i>Nature Microbiology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41564-019-0657-5\">https://doi.org/10.1038/s41564-019-0657-5</a>","ama":"Baranova NS, Radler P, Hernández-Rocamora VM, et al. Diffusion and capture permits dynamic coupling between treadmilling FtsZ filaments and cell division proteins. <i>Nature Microbiology</i>. 2020;5:407-417. doi:<a href=\"https://doi.org/10.1038/s41564-019-0657-5\">10.1038/s41564-019-0657-5</a>"},"language":[{"iso":"eng"}],"date_updated":"2026-05-13T22:30:32Z","department":[{"_id":"MaLo"}],"author":[{"first_name":"Natalia S.","id":"38661662-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3086-9124","last_name":"Baranova","full_name":"Baranova, Natalia S."},{"first_name":"Philipp","id":"40136C2A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9198-2182 ","last_name":"Radler","full_name":"Radler, Philipp"},{"first_name":"Víctor M.","full_name":"Hernández-Rocamora, Víctor M.","last_name":"Hernández-Rocamora"},{"full_name":"Alfonso, Carlos","last_name":"Alfonso","first_name":"Carlos"},{"full_name":"Lopez Pelegrin, Maria D","last_name":"Lopez Pelegrin","first_name":"Maria D","id":"319AA9CE-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Rivas, Germán","last_name":"Rivas","first_name":"Germán"},{"last_name":"Vollmer","full_name":"Vollmer, Waldemar","first_name":"Waldemar"},{"full_name":"Loose, Martin","last_name":"Loose","id":"462D4284-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7309-9724","first_name":"Martin"}],"article_processing_charge":"No","publication_status":"published","doi":"10.1038/s41564-019-0657-5","type":"journal_article","oa_version":"Submitted Version","isi":1,"status":"public"},{"publication":"Nature Genetics","OA_place":"repository","volume":52,"title":"CHESS enables quantitative comparison of chromatin contact data and automatic feature extraction","article_type":"original","_id":"8707","day":"19","publisher":"Springer Nature","pmid":1,"date_published":"2020-10-19T00:00:00Z","year":"2020","oa":1,"main_file_link":[{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7610641/","open_access":"1"}],"abstract":[{"lang":"eng","text":"Dynamic changes in the three-dimensional (3D) organization of chromatin are associated with central biological processes, such as transcription, replication and development. Therefore, the comprehensive identification and quantification of these changes is fundamental to understanding of evolutionary and regulatory mechanisms. Here, we present Comparison of Hi-C Experiments using Structural Similarity (CHESS), an algorithm for the comparison of chromatin contact maps and automatic differential feature extraction. We demonstrate the robustness of CHESS to experimental variability and showcase its biological applications on (1) interspecies comparisons of syntenic regions in human and mouse models; (2) intraspecies identification of conformational changes in Zelda-depleted Drosophila embryos; (3) patient-specific aberrant chromatin conformation in a diffuse large B-cell lymphoma sample; and (4) the systematic identification of chromatin contact differences in high-resolution Capture-C data. In summary, CHESS is a computationally efficient method for the comparison and classification of changes in chromatin contact data."}],"date_created":"2020-10-25T23:01:20Z","intvolume":"        52","quality_controlled":"1","external_id":{"pmid":["33077914"],"isi":["000579693500004"]},"OA_type":"green","acknowledgement":"Work in the Vaquerizas laboratory is funded by the Max Planck Society, the Deutsche Forschungsgemeinschaft (DFG) Priority Programme SPP 2202 ‘Spatial Genome Architecture in Development and Disease’ (project no. 422857230 to J.M.V.), the DFG Clinical Research Unit CRU326 ‘Male Germ Cells: from Genes to Function’ (project no. 329621271 to J.M.V.), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 643062—ZENCODE-ITN to J.M.V.) and the Medical Research Council in the UK. This research was partially funded by the European Union’s H2020 Framework Programme through the European Research Council (grant no. 609989 to M.A.M.-R.). We thank the support of the Spanish Ministerio de Ciencia, Innovación y Universidades through grant no. BFU2017-85926-P to M.A.M.-R. The Centre for Genomic Regulation thanks the support of the Ministerio de Ciencia, Innovación y Universidades to the European Molecular Biology Laboratory partnership, the ‘Centro de Excelencia Severo Ochoa 2013–2017’, agreement no. SEV-2012-0208, the CERCA Programme/Generalitat de Catalunya, Spanish Ministerio de Ciencia, Innovación y Universidades through the Instituto de Salud Carlos III, the Generalitat de Catalunya through the Departament de Salut and Departament d’Empresa i Coneixement and cofinancing by the Spanish Ministerio de Ciencia, Innovación y Universidades with funds from the European Regional Development Fund corresponding to the 2014–2020 Smart Growth Operating Program. S.G. thanks the support from the Company of Biologists (grant no. JCSTF181158) and the European Molecular Biology Organization Short-Term Fellowship programme.","page":"1247-1255","related_material":{"record":[{"id":"18642","status":"public","relation":"dissertation_contains"}]},"publication_identifier":{"eissn":["1546-1718"],"issn":["1061-4036"]},"month":"10","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","scopus_import":"1","citation":{"ama":"Galan S, Machnik NN, Kruse K, Díaz N, Marti-Renom MA, Vaquerizas JM. CHESS enables quantitative comparison of chromatin contact data and automatic feature extraction. <i>Nature Genetics</i>. 2020;52:1247-1255. doi:<a href=\"https://doi.org/10.1038/s41588-020-00712-y\">10.1038/s41588-020-00712-y</a>","apa":"Galan, S., Machnik, N. N., Kruse, K., Díaz, N., Marti-Renom, M. A., &#38; Vaquerizas, J. M. (2020). CHESS enables quantitative comparison of chromatin contact data and automatic feature extraction. <i>Nature Genetics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41588-020-00712-y\">https://doi.org/10.1038/s41588-020-00712-y</a>","chicago":"Galan, Silvia, Nick N Machnik, Kai Kruse, Noelia Díaz, Marc A Marti-Renom, and Juan M Vaquerizas. “CHESS Enables Quantitative Comparison of Chromatin Contact Data and Automatic Feature Extraction.” <i>Nature Genetics</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1038/s41588-020-00712-y\">https://doi.org/10.1038/s41588-020-00712-y</a>.","short":"S.  Galan, N.N. Machnik, K. Kruse, N. Díaz, M.A. Marti-Renom, J.M. Vaquerizas, Nature Genetics 52 (2020) 1247–1255.","ista":"Galan S, Machnik NN, Kruse K, Díaz N, Marti-Renom MA, Vaquerizas JM. 2020. CHESS enables quantitative comparison of chromatin contact data and automatic feature extraction. Nature Genetics. 52, 1247–1255.","ieee":"S.  Galan, N. N. Machnik, K. Kruse, N. Díaz, M. A. Marti-Renom, and J. M. Vaquerizas, “CHESS enables quantitative comparison of chromatin contact data and automatic feature extraction,” <i>Nature Genetics</i>, vol. 52. Springer Nature, pp. 1247–1255, 2020.","mla":"Galan, Silvia, et al. “CHESS Enables Quantitative Comparison of Chromatin Contact Data and Automatic Feature Extraction.” <i>Nature Genetics</i>, vol. 52, Springer Nature, 2020, pp. 1247–55, doi:<a href=\"https://doi.org/10.1038/s41588-020-00712-y\">10.1038/s41588-020-00712-y</a>."},"language":[{"iso":"eng"}],"date_updated":"2026-05-13T22:30:33Z","department":[{"_id":"FyKo"}],"author":[{"last_name":" Galan","full_name":" Galan, Silvia","first_name":"Silvia"},{"id":"3591A0AA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6617-9742","first_name":"Nick N","full_name":"Machnik, Nick N","last_name":"Machnik"},{"last_name":"Kruse","full_name":"Kruse, Kai","first_name":"Kai"},{"full_name":"Díaz, Noelia","last_name":"Díaz","first_name":"Noelia"},{"first_name":"Marc A","full_name":"Marti-Renom, Marc A","last_name":"Marti-Renom"},{"first_name":"Juan M","last_name":"Vaquerizas","full_name":"Vaquerizas, Juan M"}],"article_processing_charge":"No","doi":"10.1038/s41588-020-00712-y","publication_status":"published","oa_version":"Submitted Version","type":"journal_article","isi":1,"status":"public"},{"tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"oa":1,"date_published":"2020-03-18T00:00:00Z","year":"2020","abstract":[{"lang":"eng","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."}],"intvolume":"       105","date_created":"2020-02-10T15:59:45Z","quality_controlled":"1","volume":105,"title":"Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices","article_type":"original","ec_funded":1,"publication":"Neuron","ddc":["570"],"pmid":1,"_id":"7473","day":"18","publisher":"Elsevier","author":[{"last_name":"Borges Merjane","full_name":"Borges Merjane, Carolina","first_name":"Carolina","orcid":"0000-0003-0005-401X","id":"4305C450-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Kim, Olena","last_name":"Kim","orcid":"0000-0003-2344-1039","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","first_name":"Olena"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","first_name":"Peter M","last_name":"Jonas","full_name":"Jonas, Peter M"}],"article_processing_charge":"No","date_updated":"2026-05-13T22:30:33Z","department":[{"_id":"PeJo"}],"isi":1,"status":"public","doi":"10.1016/j.neuron.2019.12.022","publication_status":"published","oa_version":"Published Version","type":"journal_article","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","month":"03","external_id":{"isi":["000520854700008"],"pmid":["31928842"]},"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.","page":"992-1006","file":[{"file_id":"8778","access_level":"open_access","success":1,"date_created":"2020-11-20T08:58:53Z","creator":"dernst","content_type":"application/pdf","date_updated":"2020-11-20T08:58:53Z","file_name":"2020_Neuron_BorgesMerjane.pdf","relation":"main_file","checksum":"3582664addf26859e86ac5bec3e01416","file_size":9712957}],"related_material":{"link":[{"description":"News on IST Homepage","url":"https://ist.ac.at/en/news/flash-and-freeze-reveals-dynamics-of-nerve-connections/","relation":"press_release"}],"record":[{"status":"public","relation":"dissertation_contains","id":"11196"}]},"publication_identifier":{"issn":["0896-6273"]},"has_accepted_license":"1","citation":{"mla":"Borges Merjane, Carolina, et al. “Functional Electron Microscopy (‘Flash and Freeze’) of Identified Cortical Synapses in Acute Brain Slices.” <i>Neuron</i>, vol. 105, Elsevier, 2020, pp. 992–1006, doi:<a href=\"https://doi.org/10.1016/j.neuron.2019.12.022\">10.1016/j.neuron.2019.12.022</a>.","short":"C. Borges Merjane, O. Kim, P.M. Jonas, Neuron 105 (2020) 992–1006.","ieee":"C. Borges Merjane, O. Kim, and P. M. Jonas, “Functional electron microscopy (‘Flash and Freeze’) of identified cortical synapses in acute brain slices,” <i>Neuron</i>, vol. 105. Elsevier, pp. 992–1006, 2020.","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. <i>Neuron</i>. 2020;105:992-1006. doi:<a href=\"https://doi.org/10.1016/j.neuron.2019.12.022\">10.1016/j.neuron.2019.12.022</a>","chicago":"Borges Merjane, Carolina, Olena Kim, and Peter M Jonas. “Functional Electron Microscopy (‘Flash and Freeze’) of Identified Cortical Synapses in Acute Brain Slices.” <i>Neuron</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.neuron.2019.12.022\">https://doi.org/10.1016/j.neuron.2019.12.022</a>.","apa":"Borges Merjane, C., Kim, O., &#38; Jonas, P. M. (2020). Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2019.12.022\">https://doi.org/10.1016/j.neuron.2019.12.022</a>"},"language":[{"iso":"eng"}],"scopus_import":"1","file_date_updated":"2020-11-20T08:58:53Z","project":[{"call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692"},{"grant_number":"708497","_id":"25BAF7B2-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Presynaptic calcium channels distribution and impact on coupling at the hippocampal mossy fiber synapse"},{"grant_number":"Z00312","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"Synaptic communication in neuronal microcircuits"},{"name":"Zellkommunikation in Gesundheit und Krankheit","_id":"25C3DBB6-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"W01205"}],"corr_author":"1"},{"date_created":"2020-07-21T08:58:19Z","intvolume":"       133","abstract":[{"lang":"eng","text":"Clathrin-mediated endocytosis (CME) is a crucial cellular process implicated in many aspects of plant growth, development, intra- and inter-cellular signaling, nutrient uptake and pathogen defense. Despite these significant roles, little is known about the precise molecular details of how it functions in planta. In order to facilitate the direct quantitative study of plant CME, here we review current routinely used methods and present refined, standardized quantitative imaging protocols which allow the detailed characterization of CME at multiple scales in plant tissues. These include: (i) an efficient electron microscopy protocol for the imaging of Arabidopsis CME vesicles in situ, thus providing a method for the detailed characterization of the ultra-structure of clathrin-coated vesicles; (ii) a detailed protocol and analysis for quantitative live-cell fluorescence microscopy to precisely examine the temporal interplay of endocytosis components during single CME events; (iii) a semi-automated analysis to allow the quantitative characterization of global internalization of cargos in whole plant tissues; and (iv) an overview and validation of useful genetic and pharmacological tools to interrogate the molecular mechanisms and function of CME in intact plant samples."}],"quality_controlled":"1","oa":1,"date_published":"2020-08-06T00:00:00Z","year":"2020","issue":"15","ddc":["575"],"pmid":1,"_id":"8139","publisher":"The Company of Biologists","day":"06","volume":133,"ec_funded":1,"title":"Experimental toolbox for quantitative evaluation of clathrin-mediated endocytosis in the plant model Arabidopsis","article_type":"original","publication":"Journal of Cell Science","isi":1,"status":"public","publication_status":"published","doi":"10.1242/jcs.248062","type":"journal_article","oa_version":"Published Version","article_processing_charge":"No","author":[{"full_name":"Johnson, Alexander J","last_name":"Johnson","first_name":"Alexander J","orcid":"0000-0002-2739-8843","id":"46A62C3A-F248-11E8-B48F-1D18A9856A87"},{"id":"390C1120-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2198-0509","first_name":"Nataliia","last_name":"Gnyliukh","full_name":"Gnyliukh, Nataliia"},{"orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","first_name":"Walter","last_name":"Kaufmann","full_name":"Kaufmann, Walter"},{"full_name":"Narasimhan, Madhumitha","last_name":"Narasimhan","id":"44BF24D0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8600-0671","first_name":"Madhumitha"},{"first_name":"G","full_name":"Vert, G","last_name":"Vert"},{"first_name":"SY","last_name":"Bednarek","full_name":"Bednarek, SY"},{"last_name":"Friml","full_name":"Friml, Jiří","first_name":"Jiří","orcid":"0000-0002-8302-7596","id":"4159519E-F248-11E8-B48F-1D18A9856A87"}],"date_updated":"2026-05-13T22:30:37Z","department":[{"_id":"JiFr"},{"_id":"EM-Fac"}],"citation":{"chicago":"Johnson, Alexander J, Nataliia Gnyliukh, Walter Kaufmann, Madhumitha Narasimhan, G Vert, SY Bednarek, and Jiří Friml. “Experimental Toolbox for Quantitative Evaluation of Clathrin-Mediated Endocytosis in the Plant Model Arabidopsis.” <i>Journal of Cell Science</i>. The Company of Biologists, 2020. <a href=\"https://doi.org/10.1242/jcs.248062\">https://doi.org/10.1242/jcs.248062</a>.","apa":"Johnson, A. J., Gnyliukh, N., Kaufmann, W., Narasimhan, M., Vert, G., Bednarek, S., &#38; Friml, J. (2020). Experimental toolbox for quantitative evaluation of clathrin-mediated endocytosis in the plant model Arabidopsis. <i>Journal of Cell Science</i>. The Company of Biologists. <a href=\"https://doi.org/10.1242/jcs.248062\">https://doi.org/10.1242/jcs.248062</a>","ama":"Johnson AJ, Gnyliukh N, Kaufmann W, et al. Experimental toolbox for quantitative evaluation of clathrin-mediated endocytosis in the plant model Arabidopsis. <i>Journal of Cell Science</i>. 2020;133(15). doi:<a href=\"https://doi.org/10.1242/jcs.248062\">10.1242/jcs.248062</a>","mla":"Johnson, Alexander J., et al. “Experimental Toolbox for Quantitative Evaluation of Clathrin-Mediated Endocytosis in the Plant Model Arabidopsis.” <i>Journal of Cell Science</i>, vol. 133, no. 15, jcs248062, The Company of Biologists, 2020, doi:<a href=\"https://doi.org/10.1242/jcs.248062\">10.1242/jcs.248062</a>.","ieee":"A. J. Johnson <i>et al.</i>, “Experimental toolbox for quantitative evaluation of clathrin-mediated endocytosis in the plant model Arabidopsis,” <i>Journal of Cell Science</i>, vol. 133, no. 15. The Company of Biologists, 2020.","short":"A.J. Johnson, N. Gnyliukh, W. Kaufmann, M. Narasimhan, G. Vert, S. Bednarek, J. Friml, Journal of Cell Science 133 (2020).","ista":"Johnson AJ, Gnyliukh N, Kaufmann W, Narasimhan M, Vert G, Bednarek S, Friml J. 2020. Experimental toolbox for quantitative evaluation of clathrin-mediated endocytosis in the plant model Arabidopsis. Journal of Cell Science. 133(15), jcs248062."},"article_number":"jcs248062","has_accepted_license":"1","language":[{"iso":"eng"}],"scopus_import":"1","file_date_updated":"2021-08-08T22:30:03Z","project":[{"grant_number":"I03630","name":"Molecular mechanisms of endocytic cargo recognition in plants","call_identifier":"FWF","_id":"26538374-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program","grant_number":"665385"}],"month":"08","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","file":[{"date_created":"2020-11-26T17:12:51Z","access_level":"open_access","file_id":"8815","creator":"ajohnson","content_type":"application/pdf","date_updated":"2021-08-08T22:30:03Z","file_name":"2020 - Johnson - JSC - plant CME toolbox.pdf","file_size":15150403,"checksum":"2d11f79a0b4e0a380fb002b933da331a","embargo":"2021-08-07","relation":"main_file"}],"related_material":{"record":[{"id":"14510","relation":"dissertation_contains","status":"public"}]},"acknowledgement":"This paper is dedicated to the memory of Christien Merrifield. He pioneered quantitative\r\nimaging approaches in mammalian CME and his mentorship inspired the development of all\r\nthe analysis methods presented here. His joy in research, pure scientific curiosity and\r\nmicroscopy excellence remain a constant inspiration. We thank Daniel Van Damme for gifting\r\nus the CLC2-GFP x TPLATE-TagRFP plants used in this manuscript. We further thank the\r\nScientific Service Units at IST Austria; specifically, the Electron Microscopy Facility for\r\ntechnical assistance (in particular Vanessa Zheden) and the BioImaging Facility BioImaging\r\nFacility for access to equipment. ","external_id":{"isi":["000561047900021"],"pmid":["32616560"]},"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"Bio"}],"publication_identifier":{"issn":["0021-9533"],"eissn":["1477-9137"]}},{"type":"journal_article","oa_version":"Published Version","publication_status":"published","doi":"10.1073/pnas.2003346117","status":"public","isi":1,"department":[{"_id":"JiFr"},{"_id":"EvBe"}],"date_updated":"2026-05-13T22:30:46Z","author":[{"last_name":"Hörmayer","full_name":"Hörmayer, Lukas","first_name":"Lukas","orcid":"0000-0001-8295-2926","id":"2EEE7A2A-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Montesinos López","full_name":"Montesinos López, Juan C","first_name":"Juan C","id":"310A8E3E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9179-6099"},{"first_name":"Petra","id":"44E59624-F248-11E8-B48F-1D18A9856A87","full_name":"Marhavá, Petra","last_name":"Marhavá"},{"id":"38F4F166-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8510-9739","first_name":"Eva","last_name":"Benková","full_name":"Benková, Eva"},{"last_name":"Yoshida","full_name":"Yoshida, Saiko","id":"2E46069C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6111-9353","first_name":"Saiko"},{"last_name":"Friml","full_name":"Friml, Jiří","orcid":"0000-0002-8302-7596","id":"4159519E-F248-11E8-B48F-1D18A9856A87","first_name":"Jiří"}],"article_processing_charge":"Yes (in subscription journal)","corr_author":"1","project":[{"_id":"261099A6-B435-11E9-9278-68D0E5697425","name":"Tracing Evolution of Auxin Transport and Polarity in Plants","call_identifier":"H2020","grant_number":"742985"},{"grant_number":"P29988","name":"RNA-directed DNA methylation in plant development","call_identifier":"FWF","_id":"262EF96E-B435-11E9-9278-68D0E5697425"}],"file_date_updated":"2020-07-14T12:48:07Z","scopus_import":"1","language":[{"iso":"eng"}],"citation":{"mla":"Hörmayer, Lukas, et al. “Wounding-Induced Changes in Cellular Pressure and Localized Auxin Signalling Spatially Coordinate Restorative Divisions in Roots.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 117, no. 26, 202003346, National Academy of Sciences, 2020, doi:<a href=\"https://doi.org/10.1073/pnas.2003346117\">10.1073/pnas.2003346117</a>.","short":"L. Hörmayer, J.C. Montesinos López, P. Marhavá, E. Benková, S. Yoshida, J. Friml, Proceedings of the National Academy of Sciences of the United States of America 117 (2020).","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,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 117, no. 26. National Academy of Sciences, 2020.","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 of the United States of America. 117(26), 202003346.","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.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences, 2020. <a href=\"https://doi.org/10.1073/pnas.2003346117\">https://doi.org/10.1073/pnas.2003346117</a>.","apa":"Hörmayer, L., Montesinos López, J. C., Marhavá, P., Benková, E., Yoshida, S., &#38; Friml, J. (2020). Wounding-induced changes in cellular pressure and localized auxin signalling spatially coordinate restorative divisions in roots. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2003346117\">https://doi.org/10.1073/pnas.2003346117</a>","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. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2020;117(26). doi:<a href=\"https://doi.org/10.1073/pnas.2003346117\">10.1073/pnas.2003346117</a>"},"has_accepted_license":"1","article_number":"202003346","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"related_material":{"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/how-wounded-plants-coordinate-their-healing/","description":"News on IST Homepage"}],"record":[{"relation":"dissertation_contains","status":"public","id":"9992"}]},"file":[{"file_size":2407102,"checksum":"908b09437680181de9990915f2113aca","relation":"main_file","date_updated":"2020-07-14T12:48:07Z","file_name":"2020_PNAS_Hoermayer.pdf","creator":"dernst","content_type":"application/pdf","date_created":"2020-06-23T11:30:53Z","access_level":"open_access","file_id":"8009"}],"external_id":{"isi":["000565729700033"],"pmid":["32541049"]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"OA_type":"hybrid","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"06","quality_controlled":"1","abstract":[{"lang":"eng","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."}],"intvolume":"       117","date_created":"2020-06-22T13:33:52Z","year":"2020","issue":"26","date_published":"2020-06-30T00:00:00Z","oa":1,"tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"publisher":"National Academy of Sciences","day":"30","_id":"8002","pmid":1,"ddc":["580"],"publication":"Proceedings of the National Academy of Sciences of the United States of America","ec_funded":1,"article_type":"original","title":"Wounding-induced changes in cellular pressure and localized auxin signalling spatially coordinate restorative divisions in roots","volume":117,"OA_place":"publisher"},{"doi":"10.1016/j.xplc.2020.100048","publication_status":"published","oa_version":"Published Version","type":"journal_article","isi":1,"status":"public","date_updated":"2026-05-13T22:30:46Z","department":[{"_id":"EvBe"}],"article_processing_charge":"No","author":[{"id":"42FE702E-F248-11E8-B48F-1D18A9856A87","first_name":"Hana","full_name":"Semeradova, Hana","last_name":"Semeradova"},{"id":"310A8E3E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9179-6099","first_name":"Juan C","last_name":"Montesinos López","full_name":"Montesinos López, Juan C"},{"first_name":"Eva","orcid":"0000-0002-8510-9739","id":"38F4F166-F248-11E8-B48F-1D18A9856A87","last_name":"Benková","full_name":"Benková, Eva"}],"scopus_import":"1","project":[{"grant_number":"24746","name":"Molecular mechanisms of the cytokinin regulated endomembrane trafficking to coordinate plant organogenesis","_id":"261821BC-B435-11E9-9278-68D0E5697425"},{"_id":"253E54C8-B435-11E9-9278-68D0E5697425","name":"Molecular mechanism of auxindriven formative divisions delineating lateral root organogenesis in plants","grant_number":"ALTF710-2016"}],"file_date_updated":"2021-02-18T10:23:59Z","corr_author":"1","article_number":"100048","has_accepted_license":"1","citation":{"chicago":"Semerádová, Hana, Juan C Montesinos López, and Eva Benková. “All Roads Lead to Auxin: Post-Translational Regulation of Auxin Transport by Multiple Hormonal Pathways.” <i>Plant Communications</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.xplc.2020.100048\">https://doi.org/10.1016/j.xplc.2020.100048</a>.","apa":"Semerádová, H., Montesinos López, J. C., &#38; Benková, E. (2020). All roads lead to auxin: Post-translational regulation of auxin transport by multiple hormonal pathways. <i>Plant Communications</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xplc.2020.100048\">https://doi.org/10.1016/j.xplc.2020.100048</a>","ama":"Semerádová H, Montesinos López JC, Benková E. All roads lead to auxin: Post-translational regulation of auxin transport by multiple hormonal pathways. <i>Plant Communications</i>. 2020;1(3). doi:<a href=\"https://doi.org/10.1016/j.xplc.2020.100048\">10.1016/j.xplc.2020.100048</a>","mla":"Semerádová, Hana, et al. “All Roads Lead to Auxin: Post-Translational Regulation of Auxin Transport by Multiple Hormonal Pathways.” <i>Plant Communications</i>, vol. 1, no. 3, 100048, Elsevier, 2020, doi:<a href=\"https://doi.org/10.1016/j.xplc.2020.100048\">10.1016/j.xplc.2020.100048</a>.","ieee":"H. Semerádová, J. C. Montesinos López, and E. Benková, “All roads lead to auxin: Post-translational regulation of auxin transport by multiple hormonal pathways,” <i>Plant Communications</i>, vol. 1, no. 3. Elsevier, 2020.","short":"H. Semerádová, J.C. Montesinos López, E. Benková, Plant Communications 1 (2020).","ista":"Semerádová H, Montesinos López JC, Benková E. 2020. All roads lead to auxin: Post-translational regulation of auxin transport by multiple hormonal pathways. Plant Communications. 1(3), 100048."},"language":[{"iso":"eng"}],"external_id":{"pmid":["33367243"],"isi":["000654052800010"]},"OA_type":"gold","related_material":{"record":[{"id":"10135","status":"public","relation":"dissertation_contains"}]},"acknowledgement":"H.S. is the recipient of a DOC Fellowship of the Austrian Academy of Sciences at the Institute of Science and Technology, Austria. J.C.M. is the recipient of an EMBO Long-Term Fellowship (ALTF number 710-2016). We would like to thank Jiri Friml and Carina Baskett for critical reading of the manuscript and Shutang Tan and Maciek Adamowski for helpful discussions. No conflict of interest declared.","file":[{"file_size":840289,"checksum":"785b266d82a94b007cf40dbbe7c4847e","relation":"main_file","date_updated":"2021-02-18T10:23:59Z","file_name":"2020_PlantComm_Semeradova.pdf","creator":"dernst","content_type":"application/pdf","date_created":"2021-02-18T10:23:59Z","access_level":"open_access","success":1,"file_id":"9161"}],"publication_identifier":{"issn":["2590-3462"]},"month":"05","user_id":"0043cee0-e5fc-11ee-9736-f83bc23afbf0","DOAJ_listed":"1","abstract":[{"text":"Auxin is a key hormonal regulator, that governs plant growth and development in concert with other hormonal pathways. The unique feature of auxin is its polar, cell-to-cell transport that leads to the formation of local auxin maxima and gradients, which coordinate initiation and patterning of plant organs. The molecular machinery mediating polar auxin transport is one of the important points of interaction with other hormones. Multiple hormonal pathways converge at the regulation of auxin transport and form a regulatory network that integrates various developmental and environmental inputs to steer plant development. In this review, we discuss recent advances in understanding the mechanisms that underlie regulation of polar auxin transport by multiple hormonal pathways. Specifically, we focus on the post-translational mechanisms that contribute to fine-tuning of the abundance and polarity of auxin transporters at the plasma membrane and thereby enable rapid modification of the auxin flow to coordinate plant growth and development.","lang":"eng"}],"intvolume":"         1","date_created":"2021-02-18T10:18:43Z","quality_controlled":"1","date_published":"2020-05-11T00:00:00Z","issue":"3","year":"2020","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"oa":1,"_id":"9160","day":"11","publisher":"Elsevier","ddc":["580"],"pmid":1,"publication":"Plant Communications","volume":1,"OA_place":"publisher","article_type":"original","title":"All roads lead to auxin: Post-translational regulation of auxin transport by multiple hormonal pathways"},{"date_updated":"2026-05-13T22:30:47Z","department":[{"_id":"GeKa"}],"article_processing_charge":"No","author":[{"first_name":"Kushagra","orcid":"0000-0001-9985-9293","id":"b22ab905-3539-11eb-84c3-fc159dcd79cb","full_name":"Aggarwal, Kushagra","last_name":"Aggarwal"},{"full_name":"Hofmann, Andrea C","last_name":"Hofmann","id":"340F461A-F248-11E8-B48F-1D18A9856A87","first_name":"Andrea C"},{"last_name":"Jirovec","full_name":"Jirovec, Daniel","first_name":"Daniel","id":"4C473F58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7197-4801"},{"last_name":"Prieto Gonzalez","full_name":"Prieto Gonzalez, Ivan","first_name":"Ivan","id":"2A307FE2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7370-5357"},{"first_name":"Amir","last_name":"Sammak","full_name":"Sammak, Amir"},{"first_name":"Marc","last_name":"Botifoll","full_name":"Botifoll, Marc"},{"first_name":"Sara","full_name":"Marti-Sanchez, Sara","last_name":"Marti-Sanchez"},{"last_name":"Veldhorst","full_name":"Veldhorst, Menno","first_name":"Menno"},{"last_name":"Arbiol","full_name":"Arbiol, Jordi","first_name":"Jordi"},{"first_name":"Giordano","full_name":"Scappucci, Giordano","last_name":"Scappucci"},{"full_name":"Katsaros, Georgios","last_name":"Katsaros","first_name":"Georgios","id":"38DB5788-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8342-202X"}],"publication_status":"draft","doi":"10.48550/arXiv.2012.00322","type":"preprint","oa_version":"Submitted Version","status":"public","related_material":{"record":[{"id":"10559","relation":"later_version","status":"public"},{"relation":"research_data","status":"public","id":"8834"},{"id":"10058","relation":"dissertation_contains","status":"public"}]},"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).","file":[{"file_name":"Superconducting_2D_Ge.pdf","date_updated":"2020-12-02T10:42:31Z","file_size":1697939,"checksum":"22a612e206232fa94b138b2c2f957582","relation":"main_file","date_created":"2020-12-02T10:42:31Z","access_level":"open_access","file_id":"8832","creator":"gkatsaro","content_type":"application/pdf"}],"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"NanoFab"}],"external_id":{"arxiv":["2012.00322"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"12","corr_author":"1","project":[{"name":"Hybrid Semiconductor - Superconductor Quantum Devices","_id":"262116AA-B435-11E9-9278-68D0E5697425"},{"grant_number":"844511","_id":"26A151DA-B435-11E9-9278-68D0E5697425","name":"Majorana bound states in Ge/SiGe heterostructures","call_identifier":"H2020"},{"call_identifier":"H2020","_id":"237E5020-32DE-11EA-91FC-C7463DDC885E","name":"TOPOLOGICALLY PROTECTED AND SCALABLE QUANTUM BITS","grant_number":"862046"}],"file_date_updated":"2020-12-02T10:42:31Z","citation":{"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.” <i>ArXiv</i>, n.d. <a href=\"https://doi.org/10.48550/arXiv.2012.00322\">https://doi.org/10.48550/arXiv.2012.00322</a>.","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. <i>arXiv</i>. <a href=\"https://doi.org/10.48550/arXiv.2012.00322\">https://doi.org/10.48550/arXiv.2012.00322</a>","ama":"Aggarwal K, Hofmann AC, Jirovec D, et al. Enhancement of proximity induced superconductivity in planar Germanium. <i>arXiv</i>. doi:<a href=\"https://doi.org/10.48550/arXiv.2012.00322\">10.48550/arXiv.2012.00322</a>","mla":"Aggarwal, Kushagra, et al. “Enhancement of Proximity Induced Superconductivity in Planar Germanium.” <i>ArXiv</i>, 2012.00322, doi:<a href=\"https://doi.org/10.48550/arXiv.2012.00322\">10.48550/arXiv.2012.00322</a>.","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.).","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.","ieee":"K. Aggarwal <i>et al.</i>, “Enhancement of proximity induced superconductivity in planar Germanium,” <i>arXiv</i>. ."},"has_accepted_license":"1","article_number":"2012.00322","language":[{"iso":"eng"}],"date_published":"2020-12-02T00:00:00Z","year":"2020","oa":1,"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"}],"date_created":"2020-12-02T10:42:53Z","publication":"arXiv","ec_funded":1,"title":"Enhancement of proximity induced superconductivity in planar Germanium","_id":"8831","arxiv":1,"day":"02","ddc":["530"]},{"ddc":["570"],"_id":"8532","publisher":"MDPI","day":"14","volume":21,"ec_funded":1,"title":"Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses","article_type":"original","publication":"International Journal of Molecular Sciences","abstract":[{"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.","lang":"eng"}],"intvolume":"        21","date_created":"2020-09-20T22:01:35Z","quality_controlled":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"oa":1,"date_published":"2020-09-14T00:00:00Z","year":"2020","issue":"18","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. <i>International Journal of Molecular Sciences</i>. 2020;21(18). doi:<a href=\"https://doi.org/10.3390/ijms21186737\">10.3390/ijms21186737</a>","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.” <i>International Journal of Molecular Sciences</i>. MDPI, 2020. <a href=\"https://doi.org/10.3390/ijms21186737\">https://doi.org/10.3390/ijms21186737</a>.","apa":"Kleindienst, D., Montanaro-Punzengruber, J.-C., Bhandari, P., Case, M. J., Fukazawa, Y., &#38; Shigemoto, R. (2020). Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses. <i>International Journal of Molecular Sciences</i>. MDPI. <a href=\"https://doi.org/10.3390/ijms21186737\">https://doi.org/10.3390/ijms21186737</a>","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.” <i>International Journal of Molecular Sciences</i>, vol. 21, no. 18, 6737, MDPI, 2020, doi:<a href=\"https://doi.org/10.3390/ijms21186737\">10.3390/ijms21186737</a>.","short":"D. Kleindienst, J.-C. Montanaro-Punzengruber, P. Bhandari, M.J. Case, Y. Fukazawa, R. Shigemoto, International Journal of Molecular Sciences 21 (2020).","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.","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,” <i>International Journal of Molecular Sciences</i>, vol. 21, no. 18. MDPI, 2020."},"article_number":"6737","has_accepted_license":"1","language":[{"iso":"eng"}],"scopus_import":"1","corr_author":"1","project":[{"_id":"25CA28EA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","grant_number":"694539"},{"name":"Mechanism of formation and maintenance of input side-dependent asymmetry in the hippocampus","_id":"25D32BC0-B435-11E9-9278-68D0E5697425"},{"grant_number":"785907","call_identifier":"H2020","_id":"26436750-B435-11E9-9278-68D0E5697425","name":"Human Brain Project Specific Grant Agreement 2"}],"file_date_updated":"2020-09-21T14:08:58Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"09","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.","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"9562"}]},"file":[{"creator":"dernst","content_type":"application/pdf","file_id":"8551","date_created":"2020-09-21T14:08:58Z","access_level":"open_access","success":1,"checksum":"2e4f62f3cfe945b7391fc3070e5a289f","relation":"main_file","file_size":5748456,"file_name":"2020_JournMolecSciences_Kleindienst.pdf","date_updated":"2020-09-21T14:08:58Z"}],"external_id":{"isi":["000579945300001"]},"publication_identifier":{"issn":["1661-6596"],"eissn":["1422-0067"]},"isi":1,"status":"public","publication_status":"published","doi":"10.3390/ijms21186737","type":"journal_article","oa_version":"Published Version","article_processing_charge":"No","author":[{"first_name":"David","id":"42E121A4-F248-11E8-B48F-1D18A9856A87","full_name":"Kleindienst, David","last_name":"Kleindienst"},{"full_name":"Montanaro-Punzengruber, Jacqueline-Claire","last_name":"Montanaro-Punzengruber","first_name":"Jacqueline-Claire","id":"3786AB44-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Bhandari","full_name":"Bhandari, Pradeep","first_name":"Pradeep","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0863-4481"},{"last_name":"Case","full_name":"Case, Matthew J","first_name":"Matthew J","id":"44B7CA5A-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Fukazawa","full_name":"Fukazawa, Yugo","first_name":"Yugo"},{"orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi"}],"date_updated":"2026-05-13T22:30:48Z","department":[{"_id":"RySh"}]},{"title":"Perturbations of protein synthesis: from antibiotics to genetics and physiology","OA_place":"publisher","ddc":["571","530","570"],"supervisor":[{"last_name":"Tkačik","full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","first_name":"Gašper"},{"first_name":"Mark Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4398-476X","full_name":"Bollenbach, Mark Tobias","last_name":"Bollenbach"}],"publisher":"Institute of Science and Technology Austria","day":"14","_id":"8657","oa":1,"year":"2020","alternative_title":["ISTA Thesis"],"date_published":"2020-10-14T00:00:00Z","degree_awarded":"PhD","date_created":"2020-10-13T16:46:14Z","abstract":[{"text":"Synthesis of proteins – translation – is a fundamental process of life. Quantitative studies anchor translation into the context of bacterial physiology and reveal several mathematical relationships, called “growth laws,” which capture physiological feedbacks between protein synthesis and cell growth. Growth laws describe the dependency of the ribosome abundance as a function of growth rate, which can change depending on the growth conditions. Perturbations of translation reveal that bacteria employ a compensatory strategy in which the reduced translation capability results in increased expression of the translation machinery.\r\nPerturbations of translation are achieved in various ways; clinically interesting is the application of translation-targeting antibiotics – translation inhibitors. The antibiotic effects on bacterial physiology are often poorly understood. Bacterial responses to two or more simultaneously applied antibiotics are even more puzzling. The combined antibiotic effect determines the type of drug interaction, which ranges from synergy (the effect is stronger than expected) to antagonism (the effect is weaker) and suppression (one of the drugs loses its potency).\r\nIn the first part of this work, we systematically measure the pairwise interaction network for translation inhibitors that interfere with different steps in translation. We find that the interactions are surprisingly diverse and tend to be more antagonistic. To explore the underlying mechanisms, we begin with a minimal biophysical model of combined antibiotic action. We base this model on the kinetics of antibiotic uptake and binding together with the physiological response described by the growth laws. The biophysical model explains some drug interactions, but not all; it specifically fails to predict suppression.\r\nIn the second part of this work, we hypothesize that elusive suppressive drug interactions result from the interplay between ribosomes halted in different stages of translation. To elucidate this putative mechanism of drug interactions between translation inhibitors, we generate translation bottlenecks genetically using in- ducible 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 partially causes these interactions.\r\nWe extend this approach by varying two translation bottlenecks simultaneously. This approach reveals the suppression of translocation inhibition by inhibited translation. We rationalize this effect by modeling dense traffic of ribosomes that move on transcripts in a translation factor-mediated manner. This model predicts a dissolution of traffic jams caused by inhibited translocation when the density of ribosome traffic is reduced by lowered initiation. We base this model on the growth laws and quantitative relationships between different translation and growth parameters.\r\nIn the final part of this work, we describe a set of tools aimed at quantification of physiological and translation parameters. We further develop a simple model that directly connects the abundance of a translation factor with the growth rate, which allows us to extract physiological parameters describing initiation. We demonstrate the development of tools for measuring translation rate.\r\nThis thesis showcases how a combination of high-throughput growth rate mea- surements, genetics, and modeling can reveal mechanisms of drug interactions. Furthermore, by a gradual transition from combinations of antibiotics to precise genetic interventions, we demonstrated the equivalency between genetic and chemi- cal perturbations of translation. These findings tile the path for quantitative studies of antibiotic combinations and illustrate future approaches towards the quantitative description of translation.","lang":"eng"}],"month":"10","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-011-4"]},"related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"7673"},{"id":"8250","status":"public","relation":"part_of_dissertation"}]},"page":"271","file":[{"date_updated":"2021-10-07T22:30:03Z","file_name":"kavcicB_thesis202009.pdf","file_size":52636162,"checksum":"d708ecd62b6fcc3bc1feb483b8dbe9eb","embargo":"2021-10-06","relation":"main_file","date_created":"2020-10-15T06:41:20Z","access_level":"open_access","file_id":"8663","creator":"bkavcic","content_type":"application/pdf"},{"file_size":321681247,"relation":"source_file","embargo_to":"open_access","checksum":"bb35f2352a04db19164da609f00501f3","date_updated":"2021-10-07T22:30:03Z","file_name":"2020b.zip","creator":"bkavcic","content_type":"application/zip","access_level":"closed","date_created":"2020-10-15T06:41:53Z","file_id":"8664"}],"acknowledgement":"I thank Life Science Facilities for their continuous support with providing top-notch laboratory materials, keeping the devices humming, and coordinating the repairs and building of custom-designed laboratory equipment with the MIBA Machine shop.","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"M-Shop"}],"language":[{"iso":"eng"}],"citation":{"chicago":"Kavcic, Bor. “Perturbations of Protein Synthesis: From Antibiotics to Genetics and Physiology.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8657\">https://doi.org/10.15479/AT:ISTA:8657</a>.","apa":"Kavcic, B. (2020). <i>Perturbations of protein synthesis: from antibiotics to genetics and physiology</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8657\">https://doi.org/10.15479/AT:ISTA:8657</a>","ama":"Kavcic B. Perturbations of protein synthesis: from antibiotics to genetics and physiology. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8657\">10.15479/AT:ISTA:8657</a>","mla":"Kavcic, Bor. <i>Perturbations of Protein Synthesis: From Antibiotics to Genetics and Physiology</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8657\">10.15479/AT:ISTA:8657</a>.","short":"B. Kavcic, Perturbations of Protein Synthesis: From Antibiotics to Genetics and Physiology, Institute of Science and Technology Austria, 2020.","ista":"Kavcic B. 2020. Perturbations of protein synthesis: from antibiotics to genetics and physiology. Institute of Science and Technology Austria.","ieee":"B. Kavcic, “Perturbations of protein synthesis: from antibiotics to genetics and physiology,” Institute of Science and Technology Austria, 2020."},"has_accepted_license":"1","corr_author":"1","file_date_updated":"2021-10-07T22:30:03Z","article_processing_charge":"No","author":[{"first_name":"Bor","id":"350F91D2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6041-254X","last_name":"Kavcic","full_name":"Kavcic, Bor"}],"department":[{"_id":"GaTk"}],"date_updated":"2026-04-08T07:27:48Z","status":"public","type":"dissertation","oa_version":"Published Version","publication_status":"published","doi":"10.15479/AT:ISTA:8657"},{"oa":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"issue":"9","year":"2020","date_published":"2020-09-25T00:00:00Z","quality_controlled":"1","abstract":[{"text":"Concerted radial migration of newly born cortical projection neurons, from their birthplace to their final target lamina, is a key step in the assembly of the cerebral cortex. The cellular and molecular mechanisms regulating the specific sequential steps of radial neuronal migration in vivo are however still unclear, let alone the effects and interactions with the extracellular environment. In any in vivo context, cells will always be exposed to a complex extracellular environment consisting of (1) secreted factors acting as potential signaling cues, (2) the extracellular matrix, and (3) other cells providing cell–cell interaction through receptors and/or direct physical stimuli. Most studies so far have described and focused mainly on intrinsic cell-autonomous gene functions in neuronal migration but there is accumulating evidence that non-cell-autonomous-, local-, systemic-, and/or whole tissue-wide effects substantially contribute to the regulation of radial neuronal migration. These non-cell-autonomous effects may differentially affect cortical neuron migration in distinct cellular environments. However, the cellular and molecular natures of such non-cell-autonomous mechanisms are mostly unknown. Furthermore, physical forces due to collective migration and/or community effects (i.e., interactions with surrounding cells) may play important roles in neocortical projection neuron migration. In this concise review, we first outline distinct models of non-cell-autonomous interactions of cortical projection neurons along their radial migration trajectory during development. We then summarize experimental assays and platforms that can be utilized to visualize and potentially probe non-cell-autonomous mechanisms. Lastly, we define key questions to address in the future.","lang":"eng"}],"date_created":"2020-09-26T06:11:07Z","intvolume":"         8","title":"Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex","article_type":"original","ec_funded":1,"volume":8,"publication":"Frontiers in Cell and Developmental Biology","pmid":1,"ddc":["570"],"day":"25","publisher":"Frontiers","_id":"8569","author":[{"full_name":"Hansen, Andi H","last_name":"Hansen","id":"38853E16-F248-11E8-B48F-1D18A9856A87","first_name":"Andi H"},{"last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","first_name":"Simon"}],"article_processing_charge":"Yes (via OA deal)","department":[{"_id":"SiHi"}],"date_updated":"2026-05-13T22:30:51Z","status":"public","isi":1,"oa_version":"Published Version","type":"journal_article","doi":"10.3389/fcell.2020.574382","publication_status":"published","month":"09","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publication_identifier":{"issn":["2296-634X"]},"external_id":{"pmid":["33102480"],"isi":["000577915900001"]},"acknowledgement":"AH was a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences. This work also received support from IST Austria institutional funds; the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007–2013) under REA Grant Agreement No. 618444 to SH.","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"9962"}]},"file":[{"file_id":"8584","access_level":"open_access","success":1,"date_created":"2020-09-28T13:11:17Z","creator":"dernst","content_type":"application/pdf","date_updated":"2020-09-28T13:11:17Z","file_name":"2020_Frontiers_Hansen.pdf","relation":"main_file","checksum":"01f731824194c94c81a5da360d997073","file_size":5527139}],"language":[{"iso":"eng"}],"article_number":"574382","has_accepted_license":"1","citation":{"ama":"Hansen AH, Hippenmeyer S. Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex. <i>Frontiers in Cell and Developmental Biology</i>. 2020;8(9). doi:<a href=\"https://doi.org/10.3389/fcell.2020.574382\">10.3389/fcell.2020.574382</a>","chicago":"Hansen, Andi H, and Simon Hippenmeyer. “Non-Cell-Autonomous Mechanisms in Radial Projection Neuron Migration in the Developing Cerebral Cortex.” <i>Frontiers in Cell and Developmental Biology</i>. Frontiers, 2020. <a href=\"https://doi.org/10.3389/fcell.2020.574382\">https://doi.org/10.3389/fcell.2020.574382</a>.","apa":"Hansen, A. H., &#38; Hippenmeyer, S. (2020). Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex. <i>Frontiers in Cell and Developmental Biology</i>. Frontiers. <a href=\"https://doi.org/10.3389/fcell.2020.574382\">https://doi.org/10.3389/fcell.2020.574382</a>","mla":"Hansen, Andi H., and Simon Hippenmeyer. “Non-Cell-Autonomous Mechanisms in Radial Projection Neuron Migration in the Developing Cerebral Cortex.” <i>Frontiers in Cell and Developmental Biology</i>, vol. 8, no. 9, 574382, Frontiers, 2020, doi:<a href=\"https://doi.org/10.3389/fcell.2020.574382\">10.3389/fcell.2020.574382</a>.","ista":"Hansen AH, Hippenmeyer S. 2020. Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex. Frontiers in Cell and Developmental Biology. 8(9), 574382.","ieee":"A. H. Hansen and S. Hippenmeyer, “Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex,” <i>Frontiers in Cell and Developmental Biology</i>, vol. 8, no. 9. Frontiers, 2020.","short":"A.H. Hansen, S. Hippenmeyer, Frontiers in Cell and Developmental Biology 8 (2020)."},"file_date_updated":"2020-09-28T13:11:17Z","project":[{"grant_number":"24812","_id":"2625A13E-B435-11E9-9278-68D0E5697425","name":"Molecular mechanisms of radial neuronal migration"},{"grant_number":"618444","call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms of Cerebral Cortex Development"}],"corr_author":"1","scopus_import":"1"},{"project":[{"call_identifier":"FWF","name":"Revealing the mechanisms underlying drug interactions","_id":"25E9AF9E-B435-11E9-9278-68D0E5697425","grant_number":"P27201-B22"},{"call_identifier":"FWF","name":"Biophysics of information processing in gene regulation","_id":"254E9036-B435-11E9-9278-68D0E5697425","grant_number":"P28844-B27"}],"file_date_updated":"2020-08-17T07:36:57Z","scopus_import":"1","language":[{"iso":"eng"}],"article_number":"4013","has_accepted_license":"1","citation":{"mla":"Kavcic, Bor, et al. “Mechanisms of Drug Interactions between Translation-Inhibiting Antibiotics.” <i>Nature Communications</i>, vol. 11, 4013, Springer Nature, 2020, doi:<a href=\"https://doi.org/10.1038/s41467-020-17734-z\">10.1038/s41467-020-17734-z</a>.","ista":"Kavcic B, Tkačik G, Bollenbach MT. 2020. Mechanisms of drug interactions between translation-inhibiting antibiotics. Nature Communications. 11, 4013.","short":"B. Kavcic, G. Tkačik, M.T. Bollenbach, Nature Communications 11 (2020).","ieee":"B. Kavcic, G. Tkačik, and M. T. Bollenbach, “Mechanisms of drug interactions between translation-inhibiting antibiotics,” <i>Nature Communications</i>, vol. 11. Springer Nature, 2020.","chicago":"Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “Mechanisms of Drug Interactions between Translation-Inhibiting Antibiotics.” <i>Nature Communications</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1038/s41467-020-17734-z\">https://doi.org/10.1038/s41467-020-17734-z</a>.","apa":"Kavcic, B., Tkačik, G., &#38; Bollenbach, M. T. (2020). Mechanisms of drug interactions between translation-inhibiting antibiotics. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-020-17734-z\">https://doi.org/10.1038/s41467-020-17734-z</a>","ama":"Kavcic B, Tkačik G, Bollenbach MT. Mechanisms of drug interactions between translation-inhibiting antibiotics. <i>Nature Communications</i>. 2020;11. doi:<a href=\"https://doi.org/10.1038/s41467-020-17734-z\">10.1038/s41467-020-17734-z</a>"},"publication_identifier":{"issn":["2041-1723"]},"external_id":{"isi":["000562769300008"],"pmid":["32782250"]},"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.","file":[{"file_size":1965672,"checksum":"986bebb308850a55850028d3d2b5b664","relation":"main_file","date_updated":"2020-08-17T07:36:57Z","file_name":"2020_NatureComm_Kavcic.pdf","creator":"dernst","content_type":"application/pdf","date_created":"2020-08-17T07:36:57Z","access_level":"open_access","success":1,"file_id":"8275"}],"related_material":{"record":[{"id":"8657","relation":"dissertation_contains","status":"public"}]},"month":"08","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","type":"journal_article","doi":"10.1038/s41467-020-17734-z","publication_status":"published","status":"public","isi":1,"department":[{"_id":"GaTk"}],"date_updated":"2026-05-13T22:30:50Z","article_processing_charge":"No","author":[{"last_name":"Kavcic","full_name":"Kavcic, Bor","id":"350F91D2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6041-254X","first_name":"Bor"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","first_name":"Gašper","full_name":"Tkačik, Gašper","last_name":"Tkačik"},{"orcid":"0000-0003-4398-476X","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","first_name":"Tobias","full_name":"Bollenbach, Tobias","last_name":"Bollenbach"}],"day":"11","publisher":"Springer Nature","_id":"8250","pmid":1,"ddc":["570"],"publication":"Nature Communications","article_type":"original","title":"Mechanisms of drug interactions between translation-inhibiting antibiotics","volume":11,"quality_controlled":"1","date_created":"2020-08-12T09:13:50Z","intvolume":"        11","abstract":[{"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.","lang":"eng"}],"year":"2020","date_published":"2020-08-11T00:00:00Z","oa":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"}},{"acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"SSU"}],"related_material":{"record":[{"status":"public","relation":"later_version","id":"10766"},{"id":"9623","status":"public","relation":"dissertation_contains"}]},"page":"41","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.","publication":"bioRxiv","title":"Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion","ec_funded":1,"month":"11","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","day":"20","project":[{"grant_number":"291734","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme"},{"call_identifier":"H2020","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","_id":"260F1432-B435-11E9-9278-68D0E5697425","grant_number":"742573"},{"_id":"2521E28E-B435-11E9-9278-68D0E5697425","name":"Modulation of adhesion function in cell-cell contact formation by cortical tension","grant_number":"187-2013"}],"publisher":"Cold Spring Harbor Laboratory","_id":"9750","language":[{"iso":"eng"}],"citation":{"ama":"Slovakova J, Sikora MK, Caballero Mancebo S, et al. Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion. <i>bioRxiv</i>. 2020. doi:<a href=\"https://doi.org/10.1101/2020.11.20.391284\">10.1101/2020.11.20.391284</a>","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.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, 2020. <a href=\"https://doi.org/10.1101/2020.11.20.391284\">https://doi.org/10.1101/2020.11.20.391284</a>.","apa":"Slovakova, J., Sikora, M. K., Caballero Mancebo, S., Krens, G., Kaufmann, W., Huljev, K., &#38; Heisenberg, C.-P. J. (2020). Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2020.11.20.391284\">https://doi.org/10.1101/2020.11.20.391284</a>","mla":"Slovakova, Jana, et al. “Tension-Dependent Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, 2020, doi:<a href=\"https://doi.org/10.1101/2020.11.20.391284\">10.1101/2020.11.20.391284</a>.","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, <a href=\"https://doi.org/10.1101/2020.11.20.391284\">10.1101/2020.11.20.391284</a>.","short":"J. Slovakova, M.K. Sikora, S. Caballero Mancebo, G. Krens, W. Kaufmann, K. Huljev, C.-P.J. Heisenberg, BioRxiv (2020).","ieee":"J. Slovakova <i>et al.</i>, “Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory, 2020."},"department":[{"_id":"CaHe"},{"_id":"EM-Fac"},{"_id":"Bio"}],"year":"2020","date_updated":"2026-05-13T22:30:51Z","date_published":"2020-11-20T00:00:00Z","oa":1,"author":[{"id":"30F3F2F0-F248-11E8-B48F-1D18A9856A87","first_name":"Jana","full_name":"Slovakova, Jana","last_name":"Slovakova"},{"id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87","first_name":"Mateusz K","full_name":"Sikora, Mateusz K","last_name":"Sikora"},{"first_name":"Silvia","id":"2F1E1758-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5223-3346","last_name":"Caballero Mancebo","full_name":"Caballero Mancebo, Silvia"},{"first_name":"Gabriel","id":"2B819732-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4761-5996","full_name":"Krens, Gabriel","last_name":"Krens"},{"orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","first_name":"Walter","last_name":"Kaufmann","full_name":"Kaufmann, Walter"},{"last_name":"Huljev","full_name":"Huljev, Karla","first_name":"Karla","id":"44C6F6A6-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Heisenberg","full_name":"Heisenberg, Carl-Philipp J","first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566"}],"article_processing_charge":"No","oa_version":"Preprint","type":"preprint","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2020.11.20.391284"}],"doi":"10.1101/2020.11.20.391284","publication_status":"published","abstract":[{"lang":"eng","text":"Tension of the actomyosin cell cortex plays a key role in determining cell-cell contact growth and size. The level of cortical tension outside of the cell-cell contact, when pulling at the contact edge, scales with the total size to which a cell-cell contact can 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."}],"date_created":"2021-07-29T11:29:50Z","status":"public"},{"oa_version":"Preprint","type":"preprint","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2020.04.18.047886 "}],"doi":"10.1101/2020.04.18.047886","publication_status":"published","date_created":"2020-04-22T08:27:56Z","abstract":[{"lang":"eng","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."}],"status":"public","department":[{"_id":"GaTk"}],"year":"2020","date_updated":"2026-05-13T22:30:50Z","date_published":"2020-04-18T00:00:00Z","oa":1,"author":[{"last_name":"Kavcic","full_name":"Kavcic, Bor","orcid":"0000-0001-6041-254X","id":"350F91D2-F248-11E8-B48F-1D18A9856A87","first_name":"Bor"},{"last_name":"Tkačik","full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","first_name":"Gašper"},{"orcid":"0000-0003-4398-476X","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","first_name":"Tobias","last_name":"Bollenbach","full_name":"Bollenbach, Tobias"}],"article_processing_charge":"No","day":"18","project":[{"call_identifier":"FWF","_id":"25E9AF9E-B435-11E9-9278-68D0E5697425","name":"Revealing the mechanisms underlying drug interactions","grant_number":"P27201-B22"},{"grant_number":"P28844-B27","call_identifier":"FWF","_id":"254E9036-B435-11E9-9278-68D0E5697425","name":"Biophysics of information processing in gene regulation"}],"publisher":"Cold Spring Harbor Laboratory","_id":"7673","language":[{"iso":"eng"}],"citation":{"mla":"Kavcic, Bor, et al. “A Minimal Biophysical Model of Combined Antibiotic Action.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, 2020, doi:<a href=\"https://doi.org/10.1101/2020.04.18.047886\">10.1101/2020.04.18.047886</a>.","ista":"Kavcic B, Tkačik G, Bollenbach MT. 2020. A minimal biophysical model of combined antibiotic action. bioRxiv, <a href=\"https://doi.org/10.1101/2020.04.18.047886\">10.1101/2020.04.18.047886</a>.","short":"B. Kavcic, G. Tkačik, M.T. Bollenbach, BioRxiv (2020).","ieee":"B. Kavcic, G. Tkačik, and M. T. Bollenbach, “A minimal biophysical model of combined antibiotic action,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory, 2020.","ama":"Kavcic B, Tkačik G, Bollenbach MT. A minimal biophysical model of combined antibiotic action. <i>bioRxiv</i>. 2020. doi:<a href=\"https://doi.org/10.1101/2020.04.18.047886\">10.1101/2020.04.18.047886</a>","chicago":"Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “A Minimal Biophysical Model of Combined Antibiotic Action.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, 2020. <a href=\"https://doi.org/10.1101/2020.04.18.047886\">https://doi.org/10.1101/2020.04.18.047886</a>.","apa":"Kavcic, B., Tkačik, G., &#38; Bollenbach, M. T. (2020). A minimal biophysical model of combined antibiotic action. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2020.04.18.047886\">https://doi.org/10.1101/2020.04.18.047886</a>"},"publication":"bioRxiv","related_material":{"record":[{"status":"public","relation":"later_version","id":"8997"},{"relation":"dissertation_contains","status":"public","id":"8657"}]},"title":"A minimal biophysical model of combined antibiotic action","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"04"}]