[{"issue":"28","OA_place":"publisher","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","citation":{"short":"B. Zoller, A. Benichou, T. Gregor, G. Tkačik, Proceedings of the National Academy of Sciences of the United States of America 123 (2026).","ista":"Zoller B, Benichou A, Gregor T, Tkačik G. 2026. Invariant nonequilibrium dynamics in gene regulation optimize information flow. Proceedings of the National Academy of Sciences of the United States of America. 123(28), e2524855123.","chicago":"Zoller, Benjamin, Alexis Benichou, Thomas Gregor, and Gašper Tkačik. “Invariant Nonequilibrium Dynamics in Gene Regulation Optimize Information Flow.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences, 2026. <a href=\"https://doi.org/10.1073/pnas.2524855123\">https://doi.org/10.1073/pnas.2524855123</a>.","ieee":"B. Zoller, A. Benichou, T. Gregor, and G. Tkačik, “Invariant nonequilibrium dynamics in gene regulation optimize information flow,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 123, no. 28. National Academy of Sciences, 2026.","ama":"Zoller B, Benichou A, Gregor T, Tkačik G. Invariant nonequilibrium dynamics in gene regulation optimize information flow. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2026;123(28). doi:<a href=\"https://doi.org/10.1073/pnas.2524855123\">10.1073/pnas.2524855123</a>","mla":"Zoller, Benjamin, et al. “Invariant Nonequilibrium Dynamics in Gene Regulation Optimize Information Flow.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 123, no. 28, e2524855123, National Academy of Sciences, 2026, doi:<a href=\"https://doi.org/10.1073/pnas.2524855123\">10.1073/pnas.2524855123</a>.","apa":"Zoller, B., Benichou, A., Gregor, T., &#38; Tkačik, G. (2026). Invariant nonequilibrium dynamics in gene regulation optimize information flow. <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.2524855123\">https://doi.org/10.1073/pnas.2524855123</a>"},"supplementarymaterial":"yes","author":[{"full_name":"Zoller, Benjamin","first_name":"Benjamin","last_name":"Zoller"},{"last_name":"Benichou","full_name":"Benichou, Alexis","id":"3a67230c-5fc0-11ef-a673-de9a2ffadafe","first_name":"Alexis"},{"first_name":"Thomas","full_name":"Gregor, Thomas","last_name":"Gregor"},{"orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper","last_name":"Tkačik"}],"date_updated":"2026-08-04T09:21:10Z","das_tickbox":"1","month":"07","related_material":{"link":[{"url":"https://ista.ac.at/en/news/the-art-of-proper-flickering/","description":"News on ISTA website","relation":"press_release"}]},"date_published":"2026-07-14T00:00:00Z","ddc":["570"],"article_type":"original","dataavailabilitystatement":"Software code data have been deposited in Institute Pasteur GitHub (https://gitlab.pasteur.fr/tglab/invariantpromoterdynamicspaper) (51).","corr_author":"1","external_id":{"pmid":["42406962"]},"acknowledgement":"This work was supported by the French NationalResearch Agency (ANR-20-CE12-0028 “ChroDynE” and ANR-23-CE13-0021“GastruCyp” and ANR-10 LABX-73 “Revive;” all T.G.), and by funding from theEuropean Research Council (ERC-2023-SyG, “Dynatrans,” 101118866, T.G. andG.T.). This work was also supported in part by the U.S. NSF, through the Centerfor the Physics of Biological Function (PHY-1734030, T.G.), and by NIH GrantsR01GM097275, U01DA047730, and U01DK127429 (T.G.)","file_date_updated":"2026-07-20T13:12:47Z","department":[{"_id":"GaTk"}],"title":"Invariant nonequilibrium dynamics in gene regulation optimize information flow","article_processing_charge":"Yes","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"scopus_import":"1","date_created":"2026-07-19T22:01:46Z","language":[{"iso":"eng"}],"quality_controlled":"1","file":[{"creator":"dernst","date_updated":"2026-07-20T13:12:47Z","relation":"main_file","checksum":"f4d82dd706ff1629db68d71190288350","success":1,"content_type":"application/pdf","file_id":"22376","date_created":"2026-07-20T13:12:47Z","file_name":"2026_PNAS_Zoller.pdf","file_size":24580098,"access_level":"open_access"}],"oa":1,"volume":123,"doi":"10.1073/pnas.2524855123","abstract":[{"lang":"eng","text":"Eukaryotic gene regulation relies on stochastic yet controlled promoter switching, in which genes transition between transcriptionally active and inactive states. Despite the molecular complexity of this process, recent studies have revealed a surprising invariance of the “switching correlation time” (TC)—the characteristic decay time of the autocorrelation function of promoter activity fluctuations—across gene expression levels in multiple genes and organisms. A biophysically plausible explanation for this invariance has so far been lacking. Here, we show that this empirical constraint imposes stringent requirements on minimal yet realistic models of transcriptional regulation. Specifically, reproducing TC–invariance requires regulatory architectures with at least four internal states and nonequilibrium dynamics that break detailed balance. Using Bayesian inference on Drosophila gap gene expression data, we demonstrate that such models i) quantitatively reproduce the observed TC–invariance, ii) remain robust to parameter perturbations, and iii) maximize information transmission from transcription factor concentration to gene expression. Remarkably, the TC-invariant modulation strategy we identify as optimal closely parallels contemporary control-theoretic results on the modulation of stochastic switching systems. Taken together, our results suggest that eukaryotic transcriptional regulation operates in a nonequilibrium regime to balance precision, reaction-rate limitations, and energy dissipation, thereby achieving near-optimal information transmission under fundamental physical constraints."}],"project":[{"grant_number":"101118866","name":"Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryos","_id":"7bfe6a29-9f16-11ee-852c-c0da5e2045d9"}],"_id":"22363","tmp":{"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","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"publication_status":"published","publication":"Proceedings of the National Academy of Sciences of the United States of America","intvolume":"       123","article_number":"e2524855123","fulldoi":"https://doi.org/10.1073/pnas.2524855123","OA_type":"hybrid","status":"public","type":"journal_article","year":"2026","oa_version":"Published Version","publisher":"National Academy of Sciences","researchdata_availability":"yes","day":"14","pmid":1,"has_accepted_license":"1","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd"},{"tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"_id":"22733","publication_status":"published","publication":"Proceedings of the National Academy of Sciences","abstract":[{"lang":"eng","text":"Sleep need is associated with both circuit dynamics and widespread synaptic plasticity, yet the specific synaptic changes underlying sleep homeostasis remain incompletely understood. In Drosophila, sleep loss has been shown to trigger plasticity of the presynaptic active zone, marked by increasing levels of the ELKS-family scaffold protein Bruchpilot (BRP). By titrating brp gene copy number, we previously established a presynapse-specific, dosage-dependent paradigm that modulates sleep pressure. Here, to elucidate the molecular landscape of this plasticity, we performed synapse-enriched integrated-omics. Proteomic and bioinformatic analyses revealed changes in immune and stress response pathways and local translation control. Strikingly, phospho-proteomic analysis uncovered a global shift toward hypophosphorylation, particularly in presynaptic proteins, indicating a reprogramming of the phosphorylation–dephosphorylation balance. This presynaptic hypophosphorylation is likely contributed by reduced activity of Protein Kinase A (PKA) and enhanced substrate affinity of Protein Phosphatase 1 (PP1) mediated by its regulatory subunit Spinophilin (Spn). Manipulating either PKA or PP1 activity was sufficient to suppress BRP-modulated sleep phenotypes. We propose that presynaptic hypophosphorylation constitutes a molecular signature of local synaptic remodeling that adaptively tunes sleep need via reversible posttranslational modification, a mechanism likely conserved across species."}],"doi":"10.1073/pnas.2524065123","volume":123,"quality_controlled":"1","file":[{"creator":"dernst","date_updated":"2026-08-20T05:34:25Z","checksum":"3727c5ad18c1e9c65672fbb01ac6ea04","relation":"main_file","content_type":"application/pdf","file_id":"22737","success":1,"date_created":"2026-08-20T05:34:25Z","file_name":"2026_PNAS_Piao.pdf","access_level":"open_access","file_size":3915000}],"oa":1,"pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","article_number":"e2524065123","fulldoi":"https://doi.org/10.1073/pnas.2524065123","OA_type":"hybrid","status":"public","intvolume":"       123","day":"16","year":"2026","type":"journal_article","publisher":"National Academy of Sciences","oa_version":"Published Version","month":"06","PlanS_conform":"1","date_published":"2026-06-16T00:00:00Z","ddc":["570"],"citation":{"chicago":"Piao, Chengji, Ewelina Dutkiewicz, Laxmikanth Kollipara, Albert Sickmann, Sheng Huang, and Stephan J. Sigrist. “Active Zone Plasticity Couples Sleep Need to Presynaptic Hypophosphorylation.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2026. <a href=\"https://doi.org/10.1073/pnas.2524065123\">https://doi.org/10.1073/pnas.2524065123</a>.","ista":"Piao C, Dutkiewicz E, Kollipara L, Sickmann A, Huang S, Sigrist SJ. 2026. Active zone plasticity couples sleep need to presynaptic hypophosphorylation. Proceedings of the National Academy of Sciences. 123(24), e2524065123.","ieee":"C. Piao, E. Dutkiewicz, L. Kollipara, A. Sickmann, S. Huang, and S. J. Sigrist, “Active zone plasticity couples sleep need to presynaptic hypophosphorylation,” <i>Proceedings of the National Academy of Sciences</i>, vol. 123, no. 24. National Academy of Sciences, 2026.","short":"C. Piao, E. Dutkiewicz, L. Kollipara, A. Sickmann, S. Huang, S.J. Sigrist, Proceedings of the National Academy of Sciences 123 (2026).","apa":"Piao, C., Dutkiewicz, E., Kollipara, L., Sickmann, A., Huang, S., &#38; Sigrist, S. J. (2026). Active zone plasticity couples sleep need to presynaptic hypophosphorylation. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2524065123\">https://doi.org/10.1073/pnas.2524065123</a>","ama":"Piao C, Dutkiewicz E, Kollipara L, Sickmann A, Huang S, Sigrist SJ. Active zone plasticity couples sleep need to presynaptic hypophosphorylation. <i>Proceedings of the National Academy of Sciences</i>. 2026;123(24). doi:<a href=\"https://doi.org/10.1073/pnas.2524065123\">10.1073/pnas.2524065123</a>","mla":"Piao, Chengji, et al. “Active Zone Plasticity Couples Sleep Need to Presynaptic Hypophosphorylation.” <i>Proceedings of the National Academy of Sciences</i>, vol. 123, no. 24, e2524065123, National Academy of Sciences, 2026, doi:<a href=\"https://doi.org/10.1073/pnas.2524065123\">10.1073/pnas.2524065123</a>."},"OA_place":"publisher","issue":"24","date_updated":"2026-08-20T05:35:33Z","author":[{"first_name":"Chengji","full_name":"Piao, Chengji","last_name":"Piao"},{"first_name":"Ewelina","full_name":"Dutkiewicz, Ewelina","id":"0601cc46-c082-11ec-9b07-bb29641d1de9","last_name":"Dutkiewicz"},{"last_name":"Kollipara","first_name":"Laxmikanth","full_name":"Kollipara, Laxmikanth"},{"last_name":"Sickmann","first_name":"Albert","full_name":"Sickmann, Albert"},{"last_name":"Huang","full_name":"Huang, Sheng","first_name":"Sheng"},{"full_name":"Sigrist, Stephan J.","first_name":"Stephan J.","last_name":"Sigrist"}],"publication_identifier":{"issn":["0027-8424","1091-6490"]},"scopus_import":"1","file_date_updated":"2026-08-20T05:34:25Z","title":"Active zone plasticity couples sleep need to presynaptic hypophosphorylation","article_processing_charge":"Yes (in subscription journal)","date_created":"2026-08-18T10:46:33Z","language":[{"iso":"eng"}],"extern":"1","article_type":"original","external_id":{"pmid":["42258713"]}},{"volume":122,"quality_controlled":"1","file":[{"date_updated":"2025-01-20T10:10:04Z","relation":"main_file","checksum":"8dbfc7d495413340225ebfae69b0cf9a","creator":"dernst","success":1,"content_type":"application/pdf","file_id":"18862","date_created":"2025-01-20T10:10:04Z","access_level":"open_access","file_size":19073585,"file_name":"2025_PNAS_Sokolowski.pdf"}],"oa":1,"tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"publication_status":"published","_id":"18849","publication":"Proceedings of the National Academy of Sciences","doi":"10.1073/pnas.2402925121","abstract":[{"text":"Many biological systems operate near the physical limits to their performance, suggesting that aspects of their behavior and underlying mechanisms could be derived from optimization principles. However, such principles have often been applied only in simplified models. Here, we explore a detailed mechanistic model of the gap gene network in the Drosophila embryo, optimizing its 50+ parameters to maximize the information that gene expression levels provide about nuclear positions. This optimization is conducted under realistic constraints, such as limits on the number of available molecules. Remarkably, the optimal networks we derive closely match the architecture and spatial gene expression profiles observed in the real organism. Our framework quantifies the tradeoffs involved in maximizing functional performance and allows for the exploration of alternative network configurations, addressing the question of which features are necessary and which are contingent. Our results suggest that multiple solutions to the optimization problem might exist across closely related organisms, offering insights into the evolution of gene regulatory networks.","lang":"eng"}],"project":[{"_id":"254E9036-B435-11E9-9278-68D0E5697425","name":"Biophysics of information processing in gene regulation","grant_number":"P28844-B27","call_identifier":"FWF"},{"_id":"7bfe6a29-9f16-11ee-852c-c0da5e2045d9","grant_number":"101118866","name":"Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryos"},{"_id":"2665AAFE-B435-11E9-9278-68D0E5697425","name":"Can evolution minimize spurious signaling crosstalk to reach optimal performance?","grant_number":"RGP0034/2018"}],"fulldoi":"https://doi.org/10.1073/pnas.2402925121","article_number":"e2402925121","OA_type":"hybrid","status":"public","intvolume":"       122","day":"07","type":"journal_article","year":"2025","oa_version":"Published Version","publisher":"National Academy of Sciences","isi":1,"pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","citation":{"ieee":"T. R. Sokolowski, T. Gregor, W. Bialek, and G. Tkačik, “Deriving a genetic regulatory network from an optimization principle,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 1. National Academy of Sciences, 2025.","ista":"Sokolowski TR, Gregor T, Bialek W, Tkačik G. 2025. Deriving a genetic regulatory network from an optimization principle. Proceedings of the National Academy of Sciences. 122(1), e2402925121.","chicago":"Sokolowski, Thomas R, Thomas Gregor, William Bialek, and Gašper Tkačik. “Deriving a Genetic Regulatory Network from an Optimization Principle.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2402925121\">https://doi.org/10.1073/pnas.2402925121</a>.","short":"T.R. Sokolowski, T. Gregor, W. Bialek, G. Tkačik, Proceedings of the National Academy of Sciences 122 (2025).","apa":"Sokolowski, T. R., Gregor, T., Bialek, W., &#38; Tkačik, G. (2025). Deriving a genetic regulatory network from an optimization principle. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2402925121\">https://doi.org/10.1073/pnas.2402925121</a>","ama":"Sokolowski TR, Gregor T, Bialek W, Tkačik G. Deriving a genetic regulatory network from an optimization principle. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(1). doi:<a href=\"https://doi.org/10.1073/pnas.2402925121\">10.1073/pnas.2402925121</a>","mla":"Sokolowski, Thomas R., et al. “Deriving a Genetic Regulatory Network from an Optimization Principle.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 1, e2402925121, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2402925121\">10.1073/pnas.2402925121</a>."},"OA_place":"publisher","issue":"1","date_updated":"2026-02-16T12:26:51Z","author":[{"last_name":"Sokolowski","first_name":"Thomas R","full_name":"Sokolowski, Thomas R","id":"3E999752-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1287-3779"},{"last_name":"Gregor","first_name":"Thomas","full_name":"Gregor, Thomas"},{"first_name":"William","full_name":"Bialek, William","last_name":"Bialek"},{"last_name":"Tkačik","orcid":"0000-0002-6699-1455","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper"}],"month":"01","date_published":"2025-01-07T00:00:00Z","ddc":["570"],"article_type":"original","acknowledgement":"We thank Nicholas H. Barton for his comments on the manuscript, Benjamin Zoller for helpful discussions, and Aleksandra Walczak and Curtis Callan for early collaborations that shaped this work. Special thanks to Eric F. Wieschaus for many persistently inspiring conversations. This work was supported in part by the Human Frontiers Science Program; the Austrian Science Fund (FWF P28844); by the European Research Council grant DynaTrans (101118866); by U.S. NSF, through the Center for the Physics of Biological Function (PHY–1734030); by NIH Grants R01GM097275, U01DA047730, and U01DK127429; by the John Simon Guggenheim Memorial Foundation; and by the LOEWE priority program “Center for Multiscale Modeling in Life Sciences” (CMMS), sponsored by the Hessian Ministry for Science and Research, Arts and Culture (HMWK).","external_id":{"isi":["001392772400001"],"pmid":["39752518"]},"corr_author":"1","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"scopus_import":"1","department":[{"_id":"GaTk"}],"file_date_updated":"2025-01-20T10:10:04Z","title":"Deriving a genetic regulatory network from an optimization principle","article_processing_charge":"Yes (in subscription journal)","date_created":"2025-01-19T23:01:50Z","language":[{"iso":"eng"}]},{"publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"scopus_import":"1","file_date_updated":"2025-01-20T09:38:32Z","department":[{"_id":"GaTk"}],"article_processing_charge":"No","title":"Chromatin enables precise and scalable gene regulation with factors of limited specificity","date_created":"2025-01-19T23:01:51Z","language":[{"iso":"eng"}],"article_type":"original","acknowledgement":"M.L.P. was supported by the European Molecular Biology Laboratory (EMBL) Interdisciplinary Postdoc Programme (EIPOD4 fellowships), cofunded by Marie SkÅ‚odowska-Curie Actions (Grant Agreement No. 847543). J.C. and M.L.P. were supported by EMBL Core Funding and Theory@EMBL. This work is supported by European Research Council Grant DynaTrans (101118866) to G.T. We would like to thank the members of the J.C. and G.T. groups, especially Natalia Misunou, Michal Hledík, and Réka Borbély, for helpful feedback and discussion. We also thank EMBL IT Services for the use of high performance computing resources.","external_id":{"isi":["001392765300001"],"pmid":["39793086"]},"corr_author":"1","related_material":{"link":[{"url":"https://github.com/officerredshirt/network_crosstalk","relation":"software"}]},"month":"01","date_published":"2025-01-07T00:00:00Z","ddc":["570"],"citation":{"mla":"Perkins, Mindy Liu, et al. “Chromatin Enables Precise and Scalable Gene Regulation with Factors of Limited Specificity.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 1, e2411887121, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2411887121\">10.1073/pnas.2411887121</a>.","ama":"Perkins ML, Crocker J, Tkačik G. Chromatin enables precise and scalable gene regulation with factors of limited specificity. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(1). doi:<a href=\"https://doi.org/10.1073/pnas.2411887121\">10.1073/pnas.2411887121</a>","apa":"Perkins, M. L., Crocker, J., &#38; Tkačik, G. (2025). Chromatin enables precise and scalable gene regulation with factors of limited specificity. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2411887121\">https://doi.org/10.1073/pnas.2411887121</a>","short":"M.L. Perkins, J. Crocker, G. Tkačik, Proceedings of the National Academy of Sciences 122 (2025).","ista":"Perkins ML, Crocker J, Tkačik G. 2025. Chromatin enables precise and scalable gene regulation with factors of limited specificity. Proceedings of the National Academy of Sciences. 122(1), e2411887121.","chicago":"Perkins, Mindy Liu, Justin Crocker, and Gašper Tkačik. “Chromatin Enables Precise and Scalable Gene Regulation with Factors of Limited Specificity.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2411887121\">https://doi.org/10.1073/pnas.2411887121</a>.","ieee":"M. L. Perkins, J. Crocker, and G. Tkačik, “Chromatin enables precise and scalable gene regulation with factors of limited specificity,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 1. National Academy of Sciences, 2025."},"OA_place":"publisher","issue":"1","APC_amount":"3261,23 EUR","date_updated":"2026-05-06T12:43:59Z","author":[{"full_name":"Perkins, Mindy Liu","first_name":"Mindy Liu","last_name":"Perkins"},{"first_name":"Justin","full_name":"Crocker, Justin","last_name":"Crocker"},{"orcid":"0000-0002-6699-1455","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","last_name":"Tkačik"}],"isi":1,"pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","fulldoi":"https://doi.org/10.1073/pnas.2411887121","article_number":"e2411887121","OA_type":"hybrid","status":"public","intvolume":"       122","day":"07","type":"journal_article","year":"2025","oa_version":"Published Version","publisher":"National Academy of Sciences","tmp":{"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","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"_id":"18850","publication_status":"published","publication":"Proceedings of the National Academy of Sciences","doi":"10.1073/pnas.2411887121","abstract":[{"lang":"eng","text":"Biophysical constraints limit the specificity with which transcription factors (TFs) can target regulatory DNA. While individual nontarget binding events may be low affinity, the sheer number of such interactions could present a challenge for gene regulation by degrading its precision or possibly leading to an erroneous induction state. Chromatin can prevent nontarget binding by rendering DNA physically inaccessible to TFs, at the cost of energy-consuming remodeling orchestrated by pioneer factors (PFs). Under what conditions and by how much can chromatin reduce regulatory errors on a global scale? We use a theoretical approach to compare two scenarios for gene regulation: one that relies on TF binding to free DNA alone and one that uses a combination of TFs and chromatin-regulating PFs to achieve desired gene expression patterns. We find, first, that chromatin effectively silences groups of genes that should be simultaneously OFF, thereby allowing more accurate graded control of expression for the remaining ON genes. Second, chromatin buffers the deleterious consequences of nontarget binding as the number of OFF genes grows, permitting a substantial expansion in regulatory complexity. Third, chromatin-based regulation productively co-opts nontarget TF binding for ON genes in order to establish a “leaky” baseline expression level, which targeted activator or repressor binding subsequently up- or down-modulates. Thus, on a global scale, using chromatin simultaneously alleviates pressure for high specificity of regulatory interactions and enables an increase in genome size with minimal impact on global expression error."}],"project":[{"name":"Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryos","grant_number":"101118866","_id":"7bfe6a29-9f16-11ee-852c-c0da5e2045d9"}],"volume":122,"quality_controlled":"1","file":[{"file_size":30943709,"access_level":"open_access","file_name":"2025_PNAS_Perkins.pdf","date_created":"2025-01-20T09:38:32Z","file_id":"18859","content_type":"application/pdf","success":1,"relation":"main_file","date_updated":"2025-01-20T09:38:32Z","checksum":"86a8d25a6e282aeb4128f1d0b86ff911","creator":"dernst"}],"oa":1},{"acknowledgement":"We thank all members of the Letzkus lab, the Sprekeler lab, and the Vogels lab for discussions, U. Thirimanna for technical assistance, and K. Deisseroth for generously sharing reagents. This work was supported by the German Research Foundation (LE 3804/3-1, LE 3804/4-1, LE 3804/7-1, CRC-TRR 384/1 2024, - 514483642, and 460088091) and the Wellcome Trust Senior Research Fellowship 214316/Z/18/Z.\r\nElectrophysiological recordings, source code for simulations, and data analysis have been deposited in GitHub (https://github.com/LNaumann/NDNF_control_inhibition_Naumann25) (62).","external_id":{"isi":["001422380500004"],"pmid":["39841147"]},"article_type":"original","language":[{"iso":"eng"}],"date_created":"2025-02-17T09:20:19Z","title":"Layer-specific control of inhibition by NDNF interneurons","article_processing_charge":"Yes (in subscription journal)","file_date_updated":"2025-02-17T14:46:18Z","department":[{"_id":"TiVo"}],"scopus_import":"1","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"author":[{"first_name":"Laura B","full_name":"Naumann, Laura B","id":"81a3b706-8972-11ed-ae7b-8eff728700ca","last_name":"Naumann"},{"first_name":"Loreen","full_name":"Hertäg, Loreen","last_name":"Hertäg"},{"first_name":"Jennifer","full_name":"Müller, Jennifer","last_name":"Müller"},{"last_name":"Letzkus","first_name":"Johannes J.","full_name":"Letzkus, Johannes J."},{"full_name":"Sprekeler, Henning","first_name":"Henning","last_name":"Sprekeler"}],"date_updated":"2026-02-16T12:28:02Z","issue":"4","OA_place":"publisher","citation":{"mla":"Naumann, Laura B., et al. “Layer-Specific Control of Inhibition by NDNF Interneurons.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 4, e2408966122, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2408966122\">10.1073/pnas.2408966122</a>.","ama":"Naumann LB, Hertäg L, Müller J, Letzkus JJ, Sprekeler H. Layer-specific control of inhibition by NDNF interneurons. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(4). doi:<a href=\"https://doi.org/10.1073/pnas.2408966122\">10.1073/pnas.2408966122</a>","apa":"Naumann, L. B., Hertäg, L., Müller, J., Letzkus, J. J., &#38; Sprekeler, H. (2025). Layer-specific control of inhibition by NDNF interneurons. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2408966122\">https://doi.org/10.1073/pnas.2408966122</a>","short":"L.B. Naumann, L. Hertäg, J. Müller, J.J. Letzkus, H. Sprekeler, Proceedings of the National Academy of Sciences 122 (2025).","ieee":"L. B. Naumann, L. Hertäg, J. Müller, J. J. Letzkus, and H. Sprekeler, “Layer-specific control of inhibition by NDNF interneurons,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 4. National Academy of Sciences, 2025.","ista":"Naumann LB, Hertäg L, Müller J, Letzkus JJ, Sprekeler H. 2025. Layer-specific control of inhibition by NDNF interneurons. Proceedings of the National Academy of Sciences. 122(4), e2408966122.","chicago":"Naumann, Laura B, Loreen Hertäg, Jennifer Müller, Johannes J. Letzkus, and Henning Sprekeler. “Layer-Specific Control of Inhibition by NDNF Interneurons.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2408966122\">https://doi.org/10.1073/pnas.2408966122</a>."},"ddc":["570"],"date_published":"2025-01-22T00:00:00Z","related_material":{"link":[{"relation":"software","url":"https://github.com/LNaumann/NDNF_control_inhibition_Naumann25"}]},"month":"01","oa_version":"Published Version","publisher":"National Academy of Sciences","year":"2025","type":"journal_article","day":"22","intvolume":"       122","status":"public","OA_type":"hybrid","fulldoi":"https://doi.org/10.1073/pnas.2408966122","article_number":"e2408966122","has_accepted_license":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"isi":1,"oa":1,"quality_controlled":"1","file":[{"success":1,"content_type":"application/pdf","file_id":"19046","relation":"main_file","date_updated":"2025-02-17T14:46:18Z","checksum":"636d5130724e3236ebf4fc658b3945fe","creator":"dernst","access_level":"open_access","file_size":13726531,"file_name":"2025_PNAS_Naumann.pdf","date_created":"2025-02-17T14:46:18Z"}],"volume":122,"abstract":[{"lang":"eng","text":"Neuronal processing of external sensory input is shaped by internally generated top–down information. In the neocortex, top–down projections primarily target layer 1, which contains NDNF (neuron-derived neurotrophic factor)-expressing interneurons and the dendrites of pyramidal cells. Here, we investigate the hypothesis that NDNF interneurons shape cortical computations in an unconventional, layer-specific way, by exerting presynaptic inhibition on synapses in layer 1 while leaving synapses in deeper layers unaffected. We first confirm experimentally that in the auditory cortex, synapses from somatostatin-expressing (SOM) onto NDNF neurons are indeed modulated by ambient Gamma-aminobutyric acid (GABA). Shifting to a computational model, we then show that this mechanism introduces a distinct mutual inhibition motif between NDNF interneurons and the synaptic outputs of SOM interneurons. This motif can control inhibition in a layer-specific way and introduces competition between NDNF and SOM interneurons for dendritic inhibition onto pyramidal cells on different timescales. NDNF interneurons can thereby control cortical information flow by redistributing dendritic inhibition from fast to slow timescales and by gating different sources of dendritic inhibition."}],"doi":"10.1073/pnas.2408966122","tmp":{"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","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"_id":"19036","publication":"Proceedings of the National Academy of Sciences","publication_status":"published"},{"day":"10","publisher":"National Academy of Sciences","oa_version":"Published Version","type":"journal_article","ec_funded":1,"year":"2025","status":"public","OA_type":"hybrid","fulldoi":"https://doi.org/10.1073/pnas.2417025122","article_number":"e2417025122","intvolume":"       122","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","isi":1,"pmid":1,"volume":122,"oa":1,"quality_controlled":"1","file":[{"date_created":"2025-03-25T07:49:04Z","file_size":1553502,"access_level":"open_access","file_name":"2025_PNAS_Chiossi.pdf","date_updated":"2025-03-25T07:49:04Z","relation":"main_file","checksum":"1217207c254553154faa065964990988","creator":"dernst","success":1,"content_type":"application/pdf","file_id":"19454"}],"tmp":{"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","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"publication":"Proceedings of the National Academy of Sciences","_id":"19453","publication_status":"published","project":[{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","call_identifier":"H2020","name":"International IST Doctoral Program"}],"abstract":[{"lang":"eng","text":"A key feature of biological and artificial neural networks is the progressive refinement of their neural representations with experience. In neuroscience, this fact has inspired several recent studies in sensory and motor systems. However, less is known about how higher associational cortical areas, such as the hippocampus, modify representations throughout the learning of complex tasks. Here, we focus on associative learning, a process that requires forming a connection between the representations of different variables for appropriate behavioral response. We trained rats in a space-context associative task and monitored hippocampal neural activity throughout the entire learning period, over several days. This allowed us to assess changes in the representations of context, movement direction, and position, as well as their relationship to behavior. We identified a hierarchical representational structure in the encoding of these three task variables that was preserved throughout learning. Nevertheless, we also observed changes at the lower levels of the hierarchy where context was encoded. These changes were local in neural activity space and restricted to physical positions where context identification was necessary for correct decision-making, supporting better context decoding and contextual code compression. Our results demonstrate that the hippocampal code not only accommodates hierarchical relationships between different variables but also enables efficient learning through minimal changes in neural activity space. Beyond the hippocampus, our work reveals a representation learning mechanism that might be implemented in other biological and artificial networks performing similar tasks."}],"doi":"10.1073/pnas.2417025122","acknowledgement":"We would like to thank Rebecca Morse for performing the recordings in one of the animals under the supervision of H.S.C.C., Jago Wallenschus for the technical support, especially with maze design, Wiktor Mlynarski for the advice and discussions and Andrea Cumpelik for suggestions during the writing. M.N. was supported by the Howard Hughes Medical Institute. H.S.C.C. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 665385.","external_id":{"isi":["001459499500001"],"pmid":["40063792"]},"corr_author":"1","article_type":"original","language":[{"iso":"eng"}],"date_created":"2025-03-25T07:38:35Z","scopus_import":"1","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"article_processing_charge":"Yes (in subscription journal)","title":"Learning reshapes the hippocampal representation hierarchy","file_date_updated":"2025-03-25T07:49:04Z","department":[{"_id":"GaTk"},{"_id":"JoCs"}],"date_updated":"2026-05-06T13:12:01Z","APC_amount":"3317,75 EUR","author":[{"full_name":"Chiossi, Heloisa","first_name":"Heloisa","id":"2BBA502C-F248-11E8-B48F-1D18A9856A87","orcid":"0009-0004-2973-278X","last_name":"Chiossi"},{"orcid":"0000-0001-8849-6570","id":"30BD0376-F248-11E8-B48F-1D18A9856A87","first_name":"Michele","full_name":"Nardin, Michele","last_name":"Nardin"},{"orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","first_name":"Gašper","last_name":"Tkačik"},{"last_name":"Csicsvari","first_name":"Jozsef L","full_name":"Csicsvari, Jozsef L","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5193-4036"}],"citation":{"chicago":"Chiossi, Heloisa S. C., Michele Nardin, Gašper Tkačik, and Jozsef L Csicsvari. “Learning Reshapes the Hippocampal Representation Hierarchy.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2417025122\">https://doi.org/10.1073/pnas.2417025122</a>.","ista":"Chiossi HSC, Nardin M, Tkačik G, Csicsvari JL. 2025. Learning reshapes the hippocampal representation hierarchy. Proceedings of the National Academy of Sciences. 122(11), e2417025122.","ieee":"H. S. C. Chiossi, M. Nardin, G. Tkačik, and J. L. Csicsvari, “Learning reshapes the hippocampal representation hierarchy,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 11. National Academy of Sciences, 2025.","short":"H.S.C. Chiossi, M. Nardin, G. Tkačik, J.L. Csicsvari, Proceedings of the National Academy of Sciences 122 (2025).","apa":"Chiossi, H. S. C., Nardin, M., Tkačik, G., &#38; Csicsvari, J. L. (2025). Learning reshapes the hippocampal representation hierarchy. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2417025122\">https://doi.org/10.1073/pnas.2417025122</a>","ama":"Chiossi HSC, Nardin M, Tkačik G, Csicsvari JL. Learning reshapes the hippocampal representation hierarchy. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(11). doi:<a href=\"https://doi.org/10.1073/pnas.2417025122\">10.1073/pnas.2417025122</a>","mla":"Chiossi, Heloisa S. C., et al. “Learning Reshapes the Hippocampal Representation Hierarchy.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 11, e2417025122, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2417025122\">10.1073/pnas.2417025122</a>."},"issue":"11","OA_place":"publisher","ddc":["570"],"date_published":"2025-03-10T00:00:00Z","month":"03","related_material":{"record":[{"id":"18991","status":"public","relation":"research_data"}],"link":[{"url":"https://github.com/hchiossi/hpc-hierarchy","relation":"software"}]}},{"doi":"10.1073/pnas.2419273122","abstract":[{"lang":"eng","text":"Quantum hardware is inherently fragile and noisy. We find that the accuracy of traditional quantum error correction algorithms can be improved depending on the hardware. Given different hardware specifications, we automatically synthesize hardware-optimal algorithms for parity correction, qubit resetting, and GHZ (Greenberger–Horne–Zeilinger) state preparation. Using stochastic techniques from computer science, our method presents a computational tool to compute exact accuracy guarantees and synthesize optimal algorithms that are often different from traditional ones. We also show that improvements can be gained with respect to the Qiskit transpiler as we compute the hardware-optimal qubit mapping for the GHZ state-preparation problem."}],"project":[{"_id":"0599E47C-7A3F-11EA-A408-12923DDC885E","grant_number":"863818","call_identifier":"H2020","name":"Formal Methods for Stochastic Models: Algorithms and Applications"}],"_id":"19499","tmp":{"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","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"publication_status":"published","publication":"Proceedings of the National Academy of Sciences","quality_controlled":"1","file":[{"success":1,"content_type":"application/pdf","file_id":"19524","checksum":"83501b8a65ee5fdd3f5604fc28eddc22","relation":"main_file","date_updated":"2025-04-07T11:42:22Z","creator":"dernst","file_size":6805668,"access_level":"open_access","file_name":"2025_PNAS_Muroya.pdf","date_created":"2025-04-07T11:42:22Z"}],"oa":1,"volume":122,"has_accepted_license":"1","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","pmid":1,"isi":1,"year":"2025","ec_funded":1,"type":"journal_article","publisher":"National Academy of Sciences","oa_version":"Published Version","day":"25","intvolume":"       122","fulldoi":"https://doi.org/10.1073/pnas.2419273122","article_number":"e2419273122","OA_type":"hybrid","status":"public","date_published":"2025-03-25T00:00:00Z","ddc":["000"],"month":"03","related_material":{"link":[{"url":"https://github.com/smml1996/algorithm_synthesis","relation":"software"},{"description":"News on ISTA website","relation":"press_release","url":"https://ista.ac.at/en/news/hardware-optimal-quantum-algorithms/"}]},"author":[{"full_name":"Muroya Lei, Stefanie","first_name":"Stefanie","id":"a376de31-8972-11ed-ae7b-d0251c13c8ff","last_name":"Muroya Lei"},{"full_name":"Chatterjee, Krishnendu","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87","first_name":"Krishnendu","orcid":"0000-0002-4561-241X","last_name":"Chatterjee"},{"last_name":"Henzinger","orcid":"0000-0002-2985-7724","full_name":"Henzinger, Thomas A","first_name":"Thomas A","id":"40876CD8-F248-11E8-B48F-1D18A9856A87"}],"date_updated":"2026-04-28T13:41:14Z","OA_place":"publisher","issue":"12","citation":{"chicago":"Muroya Lei, Stefanie, Krishnendu Chatterjee, and Thomas A Henzinger. “Hardware-Optimal Quantum Algorithms.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2419273122\">https://doi.org/10.1073/pnas.2419273122</a>.","ista":"Muroya Lei S, Chatterjee K, Henzinger TA. 2025. Hardware-optimal quantum algorithms. Proceedings of the National Academy of Sciences. 122(12), e2419273122.","ieee":"S. Muroya Lei, K. Chatterjee, and T. A. Henzinger, “Hardware-optimal quantum algorithms,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 12. National Academy of Sciences, 2025.","short":"S. Muroya Lei, K. Chatterjee, T.A. Henzinger, Proceedings of the National Academy of Sciences 122 (2025).","apa":"Muroya Lei, S., Chatterjee, K., &#38; Henzinger, T. A. (2025). Hardware-optimal quantum algorithms. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2419273122\">https://doi.org/10.1073/pnas.2419273122</a>","mla":"Muroya Lei, Stefanie, et al. “Hardware-Optimal Quantum Algorithms.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 12, e2419273122, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2419273122\">10.1073/pnas.2419273122</a>.","ama":"Muroya Lei S, Chatterjee K, Henzinger TA. Hardware-optimal quantum algorithms. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(12). doi:<a href=\"https://doi.org/10.1073/pnas.2419273122\">10.1073/pnas.2419273122</a>"},"date_created":"2025-04-06T22:01:32Z","language":[{"iso":"eng"}],"file_date_updated":"2025-04-07T11:42:22Z","department":[{"_id":"KrCh"},{"_id":"ToHe"}],"article_processing_charge":"Yes (in subscription journal)","title":"Hardware-optimal quantum algorithms","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"scopus_import":"1","corr_author":"1","external_id":{"pmid":["40106357"],"isi":["001459435600001"]},"acknowledgement":"We thank the reviewers. In particular, they inspired us to analyze the reset and state-preparation problems, to compute optimal qubit mappings, and to apply our method to a quantum error correction scheme that includes both bitflip and phaseflip corrections. We also thank Raimundo Saona and Marek Chalupa for their time spent in insightful discussions. This research was partially supported by the European Research Council CoG 863818 (ForM-SMArt) grant.","article_type":"original"},{"project":[{"_id":"c08e9ad1-5a5b-11eb-8a69-9d1cf3b07473","grant_number":"CZI01","name":"Tools for automation and feedback microscopy"},{"_id":"bd6f94d1-d553-11ed-ba76-ae9f07250f74","grant_number":"E219","name":"Non-canonical antibiotic interactions"},{"name":"Evolutionary analysis of gene regulation","grant_number":"I05127","_id":"34e076d6-11ca-11ed-8bc3-aec76c41a181"}],"abstract":[{"lang":"eng","text":"Active regulation of gene expression, orchestrated by complex interactions of activators and repressors at promoters, controls the fate of organisms. In contrast, basal expression at uninduced promoters is considered to be a dynamically inert mode of nonfunctional “promoter leakiness,” merely a byproduct of transcriptional regulation. Here, we investigate the basal expression mode of the mar operon, the main regulator of intrinsic multiple antibiotic resistance in Escherichia coli, and link its dynamic properties to the noncanonical, yet highly conserved start codon of marR across Enterobacteriaceae. Real-time, single-cell measurements across tens of generations reveal that basal expression consists of rare stochastic gene expression pulses, which maximize variability in wildtype and, surprisingly, transiently accelerate cellular elongation rates. Competition experiments show that basal expression confers fitness advantages to wildtype across several transitions between exponential and stationary growth by shortening lag times. The dynamically rich basal expression of the mar operon has likely been evolutionarily maintained for its role in growth homeostasis of Enterobacteria within the gut environment, thereby allowing other ancillary gene regulatory roles to evolve, e.g., control of costly-to-induce multidrug efflux pumps. Understanding the complex selection forces governing genetic systems involved in intrinsic multidrug resistance is crucial for effective public health measures."}],"doi":"10.1073/pnas.2413709122","publication_status":"published","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"_id":"19626","publication":"Proceedings of the National Academy of Sciences","oa":1,"file":[{"file_size":2949523,"access_level":"open_access","file_name":"2025_PNAS_Jain.pdf","date_created":"2025-06-24T07:27:43Z","file_id":"19888","content_type":"application/pdf","success":1,"relation":"main_file","checksum":"115a687f40009660eb4b38b4f6559d41","date_updated":"2025-06-24T07:27:43Z","creator":"dernst"}],"quality_controlled":"1","volume":122,"has_accepted_license":"1","acknowledged_ssus":[{"_id":"Bio"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"isi":1,"publisher":"National Academy of Sciences","oa_version":"Published Version","type":"journal_article","year":"2025","day":"15","intvolume":"       122","OA_type":"hybrid","status":"public","fulldoi":"https://doi.org/10.1073/pnas.2413709122","article_number":"e2413709122","ddc":["570"],"date_published":"2025-04-15T00:00:00Z","related_material":{"link":[{"relation":"press_release","description":"News on ISTA website","url":"https://ista.ac.at/en/news/clockwork-just-for-antibiotic-resistance/"}],"record":[{"id":"19294","status":"public","relation":"research_data"}]},"month":"04","author":[{"id":"330F0278-F248-11E8-B48F-1D18A9856A87","first_name":"Kirti","full_name":"Jain, Kirti","orcid":"0000-0002-3809-0449","last_name":"Jain"},{"first_name":"Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522","last_name":"Hauschild"},{"first_name":"Olga","id":"C4558D3C-6102-11E9-A62E-F418E6697425","full_name":"Bochkareva, Olga","orcid":"0000-0003-1006-6639","last_name":"Bochkareva"},{"orcid":"0000-0001-9480-5261","first_name":"Roderich","full_name":"Römhild, Roderich","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","last_name":"Römhild"},{"last_name":"Tkačik","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper"},{"orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","full_name":"Guet, Calin C","last_name":"Guet"}],"date_updated":"2026-05-20T08:33:08Z","APC_amount":"5949 EUR","issue":"15","OA_place":"publisher","citation":{"apa":"Jain, K., Hauschild, R., Bochkareva, O., Römhild, R., Tkačik, G., &#38; Guet, C. C. (2025). Pulsatile basal gene expression as a fitness determinant in bacteria. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2413709122\">https://doi.org/10.1073/pnas.2413709122</a>","mla":"Jain, Kirti, et al. “Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 15, e2413709122, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2413709122\">10.1073/pnas.2413709122</a>.","ama":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. Pulsatile basal gene expression as a fitness determinant in bacteria. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(15). doi:<a href=\"https://doi.org/10.1073/pnas.2413709122\">10.1073/pnas.2413709122</a>","chicago":"Jain, Kirti, Robert Hauschild, Olga Bochkareva, Roderich Römhild, Gašper Tkačik, and Calin C Guet. “Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2413709122\">https://doi.org/10.1073/pnas.2413709122</a>.","ista":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. 2025. Pulsatile basal gene expression as a fitness determinant in bacteria. Proceedings of the National Academy of Sciences. 122(15), e2413709122.","ieee":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, and C. C. Guet, “Pulsatile basal gene expression as a fitness determinant in bacteria,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 15. National Academy of Sciences, 2025.","short":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, C.C. Guet, Proceedings of the National Academy of Sciences 122 (2025)."},"language":[{"iso":"eng"}],"date_created":"2025-04-27T22:02:13Z","article_processing_charge":"Yes (in subscription journal)","title":"Pulsatile basal gene expression as a fitness determinant in bacteria","department":[{"_id":"CaGu"},{"_id":"Bio"},{"_id":"FyKo"},{"_id":"GaTk"}],"file_date_updated":"2025-06-24T07:27:43Z","scopus_import":"1","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"corr_author":"1","acknowledgement":"K.J. thanks B. Wu, I. Tomanek, K. Tomasek for detailed discussions on the manuscript, all other members from the Guet laboratory for valuable feedback, R. Chait, & Imaging and Optics Facility, Institute of Science and Technology Austria for helping with microscopy, Dr. Sudha Rao and Dr. Raja Mugasimangalam, Genotypic Technology India for allowing time off to address the revisions. K.J. acknowledges Institute of Science and Technology fellowship IC1006FELL02, R.H. was supported in part by Chan Zuckerberg Initiative and Donor Advised-Fund grant 2020-225401 (https://doi.org/10.37921/120055ratwvi), O.O.B. acknowledges Fonds Zur Förderung der Wissenschaftlichen Forschung (FWF) Grant ESP253-B, R.R. acknowledges FWF Grant 10.55776/ESP219, C.C.G. acknowledges FWF I5127-B.","external_id":{"isi":["001471235200001"],"pmid":["40193613"]},"article_type":"original"},{"citation":{"ieee":"A. Mcavoy <i>et al.</i>, “Unilateral incentive alignment in two-agent stochastic games,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 25. National Academy of Sciences, 2025.","chicago":"Mcavoy, Alex, Udari Madhushani Sehwag, Christian Hilbe, Krishnendu Chatterjee, Wolfram Barfuss, Qi Su, Naomi Ehrich Leonard, and Joshua B. Plotkin. “Unilateral Incentive Alignment in Two-Agent Stochastic Games.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2319927121\">https://doi.org/10.1073/pnas.2319927121</a>.","ista":"Mcavoy A, Sehwag UM, Hilbe C, Chatterjee K, Barfuss W, Su Q, Leonard NE, Plotkin JB. 2025. Unilateral incentive alignment in two-agent stochastic games. Proceedings of the National Academy of Sciences. 122(25), e2319927121.","short":"A. Mcavoy, U.M. Sehwag, C. Hilbe, K. Chatterjee, W. Barfuss, Q. Su, N.E. Leonard, J.B. Plotkin, Proceedings of the National Academy of Sciences 122 (2025).","apa":"Mcavoy, A., Sehwag, U. M., Hilbe, C., Chatterjee, K., Barfuss, W., Su, Q., … Plotkin, J. B. (2025). Unilateral incentive alignment in two-agent stochastic games. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2319927121\">https://doi.org/10.1073/pnas.2319927121</a>","ama":"Mcavoy A, Sehwag UM, Hilbe C, et al. Unilateral incentive alignment in two-agent stochastic games. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(25). doi:<a href=\"https://doi.org/10.1073/pnas.2319927121\">10.1073/pnas.2319927121</a>","mla":"Mcavoy, Alex, et al. “Unilateral Incentive Alignment in Two-Agent Stochastic Games.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 25, e2319927121, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2319927121\">10.1073/pnas.2319927121</a>."},"issue":"25","OA_place":"publisher","date_updated":"2025-09-30T13:47:14Z","author":[{"last_name":"Mcavoy","full_name":"Mcavoy, Alex","first_name":"Alex"},{"first_name":"Udari Madhushani","full_name":"Sehwag, Udari Madhushani","last_name":"Sehwag"},{"last_name":"Hilbe","first_name":"Christian","full_name":"Hilbe, Christian","id":"2FDF8F3C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5116-955X"},{"id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87","full_name":"Chatterjee, Krishnendu","first_name":"Krishnendu","orcid":"0000-0002-4561-241X","last_name":"Chatterjee"},{"full_name":"Barfuss, Wolfram","first_name":"Wolfram","last_name":"Barfuss"},{"last_name":"Su","first_name":"Qi","full_name":"Su, Qi"},{"full_name":"Leonard, Naomi Ehrich","first_name":"Naomi Ehrich","last_name":"Leonard"},{"first_name":"Joshua B.","full_name":"Plotkin, Joshua B.","last_name":"Plotkin"}],"month":"06","ddc":["000"],"date_published":"2025-06-24T00:00:00Z","article_type":"original","external_id":{"isi":["001522351900001"],"pmid":["40523172"]},"acknowledgement":"We gratefully acknowledge the support from the European Research Council (Starting Grant 850529: E-DIRECT) and the Max Planck Society (C.H.), the European Research Council (Consolidator Grant 863818: ForM-SMArt) (K.C.), the Shanghai Pujiang Program (No. 23PJ1405500) (Q.S.), the Army Research Office (Grant No. W911NF-18-1-0325) (N.E.L.), and the John Templeton Foundation (Grant No. 62281) (J.B.P.).","scopus_import":"1","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"title":"Unilateral incentive alignment in two-agent stochastic games","article_processing_charge":"Yes (in subscription journal)","file_date_updated":"2025-07-08T05:52:26Z","department":[{"_id":"KrCh"}],"language":[{"iso":"eng"}],"date_created":"2025-07-06T22:01:23Z","volume":122,"oa":1,"quality_controlled":"1","file":[{"date_created":"2025-07-08T05:52:26Z","access_level":"open_access","file_size":29525932,"file_name":"2025_PNAS_McAvoy.pdf","date_updated":"2025-07-08T05:52:26Z","relation":"main_file","checksum":"3b35befd959a3e37aa9080a64a6afaf3","creator":"dernst","file_id":"19972","content_type":"application/pdf","success":1}],"tmp":{"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","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"_id":"19965","publication":"Proceedings of the National Academy of Sciences","publication_status":"published","project":[{"call_identifier":"H2020","grant_number":"863818","name":"Formal Methods for Stochastic Models: Algorithms and Applications","_id":"0599E47C-7A3F-11EA-A408-12923DDC885E"}],"doi":"10.1073/pnas.2319927121","abstract":[{"lang":"eng","text":"Multiagent learning is challenging when agents face mixed-motivation interactions, where conflicts of interest arise as agents independently try to optimize their respective outcomes. Recent advancements in evolutionary game theory have identified a class of “zero-determinant” strategies, which confer an agent with significant unilateral control over outcomes in repeated games. Building on these insights, we present a comprehensive generalization of zero-determinant strategies to stochastic games, encompassing dynamic environments. We propose an algorithm that allows an agent to discover strategies enforcing predetermined linear (or approximately linear) payoff relationships. Of particular interest is the relationship in which both payoffs are equal, which serves as a proxy for fairness in symmetric games. We demonstrate that an agent can discover strategies enforcing such relationships through experience alone, without coordinating with an opponent. In finding and using such a strategy, an agent (“enforcer”) can incentivize optimal and equitable outcomes, circumventing potential exploitation. In particular, from the opponent’s viewpoint, the enforcer transforms a mixed-motivation problem into a cooperative problem, paving the way for more collaboration and fairness in multiagent systems."}],"OA_type":"hybrid","status":"public","article_number":"e2319927121","fulldoi":"https://doi.org/10.1073/pnas.2319927121","intvolume":"       122","day":"24","publisher":"National Academy of Sciences","oa_version":"Published Version","type":"journal_article","ec_funded":1,"year":"2025","isi":1,"pmid":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","has_accepted_license":"1"},{"ddc":["570"],"date_published":"2025-08-26T00:00:00Z","related_material":{"link":[{"relation":"software","url":"https://github.com/mehmetcanucar/Self-generated-chemotaxis"}]},"PlanS_conform":"1","month":"08","date_updated":"2026-05-20T08:59:54Z","APC_amount":"5766,07 EUR","author":[{"orcid":"0000-0003-0506-4217","first_name":"Mehmet C","full_name":"Ucar, Mehmet C","id":"50B2A802-6007-11E9-A42B-EB23E6697425","last_name":"Ucar"},{"last_name":"Zane","id":"60f7509a-f652-11ea-9d86-b963d6490d7c","first_name":"Alsberga","full_name":"Zane, Alsberga","orcid":"0009-0003-0415-7603"},{"orcid":"0000-0002-7698-3061","id":"2CC12E8C-F248-11E8-B48F-1D18A9856A87","first_name":"Jonna H","full_name":"Alanko, Jonna H","last_name":"Alanko"},{"orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","full_name":"Sixt, Michael K","last_name":"Sixt"},{"last_name":"Hannezo","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","first_name":"Edouard B","full_name":"Hannezo, Edouard B"}],"citation":{"short":"M.C. Ucar, A. Zane, J.H. Alanko, M.K. Sixt, E.B. Hannezo, Proceedings of the National Academy of Sciences 122 (2025).","chicago":"Ucar, Mehmet C, Alsberga Zane, Jonna H Alanko, Michael K Sixt, and Edouard B Hannezo. “Self-Generated Chemotaxis of Mixed Cell Populations.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2504064122\">https://doi.org/10.1073/pnas.2504064122</a>.","ista":"Ucar MC, Zane A, Alanko JH, Sixt MK, Hannezo EB. 2025. Self-generated chemotaxis of mixed cell populations. Proceedings of the National Academy of Sciences. 122(34), e2504064122.","ieee":"M. C. Ucar, A. Zane, J. H. Alanko, M. K. Sixt, and E. B. Hannezo, “Self-generated chemotaxis of mixed cell populations,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 34. National Academy of Sciences, 2025.","ama":"Ucar MC, Zane A, Alanko JH, Sixt MK, Hannezo EB. Self-generated chemotaxis of mixed cell populations. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(34). doi:<a href=\"https://doi.org/10.1073/pnas.2504064122\">10.1073/pnas.2504064122</a>","mla":"Ucar, Mehmet C., et al. “Self-Generated Chemotaxis of Mixed Cell Populations.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 34, e2504064122, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2504064122\">10.1073/pnas.2504064122</a>.","apa":"Ucar, M. C., Zane, A., Alanko, J. H., Sixt, M. K., &#38; Hannezo, E. B. (2025). Self-generated chemotaxis of mixed cell populations. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2504064122\">https://doi.org/10.1073/pnas.2504064122</a>"},"issue":"34","OA_place":"publisher","language":[{"iso":"eng"}],"date_created":"2025-09-07T22:01:32Z","scopus_import":"1","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"title":"Self-generated chemotaxis of mixed cell populations","article_processing_charge":"Yes (in subscription journal)","file_date_updated":"2025-09-08T07:23:29Z","department":[{"_id":"EdHa"},{"_id":"MiSi"}],"acknowledgement":"We thank all members of the M.S. and E.H. groups for stimulating discussions.We thank the Imaging and Optics facility, the Pre-clinical and Lab Support facility of the Institute of Science and Technology Austria for their excellent support and provided resources for the experimental research. In particular, we thank Jack Merrin from the Nanofabrication facility who generated the microfabricated channel used in this study. This work received funding fromt he European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 851288 to E.H.). M.C.U.is funded by a University of Sheffield Strategic Research Fellowship in the Physics of Life and Quantitative Biology.","external_id":{"isi":["001562181600001"],"pmid":["40838890"]},"corr_author":"1","article_type":"original","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"publication_status":"published","_id":"20289","publication":"Proceedings of the National Academy of Sciences","project":[{"grant_number":"851288","call_identifier":"H2020","name":"Design Principles of Branching Morphogenesis","_id":"05943252-7A3F-11EA-A408-12923DDC885E"}],"doi":"10.1073/pnas.2504064122","abstract":[{"lang":"eng","text":"Cell and tissue movement in development, cancer invasion, and immune response relies on chemical or mechanical guidance cues. In many systems, this behavior is locally directed by self-generated signaling gradients rather than long-range, prepatterned cues. However, how heterogeneous mixtures of cells interact nonreciprocally and navigate through self-generated gradients remains largely unexplored. Here, we introduce a theoretical framework for the self-organized chemotaxis of heterogeneous cell populations. We find that the relative chemotactic sensitivities of different cell populations control their long-time coupling and comigration dynamics, with boundary conditions such as external cell and attractant reservoirs substantially influencing the migration patterns. Our model predicts an optimal parameter regime that enables robust and colocalized migration. We test our theoretical predictions with in vitro experiments demonstrating the comigration of distinct immune cell populations, and quantitatively reproduce observed migration patterns under wild-type and perturbed conditions. Interestingly, immune cell comigration occurs close to the predicted optimal regime. Finally, we incorporate mechanical interactions into our framework, revealing a nontrivial interplay between chemotactic and mechanical nonreciprocity in driving collective migration. Together, our findings suggest that self-generated chemotaxis is a robust strategy for the navigation of mixed cell populations."}],"volume":122,"oa":1,"quality_controlled":"1","file":[{"content_type":"application/pdf","file_id":"20307","success":1,"date_updated":"2025-09-08T07:23:29Z","relation":"main_file","checksum":"b36abd92673b6d76376fc9434bad52cc","creator":"dernst","file_size":16069140,"access_level":"open_access","file_name":"2025_PNAS_Ucar.pdf","date_created":"2025-09-08T07:23:29Z"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"NanoFab"}],"has_accepted_license":"1","isi":1,"pmid":1,"day":"26","oa_version":"Published Version","publisher":"National Academy of Sciences","ec_funded":1,"type":"journal_article","year":"2025","OA_type":"hybrid","status":"public","fulldoi":"https://doi.org/10.1073/pnas.2504064122","article_number":"e2504064122","intvolume":"       122"},{"language":[{"iso":"eng"}],"date_created":"2025-11-12T10:03:20Z","scopus_import":"1","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"title":"Antagonistic SnRK2 and PID kinases' action on auxin transport-mediated root gravitropism","article_processing_charge":"Yes (in subscription journal)","department":[{"_id":"JiFr"}],"file_date_updated":"2025-11-24T13:48:09Z","external_id":{"pmid":["40986351"],"isi":["001589177800001"]},"acknowledgement":"This research was funded by Biological Breeding-National Science and Technology Major Project (2023ZD0407201), China Postdoctoral Science Foundation (2024M763575), China Agricultural University Fund (2025RC042), Chinese Universities Scientific Fund (2024RC031), and Austrian Science Fund (FWF; I 6123-B).","article_type":"original","ddc":["580"],"date_published":"2025-09-23T00:00:00Z","page":"e2512274122","month":"09","PlanS_conform":"1","date_updated":"2026-02-16T12:32:51Z","author":[{"last_name":"Sheng","first_name":"F","full_name":"Sheng, F"},{"last_name":"Gao","full_name":"Gao, Y","first_name":"Y"},{"last_name":"Wang","full_name":"Wang, Y","first_name":"Y"},{"last_name":"Li","first_name":"Y","full_name":"Li, Y"},{"last_name":"Zhang","full_name":"Zhang, JA","first_name":"JA"},{"last_name":"Zhang","first_name":"Z","full_name":"Zhang, Z"},{"last_name":"Qin","first_name":"X","full_name":"Qin, X"},{"last_name":"Zhang","full_name":"Zhang, S","first_name":"S"},{"last_name":"Song","full_name":"Song, W","first_name":"W"},{"first_name":"J","full_name":"Li, J","last_name":"Li"},{"first_name":"Y","full_name":"Guo, Y","last_name":"Guo"},{"first_name":"Jiří","id":"4159519E-F248-11E8-B48F-1D18A9856A87","full_name":"Friml, Jiří","orcid":"0000-0002-8302-7596","last_name":"Friml"},{"last_name":"Gong","full_name":"Gong, Z","first_name":"Z"},{"last_name":"Zhang","first_name":"Q","full_name":"Zhang, Q"},{"first_name":"J","full_name":"Zhang, J","last_name":"Zhang"}],"citation":{"apa":"Sheng, F., Gao, Y., Wang, Y., Li, Y., Zhang, J., Zhang, Z., … Zhang, J. (2025). Antagonistic SnRK2 and PID kinases’ action on auxin transport-mediated root gravitropism. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2512274122\">https://doi.org/10.1073/pnas.2512274122</a>","mla":"Sheng, F., et al. “Antagonistic SnRK2 and PID Kinases’ Action on Auxin Transport-Mediated Root Gravitropism.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 39, National Academy of Sciences, 2025, p. e2512274122, doi:<a href=\"https://doi.org/10.1073/pnas.2512274122\">10.1073/pnas.2512274122</a>.","ama":"Sheng F, Gao Y, Wang Y, et al. Antagonistic SnRK2 and PID kinases’ action on auxin transport-mediated root gravitropism. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(39):e2512274122. doi:<a href=\"https://doi.org/10.1073/pnas.2512274122\">10.1073/pnas.2512274122</a>","ista":"Sheng F, Gao Y, Wang Y, Li Y, Zhang J, Zhang Z, Qin X, Zhang S, Song W, Li J, Guo Y, Friml J, Gong Z, Zhang Q, Zhang J. 2025. Antagonistic SnRK2 and PID kinases’ action on auxin transport-mediated root gravitropism. Proceedings of the National Academy of Sciences. 122(39), e2512274122.","chicago":"Sheng, F, Y Gao, Y Wang, Y Li, JA Zhang, Z Zhang, X Qin, et al. “Antagonistic SnRK2 and PID Kinases’ Action on Auxin Transport-Mediated Root Gravitropism.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2512274122\">https://doi.org/10.1073/pnas.2512274122</a>.","ieee":"F. Sheng <i>et al.</i>, “Antagonistic SnRK2 and PID kinases’ action on auxin transport-mediated root gravitropism,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 39. National Academy of Sciences, p. e2512274122, 2025.","short":"F. Sheng, Y. Gao, Y. Wang, Y. Li, J. Zhang, Z. Zhang, X. Qin, S. Zhang, W. Song, J. Li, Y. Guo, J. Friml, Z. Gong, Q. Zhang, J. Zhang, Proceedings of the National Academy of Sciences 122 (2025) e2512274122."},"issue":"39","OA_place":"publisher","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","isi":1,"pmid":1,"day":"23","oa_version":"Published Version","publisher":"National Academy of Sciences","type":"journal_article","year":"2025","OA_type":"hybrid","status":"public","fulldoi":"https://doi.org/10.1073/pnas.2512274122","intvolume":"       122","tmp":{"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","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"_id":"20635","publication":"Proceedings of the National Academy of Sciences","publication_status":"published","project":[{"name":"Peptide receptors for auxin canalization in Arabidopsis","grant_number":"I06123","_id":"bd76d395-d553-11ed-ba76-f678c14f9033"}],"abstract":[{"text":"Plants have evolved sophisticated mechanisms to adapt to environmental changes, with root gravitropism playing a pivotal role in nutrient and water acquisition. Our study reveals that SnRK2 kinases (SnRK2.2 and SnRK2.3) are critical regulators of root gravitropism through their direct phosphorylation of the auxin transporter PIN2 at S259. We demonstrate that SnRK2s-mediated phosphorylation modulates both the polar localization and transport activity of PIN2. Importantly, SnRK2s function antagonistically to the AGCVIII kinase PID, which phosphorylates PIN2 at a distinct site (S258), establishing a regulatory balance essential for adaptive root growth. Structural modeling and phosphorylation assays further suggest that SnRK2s-mediated phosphorylation at S259 sterically hinders access of PID to S258, providing a mechanistic basis for their antagonistic relationship. These findings uncover a novel regulatory mechanism, by which plants fine-tune root developmental programs to adapt to environmental stimuli, highlighting the evolutionary significance of multilayered kinase-mediated regulation in plant adaptation.","lang":"eng"}],"doi":"10.1073/pnas.2512274122","volume":122,"oa":1,"file":[{"relation":"main_file","date_updated":"2025-11-24T13:48:09Z","checksum":"38b723a909bf321d7ee537c9d064aa25","creator":"dernst","file_id":"20681","content_type":"application/pdf","success":1,"date_created":"2025-11-24T13:48:09Z","access_level":"open_access","file_size":2667764,"file_name":"2025_PNAS_Sheng.pdf"}],"quality_controlled":"1"},{"issue":"48","OA_place":"publisher","citation":{"ieee":"J. Bao, S. Bony, D. Takasuka, and C. J. Muller, “Tropics-wide intraseasonal oscillations,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 48. National Academy of Sciences, 2025.","ista":"Bao J, Bony S, Takasuka D, Muller CJ. 2025. Tropics-wide intraseasonal oscillations. Proceedings of the National Academy of Sciences. 122(48), e2511549122.","chicago":"Bao, Jiawei, Sandrine Bony, Daisuke Takasuka, and Caroline J Muller. “Tropics-Wide Intraseasonal Oscillations.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2511549122\">https://doi.org/10.1073/pnas.2511549122</a>.","short":"J. Bao, S. Bony, D. Takasuka, C.J. Muller, Proceedings of the National Academy of Sciences 122 (2025).","apa":"Bao, J., Bony, S., Takasuka, D., &#38; Muller, C. J. (2025). Tropics-wide intraseasonal oscillations. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2511549122\">https://doi.org/10.1073/pnas.2511549122</a>","ama":"Bao J, Bony S, Takasuka D, Muller CJ. Tropics-wide intraseasonal oscillations. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(48). doi:<a href=\"https://doi.org/10.1073/pnas.2511549122\">10.1073/pnas.2511549122</a>","mla":"Bao, Jiawei, et al. “Tropics-Wide Intraseasonal Oscillations.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 48, e2511549122, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2511549122\">10.1073/pnas.2511549122</a>."},"author":[{"id":"bb9a7399-fefd-11ed-be3c-ae648fd1d160","first_name":"Jiawei","full_name":"Bao, Jiawei","last_name":"Bao"},{"full_name":"Bony, Sandrine","first_name":"Sandrine","last_name":"Bony"},{"first_name":"Daisuke","full_name":"Takasuka, Daisuke","last_name":"Takasuka"},{"orcid":"0000-0001-5836-5350","first_name":"Caroline J","full_name":"Muller, Caroline J","id":"f978ccb0-3f7f-11eb-b193-b0e2bd13182b","last_name":"Muller"}],"APC_amount":"5651,35 EUR","date_updated":"2026-05-20T08:11:56Z","month":"12","related_material":{"link":[{"description":"News on ISTA website","relation":"press_release","url":"https://ista.ac.at/en/news/hidden-in-plain-sight/"}]},"PlanS_conform":"1","date_published":"2025-12-02T00:00:00Z","ddc":["550"],"article_type":"original","corr_author":"1","external_id":{"pmid":["41284872"]},"acknowledgement":"J.B. acknowledges funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant (grant agreement No. 101034413). S.B. acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Project Mesoscale organization of tropical convection, grant agreement No 101098063). D.T. acknowledges funding from the Japan Society for the Promotion of Science (JSPS) (Project JSPS Grants-in-Aid for Scientific Research, grant No. JP24K22893). C.M. gratefully acknowledges funding from the ERC under the European Union’s Horizon 2020 research and innovation program (Project organisation of CLoUdS, and implications for Tropical cyclones and for the Energetics of the tropics, in current and in a waRming climate, grant agreement No. 805041). We thank Martin Singh, Steven Sherwood, Bjorn Stevens, and Lokahith Agasthya for helpful discussions. JSPS Core-to-Core Program, “International Core-to-Core Project on Global Storm Resolving Analysis” (Grant Number: JPJSCCA20220001)","file_date_updated":"2025-12-15T09:17:33Z","department":[{"_id":"CaMu"}],"article_processing_charge":"Yes (in subscription journal)","title":"Tropics-wide intraseasonal oscillations","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"scopus_import":"1","date_created":"2025-12-11T10:41:13Z","language":[{"iso":"eng"}],"file":[{"date_created":"2025-12-15T09:17:33Z","file_size":30890293,"access_level":"open_access","file_name":"2025_PNAS_Bao.pdf","relation":"main_file","date_updated":"2025-12-15T09:17:33Z","checksum":"093a8685170e4a1de9176f68ee449493","creator":"dernst","content_type":"application/pdf","file_id":"20822","success":1}],"quality_controlled":"1","oa":1,"volume":122,"doi":"10.1073/pnas.2511549122","abstract":[{"lang":"eng","text":"The tropical climate variability is characterized by various oscillations across a range of timescales. Oscillations that imprint the tropical mean state are generally attributed to slow processes, such as the seasonal cycle or interannual variability. Here, we identify a pronounced tropics-wide intraseasonal oscillation (TWISO) in satellite observations and reanalyses. This oscillation, with a period of 30 to 60 d, is evident across multiple variables and involves interactions between convection, radiation, surface fluxes, and large-scale circulation. It is primarily manifested as convective perturbations in the tropical Indo-Pacific warm pool accompanied by oscillations in the large-scale tropical overturning circulation. Here, we examine the relationship between TWISO, the Madden–Julian Oscillation (MJO), and the instability of radiative-convective equilibrium. Certain phases of TWISO coincide with specific phases of the MJO, suggesting a potential connection between the two. However, although the MJO can amplify the oscillation amplitude of TWISO, it is not essential for TWISO to occur. Finally, due to its broad manifestation across the tropics, TWISO potentially exerts widespread influence on tropical weather and climate at regional scales."}],"project":[{"call_identifier":"H2020","grant_number":"101034413","name":"IST-BRIDGE: International postdoctoral program","_id":"fc2ed2f7-9c52-11eb-aca3-c01059dda49c"},{"name":"Organization of CLoUdS, and implications of Tropical  cyclones and for the Energetics of the tropics, in current and waRming climate","call_identifier":"H2020","grant_number":"805041","_id":"629205d8-2b32-11ec-9570-e1356ff73576"}],"_id":"20795","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"publication_status":"published","publication":"Proceedings of the National Academy of Sciences","intvolume":"       122","article_number":"e2511549122","fulldoi":"https://doi.org/10.1073/pnas.2511549122","OA_type":"hybrid","status":"public","year":"2025","ec_funded":1,"type":"journal_article","oa_version":"Published Version","publisher":"National Academy of Sciences","day":"02","pmid":1,"has_accepted_license":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"month":"04","related_material":{"record":[{"status":"public","id":"22857","relation":"dissertation_contains"}]},"date_published":"2025-04-15T00:00:00Z","ddc":["000"],"OA_place":"publisher","issue":"15","arxiv":1,"citation":{"short":"S. Bombari, M. Mondelli, Proceedings of the National Academy of Sciences 122 (2025).","ieee":"S. Bombari and M. Mondelli, “Privacy for free in the overparameterized regime,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 15. National Academy of Sciences, 2025.","ista":"Bombari S, Mondelli M. 2025. Privacy for free in the overparameterized regime. Proceedings of the National Academy of Sciences. 122(15), e2423072122.","chicago":"Bombari, Simone, and Marco Mondelli. “Privacy for Free in the Overparameterized Regime.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2423072122\">https://doi.org/10.1073/pnas.2423072122</a>.","mla":"Bombari, Simone, and Marco Mondelli. “Privacy for Free in the Overparameterized Regime.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 15, e2423072122, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2423072122\">10.1073/pnas.2423072122</a>.","ama":"Bombari S, Mondelli M. Privacy for free in the overparameterized regime. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(15). doi:<a href=\"https://doi.org/10.1073/pnas.2423072122\">10.1073/pnas.2423072122</a>","apa":"Bombari, S., &#38; Mondelli, M. (2025). Privacy for free in the overparameterized regime. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2423072122\">https://doi.org/10.1073/pnas.2423072122</a>"},"author":[{"last_name":"Bombari","id":"ca726dda-de17-11ea-bc14-f9da834f63aa","first_name":"Simone","full_name":"Bombari, Simone"},{"last_name":"Mondelli","id":"27EB676C-8706-11E9-9510-7717E6697425","full_name":"Mondelli, Marco","first_name":"Marco","orcid":"0000-0002-3242-7020"}],"APC_amount":"2754,32 EUR","date_updated":"2026-09-21T13:07:01Z","department":[{"_id":"MaMo"}],"file_date_updated":"2025-05-05T07:27:54Z","title":"Privacy for free in the overparameterized regime","article_processing_charge":"Yes (in subscription journal)","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"scopus_import":"1","date_created":"2025-04-27T22:02:13Z","language":[{"iso":"eng"}],"article_type":"original","corr_author":"1","external_id":{"pmid":["40215275"],"arxiv":["2410.14787"],"isi":["001471214000001"]},"acknowledgement":"This research was funded in whole, or in part, by the Austrian Science Fund (FWF) Grant number COE 12. For the purpose of open access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. The authors were also supported by the 2019 Lopez-Loreta prize, and Simone Bombari was supported by a Google PhD fellowship. We thank Diyuan Wu, Edwige Cyffers, Francesco Pedrotti, Inbar Seroussi, Nikita P. Kalinin, Pietro Pelliconi, Roodabeh Safavi, Yizhe Zhu, and Zhichao Wang for helpful discussions.","abstract":[{"text":"Differentially private gradient descent (DP-GD) is a popular algorithm to train deep learning models with provable guarantees on the privacy of the training data. In the last decade, the problem of understanding its performance cost with respect to standard GD has received remarkable attention from the research community, which formally derived upper bounds on the excess population risk  RP  in different learning settings. However, existing bounds typically degrade with over-parameterization, i.e., as the number of parameters  p  gets larger than the number of training samples  n  -- a regime which is ubiquitous in current deep-learning practice. As a result, the lack of theoretical insights leaves practitioners without clear guidance, leading some to reduce the effective number of trainable parameters to improve performance, while others use larger models to achieve better results through scale. In this work, we show that in the popular random features model with quadratic loss, for any sufficiently large  p , privacy can be obtained for free, i.e.,  |RP|=o(1) , not only when the privacy parameter  ε  has constant order, but also in the strongly private setting  ε=o(1) . This challenges the common wisdom that over-parameterization inherently hinders performance in private learning.","lang":"eng"}],"doi":"10.1073/pnas.2423072122","project":[{"name":"Prix Lopez-Loretta 2019 - Marco Mondelli","_id":"059876FA-7A3F-11EA-A408-12923DDC885E"},{"name":"Trustworthy Deep Learning Theory: Private Over-Parameterized Models and Robust LLMs","_id":"92099302-16d5-11f0-9cad-f9a785f54fbd"},{"_id":"74caaef7-b034-11f1-8f2d-e0e993bb422e","name":"Bilateral Artificial Intelligence (Mondelli)","grant_number":"COE12"}],"tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"_id":"19627","publication":"Proceedings of the National Academy of Sciences","publication_status":"published","quality_controlled":"1","file":[{"file_id":"19648","content_type":"application/pdf","success":1,"date_updated":"2025-05-05T07:27:54Z","checksum":"1ac6f78e368d35a0cafb4d2d9bd63443","relation":"main_file","creator":"dernst","access_level":"open_access","file_size":2328320,"file_name":"2025_PNAS_Bombari.pdf","date_created":"2025-05-05T07:27:54Z"}],"oa":1,"volume":122,"pmid":1,"isi":1,"has_accepted_license":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":"       122","fulldoi":"https://doi.org/10.1073/pnas.2423072122","article_number":"e2423072122","OA_type":"hybrid","status":"public","type":"journal_article","year":"2025","publisher":"National Academy of Sciences","oa_version":"Published Version","day":"15"},{"month":"03","ddc":["570"],"date_published":"2024-03-12T00:00:00Z","citation":{"ieee":"M. Habig, A. V. Grasse, J. Müller, E. H. Stukenbrock, H. Leitner, and S. Cremer, “Frequent horizontal chromosome transfer between asexual fungal insect pathogens,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 121, no. 11. National Academy of Sciences, 2024.","chicago":"Habig, Michael, Anna V Grasse, Judith Müller, Eva H. Stukenbrock, Hanna Leitner, and Sylvia Cremer. “Frequent Horizontal Chromosome Transfer between Asexual Fungal Insect Pathogens.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences, 2024. <a href=\"https://doi.org/10.1073/pnas.2316284121\">https://doi.org/10.1073/pnas.2316284121</a>.","ista":"Habig M, Grasse AV, Müller J, Stukenbrock EH, Leitner H, Cremer S. 2024. Frequent horizontal chromosome transfer between asexual fungal insect pathogens. Proceedings of the National Academy of Sciences of the United States of America. 121(11), e2316284121.","short":"M. Habig, A.V. Grasse, J. Müller, E.H. Stukenbrock, H. Leitner, S. Cremer, Proceedings of the National Academy of Sciences of the United States of America 121 (2024).","apa":"Habig, M., Grasse, A. V., Müller, J., Stukenbrock, E. H., Leitner, H., &#38; Cremer, S. (2024). Frequent horizontal chromosome transfer between asexual fungal insect pathogens. <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.2316284121\">https://doi.org/10.1073/pnas.2316284121</a>","mla":"Habig, Michael, et al. “Frequent Horizontal Chromosome Transfer between Asexual Fungal Insect Pathogens.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 121, no. 11, e2316284121, National Academy of Sciences, 2024, doi:<a href=\"https://doi.org/10.1073/pnas.2316284121\">10.1073/pnas.2316284121</a>.","ama":"Habig M, Grasse AV, Müller J, Stukenbrock EH, Leitner H, Cremer S. Frequent horizontal chromosome transfer between asexual fungal insect pathogens. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2024;121(11). doi:<a href=\"https://doi.org/10.1073/pnas.2316284121\">10.1073/pnas.2316284121</a>"},"OA_place":"publisher","issue":"11","date_updated":"2025-08-05T13:30:51Z","APC_amount":"3040,36 EUR","author":[{"first_name":"Michael","full_name":"Habig, Michael","last_name":"Habig"},{"last_name":"Grasse","full_name":"Grasse, Anna V","id":"406F989C-F248-11E8-B48F-1D18A9856A87","first_name":"Anna V"},{"first_name":"Judith","full_name":"Müller, Judith","last_name":"Müller"},{"first_name":"Eva H.","full_name":"Stukenbrock, Eva H.","last_name":"Stukenbrock"},{"last_name":"Leitner","full_name":"Leitner, Hanna","first_name":"Hanna","id":"8fc5c6f6-5903-11ec-abad-c83f046253e7"},{"first_name":"Sylvia","id":"2F64EC8C-F248-11E8-B48F-1D18A9856A87","full_name":"Cremer, Sylvia","orcid":"0000-0002-2193-3868","last_name":"Cremer"}],"scopus_import":"1","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"article_processing_charge":"Yes (in subscription journal)","title":"Frequent horizontal chromosome transfer between asexual fungal insect pathogens","file_date_updated":"2024-03-19T09:02:57Z","department":[{"_id":"SyCr"}],"language":[{"iso":"eng"}],"date_created":"2023-10-31T13:30:00Z","article_type":"original","acknowledgement":"We thank Bernhardt Steinwender, Jorgen Eilenberg, and Nicolai V. Meyling for the fungal strains. We further thank Chengshu Wang for providing the short sequencing reads for M. guizhouense ARESF977 he used for his published genome assembly, and Kristian Ullrich for help in the bioinformatics analysis for methylation pattern in Nanopore reads, and the VBC and the Max Planck Society for the use of their sequencing centers. We thank Barbara Milutinović and Hinrich Schulenburg for discussion, and Tal Dagan and Jens Rolff for comments on a previous version of the manuscript. Fig. 1A was created with BioRender.com. This study received funding by the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme (No. 771402; EPIDEMICSonCHIP) to S.C. and by the German Research Foundation (DFG grant HA9263/1-1) to M.H.","external_id":{"isi":["001207630200005"],"pmid":["38442176"]},"corr_author":"1","publication":"Proceedings of the National Academy of Sciences of the United States of America","tmp":{"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","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"_id":"14478","publication_status":"published","project":[{"name":"Epidemics in ant societies on a chip","grant_number":"771402","call_identifier":"H2020","_id":"2649B4DE-B435-11E9-9278-68D0E5697425"}],"abstract":[{"text":"Entire chromosomes are typically only transmitted vertically from one generation to the next. The horizontal transfer of such chromosomes has long been considered improbable, yet gained recent support in several pathogenic fungi where it may affect the fitness or host specificity. To date, it is unknown how these transfers occur, how common they are and whether they can occur between different species. In this study, we show multiple independent instances of horizontal transfers of the same accessory chromosome between two distinct strains of the asexual entomopathogenic fungus<jats:italic>Metarhizium robertsii</jats:italic>during experimental co-infection of its insect host, the Argentine ant. Notably, only the one chromosome – but no other – was transferred from the donor to the recipient strain. The recipient strain, now harboring the accessory chromosome, exhibited a competitive advantage under certain host conditions. By phylogenetic analysis we further demonstrate that the same accessory chromosome was horizontally transferred in a natural environment between<jats:italic>M. robertsii</jats:italic>and another congeneric insect pathogen,<jats:italic>M. guizhouense</jats:italic>. Hence horizontal chromosome transfer is not limited to the observed frequent events within species during experimental infections but also occurs naturally across species. The transferred accessory chromosome contains genes that might be involved in its preferential horizontal transfer, encoding putative histones and histone-modifying enzymes, but also putative virulence factors that may support its establishment. Our study reveals that both intra- and interspecies horizontal transfer of entire chromosomes is more frequent than previously assumed, likely representing a not uncommon mechanism for gene exchange.</jats:p><jats:sec><jats:title>Significance Statement</jats:title><jats:p>The enormous success of bacterial pathogens has been attributed to their ability to exchange genetic material between one another. Similarly, in eukaryotes, horizontal transfer of genetic material allowed the spread of virulence factors across species. The horizontal transfer of whole chromosomes could be an important pathway for such exchange of genetic material, but little is known about the origin of transferable chromosomes and how frequently they are exchanged. Here, we show that the transfer of accessory chromosomes - chromosomes that are non-essential but may provide fitness benefits - is common during fungal co-infections and is even possible between distant pathogenic species, highlighting the importance of horizontal gene transfer via chromosome transfer also for the evolution and function of eukaryotic pathogens.","lang":"eng"}],"doi":"10.1073/pnas.2316284121","volume":121,"oa":1,"file":[{"file_size":5750361,"access_level":"open_access","file_name":"2024_PNAS_Habig.pdf","date_created":"2024-03-19T09:02:57Z","file_id":"15124","content_type":"application/pdf","success":1,"checksum":"f5e871db617b682edc71fcd08670dc81","relation":"main_file","date_updated":"2024-03-19T09:02:57Z","creator":"dernst"}],"quality_controlled":"1","isi":1,"pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","status":"public","OA_type":"hybrid","article_number":"e2316284121","fulldoi":"https://doi.org/10.1073/pnas.2316284121","intvolume":"       121","day":"12","oa_version":"Published Version","publisher":"National Academy of Sciences","year":"2024","type":"journal_article","ec_funded":1},{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","pmid":1,"day":"06","publisher":"National Academy of Sciences","oa_version":"Published Version","type":"journal_article","year":"2024","OA_type":"hybrid","status":"public","fulldoi":"https://doi.org/10.1073/pnas.2317453121","article_number":"e2317453121","intvolume":"       121","tmp":{"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","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"publication_status":"published","_id":"18938","publication":"Proceedings of the National Academy of Sciences of the United States of America","doi":"10.1073/pnas.2317453121","abstract":[{"text":"The synthesis of proteins as encoded in the genome depends critically on translational fidelity. Nevertheless, errors inevitably occur, and those that result in reading frame shifts are particularly consequential because the resulting polypeptides are typically nonfunctional. Despite the generally maladaptive impact of such errors, the proper decoding of certain mRNAs, including many viral mRNAs, depends on a process known as programmed ribosomal frameshifting. The fact that these programmed events, commonly involving a shift to the –1 frame, occur at specific evolutionarily optimized “slippery” sites has facilitated mechanistic investigation. By contrast, less is known about the scope and nature of error (i.e., nonprogrammed) frameshifting. Here, we examine error frameshifting by monitoring spontaneous frameshift events that suppress the effects of single base pair deletions affecting two unrelated test proteins. To map the precise sites of frameshifting, we developed a targeted mass spectrometry–based method called “translational tiling proteomics” for interrogating the full set of possible –1 slippage events that could produce the observed frameshift suppression. Surprisingly, such events occur at many sites along the transcripts, involving up to one half of the available codons. Only a subset of these resembled canonical “slippery” sites, implicating alternative mechanisms potentially involving noncognate mispairing events. Additionally, the aggregate frequency of these events (ranging from 1 to 10% in our test cases) was higher than we might have anticipated. Our findings point to an unexpected degree of mechanistic diversity among ribosomal frameshifting events and suggest that frameshifted products may contribute more significantly to the proteome than generally assumed.","lang":"eng"}],"volume":121,"oa":1,"quality_controlled":"1","file":[{"file_id":"18939","content_type":"application/pdf","success":1,"relation":"main_file","checksum":"5bd62c7cb4287e3706a1d45d6ef61fd1","date_updated":"2025-01-29T08:43:16Z","creator":"dernst","file_size":720902,"access_level":"open_access","file_name":"2024_PNAS_Springstein.pdf","date_created":"2025-01-29T08:43:16Z"}],"language":[{"iso":"eng"}],"date_created":"2025-01-29T08:39:27Z","scopus_import":"1","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"article_processing_charge":"No","title":"Systematic analysis of nonprogrammed frameshift suppression in E.coli via translational tiling proteomics","department":[{"_id":"MaLo"}],"file_date_updated":"2025-01-29T08:43:16Z","external_id":{"pmid":["38289956"]},"acknowledgement":"We thank S. L. Dove for valuable discussion and comments on the manuscript and R. Hellmiss for artwork. This work was supported by NIH grants GM136247 to A.H., AG011085 to J.W.H., and GM132129 to J.A.P.","article_type":"original","ddc":["570"],"date_published":"2024-02-06T00:00:00Z","month":"02","date_updated":"2025-05-14T11:02:52Z","author":[{"last_name":"Springstein","full_name":"Springstein, Benjamin L","id":"b4eb62ef-ac72-11ed-9503-ed3b4d66c083","first_name":"Benjamin L","orcid":"0000-0002-3461-5391"},{"first_name":"Joao A.","full_name":"Paulo, Joao A.","last_name":"Paulo"},{"full_name":"Park, Hankum","first_name":"Hankum","last_name":"Park"},{"last_name":"Henry","first_name":"Kemardo","full_name":"Henry, Kemardo"},{"last_name":"Fleming","full_name":"Fleming, Eleanor","first_name":"Eleanor"},{"last_name":"Feder","first_name":"Zoë","full_name":"Feder, Zoë"},{"first_name":"J. Wade","full_name":"Harper, J. Wade","last_name":"Harper"},{"first_name":"Ann","full_name":"Hochschild, Ann","last_name":"Hochschild"}],"citation":{"ieee":"B. L. Springstein <i>et al.</i>, “Systematic analysis of nonprogrammed frameshift suppression in E.coli via translational tiling proteomics,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 121, no. 6. National Academy of Sciences, 2024.","chicago":"Springstein, Benjamin L, Joao A. Paulo, Hankum Park, Kemardo Henry, Eleanor Fleming, Zoë Feder, J. Wade Harper, and Ann Hochschild. “Systematic Analysis of Nonprogrammed Frameshift Suppression in E.Coli via Translational Tiling Proteomics.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences, 2024. <a href=\"https://doi.org/10.1073/pnas.2317453121\">https://doi.org/10.1073/pnas.2317453121</a>.","ista":"Springstein BL, Paulo JA, Park H, Henry K, Fleming E, Feder Z, Harper JW, Hochschild A. 2024. Systematic analysis of nonprogrammed frameshift suppression in E.coli via translational tiling proteomics. Proceedings of the National Academy of Sciences of the United States of America. 121(6), e2317453121.","short":"B.L. Springstein, J.A. Paulo, H. Park, K. Henry, E. Fleming, Z. Feder, J.W. Harper, A. Hochschild, Proceedings of the National Academy of Sciences of the United States of America 121 (2024).","apa":"Springstein, B. L., Paulo, J. A., Park, H., Henry, K., Fleming, E., Feder, Z., … Hochschild, A. (2024). Systematic analysis of nonprogrammed frameshift suppression in E.coli via translational tiling proteomics. <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.2317453121\">https://doi.org/10.1073/pnas.2317453121</a>","ama":"Springstein BL, Paulo JA, Park H, et al. Systematic analysis of nonprogrammed frameshift suppression in E.coli via translational tiling proteomics. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2024;121(6). doi:<a href=\"https://doi.org/10.1073/pnas.2317453121\">10.1073/pnas.2317453121</a>","mla":"Springstein, Benjamin L., et al. “Systematic Analysis of Nonprogrammed Frameshift Suppression in E.Coli via Translational Tiling Proteomics.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 121, no. 6, e2317453121, National Academy of Sciences, 2024, doi:<a href=\"https://doi.org/10.1073/pnas.2317453121\">10.1073/pnas.2317453121</a>."},"OA_place":"publisher","issue":"6"},{"abstract":[{"text":"In many physical situations in which many-body assemblies exist at temperature T, a characteristic quantum-mechanical time scale of approximately h/kbT can be identified in both theory and experiment, leading to speculation that it may be the shortest meaningful time in such circumstances. This behavior can be investigated by probing the scattering rate of electrons in a broad class of materials often referred to as “strongly correlated metals”. It is clear that in some cases only electron–electron scattering can be its cause, while in others it arises from high-temperature scattering of electrons from quantized lattice vibrations, i.e., phonons. In metallic oxides, which are among the most studied materials, analysis of electrical transport does not satisfactorily identify the relevant scattering mechanism at “high” temperatures near room temperature. We therefore employ a contactless optical method to measure thermal diffusivity in two Ru-based layered perovskites, Sr3Ru2O7 and Sr2RuO4, and use the measurements to extract the dimensionless Lorenz ratio. By comparing our results to the literature data on both conventional and unconventional metals, we show how the analysis of high-temperature thermal transport can both give important insight into dominant scattering mechanisms and be offered as a stringent test of theories attempting to explain anomalous scattering.","lang":"eng"}],"doi":"10.1073/pnas.2318159121","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"_id":"19809","publication_status":"published","publication":"Proceedings of the National Academy of Sciences","oa":1,"quality_controlled":"1","volume":121,"pmid":1,"has_accepted_license":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":"       121","OA_type":"hybrid","status":"public","fulldoi":"https://doi.org/10.1073/pnas.2318159121","publisher":"National Academy of Sciences","oa_version":"Published Version","year":"2024","type":"journal_article","day":"27","main_file_link":[{"url":"https://doi.org/10.1073/pnas.2318159121","open_access":"1"}],"month":"08","date_published":"2024-08-27T00:00:00Z","issue":"35","OA_place":"publisher","citation":{"ieee":"F. Sun <i>et al.</i>, “The Lorenz ratio as a guide to scattering contributions to transport in strongly correlated metals,” <i>Proceedings of the National Academy of Sciences</i>, vol. 121, no. 35. National Academy of Sciences, 2024.","ista":"Sun F, Mishra S, Stockert U, Daou R, Kikugawa N, Perry RS, Hassinger E, Hartnoll SA, Mackenzie AP, Sunko V. 2024. The Lorenz ratio as a guide to scattering contributions to transport in strongly correlated metals. Proceedings of the National Academy of Sciences. 121(35).","chicago":"Sun, Fei, Simli Mishra, Ulrike Stockert, Ramzy Daou, Naoki Kikugawa, Robin S. Perry, Elena Hassinger, Sean A. Hartnoll, Andrew P. Mackenzie, and Veronika Sunko. “The Lorenz Ratio as a Guide to Scattering Contributions to Transport in Strongly Correlated Metals.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2024. <a href=\"https://doi.org/10.1073/pnas.2318159121\">https://doi.org/10.1073/pnas.2318159121</a>.","short":"F. Sun, S. Mishra, U. Stockert, R. Daou, N. Kikugawa, R.S. Perry, E. Hassinger, S.A. Hartnoll, A.P. Mackenzie, V. Sunko, Proceedings of the National Academy of Sciences 121 (2024).","apa":"Sun, F., Mishra, S., Stockert, U., Daou, R., Kikugawa, N., Perry, R. S., … Sunko, V. (2024). The Lorenz ratio as a guide to scattering contributions to transport in strongly correlated metals. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2318159121\">https://doi.org/10.1073/pnas.2318159121</a>","mla":"Sun, Fei, et al. “The Lorenz Ratio as a Guide to Scattering Contributions to Transport in Strongly Correlated Metals.” <i>Proceedings of the National Academy of Sciences</i>, vol. 121, no. 35, National Academy of Sciences, 2024, doi:<a href=\"https://doi.org/10.1073/pnas.2318159121\">10.1073/pnas.2318159121</a>.","ama":"Sun F, Mishra S, Stockert U, et al. The Lorenz ratio as a guide to scattering contributions to transport in strongly correlated metals. <i>Proceedings of the National Academy of Sciences</i>. 2024;121(35). doi:<a href=\"https://doi.org/10.1073/pnas.2318159121\">10.1073/pnas.2318159121</a>"},"author":[{"last_name":"Sun","first_name":"Fei","full_name":"Sun, Fei"},{"last_name":"Mishra","first_name":"Simli","full_name":"Mishra, Simli"},{"last_name":"Stockert","first_name":"Ulrike","full_name":"Stockert, Ulrike"},{"first_name":"Ramzy","full_name":"Daou, Ramzy","last_name":"Daou"},{"last_name":"Kikugawa","full_name":"Kikugawa, Naoki","first_name":"Naoki"},{"last_name":"Perry","full_name":"Perry, Robin S.","first_name":"Robin S."},{"full_name":"Hassinger, Elena","first_name":"Elena","last_name":"Hassinger"},{"first_name":"Sean A.","full_name":"Hartnoll, Sean A.","last_name":"Hartnoll"},{"full_name":"Mackenzie, Andrew P.","first_name":"Andrew P.","last_name":"Mackenzie"},{"last_name":"Sunko","orcid":"0000-0003-2724-3523","id":"23cb1cf6-2c7a-11ef-91a4-f72fc19f20b3","full_name":"Sunko, Veronika","first_name":"Veronika"}],"date_updated":"2025-06-10T11:50:48Z","article_processing_charge":"No","title":"The Lorenz ratio as a guide to scattering contributions to transport in strongly correlated metals","scopus_import":"1","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"extern":"1","language":[{"iso":"eng"}],"date_created":"2025-06-10T09:12:41Z","article_type":"original","external_id":{"pmid":["39172781"]}},{"oa_version":"Published Version","publisher":"National Academy of Sciences","year":"2024","type":"journal_article","main_file_link":[{"url":"https://doi.org/10.1073/pnas.2410736121","open_access":"1"}],"day":"09","intvolume":"       121","status":"public","OA_type":"hybrid","article_number":"e2410736121","fulldoi":"https://doi.org/10.1073/pnas.2410736121","has_accepted_license":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"quality_controlled":"1","volume":121,"doi":"10.1073/pnas.2410736121","abstract":[{"text":"Allometric scaling relations are widely used to link biological processes to body size in nature. Several studies have shown that such scaling laws hold also for natural ecosystems, including individual trees and forests, riverine metabolism, and river network organization. However, the derivation of scaling laws for catchment-scale water and carbon fluxes has not been achieved so far. Here, we focus on scaling relations of catchment green metabolism, defined as the set of ecohydrological and biogeochemical processes through which vegetation assemblages in catchments maintain their structure and react to the surrounding environment. By revising existing plant size–density relationships and integrating them across large-scale domains, we show that the ecohydrological fluxes occurring at the catchment scale are invariant with respect to the above-ground vegetation biomass per unit area of the basin, while they scale linearly with catchment size. We thus demonstrate that the sublinear scaling of plant metabolism results in an isometric scaling at catchment and regional scales. Deviations from such predictions are further shown to collapse onto a common distribution, thus incorporating natural fluctuations due to resource limitations into a generalized scaling theory. Results from scaling arguments are supported by hyperresolution ecohydrological simulations and remote sensing observations.","lang":"eng"}],"publication_status":"published","tmp":{"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","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"_id":"22485","publication":"Proceedings of the National Academy of Sciences","article_type":"original","extern":"1","language":[{"iso":"eng"}],"date_created":"2026-07-27T12:30:23Z","article_processing_charge":"No","title":"Toward a metabolic theory of catchments: Scaling of water and carbon fluxes with size","scopus_import":"1","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"author":[{"last_name":"Bassani","first_name":"Francesca","full_name":"Bassani, Francesca"},{"last_name":"Fatichi","full_name":"Fatichi, Simone","id":"cf8e546b-a9b0-11f0-a43b-aa89ed1b56d6","first_name":"Simone"},{"full_name":"Rinaldo, Andrea","first_name":"Andrea","last_name":"Rinaldo"},{"full_name":"Bonetti, Sara","first_name":"Sara","last_name":"Bonetti"}],"date_updated":"2026-07-30T11:27:23Z","OA_place":"publisher","issue":"42","citation":{"ieee":"F. Bassani, S. Fatichi, A. Rinaldo, and S. Bonetti, “Toward a metabolic theory of catchments: Scaling of water and carbon fluxes with size,” <i>Proceedings of the National Academy of Sciences</i>, vol. 121, no. 42. National Academy of Sciences, 2024.","ista":"Bassani F, Fatichi S, Rinaldo A, Bonetti S. 2024. Toward a metabolic theory of catchments: Scaling of water and carbon fluxes with size. Proceedings of the National Academy of Sciences. 121(42), e2410736121.","chicago":"Bassani, Francesca, Simone Fatichi, Andrea Rinaldo, and Sara Bonetti. “Toward a Metabolic Theory of Catchments: Scaling of Water and Carbon Fluxes with Size.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2024. <a href=\"https://doi.org/10.1073/pnas.2410736121\">https://doi.org/10.1073/pnas.2410736121</a>.","short":"F. Bassani, S. Fatichi, A. Rinaldo, S. Bonetti, Proceedings of the National Academy of Sciences 121 (2024).","apa":"Bassani, F., Fatichi, S., Rinaldo, A., &#38; Bonetti, S. (2024). Toward a metabolic theory of catchments: Scaling of water and carbon fluxes with size. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2410736121\">https://doi.org/10.1073/pnas.2410736121</a>","mla":"Bassani, Francesca, et al. “Toward a Metabolic Theory of Catchments: Scaling of Water and Carbon Fluxes with Size.” <i>Proceedings of the National Academy of Sciences</i>, vol. 121, no. 42, e2410736121, National Academy of Sciences, 2024, doi:<a href=\"https://doi.org/10.1073/pnas.2410736121\">10.1073/pnas.2410736121</a>.","ama":"Bassani F, Fatichi S, Rinaldo A, Bonetti S. Toward a metabolic theory of catchments: Scaling of water and carbon fluxes with size. <i>Proceedings of the National Academy of Sciences</i>. 2024;121(42). doi:<a href=\"https://doi.org/10.1073/pnas.2410736121\">10.1073/pnas.2410736121</a>"},"ddc":["550"],"date_published":"2024-10-09T00:00:00Z","das_tickbox":"1","month":"10"},{"status":"public","OA_type":"hybrid","article_number":"e2315558121","fulldoi":"https://doi.org/10.1073/pnas.2315558121","intvolume":"       121","day":"05","publisher":"National Academy of Sciences","oa_version":"Published Version","year":"2024","type":"journal_article","ec_funded":1,"isi":1,"pmid":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","has_accepted_license":"1","volume":121,"oa":1,"file":[{"date_created":"2024-03-12T13:12:22Z","access_level":"open_access","file_size":2203220,"file_name":"2024_PNAS_Huebner.pdf","checksum":"068520e3efd4d008bb9177e8aedb7d22","date_updated":"2024-03-12T13:12:22Z","relation":"main_file","creator":"dernst","file_id":"15109","content_type":"application/pdf","success":1}],"quality_controlled":"1","tmp":{"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","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"publication":"Proceedings of the National Academy of Sciences of the United States of America","_id":"15083","publication_status":"published","project":[{"_id":"0599E47C-7A3F-11EA-A408-12923DDC885E","grant_number":"863818","call_identifier":"H2020","name":"Formal Methods for Stochastic Models: Algorithms and Applications"},{"_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","call_identifier":"H2020"}],"abstract":[{"lang":"eng","text":"Direct reciprocity is a powerful mechanism for cooperation in social dilemmas. The very logic of reciprocity, however, seems to require that individuals are symmetric, and that everyone has the same means to influence each others’ payoffs. Yet in many applications, individuals are asymmetric. Herein, we study the effect of asymmetry in linear public good games. Individuals may differ in their endowments (their ability to contribute to a public good) and in their productivities (how effective their contributions are). Given the individuals’ productivities, we ask which allocation of endowments is optimal for cooperation. To this end, we consider two notions of optimality. The first notion focuses on the resilience of cooperation. The respective endowment distribution ensures that full cooperation is feasible even under the most adverse conditions. The second notion focuses on efficiency. The corresponding endowment distribution maximizes group welfare. Using analytical methods, we fully characterize these two endowment distributions. This analysis reveals that both optimality notions favor some endowment inequality: More productive players ought to get higher endowments. Yet the two notions disagree on how unequal endowments are supposed to be. A focus on resilience results in less inequality. With additional simulations, we show that the optimal endowment allocation needs to account for both the resilience and the efficiency of cooperation."}],"doi":"10.1073/pnas.2315558121","article_type":"original","external_id":{"isi":["001207786500004"],"pmid":["38408249"]},"acknowledgement":"This work was supported by the European Research Council CoG 863818 (ForM-SMArt) (to K.C.) and the European Research Council Starting Grant 850529: E-DIRECT (to C.H.), the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant Agreement #754411 and the French Agence Nationale de la Recherche (under the Investissement d’Avenir Programme, ANR-17-EURE-0010) (to M.K.).","corr_author":"1","scopus_import":"1","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"title":"Efficiency and resilience of cooperation in asymmetric social dilemmas","article_processing_charge":"Yes (in subscription journal)","file_date_updated":"2024-03-12T13:12:22Z","department":[{"_id":"KrCh"}],"language":[{"iso":"eng"}],"date_created":"2024-03-05T09:18:49Z","citation":{"apa":"Hübner, V., Staab, M., Hilbe, C., Chatterjee, K., &#38; Kleshnina, M. (2024). Efficiency and resilience of cooperation in asymmetric social dilemmas. <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.2315558121\">https://doi.org/10.1073/pnas.2315558121</a>","ama":"Hübner V, Staab M, Hilbe C, Chatterjee K, Kleshnina M. Efficiency and resilience of cooperation in asymmetric social dilemmas. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2024;121(10). doi:<a href=\"https://doi.org/10.1073/pnas.2315558121\">10.1073/pnas.2315558121</a>","mla":"Hübner, Valentin, et al. “Efficiency and Resilience of Cooperation in Asymmetric Social Dilemmas.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 121, no. 10, e2315558121, National Academy of Sciences, 2024, doi:<a href=\"https://doi.org/10.1073/pnas.2315558121\">10.1073/pnas.2315558121</a>.","ista":"Hübner V, Staab M, Hilbe C, Chatterjee K, Kleshnina M. 2024. Efficiency and resilience of cooperation in asymmetric social dilemmas. Proceedings of the National Academy of Sciences of the United States of America. 121(10), e2315558121.","chicago":"Hübner, Valentin, Manuel Staab, Christian Hilbe, Krishnendu Chatterjee, and Maria Kleshnina. “Efficiency and Resilience of Cooperation in Asymmetric Social Dilemmas.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences, 2024. <a href=\"https://doi.org/10.1073/pnas.2315558121\">https://doi.org/10.1073/pnas.2315558121</a>.","ieee":"V. Hübner, M. Staab, C. Hilbe, K. Chatterjee, and M. Kleshnina, “Efficiency and resilience of cooperation in asymmetric social dilemmas,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 121, no. 10. National Academy of Sciences, 2024.","short":"V. Hübner, M. Staab, C. Hilbe, K. Chatterjee, M. Kleshnina, Proceedings of the National Academy of Sciences of the United States of America 121 (2024)."},"issue":"10","OA_place":"publisher","date_updated":"2026-09-16T06:58:23Z","APC_amount":"3041,76 EUR","author":[{"orcid":"0009-0001-5009-4987","id":"2c8aa207-dc7d-11ea-9b2f-f22972ecd910","full_name":"Hübner, Valentin","first_name":"Valentin","last_name":"Hübner"},{"last_name":"Staab","full_name":"Staab, Manuel","first_name":"Manuel"},{"orcid":"0000-0001-5116-955X","id":"2FDF8F3C-F248-11E8-B48F-1D18A9856A87","full_name":"Hilbe, Christian","first_name":"Christian","last_name":"Hilbe"},{"last_name":"Chatterjee","orcid":"0000-0002-4561-241X","first_name":"Krishnendu","full_name":"Chatterjee, Krishnendu","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Kleshnina","full_name":"Kleshnina, Maria","first_name":"Maria"}],"related_material":{"record":[{"relation":"research_data","id":"15108","status":"public"},{"relation":"dissertation_contains","status":"public","id":"19903"}],"link":[{"relation":"press_release","description":"News on ISTA Website","url":"https://ista.ac.at/en/news/what-math-tells-us-about-social-dilemmas/"}]},"month":"03","ddc":["000"],"date_published":"2024-03-05T00:00:00Z"},{"language":[{"iso":"eng"}],"date_created":"2024-12-22T23:01:47Z","title":"Density amplifiers of cooperation for spatial games","article_processing_charge":"Yes","file_date_updated":"2025-01-02T12:14:15Z","department":[{"_id":"KrCh"}],"scopus_import":"1","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"corr_author":"1","acknowledgement":"J.S. and K.C. were supported by the European Research Council CoG 863818 (ForM-SMArt) and Austrian Science Fund 10.55776/COE12.","external_id":{"isi":["001379596100014"],"pmid":["39642209"]},"article_type":"original","ddc":["000"],"date_published":"2024-12-10T00:00:00Z","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"20138"}]},"month":"12","author":[{"last_name":"Svoboda","orcid":"0000-0002-1419-3267","first_name":"Jakub","id":"130759D2-D7DD-11E9-87D2-DE0DE6697425","full_name":"Svoboda, Jakub"},{"id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87","full_name":"Chatterjee, Krishnendu","first_name":"Krishnendu","orcid":"0000-0002-4561-241X","last_name":"Chatterjee"}],"date_updated":"2026-09-16T06:59:33Z","APC_amount":"3143,76 EUR","OA_place":"publisher","issue":"50","citation":{"short":"J. Svoboda, K. Chatterjee, Proceedings of the National Academy of Sciences of the United States of America 121 (2024).","ista":"Svoboda J, Chatterjee K. 2024. Density amplifiers of cooperation for spatial games. Proceedings of the National Academy of Sciences of the United States of America. 121(50), e2405605121.","chicago":"Svoboda, Jakub, and Krishnendu Chatterjee. “Density Amplifiers of Cooperation for Spatial Games.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences, 2024. <a href=\"https://doi.org/10.1073/pnas.2405605121\">https://doi.org/10.1073/pnas.2405605121</a>.","ieee":"J. Svoboda and K. Chatterjee, “Density amplifiers of cooperation for spatial games,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 121, no. 50. National Academy of Sciences, 2024.","mla":"Svoboda, Jakub, and Krishnendu Chatterjee. “Density Amplifiers of Cooperation for Spatial Games.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 121, no. 50, e2405605121, National Academy of Sciences, 2024, doi:<a href=\"https://doi.org/10.1073/pnas.2405605121\">10.1073/pnas.2405605121</a>.","ama":"Svoboda J, Chatterjee K. Density amplifiers of cooperation for spatial games. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2024;121(50). doi:<a href=\"https://doi.org/10.1073/pnas.2405605121\">10.1073/pnas.2405605121</a>","apa":"Svoboda, J., &#38; Chatterjee, K. (2024). Density amplifiers of cooperation for spatial games. <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.2405605121\">https://doi.org/10.1073/pnas.2405605121</a>"},"has_accepted_license":"1","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","pmid":1,"isi":1,"oa_version":"Published Version","publisher":"National Academy of Sciences","type":"journal_article","year":"2024","ec_funded":1,"day":"10","intvolume":"       121","OA_type":"hybrid","status":"public","article_number":"e2405605121","fulldoi":"https://doi.org/10.1073/pnas.2405605121","project":[{"_id":"0599E47C-7A3F-11EA-A408-12923DDC885E","grant_number":"863818","call_identifier":"H2020","name":"Formal Methods for Stochastic Models: Algorithms and Applications"}],"abstract":[{"lang":"eng","text":"Spatial games provide a simple and elegant mathematical model to study the evolution of cooperation in networks. In spatial games, individuals reside in vertices, adopt simple strategies, and interact with neighbors to receive a payoff. Depending on their own and neighbors’ payoffs, individuals can change their strategy. The payoff is determined by the Prisoners’ Dilemma, a classical matrix game, where players cooperate or defect. While cooperation is the desired behavior, defection provides a higher payoff for a selfish individual. There are many theoretical and empirical studies related to the role of the network in the evolution of cooperation. However, the fundamental question of whether there exist networks that for low initial cooperation rate ensure a high chance of fixation, i.e., cooperation spreads across the whole population, has remained elusive for spatial games with strong selection. In this work, we answer this fundamental question in the affirmative by presenting network structures that ensure high fixation probability for cooperators in the strong selection regime. Besides, our structures have many desirable properties: (a) they ensure the spread of cooperation even for a low initial density of cooperation and high temptation of defection, (b) they have constant degrees, and (c) the number of steps, until cooperation spreads, is at most quadratic in the size of the network."}],"doi":"10.1073/pnas.2405605121","tmp":{"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","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"publication_status":"published","_id":"18703","publication":"Proceedings of the National Academy of Sciences of the United States of America","oa":1,"quality_controlled":"1","file":[{"relation":"main_file","date_updated":"2025-01-02T12:14:15Z","checksum":"0115e9090b478e0644308c6dab58605b","creator":"dernst","success":1,"content_type":"application/pdf","file_id":"18721","date_created":"2025-01-02T12:14:15Z","file_size":2491151,"access_level":"open_access","file_name":"2024_PNAS_Svoboda.pdf"}],"volume":121},{"quality_controlled":"1","file":[{"file_id":"15125","content_type":"application/pdf","success":1,"creator":"dernst","relation":"main_file","date_updated":"2024-03-19T10:22:42Z","checksum":"a3f7fdc29dd9f0a38952ab4e322b3a05","file_name":"2024_PNAS_Giubertoni.pdf","file_size":12952586,"access_level":"open_access","date_created":"2024-03-19T10:22:42Z"}],"oa":1,"volume":121,"doi":"10.1073/pnas.2313162121","abstract":[{"text":"Water is known to play an important role in collagen self-assembly, but it is still largely unclear how water–collagen interactions influence the assembly process and determine the fibril network properties. Here, we use the H2O/D2O isotope effect on the hydrogen-bond strength in water to investigate the role of hydration in collagen self-assembly. We dissolve collagen in H2O and D2O and compare the growth kinetics and the structure of the collagen assemblies formed in these water isotopomers. Surprisingly, collagen assembly occurs ten times faster in D2O than in H2O, and collagen in D2O self-assembles into much thinner fibrils, that form a more inhomogeneous and softer network, with a fourfold reduction in elastic modulus when compared to H2O. Combining spectroscopic measurements with atomistic simulations, we show that collagen in D2O is less hydrated than in H2O. This partial dehydration lowers the enthalpic penalty for water removal and reorganization at the collagen–water interface, increasing the self-assembly rate and the number of nucleation centers, leading to thinner fibrils and a softer network. Coarse-grained simulations show that the acceleration in the initial nucleation rate can be reproduced by the enhancement of electrostatic interactions. These results show that water acts as a mediator between collagen monomers, by modulating their interactions so as to optimize the assembly process and, thus, the final network properties. We believe that isotopically modulating the hydration of proteins can be a valuable method to investigate the role of water in protein structural dynamics and protein self-assembly.","lang":"eng"}],"tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"_id":"15116","publication":"Proceedings of the National Academy of Sciences of the United States of America","publication_status":"published","intvolume":"       121","article_number":"e2313162121","fulldoi":"https://doi.org/10.1073/pnas.2313162121","status":"public","type":"journal_article","year":"2024","oa_version":"Published Version","publisher":"National Academy of Sciences","researchdata_availability":"yes","day":"12","pmid":1,"isi":1,"has_accepted_license":"1","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","issue":"11","citation":{"mla":"Giubertoni, Giulia, et al. “Elucidating the Role of Water in Collagen Self-Assembly by Isotopically Modulating Collagen Hydration.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 121, no. 11, e2313162121, National Academy of Sciences, 2024, doi:<a href=\"https://doi.org/10.1073/pnas.2313162121\">10.1073/pnas.2313162121</a>.","ama":"Giubertoni G, Feng L, Klein K, et al. Elucidating the role of water in collagen self-assembly by isotopically modulating collagen hydration. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2024;121(11). doi:<a href=\"https://doi.org/10.1073/pnas.2313162121\">10.1073/pnas.2313162121</a>","apa":"Giubertoni, G., Feng, L., Klein, K., Giannetti, G., Rutten, L., Choi, Y., … Woutersen, S. (2024). Elucidating the role of water in collagen self-assembly by isotopically modulating collagen hydration. <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.2313162121\">https://doi.org/10.1073/pnas.2313162121</a>","short":"G. Giubertoni, L. Feng, K. Klein, G. Giannetti, L. Rutten, Y. Choi, A. Van Der Net, G. Castro-Linares, F. Caporaletti, D. Micha, J. Hunger, A. Deblais, D. Bonn, N. Sommerdijk, A. Šarić, I.M. Ilie, G.H. Koenderink, S. Woutersen, Proceedings of the National Academy of Sciences of the United States of America 121 (2024).","chicago":"Giubertoni, Giulia, Liru Feng, Kevin Klein, Guido Giannetti, Luco Rutten, Yeji Choi, Anouk Van Der Net, et al. “Elucidating the Role of Water in Collagen Self-Assembly by Isotopically Modulating Collagen Hydration.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences, 2024. <a href=\"https://doi.org/10.1073/pnas.2313162121\">https://doi.org/10.1073/pnas.2313162121</a>.","ista":"Giubertoni G, Feng L, Klein K, Giannetti G, Rutten L, Choi Y, Van Der Net A, Castro-Linares G, Caporaletti F, Micha D, Hunger J, Deblais A, Bonn D, Sommerdijk N, Šarić A, Ilie IM, Koenderink GH, Woutersen S. 2024. Elucidating the role of water in collagen self-assembly by isotopically modulating collagen hydration. Proceedings of the National Academy of Sciences of the United States of America. 121(11), e2313162121.","ieee":"G. Giubertoni <i>et al.</i>, “Elucidating the role of water in collagen self-assembly by isotopically modulating collagen hydration,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 121, no. 11. National Academy of Sciences, 2024."},"supplementarymaterial":"no","author":[{"first_name":"Giulia","full_name":"Giubertoni, Giulia","last_name":"Giubertoni"},{"first_name":"Liru","full_name":"Feng, Liru","last_name":"Feng"},{"full_name":"Klein, Kevin","first_name":"Kevin","last_name":"Klein"},{"last_name":"Giannetti","full_name":"Giannetti, Guido","first_name":"Guido"},{"full_name":"Rutten, Luco","first_name":"Luco","last_name":"Rutten"},{"first_name":"Yeji","full_name":"Choi, Yeji","last_name":"Choi"},{"first_name":"Anouk","full_name":"Van Der Net, Anouk","last_name":"Van Der Net"},{"full_name":"Castro-Linares, Gerard","first_name":"Gerard","last_name":"Castro-Linares"},{"last_name":"Caporaletti","full_name":"Caporaletti, Federico","first_name":"Federico"},{"first_name":"Dimitra","full_name":"Micha, Dimitra","last_name":"Micha"},{"first_name":"Johannes","full_name":"Hunger, Johannes","last_name":"Hunger"},{"last_name":"Deblais","first_name":"Antoine","full_name":"Deblais, Antoine"},{"last_name":"Bonn","full_name":"Bonn, Daniel","first_name":"Daniel"},{"full_name":"Sommerdijk, Nico","first_name":"Nico","last_name":"Sommerdijk"},{"orcid":"0000-0002-7854-2139","full_name":"Šarić, Anđela","first_name":"Anđela","id":"bf63d406-f056-11eb-b41d-f263a6566d8b","last_name":"Šarić"},{"last_name":"Ilie","first_name":"Ioana M.","full_name":"Ilie, Ioana M."},{"full_name":"Koenderink, Gijsje H.","first_name":"Gijsje H.","last_name":"Koenderink"},{"last_name":"Woutersen","full_name":"Woutersen, Sander","first_name":"Sander"}],"date_updated":"2026-09-24T10:42:11Z","das_tickbox":"1","month":"03","related_material":{"record":[{"relation":"research_data","id":"15126","status":"public"}]},"date_published":"2024-03-12T00:00:00Z","ddc":["550"],"dataavailabilitystatement":"Turbidity data; IR and 2D-IR data; TEM images; cryo-TEM images; CRM images; coarse grained simulations; molecular dynamics simulation data have been deposited in UvAauas.figshare 10.21942/uva.24829896","article_type":"original","acknowledgement":"We thank Dr. Steven Roeters (Aarhus University), Dr. Federica Burla, and Prof. Dr. Mischa Bonn (Institute for Polymer Research, Mainz, Germany) for the useful discussions. We thank Dr. Wim Roeterdink and Michiel Hilberts for technical support. G.H.K. acknowledges financial support by the “BaSyC Building a Synthetic Cell” Gravitation grant (024.003.019) of The Netherlands Ministry of Education, Culture and Science (OCW) and The Netherlands Organization for Scientific Research and from NWO grant OCENW.GROOT.2019.022. This work has received support from the National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT, under Grant No. 2022K1A3A1A04062969. This publication is part of the project (with Project Number VI.Veni.212.240) of the research programme NWO Talent Programme Veni 2021, which is financed by the Dutch Research Council (NWO). I.M.I. acknowledges support from the Sectorplan Bèta & Techniek of the Dutch Government and the Dementia Research - Synapsis Foundation Switzerland. A.Š. and K.K. acknowledge support from Royal Society and European Research Council Starting Grant. G. Giubertoni kindly thanks to the Care4Bones community and the Collagen Café community for reminding that we do not own the knowledge we create, but it is, rather, a collective resource intended for the advancement of human progress.","external_id":{"pmid":["38451946"],"isi":["001206387400001"]},"department":[{"_id":"AnSa"}],"file_date_updated":"2024-03-19T10:22:42Z","article_processing_charge":"Yes (in subscription journal)","title":"Elucidating the role of water in collagen self-assembly by isotopically modulating collagen hydration","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"scopus_import":"1","date_created":"2024-03-17T23:00:57Z","language":[{"iso":"eng"}]}]