[{"fulldoi":"https://doi.org/10.1073/pnas.2104445118","acknowledgement":"We thank W. Schackwitz, M. Joel, and the Joint Genome Institute sequencing team for generating the IR64 genome sequence and initial analysis; L. Bartley and E. Marvinney for genomic DNA preparation for IR64 resequencing; and the University of California (UC), Berkeley Sanger sequencing team for technical advice and service. This work was partially funded by NSF Grant IOS-1025890 (to R.L.F. and D.Z.), NIH Grant GM69415 (to R.L.F. and D.Z.), NIH Grant GM122968 (to P.C.R.), a Young Investigator Grant from the Arnold and Mabel Beckman Foundation (to D.Z.), an International Fulbright Science and Technology Award (to J.A.R.), and a Taiwan Ministry of Education Studying Abroad Scholarship (to P.-H.H.). This work used the Vincent J. Coates Genomics Sequencing Laboratory at UC Berkeley, supported by NIH Instrumentation Grant S10 OD018174.","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2021-08-10T19:30:41Z","publisher":"National Academy of Sciences","isi":1,"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","article_type":"original","issue":"29","file_date_updated":"2021-08-11T09:31:41Z","citation":{"short":"J.A. Rodrigues, P.-H. Hsieh, D. Ruan, T. Nishimura, M.K. Sharma, R. Sharma, X. Ye, N.D. Nguyen, S. Nijjar, P.C. Ronald, R.L. Fischer, D. Zilberman, Proceedings of the National Academy of Sciences of the United States of America 118 (2021).","chicago":"Rodrigues, Jessica A., Ping-Hung Hsieh, Deling Ruan, Toshiro Nishimura, Manoj K. Sharma, Rita Sharma, XinYi Ye, et al. “Divergence among Rice Cultivars Reveals Roles for Transposition and Epimutation in Ongoing Evolution of Genomic Imprinting.” Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 2021. https://doi.org/10.1073/pnas.2104445118.","ieee":"J. A. Rodrigues et al., “Divergence among rice cultivars reveals roles for transposition and epimutation in ongoing evolution of genomic imprinting,” Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 29. National Academy of Sciences, 2021.","ama":"Rodrigues JA, Hsieh P-H, Ruan D, et al. Divergence among rice cultivars reveals roles for transposition and epimutation in ongoing evolution of genomic imprinting. Proceedings of the National Academy of Sciences of the United States of America. 2021;118(29). doi:10.1073/pnas.2104445118","apa":"Rodrigues, J. A., Hsieh, P.-H., Ruan, D., Nishimura, T., Sharma, M. K., Sharma, R., … Zilberman, D. (2021). Divergence among rice cultivars reveals roles for transposition and epimutation in ongoing evolution of genomic imprinting. Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. https://doi.org/10.1073/pnas.2104445118","mla":"Rodrigues, Jessica A., et al. “Divergence among Rice Cultivars Reveals Roles for Transposition and Epimutation in Ongoing Evolution of Genomic Imprinting.” Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 29, e2104445118, National Academy of Sciences, 2021, doi:10.1073/pnas.2104445118.","ista":"Rodrigues JA, Hsieh P-H, Ruan D, Nishimura T, Sharma MK, Sharma R, Ye X, Nguyen ND, Nijjar S, Ronald PC, Fischer RL, Zilberman D. 2021. Divergence among rice cultivars reveals roles for transposition and epimutation in ongoing evolution of genomic imprinting. Proceedings of the National Academy of Sciences of the United States of America. 118(29), e2104445118."},"oa":1,"article_number":"e2104445118","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"year":"2021","_id":"9877","abstract":[{"text":"Parent-of-origin–dependent gene expression in mammals and flowering plants results from differing chromatin imprints (genomic imprinting) between maternally and paternally inherited alleles. Imprinted gene expression in the endosperm of seeds is associated with localized hypomethylation of maternally but not paternally inherited DNA, with certain small RNAs also displaying parent-of-origin–specific expression. To understand the evolution of imprinting mechanisms in Oryza sativa (rice), we analyzed imprinting divergence among four cultivars that span both japonica and indica subspecies: Nipponbare, Kitaake, 93-11, and IR64. Most imprinted genes are imprinted across cultivars and enriched for functions in chromatin and transcriptional regulation, development, and signaling. However, 4 to 11% of imprinted genes display divergent imprinting. Analyses of DNA methylation and small RNAs revealed that endosperm-specific 24-nt small RNA–producing loci show weak RNA-directed DNA methylation, frequently overlap genes, and are imprinted four times more often than genes. However, imprinting divergence most often correlated with local DNA methylation epimutations (9 of 17 assessable loci), which were largely stable within subspecies. Small insertion/deletion events and transposable element insertions accompanied 4 of the 9 locally epimutated loci and associated with imprinting divergence at another 4 of the remaining 8 loci. Correlating epigenetic and genetic variation occurred at key regulatory regions—the promoter and transcription start site of maternally biased genes, and the promoter and gene body of paternally biased genes. Our results reinforce models for the role of maternal-specific DNA hypomethylation in imprinting of both maternally and paternally biased genes, and highlight the role of transposition and epimutation in rice imprinting evolution.","lang":"eng"}],"publication":"Proceedings of the National Academy of Sciences of the United States of America","author":[{"first_name":"Jessica A.","full_name":"Rodrigues, Jessica A.","last_name":"Rodrigues"},{"first_name":"Ping-Hung","full_name":"Hsieh, Ping-Hung","last_name":"Hsieh"},{"first_name":"Deling","last_name":"Ruan","full_name":"Ruan, Deling"},{"full_name":"Nishimura, Toshiro","last_name":"Nishimura","first_name":"Toshiro"},{"full_name":"Sharma, Manoj K.","last_name":"Sharma","first_name":"Manoj K."},{"last_name":"Sharma","full_name":"Sharma, Rita","first_name":"Rita"},{"first_name":"XinYi","full_name":"Ye, XinYi","last_name":"Ye"},{"first_name":"Nicholas D.","last_name":"Nguyen","full_name":"Nguyen, Nicholas D."},{"first_name":"Sukhranjan","full_name":"Nijjar, Sukhranjan","last_name":"Nijjar"},{"full_name":"Ronald, Pamela C.","last_name":"Ronald","first_name":"Pamela C."},{"first_name":"Robert L.","last_name":"Fischer","full_name":"Fischer, Robert L."},{"last_name":"Zilberman","full_name":"Zilberman, Daniel","orcid":"0000-0002-0123-8649","first_name":"Daniel","id":"6973db13-dd5f-11ea-814e-b3e5455e9ed1"}],"title":"Divergence among rice cultivars reveals roles for transposition and epimutation in ongoing evolution of genomic imprinting","date_updated":"2025-05-14T10:59:43Z","day":"16","article_processing_charge":"Yes (in subscription journal)","publication_status":"published","file":[{"date_created":"2021-08-11T09:31:41Z","file_id":"9879","success":1,"access_level":"open_access","relation":"main_file","file_size":1898360,"checksum":"19e84ad8c03c60222744ee8e16cd6998","creator":"asandaue","content_type":"application/pdf","file_name":"2021_ProceedingsOfTheNationalAcademyOfSciences_Rodrigues.pdf","date_updated":"2021-08-11T09:31:41Z"}],"ddc":["580","570"],"quality_controlled":"1","month":"07","language":[{"iso":"eng"}],"volume":118,"external_id":{"pmid":["34272287"],"isi":["000685037700012"]},"oa_version":"Published Version","date_published":"2021-07-16T00:00:00Z","type":"journal_article","intvolume":" 118","has_accepted_license":"1","status":"public","department":[{"_id":"DaZi"}],"doi":"10.1073/pnas.2104445118","scopus_import":"1","pmid":1},{"article_processing_charge":"No","day":"07","publication_status":"published","extern":"1","date_updated":"2024-10-15T07:43:01Z","title":"Meeting the unmet needs of clinicians from AI systems showcased for cardiology with deep-learning–based ECG analysis","author":[{"first_name":"Yonatan","last_name":"Elul","full_name":"Elul, Yonatan"},{"last_name":"Rosenberg","full_name":"Rosenberg, Aviv A.","first_name":"Aviv A."},{"first_name":"Assaf","full_name":"Schuster, Assaf","last_name":"Schuster"},{"last_name":"Bronstein","full_name":"Bronstein, Alexander","id":"58f3726e-7cba-11ef-ad8b-e6e8cb3904e6","first_name":"Alexander","orcid":"0000-0001-9699-8730"},{"first_name":"Yael","last_name":"Yaniv","full_name":"Yaniv, Yael"}],"publication":"Proceedings of the National Academy of Sciences","abstract":[{"text":"Despite their great promise, artificial intelligence (AI) systems have yet to become ubiquitous in the daily practice of medicine largely due to several crucial unmet needs of healthcare practitioners. These include lack of explanations in clinically meaningful terms, handling the presence of unknown medical conditions, and transparency regarding the system’s limitations, both in terms of statistical performance as well as recognizing situations for which the system’s predictions are irrelevant. We articulate these unmet clinical needs as machine-learning (ML) problems and systematically address them with cutting-edge ML techniques. We focus on electrocardiogram (ECG) analysis as an example domain in which AI has great potential and tackle two challenging tasks: the detection of a heterogeneous mix of known and unknown arrhythmias from ECG and the identification of underlying cardio-pathology from segments annotated as normal sinus rhythm recorded in patients with an intermittent arrhythmia. We validate our methods by simulating a screening for arrhythmias in a large-scale population while adhering to statistical significance requirements. Specifically, our system 1) visualizes the relative importance of each part of an ECG segment for the final model decision; 2) upholds specified statistical constraints on its out-of-sample performance and provides uncertainty estimation for its predictions; 3) handles inputs containing unknown rhythm types; and 4) handles data from unseen patients while also flagging cases in which the model’s outputs are not usable for a specific patient. This work represents a significant step toward overcoming the limitations currently impeding the integration of AI into clinical practice in cardiology and medicine in general.","lang":"eng"}],"_id":"18236","year":"2021","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"article_number":"e2020620118","citation":{"ieee":"Y. Elul, A. A. Rosenberg, A. Schuster, A. M. Bronstein, and Y. Yaniv, “Meeting the unmet needs of clinicians from AI systems showcased for cardiology with deep-learning–based ECG analysis,” Proceedings of the National Academy of Sciences, vol. 118, no. 24. National Academy of Sciences, 2021.","apa":"Elul, Y., Rosenberg, A. A., Schuster, A., Bronstein, A. M., & Yaniv, Y. (2021). Meeting the unmet needs of clinicians from AI systems showcased for cardiology with deep-learning–based ECG analysis. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.2020620118","mla":"Elul, Yonatan, et al. “Meeting the Unmet Needs of Clinicians from AI Systems Showcased for Cardiology with Deep-Learning–Based ECG Analysis.” Proceedings of the National Academy of Sciences, vol. 118, no. 24, e2020620118, National Academy of Sciences, 2021, doi:10.1073/pnas.2020620118.","ama":"Elul Y, Rosenberg AA, Schuster A, Bronstein AM, Yaniv Y. Meeting the unmet needs of clinicians from AI systems showcased for cardiology with deep-learning–based ECG analysis. Proceedings of the National Academy of Sciences. 2021;118(24). doi:10.1073/pnas.2020620118","ista":"Elul Y, Rosenberg AA, Schuster A, Bronstein AM, Yaniv Y. 2021. Meeting the unmet needs of clinicians from AI systems showcased for cardiology with deep-learning–based ECG analysis. Proceedings of the National Academy of Sciences. 118(24), e2020620118.","chicago":"Elul, Yonatan, Aviv A. Rosenberg, Assaf Schuster, Alex M. Bronstein, and Yael Yaniv. “Meeting the Unmet Needs of Clinicians from AI Systems Showcased for Cardiology with Deep-Learning–Based ECG Analysis.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2021. https://doi.org/10.1073/pnas.2020620118.","short":"Y. Elul, A.A. Rosenberg, A. Schuster, A.M. Bronstein, Y. Yaniv, Proceedings of the National Academy of Sciences 118 (2021)."},"article_type":"original","issue":"24","date_created":"2024-10-08T12:58:09Z","publisher":"National Academy of Sciences","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","fulldoi":"https://doi.org/10.1073/pnas.2020620118","pmid":1,"scopus_import":"1","doi":"10.1073/pnas.2020620118","OA_place":"publisher","status":"public","date_published":"2021-06-07T00:00:00Z","type":"journal_article","intvolume":" 118","oa_version":"Published Version","language":[{"iso":"eng"}],"external_id":{"pmid":["34099565"]},"volume":118,"month":"06","quality_controlled":"1","OA_type":"free access"},{"status":"public","has_accepted_license":"1","OA_place":"publisher","scopus_import":"1","pmid":1,"doi":"10.1073/pnas.2107241118","month":"08","OA_type":"hybrid","ddc":["540"],"main_file_link":[{"url":"https://doi.org/10.1073/pnas.2107241118","open_access":"1"}],"quality_controlled":"1","oa_version":"Published Version","intvolume":" 118","type":"journal_article","date_published":"2021-08-13T00:00:00Z","external_id":{"pmid":["34389681"]},"volume":118,"language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"Hierarchically self-assembled materials—structures with order at multiple length scales—can be found everywhere. Examples range from collagen structures in human bones to engineered photonic materials. These structures usually assemble from monodisperse microscopic building blocks that interact via complex directional interactions. In this work, we show that hierarchical materials can, in fact, also be assembled from polydisperse building blocks and by entropic interactions alone. Our simple yet powerful assembly mechanism opens up avenues toward rationally exploiting the often undesired polydispersity of colloidal building blocks for programming entropy-driven self-assembly of hierarchical materials."}],"title":"Hierarchical self-assembly of polydisperse colloidal bananas into a two-dimensional vortex phase","author":[{"id":"492def71-6250-11f0-b278-d41dbd241b62","first_name":"Carla","last_name":"Fernández-Rico","full_name":"Fernández-Rico, Carla"},{"first_name":"Roel P. A.","last_name":"Dullens","full_name":"Dullens, Roel P. A."}],"publication":"Proceedings of the National Academy of Sciences","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"_id":"22211","year":"2021","extern":"1","publication_status":"published","article_processing_charge":"No","day":"13","date_updated":"2026-07-15T07:02:38Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"National Academy of Sciences","date_created":"2026-06-30T06:31:50Z","fulldoi":"https://doi.org/10.1073/pnas.2107241118","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)"},"citation":{"chicago":"Fernández-Rico, Carla, and Roel P. A. Dullens. “Hierarchical Self-Assembly of Polydisperse Colloidal Bananas into a Two-Dimensional Vortex Phase.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2021. https://doi.org/10.1073/pnas.2107241118.","short":"C. Fernández-Rico, R.P.A. Dullens, Proceedings of the National Academy of Sciences 118 (2021).","mla":"Fernández-Rico, Carla, and Roel P. A. Dullens. “Hierarchical Self-Assembly of Polydisperse Colloidal Bananas into a Two-Dimensional Vortex Phase.” Proceedings of the National Academy of Sciences, vol. 118, no. 33, e2107241118, National Academy of Sciences, 2021, doi:10.1073/pnas.2107241118.","apa":"Fernández-Rico, C., & Dullens, R. P. A. (2021). Hierarchical self-assembly of polydisperse colloidal bananas into a two-dimensional vortex phase. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.2107241118","ama":"Fernández-Rico C, Dullens RPA. Hierarchical self-assembly of polydisperse colloidal bananas into a two-dimensional vortex phase. Proceedings of the National Academy of Sciences. 2021;118(33). doi:10.1073/pnas.2107241118","ista":"Fernández-Rico C, Dullens RPA. 2021. Hierarchical self-assembly of polydisperse colloidal bananas into a two-dimensional vortex phase. Proceedings of the National Academy of Sciences. 118(33), e2107241118.","ieee":"C. Fernández-Rico and R. P. A. Dullens, “Hierarchical self-assembly of polydisperse colloidal bananas into a two-dimensional vortex phase,” Proceedings of the National Academy of Sciences, vol. 118, no. 33. National Academy of Sciences, 2021."},"article_number":"e2107241118","oa":1,"issue":"33","article_type":"original"},{"article_number":"e2102350118","oa":1,"citation":{"ieee":"G. H. Choueiri, J. M. Lopez Alonso, A. Varshney, S. Sankar, and B. Hof, “Experimental observation of the origin and structure of elastoinertial turbulence,” Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 45. National Academy of Sciences, 2021.","ista":"Choueiri GH, Lopez Alonso JM, Varshney A, Sankar S, Hof B. 2021. Experimental observation of the origin and structure of elastoinertial turbulence. Proceedings of the National Academy of Sciences of the United States of America. 118(45), e2102350118.","mla":"Choueiri, George H., et al. “Experimental Observation of the Origin and Structure of Elastoinertial Turbulence.” Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 45, e2102350118, National Academy of Sciences, 2021, doi:10.1073/pnas.2102350118.","apa":"Choueiri, G. H., Lopez Alonso, J. M., Varshney, A., Sankar, S., & Hof, B. (2021). Experimental observation of the origin and structure of elastoinertial turbulence. Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. https://doi.org/10.1073/pnas.2102350118","ama":"Choueiri GH, Lopez Alonso JM, Varshney A, Sankar S, Hof B. Experimental observation of the origin and structure of elastoinertial turbulence. Proceedings of the National Academy of Sciences of the United States of America. 2021;118(45). doi:10.1073/pnas.2102350118","chicago":"Choueiri, George H, Jose M Lopez Alonso, Atul Varshney, Sarath Sankar, and Björn Hof. “Experimental Observation of the Origin and Structure of Elastoinertial Turbulence.” Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 2021. https://doi.org/10.1073/pnas.2102350118.","short":"G.H. Choueiri, J.M. Lopez Alonso, A. Varshney, S. Sankar, B. Hof, Proceedings of the National Academy of Sciences of the United States of America 118 (2021)."},"issue":"45","article_type":"original","publisher":"National Academy of Sciences","isi":1,"date_created":"2021-11-17T13:24:24Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","fulldoi":"https://doi.org/10.1073/pnas.2102350118","acknowledgement":"We thank Y. Dubief, R. Kerswell, E. Marensi, V. Shankar, V. Steinberg, and V. Terrapon for discussions and helpful comments. A.V. and B.H. acknowledge funding from the Austrian Science Fund, grant I4188-N30, within the Deutsche Forschungsgemeinschaft research unit FOR 2688.","publication_status":"published","day":"03","article_processing_charge":"No","arxiv":1,"date_updated":"2026-10-02T22:31:05Z","publication":"Proceedings of the National Academy of Sciences of the United States of America","title":"Experimental observation of the origin and structure of elastoinertial turbulence","author":[{"first_name":"George H","id":"448BD5BC-F248-11E8-B48F-1D18A9856A87","full_name":"Choueiri, George H","last_name":"Choueiri"},{"orcid":"0000-0002-0384-2022","first_name":"Jose M","id":"40770848-F248-11E8-B48F-1D18A9856A87","last_name":"Lopez Alonso","full_name":"Lopez Alonso, Jose M"},{"orcid":"0000-0002-3072-5999","id":"2A2006B2-F248-11E8-B48F-1D18A9856A87","first_name":"Atul","full_name":"Varshney, Atul","last_name":"Varshney"},{"last_name":"Sankar","full_name":"Sankar, Sarath","first_name":"Sarath"},{"full_name":"Hof, Björn","last_name":"Hof","id":"3A374330-F248-11E8-B48F-1D18A9856A87","first_name":"Björn","orcid":"0000-0003-2057-2754"}],"abstract":[{"text":"Turbulence generally arises in shear flows if velocities and hence, inertial forces are sufficiently large. In striking contrast, viscoelastic fluids can exhibit disordered motion even at vanishing inertia. Intermediate between these cases, a state of chaotic motion, “elastoinertial turbulence” (EIT), has been observed in a narrow Reynolds number interval. We here determine the origin of EIT in experiments and show that characteristic EIT structures can be detected across an unexpectedly wide range of parameters. Close to onset, a pattern of chevron-shaped streaks emerges in qualitative agreement with linear and weakly nonlinear theory. However, in experiments, the dynamics remain weakly chaotic, and the instability can be traced to far lower Reynolds numbers than permitted by theory. For increasing inertia, the flow undergoes a transformation to a wall mode composed of inclined near-wall streaks and shear layers. This mode persists to what is known as the “maximum drag reduction limit,” and overall EIT is found to dominate viscoelastic flows across more than three orders of magnitude in Reynolds number.","lang":"eng"}],"year":"2021","_id":"10299","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"intvolume":" 118","type":"journal_article","date_published":"2021-11-03T00:00:00Z","oa_version":"Preprint","volume":118,"external_id":{"arxiv":["2103.00023"],"pmid":[" 34732570"],"isi":["000720926900019"]},"keyword":["multidisciplinary","elastoinertial turbulence","viscoelastic flows","elastic instability","drag reduction"],"language":[{"iso":"eng"}],"month":"11","main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/2103.00023"}],"quality_controlled":"1","pmid":1,"scopus_import":"1","doi":"10.1073/pnas.2102350118","related_material":{"record":[{"id":"19906","relation":"dissertation_contains","status":"public"}]},"project":[{"call_identifier":"FWF","grant_number":"I04188","name":"Instabilities in pulsating pipe flow in complex fluids","_id":"238B8092-32DE-11EA-91FC-C7463DDC885E"}],"department":[{"_id":"BjHo"}],"status":"public","corr_author":"1"},{"extern":"1","day":"22","article_processing_charge":"No","publication_status":"published","date_updated":"2023-05-08T10:53:55Z","page":"16660-16666","abstract":[{"lang":"eng","text":"Molecular mechanisms enabling the switching and maintenance of epigenetic states are not fully understood. Distinct histone modifications are often associated with ON/OFF epigenetic states, but how these states are stably maintained through DNA replication, yet in certain situations switch from one to another remains unclear. Here, we address this problem through identification of Arabidopsis INCURVATA11 (ICU11) as a Polycomb Repressive Complex 2 accessory protein. ICU11 robustly immunoprecipitated in vivo with PRC2 core components and the accessory proteins, EMBRYONIC FLOWER 1 (EMF1), LIKE HETEROCHROMATIN PROTEIN1 (LHP1), and TELOMERE_REPEAT_BINDING FACTORS (TRBs). ICU11 encodes a 2-oxoglutarate-dependent dioxygenase, an activity associated with histone demethylation in other organisms, and mutant plants show defects in multiple aspects of the Arabidopsis epigenome. To investigate its primary molecular function we identified the Arabidopsis FLOWERING LOCUS C (FLC) as a direct target and found icu11 disrupted the cold-induced, Polycomb-mediated silencing underlying vernalization. icu11 prevented reduction in H3K36me3 levels normally seen during the early cold phase, supporting a role for ICU11 in H3K36me3 demethylation. This was coincident with an attenuation of H3K27me3 at the internal nucleation site in FLC, and reduction in H3K27me3 levels across the body of the gene after plants were returned to the warm. Thus, ICU11 is required for the cold-induced epigenetic switching between the mutually exclusive chromatin states at FLC, from the active H3K36me3 state to the silenced H3K27me3 state. These data support the importance of physical coupling of histone modification activities to promote epigenetic switching between opposing chromatin states."}],"publication":"Proceedings of the National Academy of Sciences","author":[{"first_name":"Rebecca H.","full_name":"Bloomer, Rebecca H.","last_name":"Bloomer"},{"full_name":"Hutchison, Claire E.","last_name":"Hutchison","first_name":"Claire E."},{"last_name":"Bäurle","full_name":"Bäurle, Isabel","first_name":"Isabel"},{"last_name":"Walker","full_name":"Walker, James","first_name":"James"},{"full_name":"Fang, Xiaofeng","last_name":"Fang","first_name":"Xiaofeng"},{"full_name":"Perera, Pumi","last_name":"Perera","first_name":"Pumi"},{"full_name":"Velanis, Christos N.","last_name":"Velanis","first_name":"Christos N."},{"full_name":"Gümüs, Serin","last_name":"Gümüs","first_name":"Serin"},{"full_name":"Spanos, Christos","last_name":"Spanos","first_name":"Christos"},{"full_name":"Rappsilber, Juri","last_name":"Rappsilber","first_name":"Juri"},{"orcid":"0000-0002-4008-1234","first_name":"Xiaoqi","id":"e0164712-22ee-11ed-b12a-d80fcdf35958","last_name":"Feng","full_name":"Feng, Xiaoqi"},{"full_name":"Goodrich, Justin","last_name":"Goodrich","first_name":"Justin"},{"last_name":"Dean","full_name":"Dean, Caroline","first_name":"Caroline"}],"title":"The Arabidopsis epigenetic regulator ICU11 as an accessory protein of polycomb repressive complex 2","publication_identifier":{"issn":["0027-8424","1091-6490"]},"year":"2020","_id":"12188","file_date_updated":"2023-02-07T11:29:55Z","citation":{"ieee":"R. H. Bloomer et al., “The Arabidopsis epigenetic regulator ICU11 as an accessory protein of polycomb repressive complex 2,” Proceedings of the National Academy of Sciences, vol. 117, no. 28. Proceedings of the National Academy of Sciences, pp. 16660–16666, 2020.","ista":"Bloomer RH, Hutchison CE, Bäurle I, Walker J, Fang X, Perera P, Velanis CN, Gümüs S, Spanos C, Rappsilber J, Feng X, Goodrich J, Dean C. 2020. The Arabidopsis epigenetic regulator ICU11 as an accessory protein of polycomb repressive complex 2. Proceedings of the National Academy of Sciences. 117(28), 16660–16666.","apa":"Bloomer, R. H., Hutchison, C. E., Bäurle, I., Walker, J., Fang, X., Perera, P., … Dean, C. (2020). The Arabidopsis epigenetic regulator ICU11 as an accessory protein of polycomb repressive complex 2. Proceedings of the National Academy of Sciences. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1920621117","ama":"Bloomer RH, Hutchison CE, Bäurle I, et al. The Arabidopsis epigenetic regulator ICU11 as an accessory protein of polycomb repressive complex 2. Proceedings of the National Academy of Sciences. 2020;117(28):16660-16666. doi:10.1073/pnas.1920621117","mla":"Bloomer, Rebecca H., et al. “The Arabidopsis Epigenetic Regulator ICU11 as an Accessory Protein of Polycomb Repressive Complex 2.” Proceedings of the National Academy of Sciences, vol. 117, no. 28, Proceedings of the National Academy of Sciences, 2020, pp. 16660–66, doi:10.1073/pnas.1920621117.","short":"R.H. Bloomer, C.E. Hutchison, I. Bäurle, J. Walker, X. Fang, P. Perera, C.N. Velanis, S. Gümüs, C. Spanos, J. Rappsilber, X. Feng, J. Goodrich, C. Dean, Proceedings of the National Academy of Sciences 117 (2020) 16660–16666.","chicago":"Bloomer, Rebecca H., Claire E. Hutchison, Isabel Bäurle, James Walker, Xiaofeng Fang, Pumi Perera, Christos N. Velanis, et al. “The Arabidopsis Epigenetic Regulator ICU11 as an Accessory Protein of Polycomb Repressive Complex 2.” Proceedings of the National Academy of Sciences. Proceedings of the National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.1920621117."},"oa":1,"article_type":"original","issue":"28","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2023-01-16T09:15:44Z","publisher":"Proceedings of the National Academy of Sciences","fulldoi":"https://doi.org/10.1073/pnas.1920621117","acknowledgement":"We would like to thank Scott Berry for help with ICU-GFP nuclear localization microscopy, Hao Yu and Lisha Shen for assistance with 6mA DNA methylation analysis, Donna Gibson for graphic design assistance, and members of the C.D. and Howard laboratories for helpful discussions. This work was funded by the European Research Council grants to “MEXTIM” (to C.D.) and “SexMeth” (to X. Feng), by the Biotechnological and Biological Sciences Research Council (BBSRC) Institute Strategic Programmes GRO (BB/J004588/1), GEN (BB/P013511/1), BBSRC grant (to X. Feng) (BB/S009620/1), and the Marie Sklodowska–Curie Postdoctoral Fellowships “UNRAVEL” (to R.H.B.) and \"WISDOM\" (to X. Fang). Additional funding via the Wellcome Trust through a Senior Research Fellowship (to J.R.) (103139) and a multiuser equipment grant (108504). The Wellcome Centre for Cell Biology is supported by core funding from the Wellcome Trust (203149).","tmp":{"short":"CC BY (4.0)","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"},"scopus_import":"1","pmid":1,"doi":"10.1073/pnas.1920621117","has_accepted_license":"1","status":"public","department":[{"_id":"XiFe"}],"oa_version":"Published Version","date_published":"2020-05-22T00:00:00Z","type":"journal_article","intvolume":" 117","keyword":["Multidisciplinary"],"language":[{"iso":"eng"}],"external_id":{"pmid":["32601198"]},"volume":117,"month":"05","file":[{"success":1,"file_id":"12526","access_level":"open_access","date_created":"2023-02-07T11:29:55Z","file_size":1105414,"relation":"main_file","content_type":"application/pdf","checksum":"cedee184cb12f454f2fba4158ff47db9","creator":"alisjak","date_updated":"2023-02-07T11:29:55Z","file_name":"2020_PNAS_Bloomer.pdf"}],"ddc":["580"],"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368280/","open_access":"1"}],"quality_controlled":"1"},{"month":"09","ddc":["570"],"main_file_link":[{"url":"https://doi.org/10.1073/pnas.191726911","open_access":"1"}],"quality_controlled":"1","oa_version":"Published Version","intvolume":" 117","acknowledged_ssus":[{"_id":"LifeSc"}],"type":"journal_article","date_published":"2020-09-08T00:00:00Z","volume":117,"external_id":{"pmid":["32848067"]},"language":[{"iso":"eng"}],"status":"public","department":[{"_id":"CaBe"}],"pmid":1,"doi":"10.1073/pnas.1917269117","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"National Academy of Sciences","date_created":"2024-03-04T10:03:52Z","acknowledgement":"We thank the staff of the macromolecular crystallography (MX) and SAXS beamlines at the European Synchrotron Radiation facility, Diamond, and Swiss Light Source for excellent support, and the Life Sciences Facility of the Institute of Science and Technology Austria for usage of the rheometer. We thank Life Sciences editors for editing assistance. EM data were\r\nrecorded at the EM Facility of the Vienna BioCenter Core Facilities (Austria). Confocal microscopy was carried out at the Advanced Instrument Research Facility, Jawaharlal Nehru University. K.D.-C.’s research was supported by the Initial Training Network MUZIC (ITN-MUZIC) (N°238423), Austrian Science Fund (FWF) Projects I525, I1593, P22276, P19060, and W1221, Laura Bassi Centre of Optimized Structural Studies (N°253275), a Wellcome Trust Collaborative Award (201543/Z/16/Z), COST Action BM1405, Vienna Science and Technology Fund (WWTF) Chemical Biology Project LS17-008, and Christian Doppler Laboratory for High-Content Structural Biology and Biotechnology. K.Z., J.L.A., C.S., E.A.G., and A.S. were supported by the University of Vienna, J.K. by a Wellcome Trust Collaborative Award and by the Centre of Optimized Structural Studies, M.P. by FWF Project I1593, E.d.A.R. ITN-MUZIC, and FWF Projects I525 and I1593, and T.C.M. and L.C. by FWF Project I 2408-B22. E.A.G. acknowledges the PhD program Structure and Interaction of Biological Macromolecules. M.B. acknowledges the University Grant Commission, India, for a senior research fellowship. A.B. acknowledges a JC Bose Fellowship from the Science Engineering Research Council. ","fulldoi":"https://doi.org/10.1073/pnas.1917269117","citation":{"ista":"Pinotsis N, Zielinska K, Babuta M, Arolas JL, Kostan J, Khan MB, Schreiner C, Testa Salmazo AP, Ciccarelli L, Puchinger M, Gkougkoulia EA, Ribeiro E de A, Marlovits TC, Bhattacharya A, Djinovic-Carugo K. 2020. Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin. Proceedings of the National Academy of Sciences of the United States of America. 117(36), 22101–22112.","mla":"Pinotsis, Nikos, et al. “Calcium Modulates the Domain Flexibility and Function of an α-Actinin Similar to the Ancestral α-Actinin.” Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 36, National Academy of Sciences, 2020, pp. 22101–12, doi:10.1073/pnas.1917269117.","ama":"Pinotsis N, Zielinska K, Babuta M, et al. Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin. Proceedings of the National Academy of Sciences of the United States of America. 2020;117(36):22101-22112. doi:10.1073/pnas.1917269117","apa":"Pinotsis, N., Zielinska, K., Babuta, M., Arolas, J. L., Kostan, J., Khan, M. B., … Djinovic-Carugo, K. (2020). Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin. Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. https://doi.org/10.1073/pnas.1917269117","ieee":"N. Pinotsis et al., “Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin,” Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 36. National Academy of Sciences, pp. 22101–22112, 2020.","chicago":"Pinotsis, Nikos, Karolina Zielinska, Mrigya Babuta, Joan L. Arolas, Julius Kostan, Muhammad Bashir Khan, Claudia Schreiner, et al. “Calcium Modulates the Domain Flexibility and Function of an α-Actinin Similar to the Ancestral α-Actinin.” Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.1917269117.","short":"N. Pinotsis, K. Zielinska, M. Babuta, J.L. Arolas, J. Kostan, M.B. Khan, C. Schreiner, A.P. Testa Salmazo, L. Ciccarelli, M. Puchinger, E.A. Gkougkoulia, E. de A. Ribeiro, T.C. Marlovits, A. Bhattacharya, K. Djinovic-Carugo, Proceedings of the National Academy of Sciences of the United States of America 117 (2020) 22101–22112."},"oa":1,"issue":"36","article_type":"original","abstract":[{"lang":"eng","text":"The actin cytoskeleton, a dynamic network of actin filaments and associated F-actin–binding proteins, is fundamentally important in eukaryotes. α-Actinins are major F-actin bundlers that are inhibited by Ca2+ in nonmuscle cells. Here we report the mechanism of Ca2+-mediated regulation of Entamoeba histolytica α-actinin-2 (EhActn2) with features expected for the common ancestor of Entamoeba and higher eukaryotic α-actinins. Crystal structures of Ca2+-free and Ca2+-bound EhActn2 reveal a calmodulin-like domain (CaMD) uniquely inserted within the rod domain. Integrative studies reveal an exceptionally high affinity of the EhActn2 CaMD for Ca2+, binding of which can only be regulated in the presence of physiological concentrations of Mg2+. Ca2+ binding triggers an increase in protein multidomain rigidity, reducing conformational flexibility of F-actin–binding domains via interdomain cross-talk and consequently inhibiting F-actin bundling. In vivo studies uncover that EhActn2 plays an important role in phagocytic cup formation and might constitute a new drug target for amoebic dysentery."}],"page":"22101-22112","title":"Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin","author":[{"last_name":"Pinotsis","full_name":"Pinotsis, Nikos","first_name":"Nikos"},{"first_name":"Karolina","full_name":"Zielinska, Karolina","last_name":"Zielinska"},{"last_name":"Babuta","full_name":"Babuta, Mrigya","first_name":"Mrigya"},{"full_name":"Arolas, Joan L.","last_name":"Arolas","first_name":"Joan L."},{"first_name":"Julius","full_name":"Kostan, Julius","last_name":"Kostan"},{"full_name":"Khan, Muhammad Bashir","last_name":"Khan","first_name":"Muhammad Bashir"},{"full_name":"Schreiner, Claudia","last_name":"Schreiner","first_name":"Claudia"},{"last_name":"Testa Salmazo","full_name":"Testa Salmazo, Anita P","first_name":"Anita P","id":"41F1F098-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Ciccarelli, Luciano","last_name":"Ciccarelli","first_name":"Luciano"},{"first_name":"Martin","full_name":"Puchinger, Martin","last_name":"Puchinger"},{"first_name":"Eirini A.","full_name":"Gkougkoulia, Eirini A.","last_name":"Gkougkoulia"},{"full_name":"Ribeiro, Euripedes de Almeida","last_name":"Ribeiro","first_name":"Euripedes de Almeida"},{"full_name":"Marlovits, Thomas C.","last_name":"Marlovits","first_name":"Thomas C."},{"last_name":"Bhattacharya","full_name":"Bhattacharya, Alok","first_name":"Alok"},{"first_name":"Kristina","full_name":"Djinovic-Carugo, Kristina","last_name":"Djinovic-Carugo"}],"publication":"Proceedings of the National Academy of Sciences of the United States of America","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"year":"2020","_id":"15061","publication_status":"published","day":"08","article_processing_charge":"No","date_updated":"2026-06-18T17:45:21Z"},{"acknowledgement":"We thank T. C. T. Michaels for reading the manuscript. This work was supported by the Academy of Medical Science (J.K. and A.Š.), the Cambridge Center for Misfolding Diseases (T.P.J.K.), the Biotechnology and Biological Sciences Research Council (T.P.J.K.), the Frances and Augustus Newman Foundation (T.P.J.K.), the European Research Council Grant PhysProt Agreement 337969, the Wellcome Trust (A.Š. and T.P.J.K.), the Royal Society (A.Š.), the Medical Research Council (J.K. and A.Š.), and the UK Materials and Molecular Modeling Hub for computational resources, which is partially funded by Engineering and Physical Sciences Research Council Grant EP/P020194/1.","fulldoi":"https://doi.org/10.1073/pnas.2007694117","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","date_created":"2021-11-25T15:07:09Z","publisher":"National Academy of Sciences","article_type":"original","issue":"52","citation":{"short":"J. Krausser, T.P.J. Knowles, A. Šarić, Proceedings of the National Academy of Sciences 117 (2020) 33090–33098.","chicago":"Krausser, Johannes, Tuomas P. J. Knowles, and Anđela Šarić. “Physical Mechanisms of Amyloid Nucleation on Fluid Membranes.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.2007694117.","ieee":"J. Krausser, T. P. J. Knowles, and A. Šarić, “Physical mechanisms of amyloid nucleation on fluid membranes,” Proceedings of the National Academy of Sciences, vol. 117, no. 52. National Academy of Sciences, pp. 33090–33098, 2020.","ama":"Krausser J, Knowles TPJ, Šarić A. Physical mechanisms of amyloid nucleation on fluid membranes. Proceedings of the National Academy of Sciences. 2020;117(52):33090-33098. doi:10.1073/pnas.2007694117","apa":"Krausser, J., Knowles, T. P. J., & Šarić, A. (2020). Physical mechanisms of amyloid nucleation on fluid membranes. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.2007694117","mla":"Krausser, Johannes, et al. “Physical Mechanisms of Amyloid Nucleation on Fluid Membranes.” Proceedings of the National Academy of Sciences, vol. 117, no. 52, National Academy of Sciences, 2020, pp. 33090–98, doi:10.1073/pnas.2007694117.","ista":"Krausser J, Knowles TPJ, Šarić A. 2020. Physical mechanisms of amyloid nucleation on fluid membranes. Proceedings of the National Academy of Sciences. 117(52), 33090–33098."},"oa":1,"publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"year":"2020","_id":"10336","page":"33090-33098","abstract":[{"text":"Biological membranes can dramatically accelerate the aggregation of normally soluble protein molecules into amyloid fibrils and alter the fibril morphologies, yet the molecular mechanisms through which this accelerated nucleation takes place are not yet understood. Here, we develop a coarse-grained model to systematically explore the effect that the structural properties of the lipid membrane and the nature of protein–membrane interactions have on the nucleation rates of amyloid fibrils. We identify two physically distinct nucleation pathways—protein-rich and lipid-rich—and quantify how the membrane fluidity and protein–membrane affinity control the relative importance of those molecular pathways. We find that the membrane’s susceptibility to reshaping and being incorporated into the fibrillar aggregates is a key determinant of its ability to promote protein aggregation. We then characterize the rates and the free-energy profile associated with this heterogeneous nucleation process, in which the surface itself participates in the aggregate structure. Finally, we compare quantitatively our data to experiments on membrane-catalyzed amyloid aggregation of α-synuclein, a protein implicated in Parkinson’s disease that predominately nucleates on membranes. More generally, our results provide a framework for understanding macromolecular aggregation on lipid membranes in a broad biological and biotechnological context.","lang":"eng"}],"author":[{"full_name":"Krausser, Johannes","last_name":"Krausser","first_name":"Johannes"},{"first_name":"Tuomas P. J.","last_name":"Knowles","full_name":"Knowles, Tuomas P. J."},{"orcid":"0000-0002-7854-2139","first_name":"Anđela","id":"bf63d406-f056-11eb-b41d-f263a6566d8b","last_name":"Šarić","full_name":"Šarić, Anđela"}],"publication":"Proceedings of the National Academy of Sciences","title":"Physical mechanisms of amyloid nucleation on fluid membranes","date_updated":"2021-11-25T15:35:58Z","extern":"1","article_processing_charge":"No","day":"16","publication_status":"published","main_file_link":[{"url":"https://www.biorxiv.org/content/10.1101/2019.12.22.886267v2","open_access":"1"}],"quality_controlled":"1","month":"12","language":[{"iso":"eng"}],"external_id":{"pmid":["33328273"]},"volume":117,"oa_version":"Published Version","type":"journal_article","date_published":"2020-12-16T00:00:00Z","intvolume":" 117","status":"public","doi":"10.1073/pnas.2007694117","scopus_import":"1","pmid":1},{"pmid":1,"scopus_import":"1","doi":"10.1073/pnas.2006684117","status":"public","date_published":"2020-09-14T00:00:00Z","type":"journal_article","intvolume":" 117","oa_version":"Published Version","keyword":["multidisciplinary"],"language":[{"iso":"eng"}],"external_id":{"pmid":["32929030"]},"volume":117,"month":"09","quality_controlled":"1","main_file_link":[{"url":"https://www.biorxiv.org/content/10.1101/2020.02.22.960716","open_access":"1"}],"day":"14","article_processing_charge":"No","publication_status":"published","extern":"1","date_updated":"2021-11-26T08:59:06Z","publication":"Proceedings of the National Academy of Sciences","title":"Thermodynamic and kinetic design principles for amyloid-aggregation inhibitors","author":[{"last_name":"Michaels","full_name":"Michaels, Thomas C. T.","first_name":"Thomas C. T."},{"last_name":"Šarić","full_name":"Šarić, Anđela","orcid":"0000-0002-7854-2139","id":"bf63d406-f056-11eb-b41d-f263a6566d8b","first_name":"Anđela"},{"last_name":"Meisl","full_name":"Meisl, Georg","first_name":"Georg"},{"last_name":"Heller","full_name":"Heller, Gabriella T.","first_name":"Gabriella T."},{"first_name":"Samo","last_name":"Curk","full_name":"Curk, Samo"},{"full_name":"Arosio, Paolo","last_name":"Arosio","first_name":"Paolo"},{"full_name":"Linse, Sara","last_name":"Linse","first_name":"Sara"},{"first_name":"Christopher M.","full_name":"Dobson, Christopher M.","last_name":"Dobson"},{"full_name":"Vendruscolo, Michele","last_name":"Vendruscolo","first_name":"Michele"},{"first_name":"Tuomas P. J.","full_name":"Knowles, Tuomas P. J.","last_name":"Knowles"}],"page":"24251-24257","abstract":[{"text":"Understanding the mechanism of action of compounds capable of inhibiting amyloid-fibril formation is critical to the development of potential therapeutics against protein-misfolding diseases. A fundamental challenge for progress is the range of possible target species and the disparate timescales involved, since the aggregating proteins are simultaneously the reactants, products, intermediates, and catalysts of the reaction. It is a complex problem, therefore, to choose the states of the aggregating proteins that should be bound by the compounds to achieve the most potent inhibition. We present here a comprehensive kinetic theory of amyloid-aggregation inhibition that reveals the fundamental thermodynamic and kinetic signatures characterizing effective inhibitors by identifying quantitative relationships between the aggregation and binding rate constants. These results provide general physical laws to guide the design and optimization of inhibitors of amyloid-fibril formation, revealing in particular the important role of on-rates in the binding of the inhibitors.","lang":"eng"}],"year":"2020","_id":"10347","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"oa":1,"citation":{"ieee":"T. C. T. Michaels et al., “Thermodynamic and kinetic design principles for amyloid-aggregation inhibitors,” Proceedings of the National Academy of Sciences, vol. 117, no. 39. National Academy of Sciences, pp. 24251–24257, 2020.","ista":"Michaels TCT, Šarić A, Meisl G, Heller GT, Curk S, Arosio P, Linse S, Dobson CM, Vendruscolo M, Knowles TPJ. 2020. Thermodynamic and kinetic design principles for amyloid-aggregation inhibitors. Proceedings of the National Academy of Sciences. 117(39), 24251–24257.","mla":"Michaels, Thomas C. T., et al. “Thermodynamic and Kinetic Design Principles for Amyloid-Aggregation Inhibitors.” Proceedings of the National Academy of Sciences, vol. 117, no. 39, National Academy of Sciences, 2020, pp. 24251–57, doi:10.1073/pnas.2006684117.","apa":"Michaels, T. C. T., Šarić, A., Meisl, G., Heller, G. T., Curk, S., Arosio, P., … Knowles, T. P. J. (2020). Thermodynamic and kinetic design principles for amyloid-aggregation inhibitors. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.2006684117","ama":"Michaels TCT, Šarić A, Meisl G, et al. Thermodynamic and kinetic design principles for amyloid-aggregation inhibitors. Proceedings of the National Academy of Sciences. 2020;117(39):24251-24257. doi:10.1073/pnas.2006684117","chicago":"Michaels, Thomas C. T., Anđela Šarić, Georg Meisl, Gabriella T. Heller, Samo Curk, Paolo Arosio, Sara Linse, Christopher M. Dobson, Michele Vendruscolo, and Tuomas P. J. Knowles. “Thermodynamic and Kinetic Design Principles for Amyloid-Aggregation Inhibitors.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.2006684117.","short":"T.C.T. Michaels, A. Šarić, G. Meisl, G.T. Heller, S. Curk, P. Arosio, S. Linse, C.M. Dobson, M. Vendruscolo, T.P.J. Knowles, Proceedings of the National Academy of Sciences 117 (2020) 24251–24257."},"article_type":"original","issue":"39","date_created":"2021-11-26T07:48:27Z","publisher":"National Academy of Sciences","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","fulldoi":"https://doi.org/10.1073/pnas.2006684117","acknowledgement":"We acknowledge support from Peterhouse, Cambridge (T.C.T.M.); the Swiss National Science Foundation (T.C.T.M.); the Royal Society (A.S. and S.C.); the Academy of Medical Sciences (A.S.); Sidney Sussex College, Cambridge (G.M.); Newnham College, Cambridge (G.T.H.); the Wellcome Trust (T.P.J.K.); the Cambridge Center for Misfolding Diseases (T.P.J.K. and M.V.); the Biotechnology and Biological Sciences Research Council (T.P.J.K.); the Frances and Augustus Newman Foundation (T.P.J.K.); and the Synapsis Foundation for Alzheimer’s disease (P.A.). The research leading to these results has received funding from the European Research Council (ERC) under the European Union’s Seventh Framework Program (FP7/2007-2013) through the ERC Grant PhysProt (Agreement 337969)."},{"year":"2020","_id":"7580","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"title":"Stochastic activation and bistability in a Rab GTPase regulatory network","publication":"Proceedings of the National Academy of Sciences of the United States of America","author":[{"first_name":"Urban","id":"2A58201A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1365-5631","last_name":"Bezeljak","full_name":"Bezeljak, Urban"},{"first_name":"Hrushikesh","full_name":"Loya, Hrushikesh","last_name":"Loya"},{"full_name":"Kaczmarek, Beata M","last_name":"Kaczmarek","id":"36FA4AFA-F248-11E8-B48F-1D18A9856A87","first_name":"Beata M"},{"full_name":"Saunders, Timothy E.","last_name":"Saunders","first_name":"Timothy E."},{"last_name":"Loose","full_name":"Loose, Martin","orcid":"0000-0001-7309-9724","id":"462D4284-F248-11E8-B48F-1D18A9856A87","first_name":"Martin"}],"page":"6504-6549","abstract":[{"text":"The eukaryotic endomembrane system is controlled by small GTPases of the Rab family, which are activated at defined times and locations in a switch-like manner. While this switch is well understood for an individual protein, how regulatory networks produce intracellular activity patterns is currently not known. Here, we combine in vitro reconstitution experiments with computational modeling to study a minimal Rab5 activation network. We find that the molecular interactions in this system give rise to a positive feedback and bistable collective switching of Rab5. Furthermore, we find that switching near the critical point is intrinsically stochastic and provide evidence that controlling the inactive population of Rab5 on the membrane can shape the network response. Notably, we demonstrate that collective switching can spread on the membrane surface as a traveling wave of Rab5 activation. Together, our findings reveal how biochemical signaling networks control vesicle trafficking pathways and how their nonequilibrium properties define the spatiotemporal organization of the cell.","lang":"eng"}],"date_updated":"2026-04-08T07:24:55Z","article_processing_charge":"No","day":"24","publication_status":"published","fulldoi":"https://doi.org/10.1073/pnas.1921027117","date_created":"2020-03-12T05:32:26Z","publisher":"National Academy of Sciences","isi":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_type":"original","issue":"12","oa":1,"citation":{"chicago":"Bezeljak, Urban, Hrushikesh Loya, Beata M Kaczmarek, Timothy E. Saunders, and Martin Loose. “Stochastic Activation and Bistability in a Rab GTPase Regulatory Network.” Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.1921027117.","short":"U. Bezeljak, H. Loya, B.M. Kaczmarek, T.E. Saunders, M. Loose, Proceedings of the National Academy of Sciences of the United States of America 117 (2020) 6504–6549.","mla":"Bezeljak, Urban, et al. “Stochastic Activation and Bistability in a Rab GTPase Regulatory Network.” Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 12, National Academy of Sciences, 2020, pp. 6504–49, doi:10.1073/pnas.1921027117.","ama":"Bezeljak U, Loya H, Kaczmarek BM, Saunders TE, Loose M. Stochastic activation and bistability in a Rab GTPase regulatory network. Proceedings of the National Academy of Sciences of the United States of America. 2020;117(12):6504-6549. doi:10.1073/pnas.1921027117","apa":"Bezeljak, U., Loya, H., Kaczmarek, B. M., Saunders, T. E., & Loose, M. (2020). Stochastic activation and bistability in a Rab GTPase regulatory network. Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. https://doi.org/10.1073/pnas.1921027117","ista":"Bezeljak U, Loya H, Kaczmarek BM, Saunders TE, Loose M. 2020. Stochastic activation and bistability in a Rab GTPase regulatory network. Proceedings of the National Academy of Sciences of the United States of America. 117(12), 6504–6549.","ieee":"U. Bezeljak, H. Loya, B. M. Kaczmarek, T. E. Saunders, and M. Loose, “Stochastic activation and bistability in a Rab GTPase regulatory network,” Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 12. National Academy of Sciences, pp. 6504–6549, 2020."},"department":[{"_id":"MaLo"},{"_id":"CaBe"}],"project":[{"grant_number":"RGY0083/2016","name":"Reconstitution of cell polarity and axis determination in a cell-free system","_id":"2599F062-B435-11E9-9278-68D0E5697425"}],"status":"public","related_material":{"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/proteins-as-molecular-switches/","description":"News on IST Homepage"}],"record":[{"id":"8341","relation":"dissertation_contains","status":"public"}]},"doi":"10.1073/pnas.1921027117","pmid":1,"scopus_import":"1","quality_controlled":"1","main_file_link":[{"url":"https://doi.org/10.1101/776567","open_access":"1"}],"month":"03","language":[{"iso":"eng"}],"external_id":{"pmid":["32161136"],"isi":["000521821800040"]},"volume":117,"date_published":"2020-03-24T00:00:00Z","type":"journal_article","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"intvolume":" 117","oa_version":"Preprint"},{"citation":{"ieee":"D. Xu et al., “Nonlinear hydrodynamic instability and turbulence in pulsatile flow,” Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 21. National Academy of Sciences, pp. 11233–11239, 2020.","mla":"Xu, Duo, et al. “Nonlinear Hydrodynamic Instability and Turbulence in Pulsatile Flow.” Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 21, National Academy of Sciences, 2020, pp. 11233–39, doi:10.1073/pnas.1913716117.","ama":"Xu D, Varshney A, Ma X, et al. Nonlinear hydrodynamic instability and turbulence in pulsatile flow. Proceedings of the National Academy of Sciences of the United States of America. 2020;117(21):11233-11239. doi:10.1073/pnas.1913716117","apa":"Xu, D., Varshney, A., Ma, X., Song, B., Riedl, M., Avila, M., & Hof, B. (2020). Nonlinear hydrodynamic instability and turbulence in pulsatile flow. Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. https://doi.org/10.1073/pnas.1913716117","ista":"Xu D, Varshney A, Ma X, Song B, Riedl M, Avila M, Hof B. 2020. Nonlinear hydrodynamic instability and turbulence in pulsatile flow. Proceedings of the National Academy of Sciences of the United States of America. 117(21), 11233–11239.","short":"D. Xu, A. Varshney, X. Ma, B. Song, M. Riedl, M. Avila, B. Hof, Proceedings of the National Academy of Sciences of the United States of America 117 (2020) 11233–11239.","chicago":"Xu, Duo, Atul Varshney, Xingyu Ma, Baofang Song, Michael Riedl, Marc Avila, and Björn Hof. “Nonlinear Hydrodynamic Instability and Turbulence in Pulsatile Flow.” Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.1913716117."},"oa":1,"issue":"21","article_type":"original","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","isi":1,"publisher":"National Academy of Sciences","date_created":"2020-06-07T22:00:51Z","fulldoi":"https://doi.org/10.1073/pnas.1913716117","ec_funded":1,"publication_status":"published","article_processing_charge":"No","day":"26","date_updated":"2026-04-07T13:29:13Z","arxiv":1,"abstract":[{"text":"Pulsating flows through tubular geometries are laminar provided that velocities are moderate. This in particular is also believed to apply to cardiovascular flows where inertial forces are typically too low to sustain turbulence. On the other hand, flow instabilities and fluctuating shear stresses are held responsible for a variety of cardiovascular diseases. Here we report a nonlinear instability mechanism for pulsating pipe flow that gives rise to bursts of turbulence at low flow rates. Geometrical distortions of small, yet finite, amplitude are found to excite a state consisting of helical vortices during flow deceleration. The resulting flow pattern grows rapidly in magnitude, breaks down into turbulence, and eventually returns to laminar when the flow accelerates. This scenario causes shear stress fluctuations and flow reversal during each pulsation cycle. Such unsteady conditions can adversely affect blood vessels and have been shown to promote inflammation and dysfunction of the shear stress-sensitive endothelial cell layer.","lang":"eng"}],"page":"11233-11239","publication":"Proceedings of the National Academy of Sciences of the United States of America","title":"Nonlinear hydrodynamic instability and turbulence in pulsatile flow","author":[{"full_name":"Xu, Duo","last_name":"Xu","first_name":"Duo","id":"3454D55E-F248-11E8-B48F-1D18A9856A87"},{"id":"2A2006B2-F248-11E8-B48F-1D18A9856A87","first_name":"Atul","orcid":"0000-0002-3072-5999","last_name":"Varshney","full_name":"Varshney, Atul"},{"full_name":"Ma, Xingyu","last_name":"Ma","orcid":"0000-0002-0179-9737","id":"34BADBA6-F248-11E8-B48F-1D18A9856A87","first_name":"Xingyu"},{"last_name":"Song","full_name":"Song, Baofang","first_name":"Baofang"},{"last_name":"Riedl","full_name":"Riedl, Michael","orcid":"0000-0003-4844-6311","first_name":"Michael","id":"3BE60946-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Avila","full_name":"Avila, Marc","first_name":"Marc"},{"full_name":"Hof, Björn","last_name":"Hof","orcid":"0000-0003-2057-2754","id":"3A374330-F248-11E8-B48F-1D18A9856A87","first_name":"Björn"}],"publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"_id":"7932","year":"2020","oa_version":"Preprint","intvolume":" 117","date_published":"2020-05-26T00:00:00Z","type":"journal_article","external_id":{"arxiv":["2005.11190"],"pmid":["32393637"],"isi":["000536797100014"]},"volume":117,"language":[{"iso":"eng"}],"month":"05","main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/2005.11190"}],"quality_controlled":"1","scopus_import":"1","pmid":1,"doi":"10.1073/pnas.1913716117","related_material":{"record":[{"id":"12726","relation":"dissertation_contains","status":"public"},{"status":"public","id":"14530","relation":"dissertation_contains"}],"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/blood-flows-more-turbulent-than-previously-expected/","description":"News on IST Homepage"}]},"status":"public","project":[{"call_identifier":"FWF","_id":"238B8092-32DE-11EA-91FC-C7463DDC885E","grant_number":"I04188","name":"Instabilities in pulsating pipe flow in complex fluids"},{"grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"department":[{"_id":"BjHo"}]},{"month":"10","quality_controlled":"1","ddc":["570"],"file":[{"file_size":1755359,"relation":"main_file","access_level":"open_access","file_id":"8713","success":1,"date_created":"2020-10-27T14:57:50Z","date_updated":"2020-10-27T14:57:50Z","file_name":"2020_PNAS_Maoz.pdf","content_type":"application/pdf","creator":"cziletti","checksum":"c6a24fdecf3f28faf447078e7a274a88"}],"intvolume":" 117","date_published":"2020-10-06T00:00:00Z","type":"journal_article","oa_version":"Published Version","volume":117,"external_id":{"isi":["000579045200012"],"pmid":["32948691"]},"language":[{"iso":"eng"}],"department":[{"_id":"GaTk"}],"has_accepted_license":"1","status":"public","pmid":1,"scopus_import":"1","doi":"10.1073/pnas.1912804117","publisher":"National Academy of Sciences","isi":1,"date_created":"2020-10-25T23:01:16Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)"},"fulldoi":"https://doi.org/10.1073/pnas.1912804117","acknowledgement":"We thank Udi Karpas, Roy Harpaz, Tal Tamir, Adam Haber, and Amir Bar for discussions and suggestions; and especially Oren Forkosh and Walter Senn for invaluable discussions of the learning rule. This work was supported by European Research Council Grant 311238 (to E.S.) and Israel Science Foundation Grant 1629/12 (to E.S.); as well as research support from Martin Kushner Schnur and Mr. and Mrs. Lawrence Feis (E.S.); National Institute of Mental Health Grant R01MH109180 (to R.K.); a Pew Scholarship in Biomedical Sciences (to R.K.); Simons Collaboration on the Global Brain Grant 542997 (to R.K. and E.S.); and a CRCNS (Collaborative Research in Computational Neuroscience) grant (to R.K. and E.S.).","oa":1,"citation":{"chicago":"Maoz, Ori, Gašper Tkačik, Mohamad Saleh Esteki, Roozbeh Kiani, and Elad Schneidman. “Learning Probabilistic Neural Representations with Randomly Connected Circuits.” Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.1912804117.","short":"O. Maoz, G. Tkačik, M.S. Esteki, R. Kiani, E. Schneidman, Proceedings of the National Academy of Sciences of the United States of America 117 (2020) 25066–25073.","ama":"Maoz O, Tkačik G, Esteki MS, Kiani R, Schneidman E. Learning probabilistic neural representations with randomly connected circuits. Proceedings of the National Academy of Sciences of the United States of America. 2020;117(40):25066-25073. doi:10.1073/pnas.1912804117","mla":"Maoz, Ori, et al. “Learning Probabilistic Neural Representations with Randomly Connected Circuits.” Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 40, National Academy of Sciences, 2020, pp. 25066–73, doi:10.1073/pnas.1912804117.","apa":"Maoz, O., Tkačik, G., Esteki, M. S., Kiani, R., & Schneidman, E. (2020). Learning probabilistic neural representations with randomly connected circuits. Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. https://doi.org/10.1073/pnas.1912804117","ista":"Maoz O, Tkačik G, Esteki MS, Kiani R, Schneidman E. 2020. Learning probabilistic neural representations with randomly connected circuits. Proceedings of the National Academy of Sciences of the United States of America. 117(40), 25066–25073.","ieee":"O. Maoz, G. Tkačik, M. S. Esteki, R. Kiani, and E. Schneidman, “Learning probabilistic neural representations with randomly connected circuits,” Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 40. National Academy of Sciences, pp. 25066–25073, 2020."},"file_date_updated":"2020-10-27T14:57:50Z","issue":"40","article_type":"original","title":"Learning probabilistic neural representations with randomly connected circuits","publication":"Proceedings of the National Academy of Sciences of the United States of America","author":[{"first_name":"Ori","last_name":"Maoz","full_name":"Maoz, Ori"},{"first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","last_name":"Tkačik"},{"last_name":"Esteki","full_name":"Esteki, Mohamad Saleh","first_name":"Mohamad Saleh"},{"full_name":"Kiani, Roozbeh","last_name":"Kiani","first_name":"Roozbeh"},{"first_name":"Elad","full_name":"Schneidman, Elad","last_name":"Schneidman"}],"abstract":[{"lang":"eng","text":"The brain represents and reasons probabilistically about complex stimuli and motor actions using a noisy, spike-based neural code. A key building block for such neural computations, as well as the basis for supervised and unsupervised learning, is the ability to estimate the surprise or likelihood of incoming high-dimensional neural activity patterns. Despite progress in statistical modeling of neural responses and deep learning, current approaches either do not scale to large neural populations or cannot be implemented using biologically realistic mechanisms. Inspired by the sparse and random connectivity of real neuronal circuits, we present a model for neural codes that accurately estimates the likelihood of individual spiking patterns and has a straightforward, scalable, efficient, learnable, and realistic neural implementation. This model’s performance on simultaneously recorded spiking activity of >100 neurons in the monkey visual and prefrontal cortices is comparable with or better than that of state-of-the-art models. Importantly, the model can be learned using a small number of samples and using a local learning rule that utilizes noise intrinsic to neural circuits. Slower, structural changes in random connectivity, consistent with rewiring and pruning processes, further improve the efficiency and sparseness of the resulting neural representations. Our results merge insights from neuroanatomy, machine learning, and theoretical neuroscience to suggest random sparse connectivity as a key design principle for neuronal computation."}],"page":"25066-25073","year":"2020","_id":"8698","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"publication_status":"published","day":"06","article_processing_charge":"No","date_updated":"2025-07-10T11:57:16Z"},{"quality_controlled":"1","file":[{"date_updated":"2020-10-28T11:53:12Z","file_name":"2020_PNAS_Paris.pdf","content_type":"application/pdf","checksum":"1638fa36b442e2868576c6dd7d6dc505","creator":"cziletti","file_size":1176522,"relation":"main_file","success":1,"file_id":"8715","access_level":"open_access","date_created":"2020-10-28T11:53:12Z"}],"ddc":["530"],"month":"10","language":[{"iso":"eng"}],"external_id":{"pmid":["32958669"],"isi":["000579059100029"],"arxiv":["2009.12262"]},"volume":117,"type":"journal_article","date_published":"2020-10-06T00:00:00Z","intvolume":" 117","oa_version":"Published Version","department":[{"_id":"MiLe"}],"project":[{"grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"has_accepted_license":"1","status":"public","doi":"10.1073/pnas.2012043117","pmid":1,"scopus_import":"1","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)"},"fulldoi":"https://doi.org/10.1073/pnas.2012043117","acknowledgement":"We gratefully acknowledge C. Sahle for experimental support at the ID20 beamline of the ESRF. The soft X-ray experiments were carried out at the ADRESS beamline of the Swiss Light Source, Paul Scherrer Institut (PSI). E. Paris and T.S. thank X. Lu and C. Monney for valuable discussions. The work at PSI is supported by the Swiss National Science Foundation (SNSF) through Project 200021_178867, the NCCR (National Centre of Competence in Research) MARVEL (Materials’ Revolution: Computational Design and Discovery of Novel Materials) and the Sinergia network Mott Physics Beyond the Heisenberg Model (MPBH) (SNSF Research Grants CRSII2_160765/1 and CRSII2_141962). K.W. acknowledges support by the Narodowe Centrum Nauki Projects 2016/22/E/ST3/00560 and 2016/23/B/ST3/00839. E.M.P. and M.N. acknowledge funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Grant Agreements 754411 and 701647, respectively. M.R. was supported by the Swiss National Science Foundation under Project 200021 – 182695. This research used resources of the APS, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract DE-AC02-06CH11357.","date_created":"2020-10-25T23:01:17Z","isi":1,"publisher":"National Academy of Sciences","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_type":"original","issue":"40","oa":1,"file_date_updated":"2020-10-28T11:53:12Z","citation":{"ieee":"E. Paris et al., “Strain engineering of the charge and spin-orbital interactions in Sr2IrO4,” Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 40. National Academy of Sciences, pp. 24764–24770, 2020.","ista":"Paris E, Tseng Y, Paerschke E, Zhang W, Upton MH, Efimenko A, Rolfs K, McNally DE, Maurel L, Naamneh M, Caputo M, Strocov VN, Wang Z, Casa D, Schneider CW, Pomjakushina E, Wohlfeld K, Radovic M, Schmitt T. 2020. Strain engineering of the charge and spin-orbital interactions in Sr2IrO4. Proceedings of the National Academy of Sciences of the United States of America. 117(40), 24764–24770.","ama":"Paris E, Tseng Y, Paerschke E, et al. Strain engineering of the charge and spin-orbital interactions in Sr2IrO4. Proceedings of the National Academy of Sciences of the United States of America. 2020;117(40):24764-24770. doi:10.1073/pnas.2012043117","mla":"Paris, Eugenio, et al. “Strain Engineering of the Charge and Spin-Orbital Interactions in Sr2IrO4.” Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 40, National Academy of Sciences, 2020, pp. 24764–70, doi:10.1073/pnas.2012043117.","apa":"Paris, E., Tseng, Y., Paerschke, E., Zhang, W., Upton, M. H., Efimenko, A., … Schmitt, T. (2020). Strain engineering of the charge and spin-orbital interactions in Sr2IrO4. Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. https://doi.org/10.1073/pnas.2012043117","chicago":"Paris, Eugenio, Yi Tseng, Ekaterina Paerschke, Wenliang Zhang, Mary H Upton, Anna Efimenko, Katharina Rolfs, et al. “Strain Engineering of the Charge and Spin-Orbital Interactions in Sr2IrO4.” Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.2012043117.","short":"E. Paris, Y. Tseng, E. Paerschke, W. Zhang, M.H. Upton, A. Efimenko, K. Rolfs, D.E. McNally, L. Maurel, M. Naamneh, M. Caputo, V.N. Strocov, Z. Wang, D. Casa, C.W. Schneider, E. Pomjakushina, K. Wohlfeld, M. Radovic, T. Schmitt, Proceedings of the National Academy of Sciences of the United States of America 117 (2020) 24764–24770."},"year":"2020","_id":"8699","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"title":"Strain engineering of the charge and spin-orbital interactions in Sr2IrO4","publication":"Proceedings of the National Academy of Sciences of the United States of America","author":[{"last_name":"Paris","full_name":"Paris, Eugenio","first_name":"Eugenio"},{"first_name":"Yi","last_name":"Tseng","full_name":"Tseng, Yi"},{"full_name":"Paerschke, Ekaterina","last_name":"Paerschke","first_name":"Ekaterina","id":"8275014E-6063-11E9-9B7F-6338E6697425","orcid":"0000-0003-0853-8182"},{"first_name":"Wenliang","last_name":"Zhang","full_name":"Zhang, Wenliang"},{"first_name":"Mary H","last_name":"Upton","full_name":"Upton, Mary H"},{"last_name":"Efimenko","full_name":"Efimenko, Anna","first_name":"Anna"},{"full_name":"Rolfs, Katharina","last_name":"Rolfs","first_name":"Katharina"},{"first_name":"Daniel E","last_name":"McNally","full_name":"McNally, Daniel E"},{"first_name":"Laura","last_name":"Maurel","full_name":"Maurel, Laura"},{"first_name":"Muntaser","full_name":"Naamneh, Muntaser","last_name":"Naamneh"},{"full_name":"Caputo, Marco","last_name":"Caputo","first_name":"Marco"},{"last_name":"Strocov","full_name":"Strocov, Vladimir N","first_name":"Vladimir N"},{"full_name":"Wang, Zhiming","last_name":"Wang","first_name":"Zhiming"},{"first_name":"Diego","full_name":"Casa, Diego","last_name":"Casa"},{"last_name":"Schneider","full_name":"Schneider, Christof W","first_name":"Christof W"},{"full_name":"Pomjakushina, Ekaterina","last_name":"Pomjakushina","first_name":"Ekaterina"},{"last_name":"Wohlfeld","full_name":"Wohlfeld, Krzysztof","first_name":"Krzysztof"},{"first_name":"Milan","full_name":"Radovic, Milan","last_name":"Radovic"},{"last_name":"Schmitt","full_name":"Schmitt, Thorsten","first_name":"Thorsten"}],"page":"24764-24770","abstract":[{"lang":"eng","text":"In the high spin–orbit-coupled Sr2IrO4, the high sensitivity of the ground state to the details of the local lattice structure shows a large potential for the manipulation of the functional properties by inducing local lattice distortions. We use epitaxial strain to modify the Ir–O bond geometry in Sr2IrO4 and perform momentum-dependent resonant inelastic X-ray scattering (RIXS) at the metal and at the ligand sites to unveil the response of the low-energy elementary excitations. We observe that the pseudospin-wave dispersion for tensile-strained Sr2IrO4 films displays large softening along the [h,0] direction, while along the [h,h] direction it shows hardening. This evolution reveals a renormalization of the magnetic interactions caused by a strain-driven cross-over from anisotropic to isotropic interactions between the magnetic moments. Moreover, we detect dispersive electron–hole pair excitations which shift to lower (higher) energies upon compressive (tensile) strain, manifesting a reduction (increase) in the size of the charge gap. This behavior shows an intimate coupling between charge excitations and lattice distortions in Sr2IrO4, originating from the modified hopping elements between the t2g orbitals. Our work highlights the central role played by the lattice degrees of freedom in determining both the pseudospin and charge excitations of Sr2IrO4 and provides valuable information toward the control of the ground state of complex oxides in the presence of high spin–orbit coupling."}],"date_updated":"2025-07-10T11:57:17Z","arxiv":1,"day":"06","article_processing_charge":"No","publication_status":"published","ec_funded":1},{"year":"2020","_id":"9000","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"author":[{"last_name":"Grah","full_name":"Grah, Rok","first_name":"Rok","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2539-3560"},{"last_name":"Zoller","full_name":"Zoller, Benjamin","first_name":"Benjamin"},{"orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper","full_name":"Tkačik, Gašper","last_name":"Tkačik"}],"publication":"Proceedings of the National Academy of Sciences of the United States of America","title":"Nonequilibrium models of optimal enhancer function","abstract":[{"text":"In prokaryotes, thermodynamic models of gene regulation provide a highly quantitative mapping from promoter sequences to gene-expression levels that is compatible with in vivo and in vitro biophysical measurements. Such concordance has not been achieved for models of enhancer function in eukaryotes. In equilibrium models, it is difficult to reconcile the reported short transcription factor (TF) residence times on the DNA with the high specificity of regulation. In nonequilibrium models, progress is difficult due to an explosion in the number of parameters. Here, we navigate this complexity by looking for minimal nonequilibrium enhancer models that yield desired regulatory phenotypes: low TF residence time, high specificity, and tunable cooperativity. We find that a single extra parameter, interpretable as the “linking rate,” by which bound TFs interact with Mediator components, enables our models to escape equilibrium bounds and access optimal regulatory phenotypes, while remaining consistent with the reported phenomenology and simple enough to be inferred from upcoming experiments. We further find that high specificity in nonequilibrium models is in a trade-off with gene-expression noise, predicting bursty dynamics—an experimentally observed hallmark of eukaryotic transcription. By drastically reducing the vast parameter space of nonequilibrium enhancer models to a much smaller subspace that optimally realizes biological function, we deliver a rich class of models that could be tractably inferred from data in the near future.","lang":"eng"}],"page":"31614-31622","date_updated":"2025-05-14T10:57:50Z","publication_status":"published","article_processing_charge":"No","day":"15","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)"},"fulldoi":"https://doi.org/10.1073/pnas.2006731117","acknowledgement":"G.T. was supported by Human Frontiers Science Program Grant RGP0034/2018. R.G. was supported by the Austrian Academy of Sciences DOC Fellowship. R.G. thanks S. Avvakumov for helpful discussions.","publisher":"National Academy of Sciences","isi":1,"date_created":"2021-01-10T23:01:17Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","issue":"50","article_type":"original","oa":1,"citation":{"short":"R. Grah, B. Zoller, G. Tkačik, Proceedings of the National Academy of Sciences of the United States of America 117 (2020) 31614–31622.","chicago":"Grah, Rok, Benjamin Zoller, and Gašper Tkačik. “Nonequilibrium Models of Optimal Enhancer Function.” Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.2006731117.","ieee":"R. Grah, B. Zoller, and G. Tkačik, “Nonequilibrium models of optimal enhancer function,” Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 50. National Academy of Sciences, pp. 31614–31622, 2020.","ista":"Grah R, Zoller B, Tkačik G. 2020. Nonequilibrium models of optimal enhancer function. Proceedings of the National Academy of Sciences of the United States of America. 117(50), 31614–31622.","apa":"Grah, R., Zoller, B., & Tkačik, G. (2020). Nonequilibrium models of optimal enhancer function. Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. https://doi.org/10.1073/pnas.2006731117","ama":"Grah R, Zoller B, Tkačik G. Nonequilibrium models of optimal enhancer function. Proceedings of the National Academy of Sciences of the United States of America. 2020;117(50):31614-31622. doi:10.1073/pnas.2006731117","mla":"Grah, Rok, et al. “Nonequilibrium Models of Optimal Enhancer Function.” Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 50, National Academy of Sciences, 2020, pp. 31614–22, doi:10.1073/pnas.2006731117."},"file_date_updated":"2021-01-11T08:37:31Z","corr_author":"1","project":[{"_id":"2665AAFE-B435-11E9-9278-68D0E5697425","grant_number":"RGP0034/2018","name":"Can evolution minimize spurious signaling crosstalk to reach optimal performance?"},{"name":"Biophysically realistic genotype-phenotype maps for regulatory networks","_id":"267C84F4-B435-11E9-9278-68D0E5697425"}],"department":[{"_id":"GaTk"}],"has_accepted_license":"1","status":"public","doi":"10.1073/pnas.2006731117","related_material":{"link":[{"description":"News on IST Homepage","url":"https://ist.ac.at/en/news/new-compact-model-for-gene-regulation-in-higher-organisms/","relation":"press_release"}]},"pmid":1,"scopus_import":"1","quality_controlled":"1","ddc":["570"],"file":[{"date_updated":"2021-01-11T08:37:31Z","file_name":"2020_PNAS_Grah.pdf","content_type":"application/pdf","creator":"dernst","checksum":"69039cd402a571983aa6cb4815ffa863","file_size":1199247,"relation":"main_file","access_level":"open_access","file_id":"9004","success":1,"date_created":"2021-01-11T08:37:31Z"}],"month":"12","volume":117,"external_id":{"isi":["000600608300015"],"pmid":["33268497"]},"language":[{"iso":"eng"}],"intvolume":" 117","type":"journal_article","date_published":"2020-12-15T00:00:00Z","oa_version":"Published Version"},{"year":"2020","_id":"22542","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"title":"Seasonal hysteresis of surface urban heat islands","publication":"Proceedings of the National Academy of Sciences","author":[{"full_name":"Manoli, Gabriele","last_name":"Manoli","first_name":"Gabriele"},{"id":"cf8e546b-a9b0-11f0-a43b-aa89ed1b56d6","first_name":"Simone","full_name":"Fatichi, Simone","last_name":"Fatichi"},{"first_name":"Elie","full_name":"Bou-Zeid, Elie","last_name":"Bou-Zeid"},{"full_name":"Katul, Gabriel G.","last_name":"Katul","first_name":"Gabriel G."}],"page":"7082-7089","abstract":[{"text":"Temporal dynamics of urban warming have been extensivelystudied at the diurnal scale, but the impact of background cli-mate on the observed seasonality of surface urban heat islands(SUHIs) remains largely unexplored. On seasonal time scales, theintensity of urban–rural surface temperature differences (∆Ts)exhibits distinctive hysteretic cycles whose shape and loopingdirection vary across climatic zones. These observations high-light possible delays underlying the dynamics of the coupledurban–biosphere system. However, a general argument explain-ing the observed hysteretic patterns remains elusive. A coarse-grained model of SUHI coupled with a stochastic soil waterbalance is developed to demonstrate that the time lags betweenradiation forcing, air temperature, and rainfall generate a rate-dependent hysteresis, explaining the observed seasonal varia-tions of ∆Ts. If solar radiation is in phase with water availability,summer conditions cause strong SUHI intensities due to highrural evaporative cooling. Conversely, cities in seasonally dryregions where evapotranspiration is out of phase with radia-tion show a summertime oasis effect controlled by backgroundclimate and vegetation properties. These seasonal patterns ofwarming and cooling have significant implications for heat mit-igation strategies as urban green spaces can reduce ∆Ts duringsummertime, while potentially negative effects of albedo man-agement during winter are mitigated by the seasonality of solarradiation.","lang":"eng"}],"date_updated":"2026-08-07T09:21:58Z","article_processing_charge":"No","day":"31","publication_status":"published","extern":"1","fulldoi":"https://doi.org/10.1073/pnas.1917554117","date_created":"2026-07-27T12:30:24Z","publisher":"National Academy of Sciences","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","article_type":"original","issue":"13","oa":1,"das_tickbox":"1","citation":{"ieee":"G. Manoli, S. Fatichi, E. Bou-Zeid, and G. G. Katul, “Seasonal hysteresis of surface urban heat islands,” Proceedings of the National Academy of Sciences, vol. 117, no. 13. National Academy of Sciences, pp. 7082–7089, 2020.","apa":"Manoli, G., Fatichi, S., Bou-Zeid, E., & Katul, G. G. (2020). Seasonal hysteresis of surface urban heat islands. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.1917554117","mla":"Manoli, Gabriele, et al. “Seasonal Hysteresis of Surface Urban Heat Islands.” Proceedings of the National Academy of Sciences, vol. 117, no. 13, National Academy of Sciences, 2020, pp. 7082–89, doi:10.1073/pnas.1917554117.","ama":"Manoli G, Fatichi S, Bou-Zeid E, Katul GG. Seasonal hysteresis of surface urban heat islands. Proceedings of the National Academy of Sciences. 2020;117(13):7082-7089. doi:10.1073/pnas.1917554117","ista":"Manoli G, Fatichi S, Bou-Zeid E, Katul GG. 2020. Seasonal hysteresis of surface urban heat islands. Proceedings of the National Academy of Sciences. 117(13), 7082–7089.","chicago":"Manoli, Gabriele, Simone Fatichi, Elie Bou-Zeid, and Gabriel G. Katul. “Seasonal Hysteresis of Surface Urban Heat Islands.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.1917554117.","short":"G. Manoli, S. Fatichi, E. Bou-Zeid, G.G. Katul, Proceedings of the National Academy of Sciences 117 (2020) 7082–7089."},"OA_place":"publisher","status":"public","doi":"10.1073/pnas.1917554117","pmid":1,"scopus_import":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1073/pnas.1917554117"}],"quality_controlled":"1","OA_type":"free access","month":"03","keyword":["Cities","Hysteresis","Seasonality","Surface temperature","Urban heat island"],"language":[{"iso":"eng"}],"external_id":{"pmid":["32184330 "]},"volume":117,"type":"journal_article","date_published":"2020-03-31T00:00:00Z","intvolume":" 117","oa_version":"Published Version"},{"project":[{"grant_number":"742985","_id":"261099A6-B435-11E9-9278-68D0E5697425","name":"Tracing Evolution of Auxin Transport and Polarity in Plants","call_identifier":"H2020"},{"call_identifier":"FWF","name":"RNA-directed DNA methylation in plant development","grant_number":"P29988","_id":"262EF96E-B435-11E9-9278-68D0E5697425"}],"OA_place":"publisher","department":[{"_id":"JiFr"},{"_id":"EvBe"}],"has_accepted_license":"1","status":"public","corr_author":"1","pmid":1,"scopus_import":"1","doi":"10.1073/pnas.2003346117","related_material":{"record":[{"id":"9992","relation":"dissertation_contains","status":"public"}],"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/how-wounded-plants-coordinate-their-healing/","description":"News on IST Homepage"}]},"month":"06","quality_controlled":"1","OA_type":"hybrid","ddc":["580"],"file":[{"file_name":"2020_PNAS_Hoermayer.pdf","date_updated":"2020-07-14T12:48:07Z","checksum":"908b09437680181de9990915f2113aca","creator":"dernst","content_type":"application/pdf","relation":"main_file","file_size":2407102,"date_created":"2020-06-23T11:30:53Z","file_id":"8009","access_level":"open_access"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"intvolume":" 117","date_published":"2020-06-30T00:00:00Z","type":"journal_article","oa_version":"Published Version","volume":117,"external_id":{"isi":["000565729700033"],"pmid":["32541049"]},"language":[{"iso":"eng"}],"author":[{"full_name":"Hörmayer, Lukas","last_name":"Hörmayer","orcid":"0000-0001-8295-2926","id":"2EEE7A2A-F248-11E8-B48F-1D18A9856A87","first_name":"Lukas"},{"last_name":"Montesinos López","full_name":"Montesinos López, Juan C","orcid":"0000-0001-9179-6099","first_name":"Juan C","id":"310A8E3E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Marhavá, Petra","last_name":"Marhavá","id":"44E59624-F248-11E8-B48F-1D18A9856A87","first_name":"Petra"},{"id":"38F4F166-F248-11E8-B48F-1D18A9856A87","first_name":"Eva","orcid":"0000-0002-8510-9739","full_name":"Benková, Eva","last_name":"Benková"},{"last_name":"Yoshida","full_name":"Yoshida, Saiko","orcid":"0000-0001-6111-9353","first_name":"Saiko","id":"2E46069C-F248-11E8-B48F-1D18A9856A87"},{"id":"4159519E-F248-11E8-B48F-1D18A9856A87","first_name":"Jiří","orcid":"0000-0002-8302-7596","last_name":"Friml","full_name":"Friml, Jiří"}],"publication":"Proceedings of the National Academy of Sciences of the United States of America","title":"Wounding-induced changes in cellular pressure and localized auxin signalling spatially coordinate restorative divisions in roots","abstract":[{"lang":"eng","text":"Wound healing in plant tissues, consisting of rigid cell wall-encapsulated cells, represents a considerable challenge and occurs through largely unknown mechanisms distinct from those in animals. Owing to their inability to migrate, plant cells rely on targeted cell division and expansion to regenerate wounds. Strict coordination of these wound-induced responses is essential to ensure efficient, spatially restricted wound healing. Single-cell tracking by live imaging allowed us to gain mechanistic insight into the wound perception and coordination of wound responses after laser-based wounding in Arabidopsis root. We revealed a crucial contribution of the collapse of damaged cells in wound perception and detected an auxin increase specific to cells immediately adjacent to the wound. This localized auxin increase balances wound-induced cell expansion and restorative division rates in a dose-dependent manner, leading to tumorous overproliferation when the canonical TIR1 auxin signaling is disrupted. Auxin and wound-induced turgor pressure changes together also spatially define the activation of key components of regeneration, such as the transcription regulator ERF115. Our observations suggest that the wound signaling involves the sensing of collapse of damaged cells and a local auxin signaling activation to coordinate the downstream transcriptional responses in the immediate wound vicinity."}],"_id":"8002","year":"2020","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"publication_status":"published","day":"30","article_processing_charge":"Yes (in subscription journal)","ec_funded":1,"date_updated":"2026-10-02T22:30:28Z","publisher":"National Academy of Sciences","isi":1,"date_created":"2020-06-22T13:33:52Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)"},"fulldoi":"https://doi.org/10.1073/pnas.2003346117","article_number":"202003346","oa":1,"citation":{"mla":"Hörmayer, Lukas, et al. “Wounding-Induced Changes in Cellular Pressure and Localized Auxin Signalling Spatially Coordinate Restorative Divisions in Roots.” Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 26, 202003346, National Academy of Sciences, 2020, doi:10.1073/pnas.2003346117.","apa":"Hörmayer, L., Montesinos López, J. C., Marhavá, P., Benková, E., Yoshida, S., & Friml, J. (2020). Wounding-induced changes in cellular pressure and localized auxin signalling spatially coordinate restorative divisions in roots. Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. https://doi.org/10.1073/pnas.2003346117","ama":"Hörmayer L, Montesinos López JC, Marhavá P, Benková E, Yoshida S, Friml J. Wounding-induced changes in cellular pressure and localized auxin signalling spatially coordinate restorative divisions in roots. Proceedings of the National Academy of Sciences of the United States of America. 2020;117(26). doi:10.1073/pnas.2003346117","ista":"Hörmayer L, Montesinos López JC, Marhavá P, Benková E, Yoshida S, Friml J. 2020. Wounding-induced changes in cellular pressure and localized auxin signalling spatially coordinate restorative divisions in roots. Proceedings of the National Academy of Sciences of the United States of America. 117(26), 202003346.","ieee":"L. Hörmayer, J. C. Montesinos López, P. Marhavá, E. Benková, S. Yoshida, and J. Friml, “Wounding-induced changes in cellular pressure and localized auxin signalling spatially coordinate restorative divisions in roots,” Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 26. National Academy of Sciences, 2020.","short":"L. Hörmayer, J.C. Montesinos López, P. Marhavá, E. Benková, S. Yoshida, J. Friml, Proceedings of the National Academy of Sciences of the United States of America 117 (2020).","chicago":"Hörmayer, Lukas, Juan C Montesinos López, Petra Marhavá, Eva Benková, Saiko Yoshida, and Jiří Friml. “Wounding-Induced Changes in Cellular Pressure and Localized Auxin Signalling Spatially Coordinate Restorative Divisions in Roots.” Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.2003346117."},"file_date_updated":"2020-07-14T12:48:07Z","issue":"26","article_type":"original"},{"fulldoi":"https://doi.org/10.1073/pnas.1907189116","publisher":"Proceedings of the National Academy of Sciences","date_created":"2023-08-09T13:10:36Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","issue":"48","article_type":"original","oa":1,"citation":{"ista":"Baykusheva DR, Zindel D, Svoboda V, Bommeli E, Ochsner M, Tehlar A, Wörner HJ. 2019. Real-time probing of chirality during a chemical reaction. Proceedings of the National Academy of Sciences. 116(48), 23923–23929.","mla":"Baykusheva, Denitsa Rangelova, et al. “Real-Time Probing of Chirality during a Chemical Reaction.” Proceedings of the National Academy of Sciences, vol. 116, no. 48, Proceedings of the National Academy of Sciences, 2019, pp. 23923–29, doi:10.1073/pnas.1907189116.","apa":"Baykusheva, D. R., Zindel, D., Svoboda, V., Bommeli, E., Ochsner, M., Tehlar, A., & Wörner, H. J. (2019). Real-time probing of chirality during a chemical reaction. Proceedings of the National Academy of Sciences. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1907189116","ama":"Baykusheva DR, Zindel D, Svoboda V, et al. Real-time probing of chirality during a chemical reaction. Proceedings of the National Academy of Sciences. 2019;116(48):23923-23929. doi:10.1073/pnas.1907189116","ieee":"D. R. Baykusheva et al., “Real-time probing of chirality during a chemical reaction,” Proceedings of the National Academy of Sciences, vol. 116, no. 48. Proceedings of the National Academy of Sciences, pp. 23923–23929, 2019.","chicago":"Baykusheva, Denitsa Rangelova, Daniel Zindel, Vít Svoboda, Elias Bommeli, Manuel Ochsner, Andres Tehlar, and Hans Jakob Wörner. “Real-Time Probing of Chirality during a Chemical Reaction.” Proceedings of the National Academy of Sciences. Proceedings of the National Academy of Sciences, 2019. https://doi.org/10.1073/pnas.1907189116.","short":"D.R. Baykusheva, D. Zindel, V. Svoboda, E. Bommeli, M. Ochsner, A. Tehlar, H.J. Wörner, Proceedings of the National Academy of Sciences 116 (2019) 23923–23929."},"_id":"14001","year":"2019","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"publication":"Proceedings of the National Academy of Sciences","title":"Real-time probing of chirality during a chemical reaction","author":[{"last_name":"Baykusheva","full_name":"Baykusheva, Denitsa Rangelova","id":"71b4d059-2a03-11ee-914d-dfa3beed6530","first_name":"Denitsa Rangelova"},{"full_name":"Zindel, Daniel","last_name":"Zindel","first_name":"Daniel"},{"first_name":"Vít","last_name":"Svoboda","full_name":"Svoboda, Vít"},{"first_name":"Elias","last_name":"Bommeli","full_name":"Bommeli, Elias"},{"last_name":"Ochsner","full_name":"Ochsner, Manuel","first_name":"Manuel"},{"first_name":"Andres","last_name":"Tehlar","full_name":"Tehlar, Andres"},{"first_name":"Hans Jakob","full_name":"Wörner, Hans Jakob","last_name":"Wörner"}],"abstract":[{"lang":"eng","text":"Chiral molecules interact and react differently with other chiral objects, depending on their handedness. Therefore, it is essential to understand and ultimately control the evolution of molecular chirality during chemical reactions. Although highly sophisticated techniques for the controlled synthesis of chiral molecules have been developed, the observation of chirality on the natural femtosecond time scale of a chemical reaction has so far remained out of reach in the gas phase. Here, we demonstrate a general experimental technique, based on high-harmonic generation in tailored laser fields, and apply it to probe the time evolution of molecular chirality during the photodissociation of 2-iodobutane. These measurements show a change in sign and a pronounced increase in the magnitude of the chiral response over the first 100 fs, followed by its decay within less than 500 fs, revealing the photodissociation to achiral products. The observed time evolution is explained in terms of the variation of the electric and magnetic transition-dipole moments between the lowest electronic states of the cation as a function of the reaction coordinate. These results open the path to investigations of the chirality of molecular-reaction pathways, light-induced chirality in chemical processes, and the control of molecular chirality through tailored laser pulses."}],"page":"23923-23929","date_updated":"2023-08-22T07:40:05Z","arxiv":1,"publication_status":"published","article_processing_charge":"No","day":"13","extern":"1","main_file_link":[{"url":"https://doi.org/10.1073/pnas.1907189116","open_access":"1"}],"quality_controlled":"1","month":"11","volume":116,"external_id":{"pmid":["31723044"],"arxiv":["1906.10818"]},"language":[{"iso":"eng"}],"keyword":["Multidisciplinary"],"intvolume":" 116","type":"journal_article","date_published":"2019-11-13T00:00:00Z","oa_version":"Published Version","status":"public","doi":"10.1073/pnas.1907189116","pmid":1,"scopus_import":"1"},{"oa_version":"Published Version","intvolume":" 116","type":"journal_article","date_published":"2019-07-02T00:00:00Z","volume":116,"external_id":{"pmid":["31213533"]},"language":[{"iso":"eng"}],"month":"07","OA_type":"hybrid","ddc":["570"],"quality_controlled":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1073/pnas.1901795116"}],"scopus_import":"1","pmid":1,"doi":"10.1073/pnas.1901795116","status":"public","has_accepted_license":"1","OA_place":"publisher","citation":{"ieee":"R. J. Perry et al., “Leptin’s hunger-suppressing effects are mediated by the hypothalamic–pituitary–adrenocortical axis in rodents,” Proceedings of the National Academy of Sciences, vol. 116, no. 27. National Academy of Sciences, pp. 13670–13679, 2019.","ista":"Perry RJ, Resch JM, Douglass AM, Madara JC, Rabin-Court A, Kucukdereli H, Wu C, Song JD, Lowell BB, Shulman GI. 2019. Leptin’s hunger-suppressing effects are mediated by the hypothalamic–pituitary–adrenocortical axis in rodents. Proceedings of the National Academy of Sciences. 116(27), 13670–13679.","mla":"Perry, Rachel J., et al. “Leptin’s Hunger-Suppressing Effects Are Mediated by the Hypothalamic–Pituitary–Adrenocortical Axis in Rodents.” Proceedings of the National Academy of Sciences, vol. 116, no. 27, National Academy of Sciences, 2019, pp. 13670–79, doi:10.1073/pnas.1901795116.","apa":"Perry, R. J., Resch, J. M., Douglass, A. M., Madara, J. C., Rabin-Court, A., Kucukdereli, H., … Shulman, G. I. (2019). Leptin’s hunger-suppressing effects are mediated by the hypothalamic–pituitary–adrenocortical axis in rodents. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.1901795116","ama":"Perry RJ, Resch JM, Douglass AM, et al. Leptin’s hunger-suppressing effects are mediated by the hypothalamic–pituitary–adrenocortical axis in rodents. Proceedings of the National Academy of Sciences. 2019;116(27):13670-13679. doi:10.1073/pnas.1901795116","chicago":"Perry, Rachel J., Jon M. Resch, Amelia M. Douglass, Joseph C. Madara, Aviva Rabin-Court, Hakan Kucukdereli, Chen Wu, Joongyu D. Song, Bradford B. Lowell, and Gerald I. Shulman. “Leptin’s Hunger-Suppressing Effects Are Mediated by the Hypothalamic–Pituitary–Adrenocortical Axis in Rodents.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2019. https://doi.org/10.1073/pnas.1901795116.","short":"R.J. Perry, J.M. Resch, A.M. Douglass, J.C. Madara, A. Rabin-Court, H. Kucukdereli, C. Wu, J.D. Song, B.B. Lowell, G.I. Shulman, Proceedings of the National Academy of Sciences 116 (2019) 13670–13679."},"oa":1,"issue":"27","article_type":"original","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"National Academy of Sciences","date_created":"2025-04-03T12:30:19Z","fulldoi":"https://doi.org/10.1073/pnas.1901795116","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)"},"extern":"1","publication_status":"published","article_processing_charge":"Yes (in subscription journal)","day":"02","date_updated":"2025-07-10T11:51:42Z","abstract":[{"lang":"eng","text":"Leptin informs the brain about sufficiency of fuel stores. When insufficient, leptin levels fall, triggering compensatory increases in appetite. Falling leptin is first sensed by hypothalamic neurons, which then initiate adaptive responses. With regard to hunger, it is thought that leptin-sensing neurons work entirely via circuits within the central nervous system (CNS). Very unexpectedly, however, we now show this is not the case. Instead, stimulation of hunger requires an intervening endocrine step, namely activation of the hypothalamic–pituitary–adrenocortical (HPA) axis. Increased corticosterone then activates AgRP neurons to fully increase hunger. Importantly, this is true for 2 forms of low leptin-induced hunger, fasting and poorly controlled type 1 diabetes. Hypoglycemia, which also stimulates hunger by activating CNS neurons, albeit independently of leptin, similarly recruits and requires this pathway by which HPA axis activity stimulates AgRP neurons. Thus, HPA axis regulation of AgRP neurons is a previously underappreciated step in homeostatic regulation of hunger."}],"page":"13670-13679","publication":"Proceedings of the National Academy of Sciences","title":"Leptin’s hunger-suppressing effects are mediated by the hypothalamic–pituitary–adrenocortical axis in rodents","author":[{"full_name":"Perry, Rachel J.","last_name":"Perry","first_name":"Rachel J."},{"full_name":"Resch, Jon M.","last_name":"Resch","first_name":"Jon M."},{"id":"de5f6fda-80fb-11ef-996f-a8c4ecd8e289","first_name":"Amelia May Barnett","orcid":"0000-0001-5398-6473","last_name":"Douglass","full_name":"Douglass, Amelia May Barnett"},{"first_name":"Joseph C.","full_name":"Madara, Joseph C.","last_name":"Madara"},{"last_name":"Rabin-Court","full_name":"Rabin-Court, Aviva","first_name":"Aviva"},{"last_name":"Kucukdereli","full_name":"Kucukdereli, Hakan","first_name":"Hakan"},{"last_name":"Wu","full_name":"Wu, Chen","first_name":"Chen"},{"first_name":"Joongyu D.","last_name":"Song","full_name":"Song, Joongyu D."},{"last_name":"Lowell","full_name":"Lowell, Bradford B.","first_name":"Bradford B."},{"last_name":"Shulman","full_name":"Shulman, Gerald I.","first_name":"Gerald I."}],"publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"_id":"19473","year":"2019"},{"fulldoi":"https://doi.org/10.1073/pnas.1813255116","tmp":{"short":"CC BY (4.0)","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"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","isi":1,"publisher":"National Academy of Sciences","date_created":"2019-03-31T21:59:13Z","issue":"12","citation":{"ista":"Recho P, Hallou A, Hannezo EB. 2019. Theory of mechanochemical patterning in biphasic biological tissues. Proceedings of the National Academy of Sciences of the United States of America. 116(12), 5344–5349.","ama":"Recho P, Hallou A, Hannezo EB. Theory of mechanochemical patterning in biphasic biological tissues. Proceedings of the National Academy of Sciences of the United States of America. 2019;116(12):5344-5349. doi:10.1073/pnas.1813255116","apa":"Recho, P., Hallou, A., & Hannezo, E. B. (2019). Theory of mechanochemical patterning in biphasic biological tissues. Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. https://doi.org/10.1073/pnas.1813255116","mla":"Recho, Pierre, et al. “Theory of Mechanochemical Patterning in Biphasic Biological Tissues.” Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 12, National Academy of Sciences, 2019, pp. 5344–49, doi:10.1073/pnas.1813255116.","ieee":"P. Recho, A. Hallou, and E. B. Hannezo, “Theory of mechanochemical patterning in biphasic biological tissues,” Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 12. National Academy of Sciences, pp. 5344–5349, 2019.","short":"P. Recho, A. Hallou, E.B. Hannezo, Proceedings of the National Academy of Sciences of the United States of America 116 (2019) 5344–5349.","chicago":"Recho, Pierre, Adrien Hallou, and Edouard B Hannezo. “Theory of Mechanochemical Patterning in Biphasic Biological Tissues.” Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 2019. https://doi.org/10.1073/pnas.1813255116."},"file_date_updated":"2020-07-14T12:47:23Z","oa":1,"publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"year":"2019","_id":"6191","abstract":[{"lang":"eng","text":"The formation of self-organized patterns is key to the morphogenesis of multicellular organisms, although a comprehensive theory of biological pattern formation is still lacking. Here, we propose a minimal model combining tissue mechanics with morphogen turnover and transport to explore routes to patterning. Our active description couples morphogen reaction and diffusion, which impact cell differentiation and tissue mechanics, to a two-phase poroelastic rheology, where one tissue phase consists of a poroelastic cell network and the other one of a permeating extracellular fluid, which provides a feedback by actively transporting morphogens. While this model encompasses previous theories approximating tissues to inert monophasic media, such as Turing’s reaction–diffusion model, it overcomes some of their key limitations permitting pattern formation via any two-species biochemical kinetics due to mechanically induced cross-diffusion flows. Moreover, we describe a qualitatively different advection-driven Keller–Segel instability which allows for the formation of patterns with a single morphogen and whose fundamental mode pattern robustly scales with tissue size. We discuss the potential relevance of these findings for tissue morphogenesis."}],"page":"5344-5349","publication":"Proceedings of the National Academy of Sciences of the United States of America","author":[{"first_name":"Pierre","last_name":"Recho","full_name":"Recho, Pierre"},{"full_name":"Hallou, Adrien","last_name":"Hallou","first_name":"Adrien"},{"id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","first_name":"Edouard B","orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B","last_name":"Hannezo"}],"title":"Theory of mechanochemical patterning in biphasic biological tissues","date_updated":"2025-07-10T11:53:14Z","publication_status":"published","article_processing_charge":"No","day":"19","ddc":["570"],"file":[{"date_created":"2019-04-03T14:10:30Z","file_id":"6193","access_level":"open_access","relation":"main_file","file_size":3456045,"checksum":"8b67eee0ea8e5db61583e4d485215258","creator":"dernst","content_type":"application/pdf","file_name":"2019_PNAS_Recho.pdf","date_updated":"2020-07-14T12:47:23Z"}],"quality_controlled":"1","month":"03","volume":116,"external_id":{"isi":["000461679000027"],"pmid":["30819884"]},"language":[{"iso":"eng"}],"oa_version":"Published Version","intvolume":" 116","type":"journal_article","date_published":"2019-03-19T00:00:00Z","corr_author":"1","status":"public","has_accepted_license":"1","project":[{"call_identifier":"FWF","grant_number":"P31639","_id":"268294B6-B435-11E9-9278-68D0E5697425","name":"Active mechano-chemical description of the cell cytoskeleton"}],"department":[{"_id":"EdHa"}],"doi":"10.1073/pnas.1813255116","related_material":{"link":[{"url":"www.pnas.org/lookup/suppl/doi:10.1073/pnas.1813255116/-/DCSupplemental","relation":"supplementary_material"}]},"scopus_import":"1","pmid":1},{"ddc":["580"],"file":[{"file_size":1142540,"relation":"main_file","file_id":"9461","success":1,"access_level":"open_access","date_created":"2021-06-04T12:50:47Z","date_updated":"2021-06-04T12:50:47Z","file_name":"2019_PNAS_Kim.pdf","content_type":"application/pdf","checksum":"5b0ae3779b8b21b5223bd2d3cceede3a","creator":"asandaue"}],"quality_controlled":"1","month":"05","volume":116,"external_id":{"pmid":["31000601"]},"keyword":["Multidisciplinary"],"language":[{"iso":"eng"}],"oa_version":"Published Version","intvolume":" 116","date_published":"2019-05-07T00:00:00Z","type":"journal_article","has_accepted_license":"1","status":"public","department":[{"_id":"DaZi"}],"doi":"10.1073/pnas.1821435116","scopus_import":"1","pmid":1,"fulldoi":"https://doi.org/10.1073/pnas.1821435116","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)"},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","publisher":"National Academy of Sciences","date_created":"2021-06-04T12:38:20Z","issue":"19","article_type":"original","citation":{"ama":"Kim MY, Ono A, Scholten S, et al. DNA demethylation by ROS1a in rice vegetative cells promotes methylation in sperm. Proceedings of the National Academy of Sciences. 2019;116(19):9652-9657. doi:10.1073/pnas.1821435116","mla":"Kim, M. Yvonne, et al. “DNA Demethylation by ROS1a in Rice Vegetative Cells Promotes Methylation in Sperm.” Proceedings of the National Academy of Sciences, vol. 116, no. 19, National Academy of Sciences, 2019, pp. 9652–57, doi:10.1073/pnas.1821435116.","apa":"Kim, M. Y., Ono, A., Scholten, S., Kinoshita, T., Zilberman, D., Okamoto, T., & Fischer, R. L. (2019). DNA demethylation by ROS1a in rice vegetative cells promotes methylation in sperm. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.1821435116","ista":"Kim MY, Ono A, Scholten S, Kinoshita T, Zilberman D, Okamoto T, Fischer RL. 2019. DNA demethylation by ROS1a in rice vegetative cells promotes methylation in sperm. Proceedings of the National Academy of Sciences. 116(19), 9652–9657.","ieee":"M. Y. Kim et al., “DNA demethylation by ROS1a in rice vegetative cells promotes methylation in sperm,” Proceedings of the National Academy of Sciences, vol. 116, no. 19. National Academy of Sciences, pp. 9652–9657, 2019.","chicago":"Kim, M. Yvonne, Akemi Ono, Stefan Scholten, Tetsu Kinoshita, Daniel Zilberman, Takashi Okamoto, and Robert L. Fischer. “DNA Demethylation by ROS1a in Rice Vegetative Cells Promotes Methylation in Sperm.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2019. https://doi.org/10.1073/pnas.1821435116.","short":"M.Y. Kim, A. Ono, S. Scholten, T. Kinoshita, D. Zilberman, T. Okamoto, R.L. Fischer, Proceedings of the National Academy of Sciences 116 (2019) 9652–9657."},"file_date_updated":"2021-06-04T12:50:47Z","oa":1,"publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"year":"2019","_id":"9460","abstract":[{"text":"Epigenetic reprogramming is required for proper regulation of gene expression in eukaryotic organisms. In Arabidopsis, active DNA demethylation is crucial for seed viability, pollen function, and successful reproduction. The DEMETER (DME) DNA glycosylase initiates localized DNA demethylation in vegetative and central cells, so-called companion cells that are adjacent to sperm and egg gametes, respectively. In rice, the central cell genome displays local DNA hypomethylation, suggesting that active DNA demethylation also occurs in rice; however, the enzyme responsible for this process is unknown. One candidate is the rice REPRESSOR OF SILENCING 1a (ROS1a) gene, which is related to DME and is essential for rice seed viability and pollen function. Here, we report genome-wide analyses of DNA methylation in wild-type and ros1a mutant sperm and vegetative cells. We find that the rice vegetative cell genome is locally hypomethylated compared with sperm by a process that requires ROS1a activity. We show that many ROS1a target sequences in the vegetative cell are hypomethylated in the rice central cell, suggesting that ROS1a also demethylates the central cell genome. Similar to Arabidopsis, we show that sperm non-CG methylation is indirectly promoted by DNA demethylation in the vegetative cell. These results reveal that DNA glycosylase-mediated DNA demethylation processes are conserved in Arabidopsis and rice, plant species that diverged 150 million years ago. Finally, although global non-CG methylation levels of sperm and egg differ, the maternal and paternal embryo genomes show similar non-CG methylation levels, suggesting that rice gamete genomes undergo dynamic DNA methylation reprogramming after cell fusion.","lang":"eng"}],"page":"9652-9657","title":"DNA demethylation by ROS1a in rice vegetative cells promotes methylation in sperm","publication":"Proceedings of the National Academy of Sciences","author":[{"full_name":"Kim, M. Yvonne","last_name":"Kim","first_name":"M. Yvonne"},{"last_name":"Ono","full_name":"Ono, Akemi","first_name":"Akemi"},{"first_name":"Stefan","last_name":"Scholten","full_name":"Scholten, Stefan"},{"last_name":"Kinoshita","full_name":"Kinoshita, Tetsu","first_name":"Tetsu"},{"first_name":"Daniel","id":"6973db13-dd5f-11ea-814e-b3e5455e9ed1","orcid":"0000-0002-0123-8649","full_name":"Zilberman, Daniel","last_name":"Zilberman"},{"first_name":"Takashi","full_name":"Okamoto, Takashi","last_name":"Okamoto"},{"first_name":"Robert L.","last_name":"Fischer","full_name":"Fischer, Robert L."}],"date_updated":"2021-12-14T07:52:30Z","extern":"1","publication_status":"published","day":"07","article_processing_charge":"No"},{"doi":"10.1073/pnas.1815117116","pmid":1,"scopus_import":"1","status":"public","language":[{"iso":"eng"}],"external_id":{"arxiv":["1811.08630"],"pmid":["30610171"]},"volume":116,"date_published":"2019-01-22T00:00:00Z","type":"journal_article","intvolume":" 116","oa_version":"Published Version","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1073/pnas.1815117116"}],"quality_controlled":"1","month":"01","arxiv":1,"date_updated":"2023-02-23T14:05:08Z","day":"22","article_processing_charge":"No","publication_status":"published","extern":"1","_id":"9689","year":"2019","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"title":"Ab initio thermodynamics of liquid and solid water","publication":"Proceedings of the National Academy of Sciences","author":[{"id":"cbe3cda4-d82c-11eb-8dc7-8ff94289fcc9","first_name":"Bingqing","orcid":"0000-0002-3584-9632","last_name":"Cheng","full_name":"Cheng, Bingqing"},{"first_name":"Edgar A.","full_name":"Engel, Edgar A.","last_name":"Engel"},{"full_name":"Behler, Jörg","last_name":"Behler","first_name":"Jörg"},{"last_name":"Dellago","full_name":"Dellago, Christoph","first_name":"Christoph"},{"first_name":"Michele","full_name":"Ceriotti, Michele","last_name":"Ceriotti"}],"page":"1110-1115","abstract":[{"lang":"eng","text":"A central goal of computational physics and chemistry is to predict material properties by using first-principles methods based on the fundamental laws of quantum mechanics. However, the high computational costs of these methods typically prevent rigorous predictions of macroscopic quantities at finite temperatures, such as heat capacity, density, and chemical potential. Here, we enable such predictions by marrying advanced free-energy methods with data-driven machine-learning interatomic potentials. We show that, for the ubiquitous and technologically essential system of water, a first-principles thermodynamic description not only leads to excellent agreement with experiments, but also reveals the crucial role of nuclear quantum fluctuations in modulating the thermodynamic stabilities of different phases of water."}],"article_type":"original","issue":"4","oa":1,"citation":{"ista":"Cheng B, Engel EA, Behler J, Dellago C, Ceriotti M. 2019. Ab initio thermodynamics of liquid and solid water. Proceedings of the National Academy of Sciences. 116(4), 1110–1115.","ama":"Cheng B, Engel EA, Behler J, Dellago C, Ceriotti M. Ab initio thermodynamics of liquid and solid water. Proceedings of the National Academy of Sciences. 2019;116(4):1110-1115. doi:10.1073/pnas.1815117116","apa":"Cheng, B., Engel, E. A., Behler, J., Dellago, C., & Ceriotti, M. (2019). Ab initio thermodynamics of liquid and solid water. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.1815117116","mla":"Cheng, Bingqing, et al. “Ab Initio Thermodynamics of Liquid and Solid Water.” Proceedings of the National Academy of Sciences, vol. 116, no. 4, National Academy of Sciences, 2019, pp. 1110–15, doi:10.1073/pnas.1815117116.","ieee":"B. Cheng, E. A. Engel, J. Behler, C. Dellago, and M. Ceriotti, “Ab initio thermodynamics of liquid and solid water,” Proceedings of the National Academy of Sciences, vol. 116, no. 4. National Academy of Sciences, pp. 1110–1115, 2019.","chicago":"Cheng, Bingqing, Edgar A. Engel, Jörg Behler, Christoph Dellago, and Michele Ceriotti. “Ab Initio Thermodynamics of Liquid and Solid Water.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2019. https://doi.org/10.1073/pnas.1815117116.","short":"B. Cheng, E.A. Engel, J. Behler, C. Dellago, M. Ceriotti, Proceedings of the National Academy of Sciences 116 (2019) 1110–1115."},"fulldoi":"https://doi.org/10.1073/pnas.1815117116","date_created":"2021-07-19T10:17:09Z","publisher":"National Academy of Sciences","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf"}]