--- _id: '7490' abstract: - lang: eng text: In plants, clathrin mediated endocytosis (CME) represents the major route for cargo internalisation from the cell surface. It has been assumed to operate in an evolutionary conserved manner as in yeast and animals. Here we report characterisation of ultrastructure, dynamics and mechanisms of plant CME as allowed by our advancement in electron microscopy and quantitative live imaging techniques. Arabidopsis CME appears to follow the constant curvature model and the bona fide CME population generates vesicles of a predominantly hexagonal-basket type; larger and with faster kinetics than in other models. Contrary to the existing paradigm, actin is dispensable for CME events at the plasma membrane but plays a unique role in collecting endocytic vesicles, sorting of internalised cargos and directional endosome movement that itself actively promote CME events. Internalized vesicles display a strongly delayed and sequential uncoating. These unique features highlight the independent evolution of the plant CME mechanism during the autonomous rise of multicellularity in eukaryotes. acknowledged_ssus: - _id: LifeSc - _id: Bio - _id: EM-Fac article_number: e52067 article_processing_charge: No article_type: original author: - first_name: Madhumitha full_name: Narasimhan, Madhumitha id: 44BF24D0-F248-11E8-B48F-1D18A9856A87 last_name: Narasimhan orcid: 0000-0002-8600-0671 - first_name: Alexander J full_name: Johnson, Alexander J id: 46A62C3A-F248-11E8-B48F-1D18A9856A87 last_name: Johnson orcid: 0000-0002-2739-8843 - first_name: Roshan full_name: Prizak, Roshan id: 4456104E-F248-11E8-B48F-1D18A9856A87 last_name: Prizak - first_name: Walter full_name: Kaufmann, Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - first_name: Shutang full_name: Tan, Shutang id: 2DE75584-F248-11E8-B48F-1D18A9856A87 last_name: Tan orcid: 0000-0002-0471-8285 - first_name: Barbara E full_name: Casillas Perez, Barbara E id: 351ED2AA-F248-11E8-B48F-1D18A9856A87 last_name: Casillas Perez - first_name: Jiří full_name: Friml, Jiří id: 4159519E-F248-11E8-B48F-1D18A9856A87 last_name: Friml orcid: 0000-0002-8302-7596 citation: ama: Narasimhan M, Johnson AJ, Prizak R, et al. Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants. eLife. 2020;9. doi:10.7554/eLife.52067 apa: Narasimhan, M., Johnson, A. J., Prizak, R., Kaufmann, W., Tan, S., Casillas Perez, B. E., & Friml, J. (2020). Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.52067 chicago: Narasimhan, Madhumitha, Alexander J Johnson, Roshan Prizak, Walter Kaufmann, Shutang Tan, Barbara E Casillas Perez, and Jiří Friml. “Evolutionarily Unique Mechanistic Framework of Clathrin-Mediated Endocytosis in Plants.” ELife. eLife Sciences Publications, 2020. https://doi.org/10.7554/eLife.52067. ieee: M. Narasimhan et al., “Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants,” eLife, vol. 9. eLife Sciences Publications, 2020. ista: Narasimhan M, Johnson AJ, Prizak R, Kaufmann W, Tan S, Casillas Perez BE, Friml J. 2020. Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants. eLife. 9, e52067. mla: Narasimhan, Madhumitha, et al. “Evolutionarily Unique Mechanistic Framework of Clathrin-Mediated Endocytosis in Plants.” ELife, vol. 9, e52067, eLife Sciences Publications, 2020, doi:10.7554/eLife.52067. short: M. Narasimhan, A.J. Johnson, R. Prizak, W. Kaufmann, S. Tan, B.E. Casillas Perez, J. Friml, ELife 9 (2020). date_created: 2020-02-16T23:00:50Z date_published: 2020-01-23T00:00:00Z date_updated: 2023-08-18T06:33:07Z day: '23' ddc: - '570' - '580' department: - _id: JiFr - _id: GaTk - _id: EM-Fac - _id: SyCr doi: 10.7554/eLife.52067 ec_funded: 1 external_id: isi: - '000514104100001' pmid: - '31971511' file: - access_level: open_access checksum: 2052daa4be5019534f3a42f200a09f32 content_type: application/pdf creator: dernst date_created: 2020-02-18T07:21:16Z date_updated: 2020-07-14T12:47:59Z file_id: '7494' file_name: 2020_eLife_Narasimhan.pdf file_size: 7247468 relation: main_file file_date_updated: 2020-07-14T12:47:59Z has_accepted_license: '1' intvolume: ' 9' isi: 1 language: - iso: eng month: '01' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 261099A6-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '742985' name: Tracing Evolution of Auxin Transport and Polarity in Plants - _id: 26538374-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03630 name: Molecular mechanisms of endocytic cargo recognition in plants publication: eLife publication_identifier: eissn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 9 year: '2020' ... --- _id: '9779' article_processing_charge: No author: - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 - first_name: Tamar full_name: Friedlander, Tamar last_name: Friedlander citation: ama: Grah R, Friedlander T. Distribution of crosstalk values. 2020. doi:10.1371/journal.pcbi.1007642.s003 apa: Grah, R., & Friedlander, T. (2020). Distribution of crosstalk values. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007642.s003 chicago: Grah, Rok, and Tamar Friedlander. “Distribution of Crosstalk Values.” Public Library of Science, 2020. https://doi.org/10.1371/journal.pcbi.1007642.s003. ieee: R. Grah and T. Friedlander, “Distribution of crosstalk values.” Public Library of Science, 2020. ista: Grah R, Friedlander T. 2020. Distribution of crosstalk values, Public Library of Science, 10.1371/journal.pcbi.1007642.s003. mla: Grah, Rok, and Tamar Friedlander. Distribution of Crosstalk Values. Public Library of Science, 2020, doi:10.1371/journal.pcbi.1007642.s003. short: R. Grah, T. Friedlander, (2020). date_created: 2021-08-06T07:24:37Z date_published: 2020-02-25T00:00:00Z date_updated: 2023-08-18T06:47:47Z day: '25' department: - _id: GaTk doi: 10.1371/journal.pcbi.1007642.s003 month: '02' oa_version: Published Version publisher: Public Library of Science related_material: record: - id: '7569' relation: research_data status: public status: public title: Distribution of crosstalk values type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2020' ... --- _id: '9776' article_processing_charge: No author: - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 - first_name: Tamar full_name: Friedlander, Tamar last_name: Friedlander citation: ama: Grah R, Friedlander T. Supporting information. 2020. doi:10.1371/journal.pcbi.1007642.s001 apa: Grah, R., & Friedlander, T. (2020). Supporting information. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007642.s001 chicago: Grah, Rok, and Tamar Friedlander. “Supporting Information.” Public Library of Science, 2020. https://doi.org/10.1371/journal.pcbi.1007642.s001. ieee: R. Grah and T. Friedlander, “Supporting information.” Public Library of Science, 2020. ista: Grah R, Friedlander T. 2020. Supporting information, Public Library of Science, 10.1371/journal.pcbi.1007642.s001. mla: Grah, Rok, and Tamar Friedlander. Supporting Information. Public Library of Science, 2020, doi:10.1371/journal.pcbi.1007642.s001. short: R. Grah, T. Friedlander, (2020). date_created: 2021-08-06T07:15:04Z date_published: 2020-02-25T00:00:00Z date_updated: 2023-08-18T06:47:47Z day: '25' department: - _id: GaTk doi: 10.1371/journal.pcbi.1007642.s001 month: '02' oa_version: Published Version publisher: Public Library of Science related_material: record: - id: '7569' relation: used_in_publication status: public status: public title: Supporting information type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2020' ... --- _id: '7656' abstract: - lang: eng text: 'We propose that correlations among neurons are generically strong enough to organize neural activity patterns into a discrete set of clusters, which can each be viewed as a population codeword. Our reasoning starts with the analysis of retinal ganglion cell data using maximum entropy models, showing that the population is robustly in a frustrated, marginally sub-critical, or glassy, state. This leads to an argument that neural populations in many other brain areas might share this structure. Next, we use latent variable models to show that this glassy state possesses well-defined clusters of neural activity. Clusters have three appealing properties: (i) clusters exhibit error correction, i.e., they are reproducibly elicited by the same stimulus despite variability at the level of constituent neurons; (ii) clusters encode qualitatively different visual features than their constituent neurons; and (iii) clusters can be learned by downstream neural circuits in an unsupervised fashion. We hypothesize that these properties give rise to a “learnable” neural code which the cortical hierarchy uses to extract increasingly complex features without supervision or reinforcement.' article_number: '20' article_processing_charge: No article_type: original author: - first_name: Michael J. full_name: Berry, Michael J. last_name: Berry - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: 'Berry MJ, Tkačik G. Clustering of neural activity: A design principle for population codes. Frontiers in Computational Neuroscience. 2020;14. doi:10.3389/fncom.2020.00020' apa: 'Berry, M. J., & Tkačik, G. (2020). Clustering of neural activity: A design principle for population codes. Frontiers in Computational Neuroscience. Frontiers. https://doi.org/10.3389/fncom.2020.00020' chicago: 'Berry, Michael J., and Gašper Tkačik. “Clustering of Neural Activity: A Design Principle for Population Codes.” Frontiers in Computational Neuroscience. Frontiers, 2020. https://doi.org/10.3389/fncom.2020.00020.' ieee: 'M. J. Berry and G. Tkačik, “Clustering of neural activity: A design principle for population codes,” Frontiers in Computational Neuroscience, vol. 14. Frontiers, 2020.' ista: 'Berry MJ, Tkačik G. 2020. Clustering of neural activity: A design principle for population codes. Frontiers in Computational Neuroscience. 14, 20.' mla: 'Berry, Michael J., and Gašper Tkačik. “Clustering of Neural Activity: A Design Principle for Population Codes.” Frontiers in Computational Neuroscience, vol. 14, 20, Frontiers, 2020, doi:10.3389/fncom.2020.00020.' short: M.J. Berry, G. Tkačik, Frontiers in Computational Neuroscience 14 (2020). date_created: 2020-04-12T22:00:40Z date_published: 2020-03-13T00:00:00Z date_updated: 2023-08-18T10:30:11Z day: '13' ddc: - '570' department: - _id: GaTk doi: 10.3389/fncom.2020.00020 external_id: isi: - '000525543200001' pmid: - '32231528' file: - access_level: open_access checksum: 2b1da23823eae9cedbb42d701945b61e content_type: application/pdf creator: dernst date_created: 2020-04-14T12:20:39Z date_updated: 2020-07-14T12:48:01Z file_id: '7659' file_name: 2020_Frontiers_Berry.pdf file_size: 4082937 relation: main_file file_date_updated: 2020-07-14T12:48:01Z has_accepted_license: '1' intvolume: ' 14' isi: 1 language: - iso: eng month: '03' oa: 1 oa_version: Published Version pmid: 1 publication: Frontiers in Computational Neuroscience publication_identifier: eissn: - '16625188' publication_status: published publisher: Frontiers quality_controlled: '1' scopus_import: '1' status: public title: 'Clustering of neural activity: A design principle for population codes' tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 14 year: '2020' ... --- _id: '8698' 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. 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.). article_processing_charge: No article_type: original author: - first_name: Ori full_name: Maoz, Ori last_name: Maoz - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Mohamad Saleh full_name: Esteki, Mohamad Saleh last_name: Esteki - first_name: Roozbeh full_name: Kiani, Roozbeh last_name: Kiani - first_name: Elad full_name: Schneidman, Elad last_name: Schneidman citation: ama: Maoz O, Tkačik G, Esteki MS, Kiani R, Schneidman E. Learning probabilistic neural representations with randomly connected circuits. Proceedings of the National Academy of Sciences of the United States of America. 2020;117(40):25066-25073. doi:10.1073/pnas.1912804117 apa: Maoz, O., Tkačik, G., Esteki, M. S., 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. National Academy of Sciences. https://doi.org/10.1073/pnas.1912804117 chicago: Maoz, Ori, Gašper Tkačik, Mohamad Saleh Esteki, Roozbeh Kiani, and Elad Schneidman. “Learning Probabilistic Neural Representations with Randomly Connected Circuits.” Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.1912804117. ieee: O. Maoz, G. Tkačik, M. S. Esteki, R. Kiani, and E. Schneidman, “Learning probabilistic neural representations with randomly connected circuits,” Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 40. National Academy of Sciences, pp. 25066–25073, 2020. 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. mla: Maoz, Ori, et al. “Learning Probabilistic Neural Representations with Randomly Connected Circuits.” Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 40, National Academy of Sciences, 2020, pp. 25066–73, doi:10.1073/pnas.1912804117. 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. date_created: 2020-10-25T23:01:16Z date_published: 2020-10-06T00:00:00Z date_updated: 2023-08-22T12:11:23Z day: '06' ddc: - '570' department: - _id: GaTk doi: 10.1073/pnas.1912804117 external_id: isi: - '000579045200012' pmid: - '32948691' file: - access_level: open_access checksum: c6a24fdecf3f28faf447078e7a274a88 content_type: application/pdf creator: cziletti date_created: 2020-10-27T14:57:50Z date_updated: 2020-10-27T14:57:50Z file_id: '8713' file_name: 2020_PNAS_Maoz.pdf file_size: 1755359 relation: main_file success: 1 file_date_updated: 2020-10-27T14:57:50Z has_accepted_license: '1' intvolume: ' 117' isi: 1 issue: '40' language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: 25066-25073 pmid: 1 publication: Proceedings of the National Academy of Sciences of the United States of America publication_identifier: eissn: - '10916490' issn: - '00278424' publication_status: published publisher: National Academy of Sciences quality_controlled: '1' scopus_import: '1' status: public title: Learning probabilistic neural representations with randomly connected circuits tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 117 year: '2020' ... --- _id: '8955' abstract: - lang: eng 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. 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. article_number: '558070' article_processing_charge: No article_type: original author: - first_name: Rossella full_name: Rizzo, Rossella last_name: Rizzo - first_name: Xiyun full_name: Zhang, Xiyun last_name: Zhang - first_name: Jilin W.J.L. full_name: Wang, Jilin W.J.L. last_name: Wang - first_name: Fabrizio full_name: Lombardi, Fabrizio id: A057D288-3E88-11E9-986D-0CF4E5697425 last_name: Lombardi orcid: 0000-0003-2623-5249 - first_name: Plamen Ch full_name: Ivanov, Plamen Ch last_name: Ivanov citation: ama: Rizzo R, Zhang X, Wang JWJL, Lombardi F, Ivanov PC. Network physiology of cortico–muscular interactions. Frontiers in Physiology. 2020;11. doi:10.3389/fphys.2020.558070 apa: Rizzo, R., Zhang, X., Wang, J. W. J. L., Lombardi, F., & Ivanov, P. C. (2020). Network physiology of cortico–muscular interactions. Frontiers in Physiology. Frontiers. https://doi.org/10.3389/fphys.2020.558070 chicago: Rizzo, Rossella, Xiyun Zhang, Jilin W.J.L. Wang, Fabrizio Lombardi, and Plamen Ch Ivanov. “Network Physiology of Cortico–Muscular Interactions.” Frontiers in Physiology. Frontiers, 2020. https://doi.org/10.3389/fphys.2020.558070. ieee: R. Rizzo, X. Zhang, J. W. J. L. Wang, F. Lombardi, and P. C. Ivanov, “Network physiology of cortico–muscular interactions,” Frontiers in Physiology, vol. 11. Frontiers, 2020. ista: Rizzo R, Zhang X, Wang JWJL, Lombardi F, Ivanov PC. 2020. Network physiology of cortico–muscular interactions. Frontiers in Physiology. 11, 558070. mla: Rizzo, Rossella, et al. “Network Physiology of Cortico–Muscular Interactions.” Frontiers in Physiology, vol. 11, 558070, Frontiers, 2020, doi:10.3389/fphys.2020.558070. short: R. Rizzo, X. Zhang, J.W.J.L. Wang, F. Lombardi, P.C. Ivanov, Frontiers in Physiology 11 (2020). date_created: 2020-12-20T23:01:18Z date_published: 2020-11-26T00:00:00Z date_updated: 2023-08-24T11:00:45Z day: '26' ddc: - '570' department: - _id: GaTk doi: 10.3389/fphys.2020.558070 ec_funded: 1 external_id: isi: - '000596849400001' pmid: - '33324233' file: - access_level: open_access checksum: ef9515b28c5619b7126c0f347958bcb3 content_type: application/pdf creator: dernst date_created: 2020-12-21T10:37:50Z date_updated: 2020-12-21T10:37:50Z file_id: '8961' file_name: 2020_Frontiers_Rizzo.pdf file_size: 13380030 relation: main_file success: 1 file_date_updated: 2020-12-21T10:37:50Z has_accepted_license: '1' intvolume: ' 11' isi: 1 language: - iso: eng month: '11' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships publication: Frontiers in Physiology publication_identifier: eissn: - 1664042X publication_status: published publisher: Frontiers quality_controlled: '1' scopus_import: '1' status: public title: Network physiology of cortico–muscular interactions tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 11 year: '2020' ... --- _id: '9000' 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.' 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. article_processing_charge: No article_type: original author: - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 - first_name: Benjamin full_name: Zoller, Benjamin last_name: Zoller - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: Grah R, Zoller B, Tkačik G. Nonequilibrium models of optimal enhancer function. PNAS. 2020;117(50):31614-31622. doi:10.1073/pnas.2006731117 apa: Grah, R., Zoller, B., & Tkačik, G. (2020). Nonequilibrium models of optimal enhancer function. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.2006731117 chicago: Grah, Rok, Benjamin Zoller, and Gašper Tkačik. “Nonequilibrium Models of Optimal Enhancer Function.” PNAS. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.2006731117. ieee: R. Grah, B. Zoller, and G. Tkačik, “Nonequilibrium models of optimal enhancer function,” PNAS, vol. 117, no. 50. National Academy of Sciences, pp. 31614–31622, 2020. ista: Grah R, Zoller B, Tkačik G. 2020. Nonequilibrium models of optimal enhancer function. PNAS. 117(50), 31614–31622. mla: Grah, Rok, et al. “Nonequilibrium Models of Optimal Enhancer Function.” PNAS, vol. 117, no. 50, National Academy of Sciences, 2020, pp. 31614–22, doi:10.1073/pnas.2006731117. short: R. Grah, B. Zoller, G. Tkačik, PNAS 117 (2020) 31614–31622. date_created: 2021-01-10T23:01:17Z date_published: 2020-12-15T00:00:00Z date_updated: 2023-08-24T11:10:22Z day: '15' ddc: - '570' department: - _id: GaTk doi: 10.1073/pnas.2006731117 external_id: isi: - '000600608300015' pmid: - '33268497' file: - access_level: open_access checksum: 69039cd402a571983aa6cb4815ffa863 content_type: application/pdf creator: dernst date_created: 2021-01-11T08:37:31Z date_updated: 2021-01-11T08:37:31Z file_id: '9004' file_name: 2020_PNAS_Grah.pdf file_size: 1199247 relation: main_file success: 1 file_date_updated: 2021-01-11T08:37:31Z has_accepted_license: '1' intvolume: ' 117' isi: 1 issue: '50' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: 31614-31622 pmid: 1 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 publication: PNAS publication_identifier: eissn: - '10916490' issn: - '00278424' publication_status: published publisher: National Academy of Sciences quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/new-compact-model-for-gene-regulation-in-higher-organisms/ scopus_import: '1' status: public title: Nonequilibrium models of optimal enhancer function tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 117 year: '2020' ... --- _id: '8084' 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. article_processing_charge: No article_type: original author: - first_name: Fabrizio full_name: Lombardi, Fabrizio id: A057D288-3E88-11E9-986D-0CF4E5697425 last_name: Lombardi orcid: 0000-0003-2623-5249 - first_name: Manuel full_name: Gómez-Extremera, Manuel last_name: Gómez-Extremera - first_name: Pedro full_name: Bernaola-Galván, Pedro last_name: Bernaola-Galván - first_name: Ramalingam full_name: Vetrivelan, Ramalingam last_name: Vetrivelan - first_name: Clifford B. full_name: Saper, Clifford B. last_name: Saper - first_name: Thomas E. full_name: Scammell, Thomas E. last_name: Scammell - first_name: Plamen Ch. full_name: Ivanov, Plamen Ch. last_name: Ivanov citation: 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. Journal of Neuroscience. 2020;40(1):171-190. doi:10.1523/jneurosci.1278-19.2019 apa: Lombardi, F., Gómez-Extremera, M., Bernaola-Galván, P., Vetrivelan, R., Saper, C. B., Scammell, T. E., & 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. Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/jneurosci.1278-19.2019 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.” Journal of Neuroscience. Society for Neuroscience, 2020. https://doi.org/10.1523/jneurosci.1278-19.2019. ieee: F. Lombardi 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,” Journal of Neuroscience, vol. 40, no. 1. Society for Neuroscience, pp. 171–190, 2020. 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. 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.” Journal of Neuroscience, vol. 40, no. 1, Society for Neuroscience, 2020, pp. 171–90, doi:10.1523/jneurosci.1278-19.2019. 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. date_created: 2020-07-05T15:24:51Z date_published: 2020-01-02T00:00:00Z date_updated: 2023-09-05T14:02:55Z day: '02' ddc: - '570' department: - _id: GaTk doi: 10.1523/jneurosci.1278-19.2019 ec_funded: 1 external_id: isi: - '000505167600016' pmid: - '31694962' file: - access_level: open_access content_type: application/pdf creator: dernst date_created: 2020-07-22T11:44:48Z date_updated: 2020-07-22T11:44:48Z file_id: '8150' file_name: 2020_JournNeuroscience_Lombardi.pdf file_size: 6646046 relation: main_file success: 1 file_date_updated: 2020-07-22T11:44:48Z has_accepted_license: '1' intvolume: ' 40' isi: 1 issue: '1' language: - iso: eng month: '01' oa: 1 oa_version: Published Version page: 171-190 pmid: 1 project: - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships publication: Journal of Neuroscience publication_identifier: eissn: - 1529-2401 issn: - 0270-6474 publication_status: published publisher: Society for Neuroscience quality_controlled: '1' scopus_import: '1' status: public 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 type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 40 year: '2020' ... --- _id: '8155' 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. " acknowledgement: For the duration of his PhD, Rok was a recipient of a DOC fellowship of the Austrian Academy of Sciences. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 citation: ama: Grah R. Gene regulation across scales – how biophysical constraints shape evolution. 2020. doi:10.15479/AT:ISTA:8155 apa: Grah, R. (2020). Gene regulation across scales – how biophysical constraints shape evolution. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8155 chicago: Grah, Rok. “Gene Regulation across Scales – How Biophysical Constraints Shape Evolution.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8155. ieee: 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. mla: Grah, Rok. Gene Regulation across Scales – How Biophysical Constraints Shape Evolution. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8155. short: R. Grah, Gene Regulation across Scales – How Biophysical Constraints Shape Evolution, Institute of Science and Technology Austria, 2020. date_created: 2020-07-23T09:51:28Z date_published: 2020-07-24T00:00:00Z date_updated: 2023-09-07T13:13:27Z day: '24' ddc: - '530' - '570' degree_awarded: PhD department: - _id: CaGu - _id: GaTk doi: 10.15479/AT:ISTA:8155 file: - access_level: open_access content_type: application/pdf creator: rgrah date_created: 2020-07-27T12:00:07Z date_updated: 2020-07-27T12:00:07Z file_id: '8176' file_name: Thesis_RokGrah_200727_convertedNew.pdf file_size: 16638998 relation: main_file success: 1 - access_level: closed content_type: application/zip creator: rgrah date_created: 2020-07-27T12:02:23Z date_updated: 2020-07-30T13:04:55Z file_id: '8177' file_name: Thesis_new.zip file_size: 347459978 relation: main_file file_date_updated: 2020-07-30T13:04:55Z has_accepted_license: '1' language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: '310' project: - _id: 267C84F4-B435-11E9-9278-68D0E5697425 name: Biophysically realistic genotype-phenotype maps for regulatory networks publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7675' relation: part_of_dissertation status: public - id: '7569' relation: part_of_dissertation status: public - id: '7652' relation: part_of_dissertation status: public status: public supervisor: - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 title: Gene regulation across scales – how biophysical constraints shape evolution type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _id: '7675' 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 bio-physical 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 non-equilibrium models, progress is difficult due to an explosion in the number of parameters. Here, we navigate this complexity by looking for minimal non-equilibrium 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 non-equilibrium models is in a tradeoff with gene expression noise, predicting bursty dynamics — an experimentally-observed hallmark of eukaryotic transcription. By drastically reducing the vast parameter space to a much smaller subspace that optimally realizes biological function prior to inference from data, our normative approach holds promise for mathematical models in systems biology.' article_processing_charge: No author: - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 - first_name: Benjamin full_name: Zoller, Benjamin last_name: Zoller - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: Grah R, Zoller B, Tkačik G. Normative models of enhancer function. bioRxiv. 2020. doi:10.1101/2020.04.08.029405 apa: Grah, R., Zoller, B., & Tkačik, G. (2020). Normative models of enhancer function. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.04.08.029405 chicago: Grah, Rok, Benjamin Zoller, and Gašper Tkačik. “Normative Models of Enhancer Function.” BioRxiv. Cold Spring Harbor Laboratory, 2020. https://doi.org/10.1101/2020.04.08.029405. ieee: R. Grah, B. Zoller, and G. Tkačik, “Normative models of enhancer function,” bioRxiv. Cold Spring Harbor Laboratory, 2020. ista: Grah R, Zoller B, Tkačik G. 2020. Normative models of enhancer function. bioRxiv, 10.1101/2020.04.08.029405. mla: Grah, Rok, et al. “Normative Models of Enhancer Function.” BioRxiv, Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.04.08.029405. short: R. Grah, B. Zoller, G. Tkačik, BioRxiv (2020). date_created: 2020-04-23T10:12:51Z date_published: 2020-04-09T00:00:00Z date_updated: 2023-09-07T13:13:26Z day: '09' department: - _id: CaGu - _id: GaTk doi: 10.1101/2020.04.08.029405 language: - iso: eng main_file_link: - open_access: '1' url: 'https://doi.org/10.1101/2020.04.08.029405 ' month: '04' oa: 1 oa_version: Preprint 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 publication: bioRxiv publication_status: published publisher: Cold Spring Harbor Laboratory related_material: record: - id: '8155' relation: dissertation_contains status: public status: public title: Normative models of enhancer function type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ...