[{"publication":"Development","project":[{"call_identifier":"FWF","_id":"254E9036-B435-11E9-9278-68D0E5697425","grant_number":"P28844-B27","name":"Biophysics of information processing in gene regulation"}],"oa_version":"Published Version","article_number":"dev176065","month":"02","language":[{"iso":"eng"}],"type":"journal_article","date_published":"2021-02-01T00:00:00Z","publication_identifier":{"eissn":["1477-9129"]},"oa":1,"main_file_link":[{"url":"https://doi.org/10.1242/dev.176065","open_access":"1"}],"status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","scopus_import":"1","_id":"9226","pmid":1,"issue":"2","author":[{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper"},{"first_name":"Thomas","last_name":"Gregor","full_name":"Gregor, Thomas"}],"department":[{"_id":"GaTk"}],"article_processing_charge":"No","date_created":"2021-03-07T23:01:25Z","publication_status":"published","intvolume":"       148","title":"The many bits of positional information","quality_controlled":"1","publisher":"The Company of Biologists","article_type":"original","year":"2021","citation":{"apa":"Tkačik, G., &#38; Gregor, T. (2021). The many bits of positional information. <i>Development</i>. The Company of Biologists. <a href=\"https://doi.org/10.1242/dev.176065\">https://doi.org/10.1242/dev.176065</a>","ama":"Tkačik G, Gregor T. The many bits of positional information. <i>Development</i>. 2021;148(2). doi:<a href=\"https://doi.org/10.1242/dev.176065\">10.1242/dev.176065</a>","chicago":"Tkačik, Gašper, and Thomas Gregor. “The Many Bits of Positional Information.” <i>Development</i>. The Company of Biologists, 2021. <a href=\"https://doi.org/10.1242/dev.176065\">https://doi.org/10.1242/dev.176065</a>.","ieee":"G. Tkačik and T. Gregor, “The many bits of positional information,” <i>Development</i>, vol. 148, no. 2. The Company of Biologists, 2021.","mla":"Tkačik, Gašper, and Thomas Gregor. “The Many Bits of Positional Information.” <i>Development</i>, vol. 148, no. 2, dev176065, The Company of Biologists, 2021, doi:<a href=\"https://doi.org/10.1242/dev.176065\">10.1242/dev.176065</a>.","short":"G. Tkačik, T. Gregor, Development 148 (2021).","ista":"Tkačik G, Gregor T. 2021. The many bits of positional information. Development. 148(2), dev176065."},"date_updated":"2023-08-07T13:57:30Z","external_id":{"pmid":["33526425"],"isi":["000613906000007"]},"isi":1,"day":"01","doi":"10.1242/dev.176065","abstract":[{"text":"Half a century after Lewis Wolpert's seminal conceptual advance on how cellular fates distribute in space, we provide a brief historical perspective on how the concept of positional information emerged and influenced the field of developmental biology and beyond. We focus on a modern interpretation of this concept in terms of information theory, largely centered on its application to cell specification in the early Drosophila embryo. We argue that a true physical variable (position) is encoded in local concentrations of patterning molecules, that this mapping is stochastic, and that the processes by which positions and corresponding cell fates are determined based on these concentrations need to take such stochasticity into account. With this approach, we shift the focus from biological mechanisms, molecules, genes and pathways to quantitative systems-level questions: where does positional information reside, how it is transformed and accessed during development, and what fundamental limits it is subject to?","lang":"eng"}],"acknowledgement":"This work was supported in part by the National Science Foundation, through the Center for the Physics of Biological Function (PHY-1734030), by the National Institutes of Health (R01GM097275) and by the Fonds zur Förderung der wissenschaftlichen Forschung (FWF P28844). Deposited in PMC for release after 12 months.","volume":148},{"status":"public","related_material":{"record":[{"status":"public","id":"8951","relation":"research_data"}]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"file_id":"9284","creator":"bkavcic","access_level":"open_access","relation":"main_file","success":1,"date_updated":"2021-03-23T10:12:58Z","file_name":"elife-65993-v2.pdf","content_type":"application/pdf","date_created":"2021-03-23T10:12:58Z","file_size":1390469,"checksum":"3c2f44058c2dd45a5a1027f09d263f8e"}],"oa":1,"publication_identifier":{"issn":["2050-084X"]},"date_published":"2021-03-08T00:00:00Z","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"language":[{"iso":"eng"}],"keyword":["Genetics and Molecular Biology"],"month":"03","article_number":"e65993","oa_version":"Published Version","project":[{"name":"The Systems Biology of Transcriptional Read-Through in Bacteria: from Synthetic Networks to Genomic Studies","grant_number":"628377","call_identifier":"FP7","_id":"2517526A-B435-11E9-9278-68D0E5697425"},{"_id":"268BFA92-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"I03901","name":"CyberCircuits: Cybergenetic circuits to test composability of gene networks"}],"publication":"eLife","has_accepted_license":"1","ddc":["570"],"volume":10,"acknowledgement":"We thank J Bollback, L Hurst, M Lagator, C Nizak, O Rivoire, M Savageau, G Tkacik, and B Vicozo\r\nfor helpful discussions; A Dolinar and A Greshnova for technical assistance; T Bollenbach for supplying the strain JW0336; C Rusnac, and members of the Guet lab for comments. The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n˚\r\n628377 (ANS) and an Austrian Science Fund (FWF) grant n˚ I 3901-B32 (CCG).","abstract":[{"lang":"eng","text":"Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks (GRNs) remains a major challenge. Here, we use a well-defined synthetic GRN to study in Escherichia coli how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one GRN with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Transcriptional read-through is the main molecular mechanism that places one transcriptional unit (TU) within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual TUs, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of GRNs."}],"doi":"10.7554/elife.65993","day":"08","isi":1,"external_id":{"isi":["000631050900001"]},"date_updated":"2024-02-21T12:41:57Z","citation":{"ieee":"A. A. Nagy-Staron <i>et al.</i>, “Local genetic context shapes the function of a gene regulatory network,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","chicago":"Nagy-Staron, Anna A, Kathrin Tomasek, Caroline Caruso Carter, Elisabeth Sonnleitner, Bor Kavcic, Tiago Paixão, and Calin C Guet. “Local Genetic Context Shapes the Function of a Gene Regulatory Network.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/elife.65993\">https://doi.org/10.7554/elife.65993</a>.","ama":"Nagy-Staron AA, Tomasek K, Caruso Carter C, et al. Local genetic context shapes the function of a gene regulatory network. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/elife.65993\">10.7554/elife.65993</a>","apa":"Nagy-Staron, A. A., Tomasek, K., Caruso Carter, C., Sonnleitner, E., Kavcic, B., Paixão, T., &#38; Guet, C. C. (2021). Local genetic context shapes the function of a gene regulatory network. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.65993\">https://doi.org/10.7554/elife.65993</a>","ista":"Nagy-Staron AA, Tomasek K, Caruso Carter C, Sonnleitner E, Kavcic B, Paixão T, Guet CC. 2021. Local genetic context shapes the function of a gene regulatory network. eLife. 10, e65993.","short":"A.A. Nagy-Staron, K. Tomasek, C. Caruso Carter, E. Sonnleitner, B. Kavcic, T. Paixão, C.C. Guet, ELife 10 (2021).","mla":"Nagy-Staron, Anna A., et al. “Local Genetic Context Shapes the Function of a Gene Regulatory Network.” <i>ELife</i>, vol. 10, e65993, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/elife.65993\">10.7554/elife.65993</a>."},"year":"2021","article_type":"original","publisher":"eLife Sciences Publications","file_date_updated":"2021-03-23T10:12:58Z","ec_funded":1,"quality_controlled":"1","title":"Local genetic context shapes the function of a gene regulatory network","intvolume":"        10","publication_status":"published","department":[{"_id":"GaTk"},{"_id":"CaGu"}],"date_created":"2021-03-23T10:11:46Z","article_processing_charge":"Yes","author":[{"first_name":"Anna A","last_name":"Nagy-Staron","orcid":"0000-0002-1391-8377","full_name":"Nagy-Staron, Anna A","id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Tomasek","first_name":"Kathrin","full_name":"Tomasek, Kathrin","orcid":"0000-0003-3768-877X","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Caruso Carter, Caroline","last_name":"Caruso Carter","first_name":"Caroline"},{"full_name":"Sonnleitner, Elisabeth","first_name":"Elisabeth","last_name":"Sonnleitner"},{"id":"350F91D2-F248-11E8-B48F-1D18A9856A87","first_name":"Bor","last_name":"Kavcic","orcid":"0000-0001-6041-254X","full_name":"Kavcic, Bor"},{"full_name":"Paixão, Tiago","first_name":"Tiago","last_name":"Paixão"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","first_name":"Calin C","last_name":"Guet"}],"_id":"9283"},{"acknowledgement":"The authors would like to thank Ulisse Ferrari for useful discussions and feedback.","volume":16,"ddc":["570"],"date_updated":"2023-10-18T08:17:42Z","year":"2021","citation":{"ama":"Chalk MJ, Tkačik G, Marre O. Inferring the function performed by a recurrent neural network. <i>PLoS ONE</i>. 2021;16(4). doi:<a href=\"https://doi.org/10.1371/journal.pone.0248940\">10.1371/journal.pone.0248940</a>","apa":"Chalk, M. J., Tkačik, G., &#38; Marre, O. (2021). Inferring the function performed by a recurrent neural network. <i>PLoS ONE</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pone.0248940\">https://doi.org/10.1371/journal.pone.0248940</a>","chicago":"Chalk, Matthew J, Gašper Tkačik, and Olivier Marre. “Inferring the Function Performed by a Recurrent Neural Network.” <i>PLoS ONE</i>. Public Library of Science, 2021. <a href=\"https://doi.org/10.1371/journal.pone.0248940\">https://doi.org/10.1371/journal.pone.0248940</a>.","ieee":"M. J. Chalk, G. Tkačik, and O. Marre, “Inferring the function performed by a recurrent neural network,” <i>PLoS ONE</i>, vol. 16, no. 4. Public Library of Science, 2021.","short":"M.J. Chalk, G. Tkačik, O. Marre, PLoS ONE 16 (2021).","mla":"Chalk, Matthew J., et al. “Inferring the Function Performed by a Recurrent Neural Network.” <i>PLoS ONE</i>, vol. 16, no. 4, e0248940, Public Library of Science, 2021, doi:<a href=\"https://doi.org/10.1371/journal.pone.0248940\">10.1371/journal.pone.0248940</a>.","ista":"Chalk MJ, Tkačik G, Marre O. 2021. Inferring the function performed by a recurrent neural network. PLoS ONE. 16(4), e0248940."},"isi":1,"external_id":{"pmid":["33857170"],"isi":["000641474900072"]},"doi":"10.1371/journal.pone.0248940","day":"15","abstract":[{"lang":"eng","text":"A central goal in systems neuroscience is to understand the functions performed by neural circuits. Previous top-down models addressed this question by comparing the behaviour of an ideal model circuit, optimised to perform a given function, with neural recordings. However, this requires guessing in advance what function is being performed, which may not be possible for many neural systems. To address this, we propose an inverse reinforcement learning (RL) framework for inferring the function performed by a neural network from data. We assume that the responses of each neuron in a network are optimised so as to drive the network towards ‘rewarded’ states, that are desirable for performing a given function. We then show how one can use inverse RL to infer the reward function optimised by the network from observing its responses. This inferred reward function can be used to predict how the neural network should adapt its dynamics to perform the same function when the external environment or network structure changes. This could lead to theoretical predictions about how neural network dynamics adapt to deal with cell death and/or varying sensory stimulus statistics."}],"quality_controlled":"1","file_date_updated":"2021-05-04T13:22:19Z","publisher":"Public Library of Science","article_type":"original","pmid":1,"_id":"9362","scopus_import":"1","author":[{"id":"2BAAC544-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7782-4436","full_name":"Chalk, Matthew J","first_name":"Matthew J","last_name":"Chalk"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper"},{"last_name":"Marre","first_name":"Olivier","full_name":"Marre, Olivier"}],"issue":"4","publication_status":"published","article_processing_charge":"No","date_created":"2021-05-02T22:01:28Z","department":[{"_id":"GaTk"}],"title":"Inferring the function performed by a recurrent neural network","intvolume":"        16","file":[{"success":1,"access_level":"open_access","relation":"main_file","creator":"kschuh","file_id":"9371","file_size":2768282,"checksum":"c52da133850307d2031f552d998f00e8","date_created":"2021-05-04T13:22:19Z","content_type":"application/pdf","file_name":"2021_pone_Chalk.pdf","date_updated":"2021-05-04T13:22:19Z"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2021-04-15T00:00:00Z","type":"journal_article","publication_identifier":{"eissn":["19326203"]},"oa":1,"language":[{"iso":"eng"}],"publication":"PLoS ONE","has_accepted_license":"1","oa_version":"Published Version","month":"04","article_number":"e0248940"},{"ec_funded":1,"quality_controlled":"1","page":"998-1009","publisher":"Springer Nature","article_type":"original","scopus_import":"1","_id":"9439","author":[{"full_name":"Mlynarski, Wiktor F","first_name":"Wiktor F","last_name":"Mlynarski","id":"358A453A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Ann M.","last_name":"Hermundstad","full_name":"Hermundstad, Ann M."}],"date_created":"2021-05-30T22:01:24Z","department":[{"_id":"GaTk"}],"article_processing_charge":"No","publication_status":"published","intvolume":"        24","title":"Efficient and adaptive sensory codes","acknowledgement":"We thank D. Kastner and T. Münch for generously providing figures from their work. We also thank V. Jayaraman, M. Noorman, T. Ma, and K. Krishnamurthy for useful discussions and feedback on the manuscript. W.F.M. was funded by the European Union’s Horizon 2020 Research and Innovation Programme under Marie Skłodowska-Curie Grant Agreement No. 754411. A.M.H. was supported by the Howard Hughes Medical Institute.","volume":24,"year":"2021","citation":{"ieee":"W. F. Mlynarski and A. M. Hermundstad, “Efficient and adaptive sensory codes,” <i>Nature Neuroscience</i>, vol. 24. Springer Nature, pp. 998–1009, 2021.","chicago":"Mlynarski, Wiktor F, and Ann M. Hermundstad. “Efficient and Adaptive Sensory Codes.” <i>Nature Neuroscience</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41593-021-00846-0\">https://doi.org/10.1038/s41593-021-00846-0</a>.","ama":"Mlynarski WF, Hermundstad AM. Efficient and adaptive sensory codes. <i>Nature Neuroscience</i>. 2021;24:998-1009. doi:<a href=\"https://doi.org/10.1038/s41593-021-00846-0\">10.1038/s41593-021-00846-0</a>","apa":"Mlynarski, W. F., &#38; Hermundstad, A. M. (2021). Efficient and adaptive sensory codes. <i>Nature Neuroscience</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41593-021-00846-0\">https://doi.org/10.1038/s41593-021-00846-0</a>","ista":"Mlynarski WF, Hermundstad AM. 2021. Efficient and adaptive sensory codes. Nature Neuroscience. 24, 998–1009.","short":"W.F. Mlynarski, A.M. Hermundstad, Nature Neuroscience 24 (2021) 998–1009.","mla":"Mlynarski, Wiktor F., and Ann M. Hermundstad. “Efficient and Adaptive Sensory Codes.” <i>Nature Neuroscience</i>, vol. 24, Springer Nature, 2021, pp. 998–1009, doi:<a href=\"https://doi.org/10.1038/s41593-021-00846-0\">10.1038/s41593-021-00846-0</a>."},"date_updated":"2023-08-08T13:51:14Z","external_id":{"isi":["000652577300003"]},"isi":1,"day":"20","doi":"10.1038/s41593-021-00846-0","abstract":[{"text":"The ability to adapt to changes in stimulus statistics is a hallmark of sensory systems. Here, we developed a theoretical framework that can account for the dynamics of adaptation from an information processing perspective. We use this framework to optimize and analyze adaptive sensory codes, and we show that codes optimized for stationary environments can suffer from prolonged periods of poor performance when the environment changes. To mitigate the adversarial effects of these environmental changes, sensory systems must navigate tradeoffs between the ability to accurately encode incoming stimuli and the ability to rapidly detect and adapt to changes in the distribution of these stimuli. We derive families of codes that balance these objectives, and we demonstrate their close match to experimentally observed neural dynamics during mean and variance adaptation. Our results provide a unifying perspective on adaptation across a range of sensory systems, environments, and sensory tasks.","lang":"eng"}],"language":[{"iso":"eng"}],"publication":"Nature Neuroscience","project":[{"grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425"}],"oa_version":"Preprint","month":"05","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/669200 "}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","type":"journal_article","date_published":"2021-05-20T00:00:00Z","publication_identifier":{"issn":["1097-6256"],"eissn":["1546-1726"]},"oa":1},{"abstract":[{"text":"Although much is known about how single neurons in the hippocampus represent an animal’s position, how cell-cell interactions contribute to spatial coding remains poorly understood. Using a novel statistical estimator and theoretical modeling, both developed in the framework of maximum entropy models, we reveal highly structured cell-to-cell interactions whose statistics depend on familiar vs. novel environment. In both conditions the circuit interactions optimize the encoding of spatial information, but for regimes that differ in the signal-to-noise ratio of their spatial inputs. Moreover, the topology of the interactions facilitates linear decodability, making the information easy to read out by downstream circuits. These findings suggest that the efficient coding hypothesis is not applicable only to individual neuron properties in the sensory periphery, but also to neural interactions in the central brain.","lang":"eng"}],"oa":1,"doi":"10.1101/2021.09.28.460602","day":"29","date_published":"2021-09-29T00:00:00Z","type":"preprint","date_updated":"2024-03-25T23:30:09Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"citation":{"ama":"Nardin M, Csicsvari JL, Tkačik G, Savin C. The structure of hippocampal CA1 interactions optimizes spatial coding across experience. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2021.09.28.460602\">10.1101/2021.09.28.460602</a>","apa":"Nardin, M., Csicsvari, J. L., Tkačik, G., &#38; Savin, C. (n.d.). The structure of hippocampal CA1 interactions optimizes spatial coding across experience. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2021.09.28.460602\">https://doi.org/10.1101/2021.09.28.460602</a>","chicago":"Nardin, Michele, Jozsef L Csicsvari, Gašper Tkačik, and Cristina Savin. “The Structure of Hippocampal CA1 Interactions Optimizes Spatial Coding across Experience.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2021.09.28.460602\">https://doi.org/10.1101/2021.09.28.460602</a>.","ieee":"M. Nardin, J. L. Csicsvari, G. Tkačik, and C. Savin, “The structure of hippocampal CA1 interactions optimizes spatial coding across experience,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","short":"M. Nardin, J.L. Csicsvari, G. Tkačik, C. Savin, BioRxiv (n.d.).","mla":"Nardin, Michele, et al. “The Structure of Hippocampal CA1 Interactions Optimizes Spatial Coding across Experience.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2021.09.28.460602\">10.1101/2021.09.28.460602</a>.","ista":"Nardin M, Csicsvari JL, Tkačik G, Savin C. The structure of hippocampal CA1 interactions optimizes spatial coding across experience. bioRxiv, <a href=\"https://doi.org/10.1101/2021.09.28.460602\">10.1101/2021.09.28.460602</a>."},"year":"2021","status":"public","related_material":{"record":[{"status":"public","id":"11932","relation":"dissertation_contains"}]},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","acknowledgement":"We thank Peter Baracskay, Karola Kaefer and Hugo Malagon-Vina for the acquisition of the data. We thank Federico Stella for comments on an earlier version of the manuscript. MN was supported by European Union Horizon 2020 grant 665385, JC was supported by European Research Council consolidator grant 281511, GT was supported by the Austrian Science Fund (FWF) grant P34015, CS was supported by an IST fellow grant, National Institute of Mental Health Award 1R01MH125571-01, by the National Science Foundation under NSF Award No. 1922658 and a Google faculty award.","main_file_link":[{"open_access":"1","url":"https://www.biorxiv.org/content/10.1101/2021.09.28.460602"}],"month":"09","title":"The structure of hippocampal CA1 interactions optimizes spatial coding across experience","publication_status":"submitted","oa_version":"Preprint","article_processing_charge":"No","date_created":"2021-10-04T06:23:34Z","project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","grant_number":"291734"},{"call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program","grant_number":"665385"},{"_id":"257A4776-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"281511","name":"Memory-related information processing in neuronal circuits of the hippocampus and entorhinal cortex"},{"_id":"626c45b5-2b32-11ec-9570-e509828c1ba6","grant_number":"P34015","name":"Efficient coding with biophysical realism"}],"department":[{"_id":"GradSch"},{"_id":"JoCs"},{"_id":"GaTk"}],"author":[{"id":"30BD0376-F248-11E8-B48F-1D18A9856A87","full_name":"Nardin, Michele","orcid":"0000-0001-8849-6570","last_name":"Nardin","first_name":"Michele"},{"first_name":"Jozsef L","last_name":"Csicsvari","orcid":"0000-0002-5193-4036","full_name":"Csicsvari, Jozsef L","id":"3FA14672-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Tkačik","first_name":"Gašper","full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"},{"id":"3933349E-F248-11E8-B48F-1D18A9856A87","last_name":"Savin","first_name":"Cristina","full_name":"Savin, Cristina"}],"_id":"10077","publication":"bioRxiv","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","publisher":"Cold Spring Harbor Laboratory","language":[{"iso":"eng"}],"ec_funded":1},{"acknowledged_ssus":[{"_id":"ScienComp"}],"oa_version":"Published Version","month":"12","article_number":"e1009661","publication":"PLoS Computational Biology","has_accepted_license":"1","language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1553-7358"],"issn":["1553-734X"]},"oa":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2021-12-01T00:00:00Z","type":"journal_article","file":[{"date_created":"2022-05-16T08:53:11Z","checksum":"dcd185d4f7e0acee25edf1d6537f447e","file_size":2299486,"date_updated":"2022-05-16T08:53:11Z","content_type":"application/pdf","file_name":"2021_PLOsComBio_Bodova.pdf","access_level":"open_access","success":1,"relation":"main_file","file_id":"11383","creator":"dernst"}],"status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_status":"published","department":[{"_id":"NiBa"},{"_id":"GaTk"}],"article_processing_charge":"No","date_created":"2021-12-12T23:01:27Z","title":"Dynamic maximum entropy provides accurate approximation of structured population dynamics","intvolume":"        17","pmid":1,"_id":"10535","scopus_import":"1","author":[{"id":"2BA24EA0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7214-0171","full_name":"Bod'ová, Katarína","first_name":"Katarína","last_name":"Bod'ová"},{"full_name":"Szep, Eniko","first_name":"Eniko","last_name":"Szep","id":"485BB5A4-F248-11E8-B48F-1D18A9856A87"},{"id":"4880FE40-F248-11E8-B48F-1D18A9856A87","last_name":"Barton","first_name":"Nicholas H","full_name":"Barton, Nicholas H","orcid":"0000-0002-8548-5240"}],"issue":"12","publisher":"Public Library of Science","article_type":"original","quality_controlled":"1","file_date_updated":"2022-05-16T08:53:11Z","arxiv":1,"doi":"10.1371/journal.pcbi.1009661","day":"01","abstract":[{"lang":"eng","text":"Realistic models of biological processes typically involve interacting components on multiple scales, driven by changing environment and inherent stochasticity. Such models are often analytically and numerically intractable. We revisit a dynamic maximum entropy method that combines a static maximum entropy with a quasi-stationary approximation. This allows us to reduce stochastic non-equilibrium dynamics expressed by the Fokker-Planck equation to a simpler low-dimensional deterministic dynamics, without the need to track microscopic details. Although the method has been previously applied to a few (rather complicated) applications in population genetics, our main goal here is to explain and to better understand how the method works. We demonstrate the usefulness of the method for two widely studied stochastic problems, highlighting its accuracy in capturing important macroscopic quantities even in rapidly changing non-stationary conditions. For the Ornstein-Uhlenbeck process, the method recovers the exact dynamics whilst for a stochastic island model with migration from other habitats, the approximation retains high macroscopic accuracy under a wide range of scenarios in a dynamic environment."}],"date_updated":"2022-08-01T10:48:04Z","citation":{"ista":"Bodova K, Szep E, Barton NH. 2021. Dynamic maximum entropy provides accurate approximation of structured population dynamics. PLoS Computational Biology. 17(12), e1009661.","short":"K. Bodova, E. Szep, N.H. Barton, PLoS Computational Biology 17 (2021).","mla":"Bodova, Katarina, et al. “Dynamic Maximum Entropy Provides Accurate Approximation of Structured Population Dynamics.” <i>PLoS Computational Biology</i>, vol. 17, no. 12, e1009661, Public Library of Science, 2021, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1009661\">10.1371/journal.pcbi.1009661</a>.","chicago":"Bodova, Katarina, Eniko Szep, and Nicholas H Barton. “Dynamic Maximum Entropy Provides Accurate Approximation of Structured Population Dynamics.” <i>PLoS Computational Biology</i>. Public Library of Science, 2021. <a href=\"https://doi.org/10.1371/journal.pcbi.1009661\">https://doi.org/10.1371/journal.pcbi.1009661</a>.","ieee":"K. Bodova, E. Szep, and N. H. Barton, “Dynamic maximum entropy provides accurate approximation of structured population dynamics,” <i>PLoS Computational Biology</i>, vol. 17, no. 12. Public Library of Science, 2021.","ama":"Bodova K, Szep E, Barton NH. Dynamic maximum entropy provides accurate approximation of structured population dynamics. <i>PLoS Computational Biology</i>. 2021;17(12). doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1009661\">10.1371/journal.pcbi.1009661</a>","apa":"Bodova, K., Szep, E., &#38; Barton, N. H. (2021). Dynamic maximum entropy provides accurate approximation of structured population dynamics. <i>PLoS Computational Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1009661\">https://doi.org/10.1371/journal.pcbi.1009661</a>"},"year":"2021","external_id":{"pmid":["34851948"],"arxiv":["2102.03669"]},"volume":17,"acknowledgement":"Computational resources for the study were provided by the Institute of Science and Technology, Austria.\r\nKB received funding from the Scientific Grant Agency of the Slovak Republic under the Grants Nos. 1/0755/19 and 1/0521/20.","ddc":["570"]},{"author":[{"id":"350F91D2-F248-11E8-B48F-1D18A9856A87","last_name":"Kavcic","first_name":"Bor","full_name":"Kavcic, Bor","orcid":"0000-0001-6041-254X"},{"first_name":"Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"_id":"10579","publication":"arXiv","has_accepted_license":"1","title":"Token-driven totally asymmetric simple exclusion process","month":"12","article_number":"2112.13558","oa_version":"Preprint","publication_status":"submitted","department":[{"_id":"GaTk"}],"date_created":"2021-12-28T06:52:09Z","article_processing_charge":"No","language":[{"iso":"eng"}],"date_published":"2021-12-27T00:00:00Z","type":"preprint","external_id":{"arxiv":["2112.13558"]},"date_updated":"2023-05-03T10:54:05Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"citation":{"ista":"Kavcic B, Tkačik G. Token-driven totally asymmetric simple exclusion process. arXiv, 2112.13558.","mla":"Kavcic, Bor, and Gašper Tkačik. “Token-Driven Totally Asymmetric Simple Exclusion Process.” <i>ArXiv</i>, 2112.13558, doi:<a href=\"https://doi.org/10.48550/arXiv.2112.13558\">10.48550/arXiv.2112.13558</a>.","short":"B. Kavcic, G. Tkačik, ArXiv (n.d.).","ieee":"B. Kavcic and G. Tkačik, “Token-driven totally asymmetric simple exclusion process,” <i>arXiv</i>. .","chicago":"Kavcic, Bor, and Gašper Tkačik. “Token-Driven Totally Asymmetric Simple Exclusion Process.” <i>ArXiv</i>, n.d. <a href=\"https://doi.org/10.48550/arXiv.2112.13558\">https://doi.org/10.48550/arXiv.2112.13558</a>.","apa":"Kavcic, B., &#38; Tkačik, G. (n.d.). Token-driven totally asymmetric simple exclusion process. <i>arXiv</i>. <a href=\"https://doi.org/10.48550/arXiv.2112.13558\">https://doi.org/10.48550/arXiv.2112.13558</a>","ama":"Kavcic B, Tkačik G. Token-driven totally asymmetric simple exclusion process. <i>arXiv</i>. doi:<a href=\"https://doi.org/10.48550/arXiv.2112.13558\">10.48550/arXiv.2112.13558</a>"},"year":"2021","abstract":[{"lang":"eng","text":"We consider a totally asymmetric simple exclusion process (TASEP) consisting of particles on a lattice that require binding by a \"token\" to move. Using a combination of theory and simulations, we address the following questions: (i) How token binding kinetics affects the current-density relation; (ii) How the current-density relation depends on the scarcity of tokens; (iii) How tokens propagate the effects of the locally-imposed disorder (such a slow site) over the entire lattice; (iv) How a shared pool of tokens couples concurrent TASEPs running on multiple lattices; (v) How our results translate to TASEPs with open boundaries that exchange particles with the reservoir. Since real particle motion (including in systems that inspired the standard TASEP model, e.g., protein synthesis or movement of molecular motors) is often catalyzed, regulated, actuated, or otherwise mediated, the token-driven TASEP dynamics analyzed in this paper should allow for a better understanding of real systems and enable a closer match between TASEP theory and experimental observations."}],"oa":1,"arxiv":1,"doi":"10.48550/arXiv.2112.13558","day":"27","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["530"],"status":"public","acknowledgement":"B.K. thanks Stefano Elefante, Simon Rella, and Michal Hledík for their help with the usage of the cluster. B.K. additionally thanks Călin Guet and his group for help and advice. We thank M. Hennessey-Wesen for constructive comments on the manuscript. We thank Ankita Gupta (Indian Institute of Technology) for spotting a typographical error in Eq. (49) in the preprint version of this paper.","main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/2112.13558"}]},{"article_type":"original","publisher":"American Chemical Society","file_date_updated":"2021-08-09T09:44:03Z","quality_controlled":"1","ec_funded":1,"page":"35545–35560","intvolume":"        13","title":"Sequential and switchable patterning for studying cellular processes under spatiotemporal control","department":[{"_id":"MiSi"},{"_id":"GaTk"},{"_id":"Bio"},{"_id":"CaGu"}],"date_created":"2021-08-08T22:01:28Z","article_processing_charge":"Yes (in subscription journal)","publication_status":"published","issue":"30","author":[{"full_name":"Zisis, Themistoklis","first_name":"Themistoklis","last_name":"Zisis"},{"full_name":"Schwarz, Jan","last_name":"Schwarz","first_name":"Jan","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Balles, Miriam","last_name":"Balles","first_name":"Miriam"},{"full_name":"Kretschmer, Maibritt","last_name":"Kretschmer","first_name":"Maibritt"},{"full_name":"Nemethova, Maria","first_name":"Maria","last_name":"Nemethova","id":"34E27F1C-F248-11E8-B48F-1D18A9856A87"},{"id":"3464AE84-F248-11E8-B48F-1D18A9856A87","first_name":"Remy P","last_name":"Chait","orcid":"0000-0003-0876-3187","full_name":"Chait, Remy P"},{"last_name":"Hauschild","first_name":"Robert","full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Lange, Janina","last_name":"Lange","first_name":"Janina"},{"orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sixt, Michael K","orcid":"0000-0002-4561-241X","last_name":"Sixt","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Zahler","first_name":"Stefan","full_name":"Zahler, Stefan"}],"scopus_import":"1","_id":"9822","pmid":1,"ddc":["620","570"],"volume":13,"acknowledgement":"We would like to thank Charlott Leu for the production of our chromium wafers, Louise Ritter for her contribution of the IF stainings in Figure 4, Shokoufeh Teymouri for her help with the Bioinert coated slides, and finally Prof. Dr. Joachim Rädler for his valuable scientific guidance.","abstract":[{"text":"Attachment of adhesive molecules on cell culture surfaces to restrict cell adhesion to defined areas and shapes has been vital for the progress of in vitro research. In currently existing patterning methods, a combination of pattern properties such as stability, precision, specificity, high-throughput outcome, and spatiotemporal control is highly desirable but challenging to achieve. Here, we introduce a versatile and high-throughput covalent photoimmobilization technique, comprising a light-dose-dependent patterning step and a subsequent functionalization of the pattern via click chemistry. This two-step process is feasible on arbitrary surfaces and allows for generation of sustainable patterns and gradients. The method is validated in different biological systems by patterning adhesive ligands on cell-repellent surfaces, thereby constraining the growth and migration of cells to the designated areas. We then implement a sequential photopatterning approach by adding a second switchable patterning step, allowing for spatiotemporal control over two distinct surface patterns. As a proof of concept, we reconstruct the dynamics of the tip/stalk cell switch during angiogenesis. Our results show that the spatiotemporal control provided by our “sequential photopatterning” system is essential for mimicking dynamic biological processes and that our innovative approach has great potential for further applications in cell science.","lang":"eng"}],"day":"04","doi":"10.1021/acsami.1c09850","external_id":{"isi":["000683741400026"],"pmid":["34283577"]},"isi":1,"citation":{"ista":"Zisis T, Schwarz J, Balles M, Kretschmer M, Nemethova M, Chait RP, Hauschild R, Lange J, Guet CC, Sixt MK, Zahler S. 2021. Sequential and switchable patterning for studying cellular processes under spatiotemporal control. ACS Applied Materials and Interfaces. 13(30), 35545–35560.","mla":"Zisis, Themistoklis, et al. “Sequential and Switchable Patterning for Studying Cellular Processes under Spatiotemporal Control.” <i>ACS Applied Materials and Interfaces</i>, vol. 13, no. 30, American Chemical Society, 2021, pp. 35545–35560, doi:<a href=\"https://doi.org/10.1021/acsami.1c09850\">10.1021/acsami.1c09850</a>.","short":"T. Zisis, J. Schwarz, M. Balles, M. Kretschmer, M. Nemethova, R.P. Chait, R. Hauschild, J. Lange, C.C. Guet, M.K. Sixt, S. Zahler, ACS Applied Materials and Interfaces 13 (2021) 35545–35560.","chicago":"Zisis, Themistoklis, Jan Schwarz, Miriam Balles, Maibritt Kretschmer, Maria Nemethova, Remy P Chait, Robert Hauschild, et al. “Sequential and Switchable Patterning for Studying Cellular Processes under Spatiotemporal Control.” <i>ACS Applied Materials and Interfaces</i>. American Chemical Society, 2021. <a href=\"https://doi.org/10.1021/acsami.1c09850\">https://doi.org/10.1021/acsami.1c09850</a>.","ieee":"T. Zisis <i>et al.</i>, “Sequential and switchable patterning for studying cellular processes under spatiotemporal control,” <i>ACS Applied Materials and Interfaces</i>, vol. 13, no. 30. American Chemical Society, pp. 35545–35560, 2021.","apa":"Zisis, T., Schwarz, J., Balles, M., Kretschmer, M., Nemethova, M., Chait, R. P., … Zahler, S. (2021). Sequential and switchable patterning for studying cellular processes under spatiotemporal control. <i>ACS Applied Materials and Interfaces</i>. American Chemical Society. <a href=\"https://doi.org/10.1021/acsami.1c09850\">https://doi.org/10.1021/acsami.1c09850</a>","ama":"Zisis T, Schwarz J, Balles M, et al. Sequential and switchable patterning for studying cellular processes under spatiotemporal control. <i>ACS Applied Materials and Interfaces</i>. 2021;13(30):35545–35560. doi:<a href=\"https://doi.org/10.1021/acsami.1c09850\">10.1021/acsami.1c09850</a>"},"year":"2021","date_updated":"2023-08-10T14:22:48Z","language":[{"iso":"eng"}],"month":"08","project":[{"name":"Cellular navigation along spatial gradients","grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"oa_version":"Published Version","has_accepted_license":"1","publication":"ACS Applied Materials and Interfaces","status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"access_level":"open_access","relation":"main_file","success":1,"file_id":"9833","creator":"asandaue","date_created":"2021-08-09T09:44:03Z","checksum":"b043a91d9f9200e467b970b692687ed3","file_size":7123293,"date_updated":"2021-08-09T09:44:03Z","file_name":"2021_ACSAppliedMaterialsAndInterfaces_Zisis.pdf","content_type":"application/pdf"}],"oa":1,"publication_identifier":{"eissn":["19448252"],"issn":["19448244"]},"type":"journal_article","date_published":"2021-08-04T00:00:00Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"}},{"type":"journal_article","date_published":"2021-06-09T00:00:00Z","oa":1,"publication_identifier":{"eissn":["1941-0476"],"issn":["1053-587X"]},"status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/2102.04832"}],"publication":"IEEE Transactions on Signal Processing","month":"06","oa_version":"Preprint","language":[{"iso":"eng"}],"external_id":{"isi":["000682123900002"],"arxiv":["2102.04832"]},"isi":1,"citation":{"ama":"Gabrielaitis M. Fast and accurate amplitude demodulation of wideband signals. <i>IEEE Transactions on Signal Processing</i>. 2021;69:4039-4054. doi:<a href=\"https://doi.org/10.1109/TSP.2021.3087899\">10.1109/TSP.2021.3087899</a>","apa":"Gabrielaitis, M. (2021). Fast and accurate amplitude demodulation of wideband signals. <i>IEEE Transactions on Signal Processing</i>. Institute of Electrical and Electronics Engineers. <a href=\"https://doi.org/10.1109/TSP.2021.3087899\">https://doi.org/10.1109/TSP.2021.3087899</a>","ieee":"M. Gabrielaitis, “Fast and accurate amplitude demodulation of wideband signals,” <i>IEEE Transactions on Signal Processing</i>, vol. 69. Institute of Electrical and Electronics Engineers, pp. 4039–4054, 2021.","chicago":"Gabrielaitis, Mantas. “Fast and Accurate Amplitude Demodulation of Wideband Signals.” <i>IEEE Transactions on Signal Processing</i>. Institute of Electrical and Electronics Engineers, 2021. <a href=\"https://doi.org/10.1109/TSP.2021.3087899\">https://doi.org/10.1109/TSP.2021.3087899</a>.","short":"M. Gabrielaitis, IEEE Transactions on Signal Processing 69 (2021) 4039–4054.","mla":"Gabrielaitis, Mantas. “Fast and Accurate Amplitude Demodulation of Wideband Signals.” <i>IEEE Transactions on Signal Processing</i>, vol. 69, Institute of Electrical and Electronics Engineers, 2021, pp. 4039–54, doi:<a href=\"https://doi.org/10.1109/TSP.2021.3087899\">10.1109/TSP.2021.3087899</a>.","ista":"Gabrielaitis M. 2021. Fast and accurate amplitude demodulation of wideband signals. IEEE Transactions on Signal Processing. 69, 4039–4054."},"year":"2021","date_updated":"2023-08-10T14:19:33Z","abstract":[{"lang":"eng","text":"Amplitude demodulation is a classical operation used in signal processing. For a long time, its effective applications in practice have been limited to narrowband signals. In this work, we generalize amplitude demodulation to wideband signals. We pose demodulation as a recovery problem of an oversampled corrupted signal and introduce special iterative schemes belonging to the family of alternating projection algorithms to solve it. Sensibly chosen structural assumptions on the demodulation outputs allow us to reveal the high inferential accuracy of the method over a rich set of relevant signals. This new approach surpasses current state-of-the-art demodulation techniques apt to wideband signals in computational efficiency by up to many orders of magnitude with no sacrifice in quality. Such performance opens the door for applications of the amplitude demodulation procedure in new contexts. In particular, the new method makes online and large-scale offline data processing feasible, including the calculation of modulator-carrier pairs in higher dimensions and poor sampling conditions, independent of the signal bandwidth. We illustrate the utility and specifics of applications of the new method in practice by using natural speech and synthetic signals."}],"day":"09","arxiv":1,"doi":"10.1109/TSP.2021.3087899","acknowledgement":"The author thanks his colleagues K. Huszár and G. Tkačik for valuable discussions and comments on the manuscript.","volume":69,"author":[{"orcid":"0000-0002-7758-2016","full_name":"Gabrielaitis, Mantas","first_name":"Mantas","last_name":"Gabrielaitis","id":"4D5B0CBC-F248-11E8-B48F-1D18A9856A87"}],"scopus_import":"1","_id":"9828","intvolume":"        69","title":"Fast and accurate amplitude demodulation of wideband signals","article_processing_charge":"No","date_created":"2021-08-08T22:01:31Z","department":[{"_id":"GaTk"}],"publication_status":"published","quality_controlled":"1","page":"4039 - 4054","article_type":"original","publisher":"Institute of Electrical and Electronics Engineers"},{"publisher":"Society for Neuroscience","article_type":"original","quality_controlled":"1","ec_funded":1,"page":"171-190","file_date_updated":"2020-07-22T11:44:48Z","article_processing_charge":"No","date_created":"2020-07-05T15:24:51Z","department":[{"_id":"GaTk"}],"publication_status":"published","intvolume":"        40","title":"Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake","scopus_import":"1","_id":"8084","pmid":1,"issue":"1","author":[{"id":"A057D288-3E88-11E9-986D-0CF4E5697425","last_name":"Lombardi","first_name":"Fabrizio","full_name":"Lombardi, Fabrizio","orcid":"0000-0003-2623-5249"},{"full_name":"Gómez-Extremera, Manuel","last_name":"Gómez-Extremera","first_name":"Manuel"},{"first_name":"Pedro","last_name":"Bernaola-Galván","full_name":"Bernaola-Galván, Pedro"},{"full_name":"Vetrivelan, Ramalingam","last_name":"Vetrivelan","first_name":"Ramalingam"},{"last_name":"Saper","first_name":"Clifford B.","full_name":"Saper, Clifford B."},{"full_name":"Scammell, Thomas E.","first_name":"Thomas E.","last_name":"Scammell"},{"full_name":"Ivanov, Plamen Ch.","last_name":"Ivanov","first_name":"Plamen Ch."}],"volume":40,"ddc":["570"],"day":"02","doi":"10.1523/jneurosci.1278-19.2019","abstract":[{"lang":"eng","text":"Origin and functions of intermittent transitions among sleep stages, including brief awakenings and arousals, constitute a challenge to the current homeostatic framework for sleep regulation, focusing on factors modulating sleep over large time scales. Here we propose that the complex micro-architecture characterizing sleep on scales of seconds and minutes results from intrinsic non-equilibrium critical dynamics. We investigate θ- and δ-wave dynamics in control rats and in rats where the sleep-promoting ventrolateral preoptic nucleus (VLPO) is lesioned (male Sprague-Dawley rats). We demonstrate that bursts in θ and δ cortical rhythms exhibit complex temporal organization, with long-range correlations and robust duality of power-law (θ-bursts, active phase) and exponential-like (δ-bursts, quiescent phase) duration distributions, features typical of non-equilibrium systems self-organizing at criticality. We show that such non-equilibrium behavior relates to anti-correlated coupling between θ- and δ-bursts, persists across a range of time scales, and is independent of the dominant physiologic state; indications of a basic principle in sleep regulation. Further, we find that VLPO lesions lead to a modulation of cortical dynamics resulting in altered dynamical parameters of θ- and δ-bursts and significant reduction in θ–δ coupling. Our empirical findings and model simulations demonstrate that θ–δ coupling is essential for the emerging non-equilibrium critical dynamics observed across the sleep–wake cycle, and indicate that VLPO neurons may have dual role for both sleep and arousal/brief wake activation. The uncovered critical behavior in sleep- and wake-related cortical rhythms indicates a mechanism essential for the micro-architecture of spontaneous sleep-stage and arousal transitions within a novel, non-homeostatic paradigm of sleep regulation."}],"citation":{"chicago":"Lombardi, Fabrizio, Manuel Gómez-Extremera, Pedro Bernaola-Galván, Ramalingam Vetrivelan, Clifford B. Saper, Thomas E. Scammell, and Plamen Ch. Ivanov. “Critical Dynamics and Coupling in Bursts of Cortical Rhythms Indicate Non-Homeostatic Mechanism for Sleep-Stage Transitions and Dual Role of VLPO Neurons in Both Sleep and Wake.” <i>Journal of Neuroscience</i>. Society for Neuroscience, 2020. <a href=\"https://doi.org/10.1523/jneurosci.1278-19.2019\">https://doi.org/10.1523/jneurosci.1278-19.2019</a>.","ieee":"F. Lombardi <i>et al.</i>, “Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake,” <i>Journal of Neuroscience</i>, vol. 40, no. 1. Society for Neuroscience, pp. 171–190, 2020.","apa":"Lombardi, F., Gómez-Extremera, M., Bernaola-Galván, P., Vetrivelan, R., Saper, C. B., Scammell, T. E., &#38; Ivanov, P. C. (2020). Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake. <i>Journal of Neuroscience</i>. Society for Neuroscience. <a href=\"https://doi.org/10.1523/jneurosci.1278-19.2019\">https://doi.org/10.1523/jneurosci.1278-19.2019</a>","ama":"Lombardi F, Gómez-Extremera M, Bernaola-Galván P, et al. Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake. <i>Journal of Neuroscience</i>. 2020;40(1):171-190. doi:<a href=\"https://doi.org/10.1523/jneurosci.1278-19.2019\">10.1523/jneurosci.1278-19.2019</a>","ista":"Lombardi F, Gómez-Extremera M, Bernaola-Galván P, Vetrivelan R, Saper CB, Scammell TE, Ivanov PC. 2020. Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake. Journal of Neuroscience. 40(1), 171–190.","short":"F. Lombardi, M. Gómez-Extremera, P. Bernaola-Galván, R. Vetrivelan, C.B. Saper, T.E. Scammell, P.C. Ivanov, Journal of Neuroscience 40 (2020) 171–190.","mla":"Lombardi, Fabrizio, et al. “Critical Dynamics and Coupling in Bursts of Cortical Rhythms Indicate Non-Homeostatic Mechanism for Sleep-Stage Transitions and Dual Role of VLPO Neurons in Both Sleep and Wake.” <i>Journal of Neuroscience</i>, vol. 40, no. 1, Society for Neuroscience, 2020, pp. 171–90, doi:<a href=\"https://doi.org/10.1523/jneurosci.1278-19.2019\">10.1523/jneurosci.1278-19.2019</a>."},"year":"2020","date_updated":"2023-09-05T14:02:55Z","external_id":{"pmid":["31694962"],"isi":["000505167600016"]},"isi":1,"language":[{"iso":"eng"}],"project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411"}],"oa_version":"Published Version","month":"01","has_accepted_license":"1","publication":"Journal of Neuroscience","file":[{"date_created":"2020-07-22T11:44:48Z","file_size":6646046,"date_updated":"2020-07-22T11:44:48Z","content_type":"application/pdf","file_name":"2020_JournNeuroscience_Lombardi.pdf","success":1,"access_level":"open_access","relation":"main_file","file_id":"8150","creator":"dernst"}],"status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publication_identifier":{"issn":["0270-6474"],"eissn":["1529-2401"]},"oa":1,"type":"journal_article","date_published":"2020-01-02T00:00:00Z"},{"author":[{"id":"350F91D2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6041-254X","full_name":"Kavcic, Bor","first_name":"Bor","last_name":"Kavcic"}],"has_accepted_license":"1","_id":"8097","month":"07","title":"Analysis scripts and research data for the paper \"Mechanisms of drug interactions between translation-inhibiting antibiotics\"","date_created":"2020-07-06T20:40:19Z","article_processing_charge":"No","department":[{"_id":"GaTk"}],"oa_version":"Published Version","acknowledged_ssus":[{"_id":"LifeSc"}],"keyword":["Escherichia coli","antibiotic combinations","translation","growth laws","drug interactions","bacterial physiology","translation inhibitors"],"contributor":[{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","first_name":"Gašper","last_name":"Tkačik","contributor_type":"research_group"},{"first_name":"Tobias","contributor_type":"research_group","last_name":"Bollenbach","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87"}],"file_date_updated":"2020-07-14T12:48:09Z","publisher":"Institute of Science and Technology Austria","type":"research_data","date_published":"2020-07-15T00:00:00Z","year":"2020","citation":{"apa":"Kavcic, B. (2020). Analysis scripts and research data for the paper “Mechanisms of drug interactions between translation-inhibiting antibiotics.” Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8097\">https://doi.org/10.15479/AT:ISTA:8097</a>","ama":"Kavcic B. Analysis scripts and research data for the paper “Mechanisms of drug interactions between translation-inhibiting antibiotics.” 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8097\">10.15479/AT:ISTA:8097</a>","ieee":"B. Kavcic, “Analysis scripts and research data for the paper ‘Mechanisms of drug interactions between translation-inhibiting antibiotics.’” Institute of Science and Technology Austria, 2020.","chicago":"Kavcic, Bor. “Analysis Scripts and Research Data for the Paper ‘Mechanisms of Drug Interactions between Translation-Inhibiting Antibiotics.’” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8097\">https://doi.org/10.15479/AT:ISTA:8097</a>.","short":"B. Kavcic, (2020).","mla":"Kavcic, Bor. <i>Analysis Scripts and Research Data for the Paper “Mechanisms of Drug Interactions between Translation-Inhibiting Antibiotics.”</i> Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8097\">10.15479/AT:ISTA:8097</a>.","ista":"Kavcic B. 2020. Analysis scripts and research data for the paper ‘Mechanisms of drug interactions between translation-inhibiting antibiotics’, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:8097\">10.15479/AT:ISTA:8097</a>."},"date_updated":"2024-02-21T12:40:51Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"oa":1,"abstract":[{"lang":"eng","text":"Antibiotics that interfere with translation, when combined, interact in diverse and difficult-to-predict ways. Here, we explain these interactions by \"translation bottlenecks\": points in the translation cycle where antibiotics block ribosomal progression. To elucidate the underlying mechanisms of drug interactions between translation inhibitors, we generate translation bottlenecks genetically using inducible control of translation factors that regulate well-defined translation cycle steps. These perturbations accurately mimic antibiotic action and drug interactions, supporting that the interplay of different translation bottlenecks causes these interactions. We further show that growth laws, combined with drug uptake and binding kinetics, enable the direct prediction of a large fraction of observed interactions, yet fail to predict suppression. However, varying two translation bottlenecks simultaneously supports that dense traffic of ribosomes and competition for translation factors account for the previously unexplained suppression. These results highlight the importance of \"continuous epistasis\" in bacterial physiology."}],"day":"15","doi":"10.15479/AT:ISTA:8097","status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file":[{"file_id":"8098","creator":"bkavcic","relation":"main_file","access_level":"open_access","date_updated":"2020-07-14T12:48:09Z","content_type":"application/zip","file_name":"natComm_2020_scripts.zip","date_created":"2020-07-06T20:38:27Z","checksum":"5c321dbbb6d4b3c85da786fd3ebbdc98","file_size":255770756}]},{"file":[{"file_size":2197543,"date_created":"2020-07-22T06:17:11Z","file_name":"2020_EPJWebConf_Lombardi.pdf","content_type":"application/pdf","date_updated":"2020-07-22T06:17:11Z","success":1,"access_level":"open_access","relation":"main_file","creator":"dernst","file_id":"8144"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","publication_identifier":{"issn":["2100-014X"]},"oa":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"type":"journal_article","date_published":"2020-03-11T00:00:00Z","language":[{"iso":"eng"}],"oa_version":"Published Version","article_number":"00005","month":"03","has_accepted_license":"1","publication":"EPJ Web of Conferences","volume":230,"ddc":["530"],"day":"11","doi":"10.1051/epjconf/202023000005","abstract":[{"lang":"eng","text":"Physical and biological systems often exhibit intermittent dynamics with bursts or avalanches (active states) characterized by power-law size and duration distributions. These emergent features are typical of systems at the critical point of continuous phase transitions, and have led to the hypothesis that such systems may self-organize at criticality, i.e. without any fine tuning of parameters. Since the introduction of the Bak-Tang-Wiesenfeld (BTW) model, the paradigm of self-organized criticality (SOC) has been very fruitful for the analysis of emergent collective behaviors in a number of systems, including the brain. Although considerable effort has been devoted in identifying and modeling scaling features of burst and avalanche statistics, dynamical aspects related to the temporal organization of bursts remain often poorly understood or controversial. Of crucial importance to understand the mechanisms responsible for emergent behaviors is the relationship between active and quiet periods, and the nature of the correlations. Here we investigate the dynamics of active (θ-bursts) and quiet states (δ-bursts) in brain activity during the sleep-wake cycle. We show the duality of power-law (θ, active phase) and exponential-like (δ, quiescent phase) duration distributions, typical of SOC, jointly emerge with power-law temporal correlations and anti-correlated coupling between active and quiet states. Importantly, we demonstrate that such temporal organization shares important similarities with earthquake dynamics, and propose that specific power-law correlations and coupling between active and quiet states are distinctive characteristics of a class of systems with self-organization at criticality."}],"year":"2020","citation":{"short":"F. Lombardi, J.W.J.L. Wang, X. Zhang, P.C. Ivanov, EPJ Web of Conferences 230 (2020).","mla":"Lombardi, Fabrizio, et al. “Power-Law Correlations and Coupling of Active and Quiet States Underlie a Class of Complex Systems with Self-Organization at Criticality.” <i>EPJ Web of Conferences</i>, vol. 230, 00005, EDP Sciences, 2020, doi:<a href=\"https://doi.org/10.1051/epjconf/202023000005\">10.1051/epjconf/202023000005</a>.","ista":"Lombardi F, Wang JWJL, Zhang X, Ivanov PC. 2020. Power-law correlations and coupling of active and quiet states underlie a class of complex systems with self-organization at criticality. EPJ Web of Conferences. 230, 00005.","ama":"Lombardi F, Wang JWJL, Zhang X, Ivanov PC. Power-law correlations and coupling of active and quiet states underlie a class of complex systems with self-organization at criticality. <i>EPJ Web of Conferences</i>. 2020;230. doi:<a href=\"https://doi.org/10.1051/epjconf/202023000005\">10.1051/epjconf/202023000005</a>","apa":"Lombardi, F., Wang, J. W. J. L., Zhang, X., &#38; Ivanov, P. C. (2020). Power-law correlations and coupling of active and quiet states underlie a class of complex systems with self-organization at criticality. <i>EPJ Web of Conferences</i>. EDP Sciences. <a href=\"https://doi.org/10.1051/epjconf/202023000005\">https://doi.org/10.1051/epjconf/202023000005</a>","ieee":"F. Lombardi, J. W. J. L. Wang, X. Zhang, and P. C. Ivanov, “Power-law correlations and coupling of active and quiet states underlie a class of complex systems with self-organization at criticality,” <i>EPJ Web of Conferences</i>, vol. 230. EDP Sciences, 2020.","chicago":"Lombardi, Fabrizio, Jilin W.J.L. Wang, Xiyun Zhang, and Plamen Ch Ivanov. “Power-Law Correlations and Coupling of Active and Quiet States Underlie a Class of Complex Systems with Self-Organization at Criticality.” <i>EPJ Web of Conferences</i>. EDP Sciences, 2020. <a href=\"https://doi.org/10.1051/epjconf/202023000005\">https://doi.org/10.1051/epjconf/202023000005</a>."},"date_updated":"2021-01-12T08:16:55Z","publisher":"EDP Sciences","article_type":"original","quality_controlled":"1","file_date_updated":"2020-07-22T06:17:11Z","article_processing_charge":"No","department":[{"_id":"GaTk"}],"date_created":"2020-07-12T16:20:33Z","publication_status":"published","intvolume":"       230","title":"Power-law correlations and coupling of active and quiet states underlie a class of complex systems with self-organization at criticality","_id":"8105","author":[{"first_name":"Fabrizio","last_name":"Lombardi","orcid":"0000-0003-2623-5249","full_name":"Lombardi, Fabrizio","id":"A057D288-3E88-11E9-986D-0CF4E5697425"},{"full_name":"Wang, Jilin W.J.L.","last_name":"Wang","first_name":"Jilin W.J.L."},{"full_name":"Zhang, Xiyun","last_name":"Zhang","first_name":"Xiyun"},{"full_name":"Ivanov, Plamen Ch","first_name":"Plamen Ch","last_name":"Ivanov"}]},{"publisher":"Institute of Science and Technology Austria","file_date_updated":"2020-07-30T13:04:55Z","page":"310","title":"Gene regulation across scales – how biophysical constraints shape evolution","alternative_title":["ISTA Thesis"],"publication_status":"published","article_processing_charge":"No","date_created":"2020-07-23T09:51:28Z","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"author":[{"id":"483E70DE-F248-11E8-B48F-1D18A9856A87","last_name":"Grah","first_name":"Rok","full_name":"Grah, Rok","orcid":"0000-0003-2539-3560"}],"_id":"8155","ddc":["530","570"],"acknowledgement":"For the duration of his PhD, Rok was a recipient of a DOC fellowship of the Austrian Academy of Sciences.","abstract":[{"lang":"eng","text":"In the thesis we focus on the interplay of the biophysics and evolution of gene regulation. We start by addressing how the type of prokaryotic gene regulation – activation and repression – affects spurious binding to DNA, also known as\r\ntranscriptional crosstalk. We propose that regulatory interference caused by excess regulatory proteins in the dense cellular medium – global crosstalk – could be a factor in determining which type of gene regulatory network is evolutionarily preferred. Next,we use a normative approach in eukaryotic gene regulation to describe minimal\r\nnon-equilibrium enhancer models that optimize so-called regulatory phenotypes. We find a class of models that differ from standard thermodynamic equilibrium models by a single parameter that notably increases the regulatory performance. Next chapter addresses the question of genotype-phenotype-fitness maps of higher dimensional phenotypes. We show that our biophysically realistic approach allows us to understand how the mechanisms of promoter function constrain genotypephenotype maps, and how they affect the evolutionary trajectories of promoters.\r\nIn the last chapter we ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. Using mathematical modeling, we show that amplifications can tune gene expression in many environments, including those where transcription factor-based schemes are\r\nhard to evolve or maintain. "}],"degree_awarded":"PhD","doi":"10.15479/AT:ISTA:8155","day":"24","date_updated":"2023-09-07T13:13:27Z","year":"2020","citation":{"mla":"Grah, Rok. <i>Gene Regulation across Scales – How Biophysical Constraints Shape Evolution</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8155\">10.15479/AT:ISTA:8155</a>.","short":"R. Grah, Gene Regulation across Scales – How Biophysical Constraints Shape Evolution, Institute of Science and Technology Austria, 2020.","ista":"Grah R. 2020. Gene regulation across scales – how biophysical constraints shape evolution. Institute of Science and Technology Austria.","ama":"Grah R. Gene regulation across scales – how biophysical constraints shape evolution. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8155\">10.15479/AT:ISTA:8155</a>","apa":"Grah, R. (2020). <i>Gene regulation across scales – how biophysical constraints shape evolution</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8155\">https://doi.org/10.15479/AT:ISTA:8155</a>","chicago":"Grah, Rok. “Gene Regulation across Scales – How Biophysical Constraints Shape Evolution.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8155\">https://doi.org/10.15479/AT:ISTA:8155</a>.","ieee":"R. Grah, “Gene regulation across scales – how biophysical constraints shape evolution,” Institute of Science and Technology Austria, 2020."},"language":[{"iso":"eng"}],"month":"07","oa_version":"Published Version","project":[{"_id":"267C84F4-B435-11E9-9278-68D0E5697425","name":"Biophysically realistic genotype-phenotype maps for regulatory networks"}],"has_accepted_license":"1","related_material":{"record":[{"relation":"part_of_dissertation","id":"7675","status":"public"},{"relation":"part_of_dissertation","id":"7569","status":"public"},{"status":"public","relation":"part_of_dissertation","id":"7652"}]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","file":[{"file_id":"8176","creator":"rgrah","access_level":"open_access","relation":"main_file","success":1,"date_updated":"2020-07-27T12:00:07Z","content_type":"application/pdf","file_name":"Thesis_RokGrah_200727_convertedNew.pdf","date_created":"2020-07-27T12:00:07Z","file_size":16638998},{"date_created":"2020-07-27T12:02:23Z","file_size":347459978,"date_updated":"2020-07-30T13:04:55Z","content_type":"application/zip","file_name":"Thesis_new.zip","relation":"main_file","access_level":"closed","file_id":"8177","creator":"rgrah"}],"supervisor":[{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet","first_name":"Calin C"},{"last_name":"Tkačik","first_name":"Gašper","full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"oa":1,"publication_identifier":{"issn":["2663-337X"]},"date_published":"2020-07-24T00:00:00Z","type":"dissertation"},{"file":[{"relation":"main_file","access_level":"open_access","success":1,"creator":"dernst","file_id":"8275","file_size":1965672,"checksum":"986bebb308850a55850028d3d2b5b664","date_created":"2020-08-17T07:36:57Z","file_name":"2020_NatureComm_Kavcic.pdf","content_type":"application/pdf","date_updated":"2020-08-17T07:36:57Z"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","related_material":{"record":[{"id":"8657","relation":"dissertation_contains","status":"public"}]},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2020-08-11T00:00:00Z","type":"journal_article","publication_identifier":{"issn":["2041-1723"]},"oa":1,"language":[{"iso":"eng"}],"publication":"Nature Communications","has_accepted_license":"1","oa_version":"Published Version","project":[{"grant_number":"P27201-B22","name":"Revealing the mechanisms underlying drug interactions","call_identifier":"FWF","_id":"25E9AF9E-B435-11E9-9278-68D0E5697425"},{"grant_number":"P28844-B27","name":"Biophysics of information processing in gene regulation","call_identifier":"FWF","_id":"254E9036-B435-11E9-9278-68D0E5697425"}],"month":"08","article_number":"4013","volume":11,"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.","ddc":["570"],"date_updated":"2024-03-25T23:30:05Z","citation":{"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).","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>.","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>.","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.","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>"},"year":"2020","isi":1,"external_id":{"isi":["000562769300008"]},"doi":"10.1038/s41467-020-17734-z","day":"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"}],"quality_controlled":"1","file_date_updated":"2020-08-17T07:36:57Z","publisher":"Springer Nature","article_type":"original","_id":"8250","author":[{"id":"350F91D2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6041-254X","full_name":"Kavcic, Bor","first_name":"Bor","last_name":"Kavcic"},{"full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","last_name":"Tkačik","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"},{"id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","first_name":"Tobias","last_name":"Bollenbach","orcid":"0000-0003-4398-476X","full_name":"Bollenbach, Tobias"}],"publication_status":"published","article_processing_charge":"No","department":[{"_id":"GaTk"}],"date_created":"2020-08-12T09:13:50Z","title":"Mechanisms of drug interactions between translation-inhibiting antibiotics","intvolume":"        11"},{"language":[{"iso":"eng"}],"month":"10","oa_version":"Published Version","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"M-Shop"}],"has_accepted_license":"1","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","related_material":{"record":[{"status":"public","id":"7673","relation":"part_of_dissertation"},{"status":"public","id":"8250","relation":"part_of_dissertation"}]},"file":[{"file_id":"8663","creator":"bkavcic","relation":"main_file","access_level":"open_access","date_updated":"2021-10-07T22:30:03Z","content_type":"application/pdf","file_name":"kavcicB_thesis202009.pdf","date_created":"2020-10-15T06:41:20Z","embargo":"2021-10-06","file_size":52636162,"checksum":"d708ecd62b6fcc3bc1feb483b8dbe9eb"},{"file_id":"8664","creator":"bkavcic","access_level":"closed","relation":"source_file","date_updated":"2021-10-07T22:30:03Z","content_type":"application/zip","file_name":"2020b.zip","date_created":"2020-10-15T06:41:53Z","embargo_to":"open_access","checksum":"bb35f2352a04db19164da609f00501f3","file_size":321681247}],"oa":1,"supervisor":[{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","last_name":"Tkačik","first_name":"Gašper"},{"last_name":"Bollenbach","first_name":"Mark Tobias","full_name":"Bollenbach, Mark Tobias","orcid":"0000-0003-4398-476X","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87"}],"publication_identifier":{"isbn":["978-3-99078-011-4"],"issn":["2663-337X"]},"type":"dissertation","date_published":"2020-10-14T00:00:00Z","publisher":"Institute of Science and Technology Austria","file_date_updated":"2021-10-07T22:30:03Z","page":"271","title":"Perturbations of protein synthesis: from antibiotics to genetics and physiology","alternative_title":["ISTA Thesis"],"date_created":"2020-10-13T16:46:14Z","article_processing_charge":"No","department":[{"_id":"GaTk"}],"publication_status":"published","author":[{"id":"350F91D2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6041-254X","full_name":"Kavcic, Bor","first_name":"Bor","last_name":"Kavcic"}],"_id":"8657","ddc":["571","530","570"],"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.","abstract":[{"lang":"eng","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."}],"day":"14","degree_awarded":"PhD","doi":"10.15479/AT:ISTA:8657","year":"2020","citation":{"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>","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>.","ieee":"B. Kavcic, “Perturbations of protein synthesis: from antibiotics to genetics and physiology,” Institute of Science and Technology Austria, 2020.","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."},"date_updated":"2023-09-07T13:20:48Z"},{"language":[{"iso":"eng"}],"month":"10","oa_version":"Published Version","has_accepted_license":"1","publication":"Proceedings of the National Academy of Sciences of the United States of America","status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"success":1,"access_level":"open_access","relation":"main_file","creator":"cziletti","file_id":"8713","file_size":1755359,"checksum":"c6a24fdecf3f28faf447078e7a274a88","date_created":"2020-10-27T14:57:50Z","file_name":"2020_PNAS_Maoz.pdf","content_type":"application/pdf","date_updated":"2020-10-27T14:57:50Z"}],"oa":1,"publication_identifier":{"issn":["00278424"],"eissn":["10916490"]},"type":"journal_article","date_published":"2020-10-06T00:00:00Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"article_type":"original","publisher":"National Academy of Sciences","file_date_updated":"2020-10-27T14:57:50Z","quality_controlled":"1","page":"25066-25073","intvolume":"       117","title":"Learning probabilistic neural representations with randomly connected circuits","article_processing_charge":"No","date_created":"2020-10-25T23:01:16Z","department":[{"_id":"GaTk"}],"publication_status":"published","issue":"40","author":[{"full_name":"Maoz, Ori","last_name":"Maoz","first_name":"Ori"},{"full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","last_name":"Tkačik","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Esteki, Mohamad Saleh","last_name":"Esteki","first_name":"Mohamad Saleh"},{"last_name":"Kiani","first_name":"Roozbeh","full_name":"Kiani, Roozbeh"},{"full_name":"Schneidman, Elad","last_name":"Schneidman","first_name":"Elad"}],"scopus_import":"1","_id":"8698","pmid":1,"ddc":["570"],"acknowledgement":"We thank Udi Karpas, Roy Harpaz, Tal Tamir, Adam Haber, and Amir Bar for discussions and suggestions; and especially Oren Forkosh and Walter Senn for invaluable discussions of the learning rule. This work was supported by European Research Council Grant 311238 (to E.S.) and Israel Science Foundation Grant 1629/12 (to E.S.); as well as research support from Martin Kushner Schnur and Mr. and Mrs. Lawrence Feis (E.S.); National Institute of Mental Health Grant R01MH109180 (to R.K.); a Pew Scholarship in Biomedical Sciences (to R.K.); Simons Collaboration on the Global Brain Grant 542997 (to R.K. and E.S.); and a CRCNS (Collaborative Research in Computational Neuroscience) grant (to R.K. and E.S.).","volume":117,"abstract":[{"lang":"eng","text":"The brain represents and reasons probabilistically about complex stimuli and motor actions using a noisy, spike-based neural code. A key building block for such neural computations, as well as the basis for supervised and unsupervised learning, is the ability to estimate the surprise or likelihood of incoming high-dimensional neural activity patterns. Despite progress in statistical modeling of neural responses and deep learning, current approaches either do not scale to large neural populations or cannot be implemented using biologically realistic mechanisms. Inspired by the sparse and random connectivity of real neuronal circuits, we present a model for neural codes that accurately estimates the likelihood of individual spiking patterns and has a straightforward, scalable, efficient, learnable, and realistic neural implementation. This model’s performance on simultaneously recorded spiking activity of >100 neurons in the monkey visual and prefrontal cortices is comparable with or better than that of state-of-the-art models. Importantly, the model can be learned using a small number of samples and using a local learning rule that utilizes noise intrinsic to neural circuits. Slower, structural changes in random connectivity, consistent with rewiring and pruning processes, further improve the efficiency and sparseness of the resulting neural representations. Our results merge insights from neuroanatomy, machine learning, and theoretical neuroscience to suggest random sparse connectivity as a key design principle for neuronal computation."}],"day":"06","doi":"10.1073/pnas.1912804117","external_id":{"pmid":["32948691"],"isi":["000579045200012"]},"isi":1,"citation":{"chicago":"Maoz, Ori, Gašper Tkačik, Mohamad Saleh Esteki, Roozbeh Kiani, and Elad Schneidman. “Learning Probabilistic Neural Representations with Randomly Connected Circuits.” <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.1912804117\">https://doi.org/10.1073/pnas.1912804117</a>.","ieee":"O. Maoz, G. Tkačik, M. S. Esteki, R. Kiani, and E. Schneidman, “Learning probabilistic neural representations with randomly connected circuits,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 117, no. 40. National Academy of Sciences, pp. 25066–25073, 2020.","apa":"Maoz, O., Tkačik, G., Esteki, M. S., Kiani, R., &#38; Schneidman, E. (2020). Learning probabilistic neural representations with randomly connected circuits. <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.1912804117\">https://doi.org/10.1073/pnas.1912804117</a>","ama":"Maoz O, Tkačik G, Esteki MS, Kiani R, Schneidman E. Learning probabilistic neural representations with randomly connected circuits. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2020;117(40):25066-25073. doi:<a href=\"https://doi.org/10.1073/pnas.1912804117\">10.1073/pnas.1912804117</a>","ista":"Maoz O, Tkačik G, Esteki MS, Kiani R, Schneidman E. 2020. Learning probabilistic neural representations with randomly connected circuits. Proceedings of the National Academy of Sciences of the United States of America. 117(40), 25066–25073.","short":"O. Maoz, G. Tkačik, M.S. Esteki, R. Kiani, E. Schneidman, Proceedings of the National Academy of Sciences of the United States of America 117 (2020) 25066–25073.","mla":"Maoz, Ori, et al. “Learning Probabilistic Neural Representations with Randomly Connected Circuits.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 117, no. 40, National Academy of Sciences, 2020, pp. 25066–73, doi:<a href=\"https://doi.org/10.1073/pnas.1912804117\">10.1073/pnas.1912804117</a>."},"year":"2020","date_updated":"2023-08-22T12:11:23Z"},{"publisher":"Institute of Science and Technology Austria","keyword":["Escherichia coli","antibiotic combinations","translation","growth laws","drug interactions","bacterial physiology","translation inhibitors"],"file_date_updated":"2020-12-09T15:00:19Z","contributor":[{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkačik","contributor_type":"supervisor","first_name":"Gašper","orcid":"0000-0002-6699-1455"},{"id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","contributor_type":"supervisor","last_name":"Bollenbach","first_name":"Tobias"}],"title":"Analysis scripts and research data for the paper \"Minimal biophysical model of combined antibiotic action\"","month":"12","date_created":"2020-12-09T15:04:02Z","department":[{"_id":"GaTk"}],"article_processing_charge":"No","oa_version":"Published Version","author":[{"id":"350F91D2-F248-11E8-B48F-1D18A9856A87","first_name":"Bor","last_name":"Kavcic","orcid":"0000-0001-6041-254X","full_name":"Kavcic, Bor"}],"has_accepted_license":"1","_id":"8930","status":"public","ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","related_material":{"record":[{"status":"public","id":"8997","relation":"used_in_publication"}]},"file":[{"relation":"main_file","success":1,"access_level":"open_access","file_id":"8932","creator":"bkavcic","date_created":"2020-12-09T15:00:19Z","checksum":"60a818edeffaa7da1ebf5f8fbea9ba18","file_size":315494370,"date_updated":"2020-12-09T15:00:19Z","content_type":"application/zip","file_name":"PLoSCompBiol2020_datarep.zip"}],"oa":1,"abstract":[{"lang":"eng","text":"Phenomenological relations such as Ohm’s or Fourier’s law have a venerable history in physics but are still scarce in biology. This situation restrains predictive theory. Here, we build on bacterial “growth laws,” which capture physiological feedback between translation and cell growth, to construct a minimal biophysical model for the combined action of ribosome-targeting antibiotics. Our model predicts drug interactions like antagonism or synergy solely from responses to individual drugs. We provide analytical results for limiting cases, which agree well with numerical results. We systematically refine the model by including direct physical interactions of different antibiotics on the ribosome. In a limiting case, our model provides a mechanistic underpinning for recent predictions of higher-order interactions that were derived using entropy maximization. We further refine the model to include the effects of antibiotics that mimic starvation and the presence of resistance genes. We describe the impact of a starvation-mimicking antibiotic on drug interactions analytically and verify it experimentally. Our extended model suggests a change in the type of drug interaction that depends on the strength of resistance, which challenges established rescaling paradigms. We experimentally show that the presence of unregulated resistance genes can lead to altered drug interaction, which agrees with the prediction of the model. While minimal, the model is readily adaptable and opens the door to predicting interactions of second and higher-order in a broad range of biological systems."}],"day":"10","doi":"10.15479/AT:ISTA:8930","type":"research_data","date_published":"2020-12-10T00:00:00Z","year":"2020","citation":{"mla":"Kavcic, Bor. <i>Analysis Scripts and Research Data for the Paper “Minimal Biophysical Model of Combined Antibiotic Action.”</i> Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8930\">10.15479/AT:ISTA:8930</a>.","short":"B. Kavcic, (2020).","ista":"Kavcic B. 2020. Analysis scripts and research data for the paper ‘Minimal biophysical model of combined antibiotic action’, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:8930\">10.15479/AT:ISTA:8930</a>.","apa":"Kavcic, B. (2020). Analysis scripts and research data for the paper “Minimal biophysical model of combined antibiotic action.” Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8930\">https://doi.org/10.15479/AT:ISTA:8930</a>","ama":"Kavcic B. Analysis scripts and research data for the paper “Minimal biophysical model of combined antibiotic action.” 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8930\">10.15479/AT:ISTA:8930</a>","chicago":"Kavcic, Bor. “Analysis Scripts and Research Data for the Paper ‘Minimal Biophysical Model of Combined Antibiotic Action.’” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8930\">https://doi.org/10.15479/AT:ISTA:8930</a>.","ieee":"B. Kavcic, “Analysis scripts and research data for the paper ‘Minimal biophysical model of combined antibiotic action.’” Institute of Science and Technology Austria, 2020."},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_updated":"2024-02-21T12:41:42Z"},{"article_type":"original","publisher":"Frontiers","file_date_updated":"2020-12-21T10:37:50Z","ec_funded":1,"quality_controlled":"1","intvolume":"        11","title":"Network physiology of cortico–muscular interactions","date_created":"2020-12-20T23:01:18Z","article_processing_charge":"No","department":[{"_id":"GaTk"}],"publication_status":"published","author":[{"first_name":"Rossella","last_name":"Rizzo","full_name":"Rizzo, Rossella"},{"full_name":"Zhang, Xiyun","last_name":"Zhang","first_name":"Xiyun"},{"full_name":"Wang, Jilin W.J.L.","first_name":"Jilin W.J.L.","last_name":"Wang"},{"first_name":"Fabrizio","last_name":"Lombardi","orcid":"0000-0003-2623-5249","full_name":"Lombardi, Fabrizio","id":"A057D288-3E88-11E9-986D-0CF4E5697425"},{"full_name":"Ivanov, Plamen Ch","first_name":"Plamen Ch","last_name":"Ivanov"}],"scopus_import":"1","pmid":1,"_id":"8955","ddc":["570"],"volume":11,"acknowledgement":"We acknowledge support from the W. M. Keck Foundation, National Institutes of Health (NIH Grant 1R01-HL098437), the US-Israel Binational Science Foundation (BSF Grant 2012219), and the Office of Naval Research (ONR Grant 000141010078). FL acknowledges support also from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Grant Agreement No. 754411.","abstract":[{"text":"Skeletal muscle activity is continuously modulated across physiologic states to provide coordination, flexibility and responsiveness to body tasks and external inputs. Despite the central role the muscular system plays in facilitating vital body functions, the network of brain-muscle interactions required to control hundreds of muscles and synchronize their activation in relation to distinct physiologic states has not been investigated. Recent approaches have focused on general associations between individual brain rhythms and muscle activation during movement tasks. However, the specific forms of coupling, the functional network of cortico-muscular coordination, and how network structure and dynamics are modulated by autonomic regulation across physiologic states remains unknown. To identify and quantify the cortico-muscular interaction network and uncover basic features of neuro-autonomic control of muscle function, we investigate the coupling between synchronous bursts in cortical rhythms and peripheral muscle activation during sleep and wake. Utilizing the concept of time delay stability and a novel network physiology approach, we find that the brain-muscle network exhibits complex dynamic patterns of communication involving multiple brain rhythms across cortical locations and different electromyographic frequency bands. Moreover, our results show that during each physiologic state the cortico-muscular network is characterized by a specific profile of network links strength, where particular brain rhythms play role of main mediators of interaction and control. Further, we discover a hierarchical reorganization in network structure across physiologic states, with high connectivity and network link strength during wake, intermediate during REM and light sleep, and low during deep sleep, a sleep-stage stratification that demonstrates a unique association between physiologic states and cortico-muscular network structure. The reported empirical observations are consistent across individual subjects, indicating universal behavior in network structure and dynamics, and high sensitivity of cortico-muscular control to changes in autonomic regulation, even at low levels of physical activity and muscle tone during sleep. Our findings demonstrate previously unrecognized basic principles of brain-muscle network communication and control, and provide new perspectives on the regulatory mechanisms of brain dynamics and locomotor activation, with potential clinical implications for neurodegenerative, movement and sleep disorders, and for developing efficient treatment strategies.","lang":"eng"}],"day":"26","doi":"10.3389/fphys.2020.558070","external_id":{"isi":["000596849400001"],"pmid":["33324233"]},"isi":1,"citation":{"short":"R. Rizzo, X. Zhang, J.W.J.L. Wang, F. Lombardi, P.C. Ivanov, Frontiers in Physiology 11 (2020).","mla":"Rizzo, Rossella, et al. “Network Physiology of Cortico–Muscular Interactions.” <i>Frontiers in Physiology</i>, vol. 11, 558070, Frontiers, 2020, doi:<a href=\"https://doi.org/10.3389/fphys.2020.558070\">10.3389/fphys.2020.558070</a>.","ista":"Rizzo R, Zhang X, Wang JWJL, Lombardi F, Ivanov PC. 2020. Network physiology of cortico–muscular interactions. Frontiers in Physiology. 11, 558070.","apa":"Rizzo, R., Zhang, X., Wang, J. W. J. L., Lombardi, F., &#38; Ivanov, P. C. (2020). Network physiology of cortico–muscular interactions. <i>Frontiers in Physiology</i>. Frontiers. <a href=\"https://doi.org/10.3389/fphys.2020.558070\">https://doi.org/10.3389/fphys.2020.558070</a>","ama":"Rizzo R, Zhang X, Wang JWJL, Lombardi F, Ivanov PC. Network physiology of cortico–muscular interactions. <i>Frontiers in Physiology</i>. 2020;11. doi:<a href=\"https://doi.org/10.3389/fphys.2020.558070\">10.3389/fphys.2020.558070</a>","ieee":"R. Rizzo, X. Zhang, J. W. J. L. Wang, F. Lombardi, and P. C. Ivanov, “Network physiology of cortico–muscular interactions,” <i>Frontiers in Physiology</i>, vol. 11. Frontiers, 2020.","chicago":"Rizzo, Rossella, Xiyun Zhang, Jilin W.J.L. Wang, Fabrizio Lombardi, and Plamen Ch Ivanov. “Network Physiology of Cortico–Muscular Interactions.” <i>Frontiers in Physiology</i>. Frontiers, 2020. <a href=\"https://doi.org/10.3389/fphys.2020.558070\">https://doi.org/10.3389/fphys.2020.558070</a>."},"year":"2020","date_updated":"2023-08-24T11:00:45Z","language":[{"iso":"eng"}],"article_number":"558070","month":"11","project":[{"grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"oa_version":"Published Version","has_accepted_license":"1","publication":"Frontiers in Physiology","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","file":[{"file_id":"8961","creator":"dernst","relation":"main_file","access_level":"open_access","success":1,"date_updated":"2020-12-21T10:37:50Z","content_type":"application/pdf","file_name":"2020_Frontiers_Rizzo.pdf","date_created":"2020-12-21T10:37:50Z","checksum":"ef9515b28c5619b7126c0f347958bcb3","file_size":13380030}],"oa":1,"publication_identifier":{"eissn":["1664042X"]},"type":"journal_article","date_published":"2020-11-26T00:00:00Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"}},{"related_material":{"link":[{"url":"https://ist.ac.at/en/news/new-compact-model-for-gene-regulation-in-higher-organisms/","relation":"press_release","description":"News on IST Homepage"}]},"status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"file_id":"9004","creator":"dernst","relation":"main_file","success":1,"access_level":"open_access","date_updated":"2021-01-11T08:37:31Z","file_name":"2020_PNAS_Grah.pdf","content_type":"application/pdf","date_created":"2021-01-11T08:37:31Z","checksum":"69039cd402a571983aa6cb4815ffa863","file_size":1199247}],"type":"journal_article","date_published":"2020-12-15T00:00:00Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"oa":1,"publication_identifier":{"eissn":["10916490"],"issn":["00278424"]},"language":[{"iso":"eng"}],"has_accepted_license":"1","publication":"PNAS","month":"12","project":[{"_id":"2665AAFE-B435-11E9-9278-68D0E5697425","grant_number":"RGP0034/2018","name":"Can evolution minimize spurious signaling crosstalk to reach optimal performance?"},{"_id":"267C84F4-B435-11E9-9278-68D0E5697425","name":"Biophysically realistic genotype-phenotype maps for regulatory networks"}],"oa_version":"Published Version","ddc":["570"],"volume":117,"acknowledgement":"G.T. was supported by Human Frontiers Science Program Grant RGP0034/2018. R.G. was supported by the Austrian Academy of Sciences DOC Fellowship. R.G. thanks S. Avvakumov for helpful discussions.","external_id":{"pmid":["33268497"],"isi":["000600608300015"]},"isi":1,"citation":{"apa":"Grah, R., Zoller, B., &#38; Tkačik, G. (2020). Nonequilibrium models of optimal enhancer function. <i>PNAS</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2006731117\">https://doi.org/10.1073/pnas.2006731117</a>","ama":"Grah R, Zoller B, Tkačik G. Nonequilibrium models of optimal enhancer function. <i>PNAS</i>. 2020;117(50):31614-31622. doi:<a href=\"https://doi.org/10.1073/pnas.2006731117\">10.1073/pnas.2006731117</a>","chicago":"Grah, Rok, Benjamin Zoller, and Gašper Tkačik. “Nonequilibrium Models of Optimal Enhancer Function.” <i>PNAS</i>. National Academy of Sciences, 2020. <a href=\"https://doi.org/10.1073/pnas.2006731117\">https://doi.org/10.1073/pnas.2006731117</a>.","ieee":"R. Grah, B. Zoller, and G. Tkačik, “Nonequilibrium models of optimal enhancer function,” <i>PNAS</i>, vol. 117, no. 50. National Academy of Sciences, pp. 31614–31622, 2020.","mla":"Grah, Rok, et al. “Nonequilibrium Models of Optimal Enhancer Function.” <i>PNAS</i>, vol. 117, no. 50, National Academy of Sciences, 2020, pp. 31614–22, doi:<a href=\"https://doi.org/10.1073/pnas.2006731117\">10.1073/pnas.2006731117</a>.","short":"R. Grah, B. Zoller, G. Tkačik, PNAS 117 (2020) 31614–31622.","ista":"Grah R, Zoller B, Tkačik G. 2020. Nonequilibrium models of optimal enhancer function. PNAS. 117(50), 31614–31622."},"year":"2020","date_updated":"2023-08-24T11:10:22Z","abstract":[{"lang":"eng","text":"In prokaryotes, thermodynamic models of gene regulation provide a highly quantitative mapping from promoter sequences to gene-expression levels that is compatible with in vivo and in vitro biophysical measurements. Such concordance has not been achieved for models of enhancer function in eukaryotes. In equilibrium models, it is difficult to reconcile the reported short transcription factor (TF) residence times on the DNA with the high specificity of regulation. In nonequilibrium models, progress is difficult due to an explosion in the number of parameters. Here, we navigate this complexity by looking for minimal nonequilibrium enhancer models that yield desired regulatory phenotypes: low TF residence time, high specificity, and tunable cooperativity. We find that a single extra parameter, interpretable as the “linking rate,” by which bound TFs interact with Mediator components, enables our models to escape equilibrium bounds and access optimal regulatory phenotypes, while remaining consistent with the reported phenomenology and simple enough to be inferred from upcoming experiments. We further find that high specificity in nonequilibrium models is in a trade-off with gene-expression noise, predicting bursty dynamics—an experimentally observed hallmark of eukaryotic transcription. By drastically reducing the vast parameter space of nonequilibrium enhancer models to a much smaller subspace that optimally realizes biological function, we deliver a rich class of models that could be tractably inferred from data in the near future."}],"day":"15","doi":"10.1073/pnas.2006731117","file_date_updated":"2021-01-11T08:37:31Z","quality_controlled":"1","page":"31614-31622","article_type":"original","publisher":"National Academy of Sciences","issue":"50","author":[{"full_name":"Grah, Rok","orcid":"0000-0003-2539-3560","last_name":"Grah","first_name":"Rok","id":"483E70DE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Benjamin","last_name":"Zoller","full_name":"Zoller, Benjamin"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper"}],"scopus_import":"1","pmid":1,"_id":"9000","intvolume":"       117","title":"Nonequilibrium models of optimal enhancer function","date_created":"2021-01-10T23:01:17Z","department":[{"_id":"GaTk"}],"article_processing_charge":"No","publication_status":"published"},{"file":[{"creator":"rgrah","file_id":"7384","relation":"main_file","access_level":"open_access","file_name":"Scripts.zip","content_type":"application/zip","date_updated":"2020-07-14T12:47:57Z","checksum":"9d292cf5207b3829225f44c044cdb3fd","file_size":73363365,"date_created":"2020-01-28T10:39:40Z"},{"date_created":"2020-01-28T10:39:30Z","checksum":"4076ceab32ef588cc233802bab24c1ab","file_size":962,"date_updated":"2020-07-14T12:47:57Z","content_type":"text/plain","file_name":"READ_ME_MAIN.txt","access_level":"open_access","relation":"main_file","file_id":"7385","creator":"rgrah"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","related_material":{"record":[{"status":"public","id":"7652","relation":"used_in_publication"}]},"status":"public","day":"28","doi":"10.15479/AT:ISTA:7383","oa":1,"abstract":[{"text":"Organisms cope with change by employing transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. We ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. By real-time monitoring of gene copy number mutations in E. coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy number, and hence expression level, polymorphism. This ‘amplification-mediated gene expression tuning’ occurs on timescales similar to canonical gene regulation and can deal with rapid environmental changes. Mathematical modeling shows that amplifications also tune gene expression in stochastic environments where transcription factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune expression of any gene, without leaving any genomic signature.","lang":"eng"}],"citation":{"apa":"Grah, R. (2020). Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:7383\">https://doi.org/10.15479/AT:ISTA:7383</a>","ama":"Grah R. Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7383\">10.15479/AT:ISTA:7383</a>","chicago":"Grah, Rok. “Matlab Scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression Regulation.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:7383\">https://doi.org/10.15479/AT:ISTA:7383</a>.","ieee":"R. Grah, “Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation.” Institute of Science and Technology Austria, 2020.","mla":"Grah, Rok. <i>Matlab Scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression Regulation</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7383\">10.15479/AT:ISTA:7383</a>.","short":"R. Grah, (2020).","ista":"Grah R. 2020. Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:7383\">10.15479/AT:ISTA:7383</a>."},"year":"2020","date_updated":"2024-02-21T12:42:31Z","type":"research_data","date_published":"2020-01-28T00:00:00Z","publisher":"Institute of Science and Technology Austria","keyword":["Matlab scripts","analysis of microfluidics","mathematical model"],"file_date_updated":"2020-07-14T12:47:57Z","contributor":[{"orcid":"0000-0001-6220-2052","first_name":"Calin C","contributor_type":"project_leader","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"date_created":"2020-01-28T10:41:49Z","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"article_processing_charge":"No","oa_version":"Published Version","month":"01","title":"Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation","has_accepted_license":"1","_id":"7383","author":[{"id":"483E70DE-F248-11E8-B48F-1D18A9856A87","first_name":"Rok","last_name":"Grah","orcid":"0000-0003-2539-3560","full_name":"Grah, Rok"}]}]