[{"intvolume":"         5","status":"public","external_id":{"isi":["000386196100008"]},"author":[{"last_name":"Gnügge","first_name":"Robert","full_name":"Gnügge, Robert"},{"first_name":"Lekshmi","full_name":"Dharmarajan, Lekshmi","last_name":"Dharmarajan"},{"id":"29E0800A-F248-11E8-B48F-1D18A9856A87","full_name":"Lang, Moritz","first_name":"Moritz","last_name":"Lang"},{"last_name":"Stelling","first_name":"Jörg","full_name":"Stelling, Jörg"}],"language":[{"iso":"eng"}],"title":"An orthogonal permease–inducer–repressor feedback loop shows bistability","quality_controlled":"1","page":"1098 - 1107","volume":5,"date_created":"2018-12-11T11:49:40Z","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","acknowledgement":"We thank Julio Polaina (Instituto de Agroqu ı ́ mica y Tecnolog ı ́ a de Alimentos, C.S.I.C., Paterna, Spain) for the gift of plasmid pMR4, Gregor W. Schmidt for provision of and support with the micro fl uidic device, Markus Du ̈ rr for the cell tracking R script, and Lukas Widmer for the script for MEIGO using “ parfor ” in MATLAB. We acknowledge the members of the Stelling group for discussions, comments, and support.","doi":"10.1021/acssynbio.6b00013","department":[{"_id":"CaGu"}],"type":"journal_article","citation":{"mla":"Gnügge, Robert, et al. “An Orthogonal Permease–Inducer–Repressor Feedback Loop Shows Bistability.” <i>ACS Synthetic Biology</i>, vol. 5, no. 10, American Chemical Society, 2016, pp. 1098–107, doi:<a href=\"https://doi.org/10.1021/acssynbio.6b00013\">10.1021/acssynbio.6b00013</a>.","ama":"Gnügge R, Dharmarajan L, Lang M, Stelling J. An orthogonal permease–inducer–repressor feedback loop shows bistability. <i>ACS Synthetic Biology</i>. 2016;5(10):1098-1107. doi:<a href=\"https://doi.org/10.1021/acssynbio.6b00013\">10.1021/acssynbio.6b00013</a>","short":"R. Gnügge, L. Dharmarajan, M. Lang, J. Stelling, ACS Synthetic Biology 5 (2016) 1098–1107.","apa":"Gnügge, R., Dharmarajan, L., Lang, M., &#38; Stelling, J. (2016). An orthogonal permease–inducer–repressor feedback loop shows bistability. <i>ACS Synthetic Biology</i>. American Chemical Society. <a href=\"https://doi.org/10.1021/acssynbio.6b00013\">https://doi.org/10.1021/acssynbio.6b00013</a>","ista":"Gnügge R, Dharmarajan L, Lang M, Stelling J. 2016. An orthogonal permease–inducer–repressor feedback loop shows bistability. ACS Synthetic Biology. 5(10), 1098–1107.","ieee":"R. Gnügge, L. Dharmarajan, M. Lang, and J. Stelling, “An orthogonal permease–inducer–repressor feedback loop shows bistability,” <i>ACS Synthetic Biology</i>, vol. 5, no. 10. American Chemical Society, pp. 1098–1107, 2016.","chicago":"Gnügge, Robert, Lekshmi Dharmarajan, Moritz Lang, and Jörg Stelling. “An Orthogonal Permease–Inducer–Repressor Feedback Loop Shows Bistability.” <i>ACS Synthetic Biology</i>. American Chemical Society, 2016. <a href=\"https://doi.org/10.1021/acssynbio.6b00013\">https://doi.org/10.1021/acssynbio.6b00013</a>."},"issue":"10","publication":"ACS Synthetic Biology","day":"05","_id":"1008","publist_id":"6390","abstract":[{"text":"Feedback loops in biological networks, among others, enable differentiation and cell cycle progression, and increase robustness in signal transduction. In natural networks, feedback loops are often complex and intertwined, making it challenging to identify which loops are mainly responsible for an observed behavior. However, minimal synthetic replicas could allow for such identification. Here, we engineered a synthetic permease-inducer-repressor system in Saccharomyces cerevisiae to analyze if a transport-mediated positive feedback loop could be a core mechanism for the switch-like behavior in the regulation of metabolic gene networks such as the S. cerevisiae GAL system or the Escherichia coli lac operon. We characterized the synthetic circuit using deterministic and stochastic mathematical models. Similar to its natural counterparts, our synthetic system shows bistable and hysteretic behavior, and the inducer concentration range for bistability as well as the switching rates between the two stable states depend on the repressor concentration. Our results indicate that a generic permease–inducer–repressor circuit with a single feedback loop is sufficient to explain the experimentally observed bistable behavior of the natural systems. We anticipate that the approach of reimplementing natural systems with orthogonal parts to identify crucial network components is applicable to other natural systems such as signaling pathways.","lang":"eng"}],"year":"2016","isi":1,"month":"05","date_updated":"2025-09-22T14:20:45Z","publisher":"American Chemical Society","date_published":"2016-05-05T00:00:00Z","publication_status":"published","article_processing_charge":"No","oa_version":"None"},{"day":"19","_id":"9873","title":"Quantification of the growth rate reduction as a consequence of age-specific mortality","author":[{"last_name":"Boehm","full_name":"Boehm, Alex","first_name":"Alex"},{"full_name":"Arnoldini, Markus","first_name":"Markus","last_name":"Arnoldini"},{"orcid":"0000-0001-5396-4346","last_name":"Bergmiller","first_name":"Tobias","full_name":"Bergmiller, Tobias","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Röösli, Thomas","first_name":"Thomas","last_name":"Röösli"},{"last_name":"Bigosch","full_name":"Bigosch, Colette","first_name":"Colette"},{"first_name":"Martin","full_name":"Ackermann, Martin","last_name":"Ackermann"}],"department":[{"_id":"CaGu"}],"type":"research_data_reference","citation":{"ieee":"A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, and M. Ackermann, “Quantification of the growth rate reduction as a consequence of age-specific mortality.” Public Library of Science, 2016.","chicago":"Boehm, Alex, Markus Arnoldini, Tobias Bergmiller, Thomas Röösli, Colette Bigosch, and Martin Ackermann. “Quantification of the Growth Rate Reduction as a Consequence of Age-Specific Mortality.” Public Library of Science, 2016. <a href=\"https://doi.org/10.1371/journal.pgen.1005974.s015\">https://doi.org/10.1371/journal.pgen.1005974.s015</a>.","short":"A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, M. Ackermann, (2016).","mla":"Boehm, Alex, et al. <i>Quantification of the Growth Rate Reduction as a Consequence of Age-Specific Mortality</i>. Public Library of Science, 2016, doi:<a href=\"https://doi.org/10.1371/journal.pgen.1005974.s015\">10.1371/journal.pgen.1005974.s015</a>.","ama":"Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. Quantification of the growth rate reduction as a consequence of age-specific mortality. 2016. doi:<a href=\"https://doi.org/10.1371/journal.pgen.1005974.s015\">10.1371/journal.pgen.1005974.s015</a>","ista":"Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. 2016. Quantification of the growth rate reduction as a consequence of age-specific mortality, Public Library of Science, <a href=\"https://doi.org/10.1371/journal.pgen.1005974.s015\">10.1371/journal.pgen.1005974.s015</a>.","apa":"Boehm, A., Arnoldini, M., Bergmiller, T., Röösli, T., Bigosch, C., &#38; Ackermann, M. (2016). Quantification of the growth rate reduction as a consequence of age-specific mortality. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pgen.1005974.s015\">https://doi.org/10.1371/journal.pgen.1005974.s015</a>"},"doi":"10.1371/journal.pgen.1005974.s015","status":"public","oa_version":"Published Version","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","article_processing_charge":"No","date_created":"2021-08-10T09:42:34Z","publisher":"Public Library of Science","related_material":{"record":[{"id":"1250","relation":"used_in_publication","status":"public"}]},"year":"2016","month":"04","date_updated":"2025-09-22T09:10:03Z"},{"citation":{"chicago":"Friedlander, Tamar, Roshan Prizak, Calin C Guet, Nicholas H Barton, and Gašper Tkačik. “Intrinsic Limits to Gene Regulation by Global Crosstalk.” <i>Nature Communications</i>. Nature Publishing Group, 2016. <a href=\"https://doi.org/10.1038/ncomms12307\">https://doi.org/10.1038/ncomms12307</a>.","ieee":"T. Friedlander, R. Prizak, C. C. Guet, N. H. Barton, and G. Tkačik, “Intrinsic limits to gene regulation by global crosstalk,” <i>Nature Communications</i>, vol. 7. Nature Publishing Group, 2016.","apa":"Friedlander, T., Prizak, R., Guet, C. C., Barton, N. H., &#38; Tkačik, G. (2016). Intrinsic limits to gene regulation by global crosstalk. <i>Nature Communications</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/ncomms12307\">https://doi.org/10.1038/ncomms12307</a>","ista":"Friedlander T, Prizak R, Guet CC, Barton NH, Tkačik G. 2016. Intrinsic limits to gene regulation by global crosstalk. Nature Communications. 7, 12307.","mla":"Friedlander, Tamar, et al. “Intrinsic Limits to Gene Regulation by Global Crosstalk.” <i>Nature Communications</i>, vol. 7, 12307, Nature Publishing Group, 2016, doi:<a href=\"https://doi.org/10.1038/ncomms12307\">10.1038/ncomms12307</a>.","ama":"Friedlander T, Prizak R, Guet CC, Barton NH, Tkačik G. Intrinsic limits to gene regulation by global crosstalk. <i>Nature Communications</i>. 2016;7. doi:<a href=\"https://doi.org/10.1038/ncomms12307\">10.1038/ncomms12307</a>","short":"T. Friedlander, R. Prizak, C.C. Guet, N.H. Barton, G. Tkačik, Nature Communications 7 (2016)."},"type":"journal_article","department":[{"_id":"GaTk"},{"_id":"NiBa"},{"_id":"CaGu"}],"oa":1,"doi":"10.1038/ncomms12307","publist_id":"5887","day":"04","_id":"1358","publication":"Nature Communications","file_date_updated":"2020-07-14T12:44:46Z","pubrep_id":"627","date_published":"2016-08-04T00:00:00Z","publisher":"Nature Publishing Group","date_updated":"2026-04-08T13:54:24Z","month":"08","isi":1,"year":"2016","scopus_import":"1","abstract":[{"text":"Gene regulation relies on the specificity of transcription factor (TF)–DNA interactions. Limited specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to noncognate TF–DNA interactions or remains erroneously inactive. As each TF can have numerous interactions with noncognate cis-regulatory elements, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyse the effects of global crosstalk on gene regulation. We find that crosstalk presents a significant challenge for organisms with low-specificity TFs, such as metazoans. Crosstalk is not easily mitigated by known regulatory schemes acting at equilibrium, including variants of cooperativity and combinatorial regulation. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements.","lang":"eng"}],"file":[{"access_level":"open_access","creator":"system","date_created":"2018-12-12T10:12:01Z","relation":"main_file","file_id":"4919","file_size":861805,"date_updated":"2020-07-14T12:44:46Z","content_type":"application/pdf","file_name":"IST-2016-627-v1+1_ncomms12307.pdf","checksum":"fe3f3a1526d180b29fe691ab11435b78"},{"file_id":"4920","creator":"system","access_level":"open_access","relation":"main_file","date_created":"2018-12-12T10:12:02Z","content_type":"application/pdf","checksum":"164864a1a675f3ad80e9917c27aba07f","file_name":"IST-2016-627-v1+2_ncomms12307-s1.pdf","file_size":1084703,"date_updated":"2020-07-14T12:44:46Z"}],"oa_version":"Published Version","article_processing_charge":"No","project":[{"name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"291734"},{"grant_number":"250152","call_identifier":"FP7","name":"Limits to selection in biology and in evolutionary computation","_id":"25B07788-B435-11E9-9278-68D0E5697425"},{"name":"Biophysics of information processing in gene regulation","_id":"254E9036-B435-11E9-9278-68D0E5697425","grant_number":"P28844-B27","call_identifier":"FWF"}],"publication_status":"published","language":[{"iso":"eng"}],"author":[{"last_name":"Friedlander","full_name":"Friedlander, Tamar","first_name":"Tamar","id":"36A5845C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Prizak","full_name":"Prizak, Roshan","first_name":"Roshan","id":"4456104E-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-6220-2052","last_name":"Guet","full_name":"Guet, Calin C","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-8548-5240","last_name":"Barton","full_name":"Barton, Nicholas H","first_name":"Nicholas H","id":"4880FE40-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-6699-1455","last_name":"Tkacik","first_name":"Gasper","full_name":"Tkacik, Gasper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"external_id":{"isi":["000380858400001"]},"status":"public","intvolume":"         7","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"quality_controlled":"1","title":"Intrinsic limits to gene regulation by global crosstalk","has_accepted_license":"1","ec_funded":1,"volume":7,"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"6071"}]},"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","article_number":"12307","date_created":"2018-12-11T11:51:34Z","ddc":["576"],"corr_author":"1"},{"_id":"1243","day":"08","publist_id":"6087","issue":"3","publication":"Current Biology","citation":{"ieee":"M. Pleska <i>et al.</i>, “Bacterial autoimmunity due to a restriction-modification system,” <i>Current Biology</i>, vol. 26, no. 3. Cell Press, pp. 404–409, 2016.","chicago":"Pleska, Maros, Long Qian, Reiko Okura, Tobias Bergmiller, Yuichi Wakamoto, Edo Kussell, and Calin C Guet. “Bacterial Autoimmunity Due to a Restriction-Modification System.” <i>Current Biology</i>. Cell Press, 2016. <a href=\"https://doi.org/10.1016/j.cub.2015.12.041\">https://doi.org/10.1016/j.cub.2015.12.041</a>.","short":"M. Pleska, L. Qian, R. Okura, T. Bergmiller, Y. Wakamoto, E. Kussell, C.C. Guet, Current Biology 26 (2016) 404–409.","ama":"Pleska M, Qian L, Okura R, et al. Bacterial autoimmunity due to a restriction-modification system. <i>Current Biology</i>. 2016;26(3):404-409. doi:<a href=\"https://doi.org/10.1016/j.cub.2015.12.041\">10.1016/j.cub.2015.12.041</a>","mla":"Pleska, Maros, et al. “Bacterial Autoimmunity Due to a Restriction-Modification System.” <i>Current Biology</i>, vol. 26, no. 3, Cell Press, 2016, pp. 404–09, doi:<a href=\"https://doi.org/10.1016/j.cub.2015.12.041\">10.1016/j.cub.2015.12.041</a>.","apa":"Pleska, M., Qian, L., Okura, R., Bergmiller, T., Wakamoto, Y., Kussell, E., &#38; Guet, C. C. (2016). Bacterial autoimmunity due to a restriction-modification system. <i>Current Biology</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cub.2015.12.041\">https://doi.org/10.1016/j.cub.2015.12.041</a>","ista":"Pleska M, Qian L, Okura R, Bergmiller T, Wakamoto Y, Kussell E, Guet CC. 2016. Bacterial autoimmunity due to a restriction-modification system. Current Biology. 26(3), 404–409."},"department":[{"_id":"CaGu"}],"type":"journal_article","doi":"10.1016/j.cub.2015.12.041","acknowledgement":"This work was funded by an HFSP Young Investigators’ grant. M.P. is a recipient of a DOC Fellowship of the Austrian Academy of Science at the Institute of Science and Technology Austria. R.O. and Y.W. were supported by the Platform for Dynamic Approaches to Living System from MEXT, Japan. We wish to thank I. Kobayashi for providing us with the EcoRI and EcoRV plasmids, and A. Campbell for providing us with the λ vir phage. We thank D. Siekhaus and C. Uhler and members of the C.C.G. and J.P. Bollback laboratories for in-depth discussions. We thank B. Stern for comments on an earlier version of the manuscript. We especially thank B.R. Levin for advice and comments, and the anonymous reviewers for significantly improving the manuscript.","oa_version":"None","publication_status":"published","project":[{"name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level","_id":"251D65D8-B435-11E9-9278-68D0E5697425","grant_number":"24210"}],"article_processing_charge":"No","date_published":"2016-02-08T00:00:00Z","publisher":"Cell Press","year":"2016","abstract":[{"lang":"eng","text":"Restriction-modification (RM) systems represent a minimal and ubiquitous biological system of self/non-self discrimination in prokaryotes [1], which protects hosts from exogenous DNA [2]. The mechanism is based on the balance between methyltransferase (M) and cognate restriction endonuclease (R). M tags endogenous DNA as self by methylating short specific DNA sequences called restriction sites, whereas R recognizes unmethylated restriction sites as non-self and introduces a double-stranded DNA break [3]. Restriction sites are significantly underrepresented in prokaryotic genomes [4-7], suggesting that the discrimination mechanism is imperfect and occasionally leads to autoimmunity due to self-DNA cleavage (self-restriction) [8]. Furthermore, RM systems can promote DNA recombination [9] and contribute to genetic variation in microbial populations, thus facilitating adaptive evolution [10]. However, cleavage of self-DNA by RM systems as elements shaping prokaryotic genomes has not been directly detected, and its cause, frequency, and outcome are unknown. We quantify self-restriction caused by two RM systems of Escherichia coli and find that, in agreement with levels of restriction site avoidance, EcoRI, but not EcoRV, cleaves self-DNA at a measurable rate. Self-restriction is a stochastic process, which temporarily induces the SOS response, and is followed by DNA repair, maintaining cell viability. We find that RM systems with higher restriction efficiency against bacteriophage infections exhibit a higher rate of self-restriction, and that this rate can be further increased by stochastic imbalance between R and M. Our results identify molecular noise in RM systems as a factor shaping prokaryotic genomes."}],"scopus_import":"1","date_updated":"2026-04-08T14:19:43Z","month":"02","isi":1,"page":"404 - 409","quality_controlled":"1","title":"Bacterial autoimmunity due to a restriction-modification system","language":[{"iso":"eng"}],"external_id":{"isi":["000369502900034"]},"author":[{"first_name":"Maros","full_name":"Pleska, Maros","orcid":"0000-0001-7460-7479","last_name":"Pleska","id":"4569785E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Qian, Long","first_name":"Long","last_name":"Qian"},{"last_name":"Okura","first_name":"Reiko","full_name":"Okura, Reiko"},{"id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","last_name":"Bergmiller","orcid":"0000-0001-5396-4346","full_name":"Bergmiller, Tobias","first_name":"Tobias"},{"last_name":"Wakamoto","full_name":"Wakamoto, Yuichi","first_name":"Yuichi"},{"first_name":"Edo","full_name":"Kussell, Edo","last_name":"Kussell"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet"}],"intvolume":"        26","status":"public","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","date_created":"2018-12-11T11:50:54Z","volume":26,"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"202"}]}},{"date_created":"2018-12-11T11:50:06Z","ddc":["004"],"article_number":"20","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","conference":{"start_date":"2016-08-23","name":"CONCUR: Concurrency Theory","end_date":"2016-08-26","location":"Quebec City; Canada"},"volume":59,"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"1155"}]},"ec_funded":1,"has_accepted_license":"1","quality_controlled":"1","title":"Linear distances between Markov chains","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"intvolume":"        59","status":"public","language":[{"iso":"eng"}],"author":[{"last_name":"Daca","full_name":"Daca, Przemyslaw","first_name":"Przemyslaw","id":"49351290-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000−0002−2985−7724","last_name":"Henzinger","first_name":"Thomas A","full_name":"Henzinger, Thomas A","id":"40876CD8-F248-11E8-B48F-1D18A9856A87"},{"id":"44CEF464-F248-11E8-B48F-1D18A9856A87","full_name":"Kretinsky, Jan","first_name":"Jan","orcid":"0000-0002-8122-2881","last_name":"Kretinsky"},{"first_name":"Tatjana","full_name":"Petrov, Tatjana","orcid":"0000-0002-9041-0905","last_name":"Petrov","id":"3D5811FC-F248-11E8-B48F-1D18A9856A87"}],"publication_status":"published","project":[{"grant_number":"267989","call_identifier":"FP7","name":"Quantitative Reactive Modeling","_id":"25EE3708-B435-11E9-9278-68D0E5697425"},{"grant_number":"S 11407_N23","call_identifier":"FWF","_id":"25832EC2-B435-11E9-9278-68D0E5697425","name":"Rigorous Systems Engineering"},{"name":"Formal methods for the design and analysis of complex systems","_id":"25F42A32-B435-11E9-9278-68D0E5697425","grant_number":"Z211","call_identifier":"FWF"}],"oa_version":"Published Version","file":[{"file_name":"IST-2017-794-v1+1_LIPIcs-CONCUR-2016-20.pdf","content_type":"application/pdf","date_updated":"2018-12-12T10:11:39Z","file_size":501827,"file_id":"4895","date_created":"2018-12-12T10:11:39Z","relation":"main_file","access_level":"open_access","creator":"system"}],"alternative_title":["LIPIcs"],"abstract":[{"lang":"eng","text":"We introduce a general class of distances (metrics) between Markov chains, which are based on linear behaviour. This class encompasses distances given topologically (such as the total variation distance or trace distance) as well as by temporal logics or automata. We investigate which of the distances can be approximated by observing the systems, i.e. by black-box testing or simulation, and we provide both negative and positive results. "}],"year":"2016","scopus_import":1,"date_updated":"2026-04-15T10:02:12Z","month":"08","date_published":"2016-08-01T00:00:00Z","publisher":"Schloss Dagstuhl - Leibniz-Zentrum für Informatik","pubrep_id":"794","file_date_updated":"2018-12-12T10:11:39Z","_id":"1093","day":"01","publist_id":"6283","doi":"10.4230/LIPIcs.CONCUR.2016.20","acknowledgement":"This research was funded in part by the European Research Council (ERC) under grant agreement 267989\r\n(QUAREM), the Austrian Science Fund (FWF) under grants project S11402-N23 (RiSE and SHiNE)\r\nand Z211-N23 (Wittgenstein Award), by the Czech Science Foundation Grant No. P202/12/G061, and\r\nby the SNSF Advanced Postdoc. Mobility Fellowship – grant number P300P2_161067.","oa":1,"type":"conference","department":[{"_id":"ToHe"},{"_id":"KrCh"},{"_id":"CaGu"}],"citation":{"chicago":"Daca, Przemyslaw, Thomas A Henzinger, Jan Kretinsky, and Tatjana Petrov. “Linear Distances between Markov Chains,” Vol. 59. Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2016. <a href=\"https://doi.org/10.4230/LIPIcs.CONCUR.2016.20\">https://doi.org/10.4230/LIPIcs.CONCUR.2016.20</a>.","ieee":"P. Daca, T. A. Henzinger, J. Kretinsky, and T. Petrov, “Linear distances between Markov chains,” presented at the CONCUR: Concurrency Theory, Quebec City; Canada, 2016, vol. 59.","ista":"Daca P, Henzinger TA, Kretinsky J, Petrov T. 2016. Linear distances between Markov chains. CONCUR: Concurrency Theory, LIPIcs, vol. 59, 20.","apa":"Daca, P., Henzinger, T. A., Kretinsky, J., &#38; Petrov, T. (2016). Linear distances between Markov chains (Vol. 59). Presented at the CONCUR: Concurrency Theory, Quebec City; Canada: Schloss Dagstuhl - Leibniz-Zentrum für Informatik. <a href=\"https://doi.org/10.4230/LIPIcs.CONCUR.2016.20\">https://doi.org/10.4230/LIPIcs.CONCUR.2016.20</a>","short":"P. Daca, T.A. Henzinger, J. Kretinsky, T. Petrov, in:, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2016.","mla":"Daca, Przemyslaw, et al. <i>Linear Distances between Markov Chains</i>. Vol. 59, 20, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2016, doi:<a href=\"https://doi.org/10.4230/LIPIcs.CONCUR.2016.20\">10.4230/LIPIcs.CONCUR.2016.20</a>.","ama":"Daca P, Henzinger TA, Kretinsky J, Petrov T. Linear distances between Markov chains. In: Vol 59. Schloss Dagstuhl - Leibniz-Zentrum für Informatik; 2016. doi:<a href=\"https://doi.org/10.4230/LIPIcs.CONCUR.2016.20\">10.4230/LIPIcs.CONCUR.2016.20</a>"}},{"acknowledgement":"This research was funded in part by the European Research Council (ERC) under\r\ngrant  agreement  267989  (QUAREM),  the  Austrian  Science  Fund  (FWF)  under\r\ngrants project S11402-N23 (RiSE) and Z211-N23 (Wittgenstein Award), the Peo-\r\nple Programme (Marie Curie Actions) of the European Union’s Seventh Framework\r\nProgramme (FP7/2007-2013) REA Grant No 291734, the SNSF Advanced Postdoc.\r\nMobility Fellowship – grant number P300P2\r\n161067, and the Czech Science Foun-\r\ndation under grant agreement P202/12/G061.","doi":"10.1007/978-3-662-49674-9_7","oa":1,"citation":{"mla":"Daca, Przemyslaw, et al. <i>Faster Statistical Model Checking for Unbounded Temporal Properties</i>. Vol. 9636, Springer, 2016, pp. 112–29, doi:<a href=\"https://doi.org/10.1007/978-3-662-49674-9_7\">10.1007/978-3-662-49674-9_7</a>.","ama":"Daca P, Henzinger TA, Kretinsky J, Petrov T. Faster statistical model checking for unbounded temporal properties. In: Vol 9636. Springer; 2016:112-129. doi:<a href=\"https://doi.org/10.1007/978-3-662-49674-9_7\">10.1007/978-3-662-49674-9_7</a>","short":"P. Daca, T.A. Henzinger, J. Kretinsky, T. Petrov, in:, Springer, 2016, pp. 112–129.","ista":"Daca P, Henzinger TA, Kretinsky J, Petrov T. 2016. Faster statistical model checking for unbounded temporal properties. TACAS: Tools and Algorithms for the Construction and Analysis of Systems, LNCS, vol. 9636, 112–129.","apa":"Daca, P., Henzinger, T. A., Kretinsky, J., &#38; Petrov, T. (2016). Faster statistical model checking for unbounded temporal properties (Vol. 9636, pp. 112–129). Presented at the TACAS: Tools and Algorithms for the Construction and Analysis of Systems, Eindhoven, The Netherlands: Springer. <a href=\"https://doi.org/10.1007/978-3-662-49674-9_7\">https://doi.org/10.1007/978-3-662-49674-9_7</a>","ieee":"P. Daca, T. A. Henzinger, J. Kretinsky, and T. Petrov, “Faster statistical model checking for unbounded temporal properties,” presented at the TACAS: Tools and Algorithms for the Construction and Analysis of Systems, Eindhoven, The Netherlands, 2016, vol. 9636, pp. 112–129.","chicago":"Daca, Przemyslaw, Thomas A Henzinger, Jan Kretinsky, and Tatjana Petrov. “Faster Statistical Model Checking for Unbounded Temporal Properties,” 9636:112–29. Springer, 2016. <a href=\"https://doi.org/10.1007/978-3-662-49674-9_7\">https://doi.org/10.1007/978-3-662-49674-9_7</a>."},"type":"conference","department":[{"_id":"ToHe"},{"_id":"CaGu"}],"_id":"1234","day":"01","publist_id":"6099","abstract":[{"text":"We present a new algorithm for the statistical model checking of Markov chains with respect to unbounded temporal properties, including full linear temporal logic. The main idea is that we monitor each simulation run on the fly, in order to detect quickly if a bottom strongly connected component is entered with high probability, in which case the simulation run can be terminated early. As a result, our simulation runs are often much shorter than required by termination bounds that are computed a priori for a desired level of confidence on a large state space. In comparison to previous algorithms for statistical model checking our method is not only faster in many cases but also requires less information about the system, namely, only the minimum transition probability that occurs in the Markov chain. In addition, our method can be generalised to unbounded quantitative properties such as mean-payoff bounds.","lang":"eng"}],"scopus_import":"1","year":"2016","alternative_title":["LNCS"],"month":"01","isi":1,"arxiv":1,"date_updated":"2026-04-15T10:02:12Z","publisher":"Springer","date_published":"2016-01-01T00:00:00Z","main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/1504.05739"}],"publication_status":"published","project":[{"name":"Quantitative Reactive Modeling","_id":"25EE3708-B435-11E9-9278-68D0E5697425","grant_number":"267989","call_identifier":"FP7"},{"_id":"25832EC2-B435-11E9-9278-68D0E5697425","name":"Rigorous Systems Engineering","call_identifier":"FWF","grant_number":"S 11407_N23"},{"grant_number":"Z211","call_identifier":"FWF","name":"Formal methods for the design and analysis of complex systems","_id":"25F42A32-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FP7","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme"}],"article_processing_charge":"No","oa_version":"Preprint","intvolume":"      9636","status":"public","author":[{"last_name":"Daca","first_name":"Przemyslaw","full_name":"Daca, Przemyslaw","id":"49351290-F248-11E8-B48F-1D18A9856A87"},{"id":"40876CD8-F248-11E8-B48F-1D18A9856A87","orcid":"0000−0002−2985−7724","last_name":"Henzinger","full_name":"Henzinger, Thomas A","first_name":"Thomas A"},{"orcid":"0000-0002-8122-2881","last_name":"Kretinsky","first_name":"Jan","full_name":"Kretinsky, Jan","id":"44CEF464-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Petrov","orcid":"0000-0002-9041-0905","first_name":"Tatjana","full_name":"Petrov, Tatjana","id":"3D5811FC-F248-11E8-B48F-1D18A9856A87"}],"external_id":{"isi":["000406428000007"],"arxiv":["1504.05739"]},"language":[{"iso":"eng"}],"title":"Faster statistical model checking for unbounded temporal properties","quality_controlled":"1","page":"112 - 129","related_material":{"record":[{"status":"public","relation":"later_version","id":"471"},{"id":"1155","relation":"dissertation_contains","status":"public"}]},"volume":9636,"ec_funded":1,"date_created":"2018-12-11T11:50:51Z","conference":{"location":"Eindhoven, The Netherlands","end_date":"2016-04-08","name":"TACAS: Tools and Algorithms for the Construction and Analysis of Systems","start_date":"2016-04-02"},"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345"},{"pubrep_id":"587","publisher":"Oxford University Press","date_published":"2016-03-01T00:00:00Z","isi":1,"month":"03","date_updated":"2026-04-29T05:57:02Z","year":"2016","abstract":[{"text":"Parasitism creates selection for resistance mechanisms in host populations and is hypothesized to promote increased host evolvability. However, the influence of these traits on host evolution when parasites are no longer present is unclear. We used experimental evolution and whole-genome sequencing of Escherichia coli to determine the effects of past and present exposure to parasitic viruses (phages) on the spread of mutator alleles, resistance, and bacterial competitive fitness. We found that mutator alleles spread rapidly during adaptation to any of four different phage species, and this pattern was even more pronounced with multiple phages present simultaneously. However, hypermutability did not detectably accelerate adaptation in the absence of phages and recovery of fitness costs associated with resistance. Several lineages evolved phage resistance through elevated mucoidy, and during subsequent evolution in phage-free conditions they rapidly reverted to nonmucoid, phage-susceptible phenotypes. Genome sequencing revealed that this phenotypic reversion was achieved by additional genetic changes rather than by genotypic reversion of the initial resistance mutations. Insertion sequence (IS) elements played a key role in both the acquisition of resistance and adaptation in the absence of parasites; unlike single nucleotide polymorphisms, IS insertions were not more frequent in mutator lineages. Our results provide a genetic explanation for rapid reversion of mucoidy, a phenotype observed in other bacterial species including human pathogens. Moreover, this demonstrates that the types of genetic change underlying adaptation to fitness costs, and consequently the impact of evolvability mechanisms such as increased point-mutation rates, depend critically on the mechanism of resistance.","lang":"eng"}],"scopus_import":"1","oa_version":"Published Version","file":[{"date_created":"2018-12-18T13:21:45Z","relation":"main_file","access_level":"open_access","creator":"dernst","file_id":"5750","date_updated":"2020-07-14T12:47:10Z","file_size":634037,"file_name":"2016_MolBiolEvol_Wielgoss.pdf","checksum":"47d9010690b6c5c17f2ac830cc63ac5c","content_type":"application/pdf"}],"article_processing_charge":"No","publication_status":"published","OA_place":"publisher","citation":{"ista":"Wielgoss S, Bergmiller T, Bischofberger AM, Hall AR. 2016. Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria. Molecular Biology and Evolution. 33(3), 770–782.","apa":"Wielgoss, S., Bergmiller, T., Bischofberger, A. M., &#38; Hall, A. R. (2016). Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria. <i>Molecular Biology and Evolution</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/molbev/msv270\">https://doi.org/10.1093/molbev/msv270</a>","short":"S. Wielgoss, T. Bergmiller, A.M. Bischofberger, A.R. Hall, Molecular Biology and Evolution 33 (2016) 770–782.","ama":"Wielgoss S, Bergmiller T, Bischofberger AM, Hall AR. Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria. <i>Molecular Biology and Evolution</i>. 2016;33(3):770-782. doi:<a href=\"https://doi.org/10.1093/molbev/msv270\">10.1093/molbev/msv270</a>","mla":"Wielgoss, Sébastien, et al. “Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Nonmutator Bacteria.” <i>Molecular Biology and Evolution</i>, vol. 33, no. 3, Oxford University Press, 2016, pp. 770–82, doi:<a href=\"https://doi.org/10.1093/molbev/msv270\">10.1093/molbev/msv270</a>.","chicago":"Wielgoss, Sébastien, Tobias Bergmiller, Anna M. Bischofberger, and Alex R. Hall. “Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Nonmutator Bacteria.” <i>Molecular Biology and Evolution</i>. Oxford University Press, 2016. <a href=\"https://doi.org/10.1093/molbev/msv270\">https://doi.org/10.1093/molbev/msv270</a>.","ieee":"S. Wielgoss, T. Bergmiller, A. M. Bischofberger, and A. R. Hall, “Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria,” <i>Molecular Biology and Evolution</i>, vol. 33, no. 3. Oxford University Press, pp. 770–782, 2016."},"type":"journal_article","department":[{"_id":"CaGu"}],"oa":1,"acknowledgement":"The authors thank three anonymous reviewers and the editor for helpful comments on the manuscript, as well as Dominique Schneider for feedback on an earlier draft, Jenna Gallie for lytic λ and Julien Capelle for T5 and T6. This work was supported by the Swiss National Science Foundation (PZ00P3_148255 to A.H.) and an EU Marie Curie PEOPLE Postdoctoral Fellowship for Career Development (FP7-PEOPLE-2012-IEF-331824 to S.W.).","publication_identifier":{"eissn":["1537-1719"],"issn":["0737-4038"]},"doi":"10.1093/molbev/msv270","_id":"5749","day":"01","publication":"Molecular Biology and Evolution","issue":"3","file_date_updated":"2020-07-14T12:47:10Z","OA_type":"gold","has_accepted_license":"1","related_material":{"record":[{"id":"9719","relation":"research_data","status":"public"}]},"volume":33,"pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["576"],"date_created":"2018-12-18T13:18:10Z","article_type":"original","author":[{"first_name":"Sébastien","full_name":"Wielgoss, Sébastien","last_name":"Wielgoss"},{"full_name":"Bergmiller, Tobias","first_name":"Tobias","last_name":"Bergmiller","orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Bischofberger, Anna M.","first_name":"Anna M.","last_name":"Bischofberger"},{"full_name":"Hall, Alex R.","first_name":"Alex R.","last_name":"Hall"}],"external_id":{"pmid":["26609077"],"isi":["000371219500015"]},"language":[{"iso":"eng"}],"status":"public","intvolume":"        33","page":"770-782","DOAJ_listed":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)"},"title":"Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria","quality_controlled":"1","license":"https://creativecommons.org/licenses/by-nc/4.0/"},{"year":"2015","scopus_import":"1","abstract":[{"text":"Evolutionary algorithms (EAs) form a popular optimisation paradigm inspired by natural evolution. In recent years the field of evolutionary computation has developed a rigorous analytical theory to analyse their runtime on many illustrative problems. Here we apply this theory to a simple model of natural evolution. In the Strong Selection Weak Mutation (SSWM) evolutionary regime the time between occurrence of new mutations is much longer than the time it takes for a new beneficial mutation to take over the population. In this situation, the population only contains copies of one genotype and evolution can be modelled as a (1+1)-type process where the probability of accepting a new genotype (improvements or worsenings) depends on the change in fitness. We present an initial runtime analysis of SSWM, quantifying its performance for various parameters and investigating differences to the (1+1) EA. We show that SSWM can have a moderate advantage over the (1+1) EA at crossing fitness valleys and study an example where SSWM outperforms the (1+1) EA by taking advantage of information on the fitness gradient.","lang":"eng"}],"arxiv":1,"date_updated":"2025-09-23T08:50:33Z","month":"07","isi":1,"main_file_link":[{"open_access":"1","url":"http://arxiv.org/abs/1504.06260"}],"date_published":"2015-07-11T00:00:00Z","publisher":"ACM","publication_status":"published","article_processing_charge":"No","project":[{"name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"618091"}],"oa_version":"Preprint","doi":"10.1145/2739480.2754758","oa":1,"department":[{"_id":"NiBa"},{"_id":"CaGu"}],"citation":{"ieee":"T. Paixao, D. Sudholt, J. Heredia, and B. Trubenova, “First steps towards a runtime comparison of natural and artificial evolution,” in <i>Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation</i>, Madrid, Spain, 2015, pp. 1455–1462.","chicago":"Paixao, Tiago, Dirk Sudholt, Jorge Heredia, and Barbora Trubenova. “First Steps towards a Runtime Comparison of Natural and Artificial Evolution.” In <i>Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation</i>, 1455–62. ACM, 2015. <a href=\"https://doi.org/10.1145/2739480.2754758\">https://doi.org/10.1145/2739480.2754758</a>.","ama":"Paixao T, Sudholt D, Heredia J, Trubenova B. First steps towards a runtime comparison of natural and artificial evolution. In: <i>Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation</i>. ACM; 2015:1455-1462. doi:<a href=\"https://doi.org/10.1145/2739480.2754758\">10.1145/2739480.2754758</a>","mla":"Paixao, Tiago, et al. “First Steps towards a Runtime Comparison of Natural and Artificial Evolution.” <i>Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation</i>, ACM, 2015, pp. 1455–62, doi:<a href=\"https://doi.org/10.1145/2739480.2754758\">10.1145/2739480.2754758</a>.","short":"T. Paixao, D. Sudholt, J. Heredia, B. Trubenova, in:, Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation, ACM, 2015, pp. 1455–1462.","ista":"Paixao T, Sudholt D, Heredia J, Trubenova B. 2015. First steps towards a runtime comparison of natural and artificial evolution. Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation. GECCO: Genetic and evolutionary computation conference, 1455–1462.","apa":"Paixao, T., Sudholt, D., Heredia, J., &#38; Trubenova, B. (2015). First steps towards a runtime comparison of natural and artificial evolution. In <i>Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation</i> (pp. 1455–1462). Madrid, Spain: ACM. <a href=\"https://doi.org/10.1145/2739480.2754758\">https://doi.org/10.1145/2739480.2754758</a>"},"type":"conference","publication":"Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation","day":"11","_id":"1430","publist_id":"5768","ec_funded":1,"date_created":"2018-12-11T11:51:58Z","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","conference":{"location":"Madrid, Spain","start_date":"2015-07-11","end_date":"2015-07-15","name":"GECCO: Genetic and evolutionary computation conference"},"status":"public","language":[{"iso":"eng"}],"author":[{"id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","last_name":"Paixao","orcid":"0000-0003-2361-3953","full_name":"Paixao, Tiago","first_name":"Tiago"},{"full_name":"Sudholt, Dirk","first_name":"Dirk","last_name":"Sudholt"},{"full_name":"Heredia, Jorge","first_name":"Jorge","last_name":"Heredia"},{"id":"42302D54-F248-11E8-B48F-1D18A9856A87","last_name":"Trubenova","orcid":"0000-0002-6873-2967","first_name":"Barbora","full_name":"Trubenova, Barbora"}],"external_id":{"isi":["000358795700182"],"arxiv":["1504.06260"]},"quality_controlled":"1","title":"First steps towards a runtime comparison of natural and artificial evolution","page":"1455 - 1462"},{"oa_version":"Preprint","publication_status":"published","series_title":"Lecture Notes in Computer Science","project":[{"grant_number":"267989","call_identifier":"FP7","name":"Quantitative Reactive Modeling","_id":"25EE3708-B435-11E9-9278-68D0E5697425"},{"name":"Rigorous Systems Engineering","_id":"25832EC2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"S 11407_N23"},{"call_identifier":"FWF","grant_number":"Z211","_id":"25F42A32-B435-11E9-9278-68D0E5697425","name":"Formal methods for the design and analysis of complex systems"},{"_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","call_identifier":"FP7","grant_number":"618091"},{"grant_number":"250152","call_identifier":"FP7","name":"Limits to selection in biology and in evolutionary computation","_id":"25B07788-B435-11E9-9278-68D0E5697425"},{"_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","grant_number":"291734"}],"article_processing_charge":"No","publisher":"Springer","date_published":"2015-04-01T00:00:00Z","main_file_link":[{"url":"http://arxiv.org/abs/1410.7704","open_access":"1"}],"scopus_import":"1","year":"2015","abstract":[{"text":"The behaviour of gene regulatory networks (GRNs) is typically analysed using simulation-based statistical testing-like methods. In this paper, we demonstrate that we can replace this approach by a formal verification-like method that gives higher assurance and scalability. We focus on Wagner’s weighted GRN model with varying weights, which is used in evolutionary biology. In the model, weight parameters represent the gene interaction strength that may change due to genetic mutations. For a property of interest, we synthesise the constraints over the parameter space that represent the set of GRNs satisfying the property. We experimentally show that our parameter synthesis procedure computes the mutational robustness of GRNs –an important problem of interest in evolutionary biology– more efficiently than the classical simulation method. We specify the property in linear temporal logics. We employ symbolic bounded model checking and SMT solving to compute the space of GRNs that satisfy the property, which amounts to synthesizing a set of linear constraints on the weights.","lang":"eng"}],"alternative_title":["LNCS"],"month":"04","date_updated":"2025-07-10T11:50:42Z","arxiv":1,"_id":"1835","day":"01","publist_id":"5267","oa":1,"type":"conference","citation":{"ista":"Giacobbe M, Guet CC, Gupta A, Henzinger TA, Paixao T, Petrov T. 2015. Model checking gene regulatory networks. 9035, 469–483.","apa":"Giacobbe, M., Guet, C. C., Gupta, A., Henzinger, T. A., Paixao, T., &#38; Petrov, T. (2015). Model checking gene regulatory networks. Presented at the TACAS: Tools and Algorithms for the Construction and Analysis of Systems, London, United Kingdom: Springer. <a href=\"https://doi.org/10.1007/978-3-662-46681-0_47\">https://doi.org/10.1007/978-3-662-46681-0_47</a>","ama":"Giacobbe M, Guet CC, Gupta A, Henzinger TA, Paixao T, Petrov T. Model checking gene regulatory networks. 2015;9035:469-483. doi:<a href=\"https://doi.org/10.1007/978-3-662-46681-0_47\">10.1007/978-3-662-46681-0_47</a>","mla":"Giacobbe, Mirco, et al. <i>Model Checking Gene Regulatory Networks</i>. Vol. 9035, Springer, 2015, pp. 469–83, doi:<a href=\"https://doi.org/10.1007/978-3-662-46681-0_47\">10.1007/978-3-662-46681-0_47</a>.","short":"M. Giacobbe, C.C. Guet, A. Gupta, T.A. Henzinger, T. Paixao, T. Petrov, 9035 (2015) 469–483.","chicago":"Giacobbe, Mirco, Calin C Guet, Ashutosh Gupta, Thomas A Henzinger, Tiago Paixao, and Tatjana Petrov. “Model Checking Gene Regulatory Networks.” Lecture Notes in Computer Science. Springer, 2015. <a href=\"https://doi.org/10.1007/978-3-662-46681-0_47\">https://doi.org/10.1007/978-3-662-46681-0_47</a>.","ieee":"M. Giacobbe, C. C. Guet, A. Gupta, T. A. Henzinger, T. Paixao, and T. Petrov, “Model checking gene regulatory networks,” vol. 9035. Springer, pp. 469–483, 2015."},"department":[{"_id":"ToHe"},{"_id":"CaGu"},{"_id":"NiBa"}],"acknowledgement":"SNSF Early Postdoc.Mobility Fellowship, the grant number P2EZP2 148797.\r\n","doi":"10.1007/978-3-662-46681-0_47","conference":{"start_date":"2015-04-11","name":"TACAS: Tools and Algorithms for the Construction and Analysis of Systems","end_date":"2015-04-18","location":"London, United Kingdom"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2018-12-11T11:54:16Z","related_material":{"record":[{"status":"public","relation":"later_version","id":"1351"}]},"volume":9035,"ec_funded":1,"page":"469 - 483","title":"Model checking gene regulatory networks","quality_controlled":"1","author":[{"id":"3444EA5E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8180-0904","last_name":"Giacobbe","full_name":"Giacobbe, Mirco","first_name":"Mirco"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","last_name":"Guet","full_name":"Guet, Calin C","first_name":"Calin C"},{"id":"335E5684-F248-11E8-B48F-1D18A9856A87","first_name":"Ashutosh","full_name":"Gupta, Ashutosh","last_name":"Gupta"},{"first_name":"Thomas A","full_name":"Henzinger, Thomas A","orcid":"0000−0002−2985−7724","last_name":"Henzinger","id":"40876CD8-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Tiago","full_name":"Paixao, Tiago","last_name":"Paixao","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87"},{"id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","first_name":"Tatjana","full_name":"Petrov, Tatjana","orcid":"0000-0002-9041-0905","last_name":"Petrov"}],"external_id":{"arxiv":["1410.7704"]},"language":[{"iso":"eng"}],"intvolume":"      9035","status":"public"},{"article_processing_charge":"No","publication_status":"published","oa_version":"Preprint","month":"04","isi":1,"date_updated":"2025-09-23T09:45:33Z","arxiv":1,"year":"2015","scopus_import":"1","abstract":[{"text":"In this paper, we present a method for reducing a regular, discrete-time Markov chain (DTMC) to another DTMC with a given, typically much smaller number of states. The cost of reduction is defined as the Kullback-Leibler divergence rate between a projection of the original process through a partition function and a DTMC on the correspondingly partitioned state space. Finding the reduced model with minimal cost is computationally expensive, as it requires an exhaustive search among all state space partitions, and an exact evaluation of the reduction cost for each candidate partition. Our approach deals with the latter problem by minimizing an upper bound on the reduction cost instead of minimizing the exact cost. The proposed upper bound is easy to compute and it is tight if the original chain is lumpable with respect to the partition. Then, we express the problem in the form of information bottleneck optimization, and propose using the agglomerative information bottleneck algorithm for searching a suboptimal partition greedily, rather than exhaustively. The theory is illustrated with examples and one application scenario in the context of modeling bio-molecular interactions.","lang":"eng"}],"publisher":"IEEE","date_published":"2015-04-01T00:00:00Z","main_file_link":[{"url":"http://arxiv.org/abs/1304.6603","open_access":"1"}],"publication":"IEEE Transactions on Automatic Control","issue":"4","publist_id":"5262","_id":"1840","day":"01","publication_identifier":{"issn":["0018-9286"]},"acknowledgement":"This work was supported by the Austrian Research Association under Project 06/12684, by the Swiss National Science Foundation (SNSF) under Grant PP00P2 128503/1, by the SystemsX.ch (the Swiss Inititative for Systems Biology), and by a SNSF Early Postdoc.Mobility Fellowship grant P2EZP2_148797.\r\n","doi":"10.1109/TAC.2014.2364971","department":[{"_id":"CaGu"},{"_id":"ToHe"}],"citation":{"mla":"Geiger, Bernhard, et al. “Optimal Kullback-Leibler Aggregation via Information Bottleneck.” <i>IEEE Transactions on Automatic Control</i>, vol. 60, no. 4, IEEE, 2015, pp. 1010–22, doi:<a href=\"https://doi.org/10.1109/TAC.2014.2364971\">10.1109/TAC.2014.2364971</a>.","ama":"Geiger B, Petrov T, Kubin G, Koeppl H. Optimal Kullback-Leibler aggregation via information bottleneck. <i>IEEE Transactions on Automatic Control</i>. 2015;60(4):1010-1022. doi:<a href=\"https://doi.org/10.1109/TAC.2014.2364971\">10.1109/TAC.2014.2364971</a>","short":"B. Geiger, T. Petrov, G. Kubin, H. Koeppl, IEEE Transactions on Automatic Control 60 (2015) 1010–1022.","ista":"Geiger B, Petrov T, Kubin G, Koeppl H. 2015. Optimal Kullback-Leibler aggregation via information bottleneck. IEEE Transactions on Automatic Control. 60(4), 1010–1022.","apa":"Geiger, B., Petrov, T., Kubin, G., &#38; Koeppl, H. (2015). Optimal Kullback-Leibler aggregation via information bottleneck. <i>IEEE Transactions on Automatic Control</i>. IEEE. <a href=\"https://doi.org/10.1109/TAC.2014.2364971\">https://doi.org/10.1109/TAC.2014.2364971</a>","ieee":"B. Geiger, T. Petrov, G. Kubin, and H. Koeppl, “Optimal Kullback-Leibler aggregation via information bottleneck,” <i>IEEE Transactions on Automatic Control</i>, vol. 60, no. 4. IEEE, pp. 1010–1022, 2015.","chicago":"Geiger, Bernhard, Tatjana Petrov, Gernot Kubin, and Heinz Koeppl. “Optimal Kullback-Leibler Aggregation via Information Bottleneck.” <i>IEEE Transactions on Automatic Control</i>. IEEE, 2015. <a href=\"https://doi.org/10.1109/TAC.2014.2364971\">https://doi.org/10.1109/TAC.2014.2364971</a>."},"type":"journal_article","oa":1,"date_created":"2018-12-11T11:54:18Z","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","volume":60,"title":"Optimal Kullback-Leibler aggregation via information bottleneck","quality_controlled":"1","page":"1010 - 1022","status":"public","intvolume":"        60","author":[{"first_name":"Bernhard","full_name":"Geiger, Bernhard","last_name":"Geiger"},{"id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9041-0905","last_name":"Petrov","first_name":"Tatjana","full_name":"Petrov, Tatjana"},{"full_name":"Kubin, Gernot","first_name":"Gernot","last_name":"Kubin"},{"last_name":"Koeppl","full_name":"Koeppl, Heinz","first_name":"Heinz"}],"external_id":{"arxiv":["1304.6603"],"isi":["000351731600009"]},"language":[{"iso":"eng"}]},{"oa_version":"Published Version","file":[{"date_created":"2018-12-12T10:16:53Z","relation":"main_file","access_level":"open_access","creator":"system","file_id":"5244","date_updated":"2020-07-14T12:45:01Z","file_size":595307,"file_name":"IST-2016-483-v1+1_1-s2.0-S0022519315003409-main.pdf","checksum":"33b60ecfea60764756a9ee9df5eb65ca","content_type":"application/pdf"}],"article_processing_charge":"No","project":[{"_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","call_identifier":"FP7","grant_number":"618091"},{"_id":"25B07788-B435-11E9-9278-68D0E5697425","name":"Limits to selection in biology and in evolutionary computation","grant_number":"250152","call_identifier":"FP7"}],"publication_status":"published","pubrep_id":"483","publisher":"Elsevier","date_published":"2015-10-21T00:00:00Z","isi":1,"month":"10","date_updated":"2025-09-23T14:55:02Z","abstract":[{"lang":"eng","text":"The theory of population genetics and evolutionary computation have been evolving separately for nearly 30 years. Many results have been independently obtained in both fields and many others are unique to its respective field. We aim to bridge this gap by developing a unifying framework for evolutionary processes that allows both evolutionary algorithms and population genetics models to be cast in the same formal framework. The framework we present here decomposes the evolutionary process into its several components in order to facilitate the identification of similarities between different models. In particular, we propose a classification of evolutionary operators based on the defining properties of the different components. We cast several commonly used operators from both fields into this common framework. Using this, we map different evolutionary and genetic algorithms to different evolutionary regimes and identify candidates with the most potential for the translation of results between the fields. This provides a unified description of evolutionary processes and represents a stepping stone towards new tools and results to both fields. "}],"scopus_import":"1","year":"2015","publist_id":"5629","_id":"1542","day":"21","publication":" Journal of Theoretical Biology","file_date_updated":"2020-07-14T12:45:01Z","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"citation":{"ieee":"T. Paixao <i>et al.</i>, “Toward a unifying framework for evolutionary processes,” <i> Journal of Theoretical Biology</i>, vol. 383. Elsevier, pp. 28–43, 2015.","chicago":"Paixao, Tiago, Golnaz Badkobeh, Nicholas H Barton, Doğan Çörüş, Duccuong Dang, Tobias Friedrich, Per Lehre, Dirk Sudholt, Andrew Sutton, and Barbora Trubenova. “Toward a Unifying Framework for Evolutionary Processes.” <i> Journal of Theoretical Biology</i>. Elsevier, 2015. <a href=\"https://doi.org/10.1016/j.jtbi.2015.07.011\">https://doi.org/10.1016/j.jtbi.2015.07.011</a>.","short":"T. Paixao, G. Badkobeh, N.H. Barton, D. Çörüş, D. Dang, T. Friedrich, P. Lehre, D. Sudholt, A. Sutton, B. Trubenova,  Journal of Theoretical Biology 383 (2015) 28–43.","ama":"Paixao T, Badkobeh G, Barton NH, et al. Toward a unifying framework for evolutionary processes. <i> Journal of Theoretical Biology</i>. 2015;383:28-43. doi:<a href=\"https://doi.org/10.1016/j.jtbi.2015.07.011\">10.1016/j.jtbi.2015.07.011</a>","mla":"Paixao, Tiago, et al. “Toward a Unifying Framework for Evolutionary Processes.” <i> Journal of Theoretical Biology</i>, vol. 383, Elsevier, 2015, pp. 28–43, doi:<a href=\"https://doi.org/10.1016/j.jtbi.2015.07.011\">10.1016/j.jtbi.2015.07.011</a>.","ista":"Paixao T, Badkobeh G, Barton NH, Çörüş D, Dang D, Friedrich T, Lehre P, Sudholt D, Sutton A, Trubenova B. 2015. Toward a unifying framework for evolutionary processes.  Journal of Theoretical Biology. 383, 28–43.","apa":"Paixao, T., Badkobeh, G., Barton, N. H., Çörüş, D., Dang, D., Friedrich, T., … Trubenova, B. (2015). Toward a unifying framework for evolutionary processes. <i> Journal of Theoretical Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.jtbi.2015.07.011\">https://doi.org/10.1016/j.jtbi.2015.07.011</a>"},"type":"journal_article","oa":1,"doi":"10.1016/j.jtbi.2015.07.011","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","ddc":["570"],"date_created":"2018-12-11T11:52:37Z","corr_author":"1","has_accepted_license":"1","ec_funded":1,"volume":383,"page":"28 - 43","tmp":{"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)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"title":"Toward a unifying framework for evolutionary processes","quality_controlled":"1","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","external_id":{"isi":["000362056300005"]},"author":[{"id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","last_name":"Paixao","orcid":"0000-0003-2361-3953","first_name":"Tiago","full_name":"Paixao, Tiago"},{"first_name":"Golnaz","full_name":"Badkobeh, Golnaz","last_name":"Badkobeh"},{"id":"4880FE40-F248-11E8-B48F-1D18A9856A87","full_name":"Barton, Nicholas H","first_name":"Nicholas H","last_name":"Barton","orcid":"0000-0002-8548-5240"},{"first_name":"Doğan","full_name":"Çörüş, Doğan","last_name":"Çörüş"},{"first_name":"Duccuong","full_name":"Dang, Duccuong","last_name":"Dang"},{"last_name":"Friedrich","first_name":"Tobias","full_name":"Friedrich, Tobias"},{"last_name":"Lehre","first_name":"Per","full_name":"Lehre, Per"},{"last_name":"Sudholt","first_name":"Dirk","full_name":"Sudholt, Dirk"},{"last_name":"Sutton","first_name":"Andrew","full_name":"Sutton, Andrew"},{"id":"42302D54-F248-11E8-B48F-1D18A9856A87","full_name":"Trubenova, Barbora","first_name":"Barbora","orcid":"0000-0002-6873-2967","last_name":"Trubenova"}],"language":[{"iso":"eng"}],"status":"public","intvolume":"       383"},{"doi":"10.1371/journal.pgen.1005639.s001","status":"public","author":[{"orcid":"0000-0002-8523-0758","last_name":"Tugrul","first_name":"Murat","full_name":"Tugrul, Murat","id":"37C323C6-F248-11E8-B48F-1D18A9856A87"},{"id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","first_name":"Tiago","full_name":"Paixao, Tiago","orcid":"0000-0003-2361-3953","last_name":"Paixao"},{"first_name":"Nicholas H","full_name":"Barton, Nicholas H","last_name":"Barton","orcid":"0000-0002-8548-5240","id":"4880FE40-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Tkačik, Gašper","first_name":"Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"citation":{"ieee":"M. Tugrul, T. Paixao, N. H. Barton, and G. Tkačik, “Other fitness models for comparison &#38; for interacting TFBSs.” Public Library of Science, 2015.","chicago":"Tugrul, Murat, Tiago Paixao, Nicholas H Barton, and Gašper Tkačik. “Other Fitness Models for Comparison &#38; for Interacting TFBSs.” Public Library of Science, 2015. <a href=\"https://doi.org/10.1371/journal.pgen.1005639.s001\">https://doi.org/10.1371/journal.pgen.1005639.s001</a>.","short":"M. Tugrul, T. Paixao, N.H. Barton, G. Tkačik, (2015).","ama":"Tugrul M, Paixao T, Barton NH, Tkačik G. Other fitness models for comparison &#38; for interacting TFBSs. 2015. doi:<a href=\"https://doi.org/10.1371/journal.pgen.1005639.s001\">10.1371/journal.pgen.1005639.s001</a>","mla":"Tugrul, Murat, et al. <i>Other Fitness Models for Comparison &#38; for Interacting TFBSs</i>. Public Library of Science, 2015, doi:<a href=\"https://doi.org/10.1371/journal.pgen.1005639.s001\">10.1371/journal.pgen.1005639.s001</a>.","ista":"Tugrul M, Paixao T, Barton NH, Tkačik G. 2015. Other fitness models for comparison &#38; for interacting TFBSs, Public Library of Science, <a href=\"https://doi.org/10.1371/journal.pgen.1005639.s001\">10.1371/journal.pgen.1005639.s001</a>.","apa":"Tugrul, M., Paixao, T., Barton, N. H., &#38; Tkačik, G. (2015). Other fitness models for comparison &#38; for interacting TFBSs. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pgen.1005639.s001\">https://doi.org/10.1371/journal.pgen.1005639.s001</a>"},"type":"research_data_reference","department":[{"_id":"NiBa"},{"_id":"CaGu"},{"_id":"GaTk"}],"title":"Other fitness models for comparison & for interacting TFBSs","_id":"9712","day":"06","related_material":{"record":[{"relation":"used_in_publication","status":"public","id":"1666"}]},"year":"2015","date_updated":"2025-09-23T08:31:14Z","month":"11","date_published":"2015-11-06T00:00:00Z","publisher":"Public Library of Science","article_processing_charge":"No","date_created":"2021-07-23T12:00:37Z","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","oa_version":"Published Version"},{"has_accepted_license":"1","related_material":{"record":[{"relation":"research_data","status":"public","id":"9712"},{"relation":"dissertation_contains","status":"public","id":"1131"}]},"volume":11,"ec_funded":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","ddc":["576"],"date_created":"2018-12-11T11:53:21Z","author":[{"id":"37C323C6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8523-0758","last_name":"Tugrul","full_name":"Tugrul, Murat","first_name":"Murat"},{"orcid":"0000-0003-2361-3953","last_name":"Paixao","first_name":"Tiago","full_name":"Paixao, Tiago","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87"},{"id":"4880FE40-F248-11E8-B48F-1D18A9856A87","last_name":"Barton","orcid":"0000-0002-8548-5240","full_name":"Barton, Nicholas H","first_name":"Nicholas H"},{"full_name":"Tkacik, Gasper","first_name":"Gasper","orcid":"0000-0002-6699-1455","last_name":"Tkacik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"external_id":{"isi":["000366179000022"]},"language":[{"iso":"eng"}],"intvolume":"        11","status":"public","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"title":"Dynamics of transcription factor binding site evolution","quality_controlled":"1","publisher":"Public Library of Science","date_published":"2015-11-06T00:00:00Z","pubrep_id":"463","scopus_import":"1","year":"2015","abstract":[{"lang":"eng","text":"Evolution of gene regulation is crucial for our understanding of the phenotypic differences between species, populations and individuals. Sequence-specific binding of transcription factors to the regulatory regions on the DNA is a key regulatory mechanism that determines gene expression and hence heritable phenotypic variation. We use a biophysical model for directional selection on gene expression to estimate the rates of gain and loss of transcription factor binding sites (TFBS) in finite populations under both point and insertion/deletion mutations. Our results show that these rates are typically slow for a single TFBS in an isolated DNA region, unless the selection is extremely strong. These rates decrease drastically with increasing TFBS length or increasingly specific protein-DNA interactions, making the evolution of sites longer than ∼ 10 bp unlikely on typical eukaryotic speciation timescales. Similarly, evolution converges to the stationary distribution of binding sequences very slowly, making the equilibrium assumption questionable. The availability of longer regulatory sequences in which multiple binding sites can evolve simultaneously, the presence of “pre-sites” or partially decayed old sites in the initial sequence, and biophysical cooperativity between transcription factors, can all facilitate gain of TFBS and reconcile theoretical calculations with timescales inferred from comparative genomics."}],"isi":1,"month":"11","date_updated":"2026-04-09T10:52:40Z","file":[{"date_updated":"2020-07-14T12:45:10Z","file_size":2580778,"file_name":"IST-2016-463-v1+1_journal.pgen.1005639.pdf","checksum":"a4e72fca5ccf40ddacf4d08c8e46b554","content_type":"application/pdf","date_created":"2018-12-12T10:07:58Z","relation":"main_file","access_level":"open_access","creator":"system","file_id":"4657"}],"oa_version":"Published Version","publication_status":"published","project":[{"grant_number":"250152","call_identifier":"FP7","name":"Limits to selection in biology and in evolutionary computation","_id":"25B07788-B435-11E9-9278-68D0E5697425"}],"article_processing_charge":"No","oa":1,"citation":{"ieee":"M. Tugrul, T. Paixao, N. H. Barton, and G. Tkačik, “Dynamics of transcription factor binding site evolution,” <i>PLoS Genetics</i>, vol. 11, no. 11. Public Library of Science, 2015.","chicago":"Tugrul, Murat, Tiago Paixao, Nicholas H Barton, and Gašper Tkačik. “Dynamics of Transcription Factor Binding Site Evolution.” <i>PLoS Genetics</i>. Public Library of Science, 2015. <a href=\"https://doi.org/10.1371/journal.pgen.1005639\">https://doi.org/10.1371/journal.pgen.1005639</a>.","mla":"Tugrul, Murat, et al. “Dynamics of Transcription Factor Binding Site Evolution.” <i>PLoS Genetics</i>, vol. 11, no. 11, Public Library of Science, 2015, doi:<a href=\"https://doi.org/10.1371/journal.pgen.1005639\">10.1371/journal.pgen.1005639</a>.","ama":"Tugrul M, Paixao T, Barton NH, Tkačik G. Dynamics of transcription factor binding site evolution. <i>PLoS Genetics</i>. 2015;11(11). doi:<a href=\"https://doi.org/10.1371/journal.pgen.1005639\">10.1371/journal.pgen.1005639</a>","short":"M. Tugrul, T. Paixao, N.H. Barton, G. Tkačik, PLoS Genetics 11 (2015).","ista":"Tugrul M, Paixao T, Barton NH, Tkačik G. 2015. Dynamics of transcription factor binding site evolution. PLoS Genetics. 11(11).","apa":"Tugrul, M., Paixao, T., Barton, N. H., &#38; Tkačik, G. (2015). Dynamics of transcription factor binding site evolution. <i>PLoS Genetics</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pgen.1005639\">https://doi.org/10.1371/journal.pgen.1005639</a>"},"type":"journal_article","department":[{"_id":"NiBa"},{"_id":"CaGu"},{"_id":"GaTk"}],"doi":"10.1371/journal.pgen.1005639","_id":"1666","day":"06","publist_id":"5483","issue":"11","file_date_updated":"2020-07-14T12:45:10Z","publication":"PLoS Genetics"},{"oa":1,"author":[{"first_name":"Sébastien","full_name":"Wielgoss, Sébastien","last_name":"Wielgoss"},{"last_name":"Bergmiller","orcid":"0000-0001-5396-4346","first_name":"Tobias","full_name":"Bergmiller, Tobias","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Bischofberger","first_name":"Anna M.","full_name":"Bischofberger, Anna M."},{"last_name":"Hall","first_name":"Alex R.","full_name":"Hall, Alex R."}],"department":[{"_id":"CaGu"}],"type":"research_data_reference","citation":{"mla":"Wielgoss, Sébastien, et al. <i>Data from: Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Non-Mutator Bacteria</i>. Dryad, 2015, doi:<a href=\"https://doi.org/10.5061/dryad.cj910\">10.5061/dryad.cj910</a>.","ama":"Wielgoss S, Bergmiller T, Bischofberger AM, Hall AR. Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria. 2015. doi:<a href=\"https://doi.org/10.5061/dryad.cj910\">10.5061/dryad.cj910</a>","short":"S. Wielgoss, T. Bergmiller, A.M. Bischofberger, A.R. Hall, (2015).","ista":"Wielgoss S, Bergmiller T, Bischofberger AM, Hall AR. 2015. Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria, Dryad, <a href=\"https://doi.org/10.5061/dryad.cj910\">10.5061/dryad.cj910</a>.","apa":"Wielgoss, S., Bergmiller, T., Bischofberger, A. M., &#38; Hall, A. R. (2015). Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria. Dryad. <a href=\"https://doi.org/10.5061/dryad.cj910\">https://doi.org/10.5061/dryad.cj910</a>","ieee":"S. Wielgoss, T. Bergmiller, A. M. Bischofberger, and A. R. Hall, “Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria.” Dryad, 2015.","chicago":"Wielgoss, Sébastien, Tobias Bergmiller, Anna M. Bischofberger, and Alex R. Hall. “Data from: Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Non-Mutator Bacteria.” Dryad, 2015. <a href=\"https://doi.org/10.5061/dryad.cj910\">https://doi.org/10.5061/dryad.cj910</a>."},"doi":"10.5061/dryad.cj910","status":"public","_id":"9719","day":"21","title":"Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria","main_file_link":[{"open_access":"1","url":"https://doi.org/10.5061/dryad.cj910"}],"date_published":"2015-12-21T00:00:00Z","publisher":"Dryad","year":"2015","related_material":{"record":[{"id":"5749","relation":"used_in_publication","status":"public"}]},"abstract":[{"text":"Parasitism creates selection for resistance mechanisms in host populations and is hypothesized to promote increased host evolvability. However, the influence of these traits on host evolution when parasites are no longer present is unclear. We used experimental evolution and whole-genome sequencing of Escherichia coli to determine the effects of past and present exposure to parasitic viruses (phages) on the spread of mutator alleles, resistance, and bacterial competitive fitness. We found that mutator alleles spread rapidly during adaptation to any of four different phage species, and this pattern was even more pronounced with multiple phages present simultaneously. However, hypermutability did not detectably accelerate adaptation in the absence of phages and recovery of fitness costs associated with resistance. Several lineages evolved phage resistance through elevated mucoidy, and during subsequent evolution in phage-free conditions they rapidly reverted to nonmucoid, phage-susceptible phenotypes. Genome sequencing revealed that this phenotypic reversion was achieved by additional genetic changes rather than by genotypic reversion of the initial resistance mutations. Insertion sequence (IS) elements played a key role in both the acquisition of resistance and adaptation in the absence of parasites; unlike single nucleotide polymorphisms, IS insertions were not more frequent in mutator lineages. Our results provide a genetic explanation for rapid reversion of mucoidy, a phenotype observed in other bacterial species including human pathogens. Moreover, this demonstrates that the types of genetic change underlying adaptation to fitness costs, and consequently the impact of evolvability mechanisms such as increased point-mutation rates, depend critically on the mechanism of resistance.","lang":"eng"}],"date_updated":"2026-04-29T05:57:01Z","month":"12","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","oa_version":"Published Version","article_processing_charge":"No","date_created":"2021-07-26T08:44:04Z"},{"acknowledgement":"The project was supported by Leverhulme Trust.","doi":"10.1098/rspb.2014.1679","oa":1,"department":[{"_id":"CaGu"}],"citation":{"ieee":"M. Lagator, N. Colegrave, and P. Neve, “Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses,” <i>Proceedings of the Royal Society of London Series B Biological Sciences</i>, vol. 281, no. 1794. Royal Society, The, 2014.","chicago":"Lagator, Mato, Nick Colegrave, and Paul Neve. “Selection History and Epistatic Interactions Impact Dynamics of Adaptation to Novel Environmental Stresses.” <i>Proceedings of the Royal Society of London Series B Biological Sciences</i>. Royal Society, The, 2014. <a href=\"https://doi.org/10.1098/rspb.2014.1679\">https://doi.org/10.1098/rspb.2014.1679</a>.","ama":"Lagator M, Colegrave N, Neve P. Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses. <i>Proceedings of the Royal Society of London Series B Biological Sciences</i>. 2014;281(1794). doi:<a href=\"https://doi.org/10.1098/rspb.2014.1679\">10.1098/rspb.2014.1679</a>","mla":"Lagator, Mato, et al. “Selection History and Epistatic Interactions Impact Dynamics of Adaptation to Novel Environmental Stresses.” <i>Proceedings of the Royal Society of London Series B Biological Sciences</i>, vol. 281, no. 1794, 20141679, Royal Society, The, 2014, doi:<a href=\"https://doi.org/10.1098/rspb.2014.1679\">10.1098/rspb.2014.1679</a>.","short":"M. Lagator, N. Colegrave, P. Neve, Proceedings of the Royal Society of London Series B Biological Sciences 281 (2014).","apa":"Lagator, M., Colegrave, N., &#38; Neve, P. (2014). Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses. <i>Proceedings of the Royal Society of London Series B Biological Sciences</i>. Royal Society, The. <a href=\"https://doi.org/10.1098/rspb.2014.1679\">https://doi.org/10.1098/rspb.2014.1679</a>","ista":"Lagator M, Colegrave N, Neve P. 2014. Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses. Proceedings of the Royal Society of London Series B Biological Sciences. 281(1794), 20141679."},"type":"journal_article","issue":"1794","publication":"Proceedings of the Royal Society of London Series B Biological Sciences","day":"17","_id":"2036","publist_id":"5019","abstract":[{"text":" In rapidly changing environments, selection history may impact the dynamics of adaptation. Mutations selected in one environment may result in pleiotropic fitness trade-offs in subsequent novel environments, slowing the rates of adaptation. Epistatic interactions between mutations selected in sequential stressful environments may slow or accelerate subsequent rates of adaptation, depending on the nature of that interaction. We explored the dynamics of adaptation during sequential exposure to herbicides with different modes of action in Chlamydomonas reinhardtii. Evolution of resistance to two of the herbicides was largely independent of selection history. For carbetamide, previous adaptation to other herbicide modes of action positively impacted the likelihood of adaptation to this herbicide. Furthermore, while adaptation to all individual herbicides was associated with pleiotropic fitness costs in stress-free environments, we observed that accumulation of resistance mechanisms was accompanied by a reduction in overall fitness costs. We suggest that antagonistic epistasis may be a driving mechanism that enables populations to more readily adapt in novel environments. These findings highlight the potential for sequences of xenobiotics to facilitate the rapid evolution of multiple-drug and -pesticide resistance, as well as the potential for epistatic interactions between adaptive mutations to facilitate evolutionary rescue in rapidly changing environments. ","lang":"eng"}],"year":"2014","scopus_import":"1","month":"09","isi":1,"date_updated":"2025-09-29T11:54:46Z","publisher":"Royal Society, The","main_file_link":[{"url":"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211454/","open_access":"1"}],"date_published":"2014-09-17T00:00:00Z","publication_status":"published","article_processing_charge":"No","oa_version":"Submitted Version","intvolume":"       281","status":"public","external_id":{"isi":["000341922700009"]},"author":[{"id":"345D25EC-F248-11E8-B48F-1D18A9856A87","full_name":"Lagator, Mato","first_name":"Mato","last_name":"Lagator"},{"first_name":"Nick","full_name":"Colegrave, Nick","last_name":"Colegrave"},{"first_name":"Paul","full_name":"Neve, Paul","last_name":"Neve"}],"language":[{"iso":"eng"}],"title":"Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses","quality_controlled":"1","related_material":{"record":[{"id":"9741","relation":"research_data","status":"public"}]},"volume":281,"date_created":"2018-12-11T11:55:21Z","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","article_number":"20141679"},{"external_id":{"arxiv":["1303.4532"],"isi":["000340588700008"]},"author":[{"last_name":"Ganguly","first_name":"Arnab","full_name":"Ganguly, Arnab"},{"id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","last_name":"Petrov","orcid":"0000-0002-9041-0905","full_name":"Petrov, Tatjana","first_name":"Tatjana"},{"last_name":"Koeppl","first_name":"Heinz","full_name":"Koeppl, Heinz"}],"language":[{"iso":"eng"}],"intvolume":"        69","status":"public","page":"767 - 797","title":"Markov chain aggregation and its applications to combinatorial reaction networks","quality_controlled":"1","volume":69,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","date_created":"2018-12-11T11:55:28Z","oa":1,"department":[{"_id":"CaGu"},{"_id":"ToHe"}],"citation":{"ieee":"A. Ganguly, T. Petrov, and H. Koeppl, “Markov chain aggregation and its applications to combinatorial reaction networks,” <i>Journal of Mathematical Biology</i>, vol. 69, no. 3. Springer, pp. 767–797, 2014.","chicago":"Ganguly, Arnab, Tatjana Petrov, and Heinz Koeppl. “Markov Chain Aggregation and Its Applications to Combinatorial Reaction Networks.” <i>Journal of Mathematical Biology</i>. Springer, 2014. <a href=\"https://doi.org/10.1007/s00285-013-0738-7\">https://doi.org/10.1007/s00285-013-0738-7</a>.","short":"A. Ganguly, T. Petrov, H. Koeppl, Journal of Mathematical Biology 69 (2014) 767–797.","ama":"Ganguly A, Petrov T, Koeppl H. Markov chain aggregation and its applications to combinatorial reaction networks. <i>Journal of Mathematical Biology</i>. 2014;69(3):767-797. doi:<a href=\"https://doi.org/10.1007/s00285-013-0738-7\">10.1007/s00285-013-0738-7</a>","mla":"Ganguly, Arnab, et al. “Markov Chain Aggregation and Its Applications to Combinatorial Reaction Networks.” <i>Journal of Mathematical Biology</i>, vol. 69, no. 3, Springer, 2014, pp. 767–97, doi:<a href=\"https://doi.org/10.1007/s00285-013-0738-7\">10.1007/s00285-013-0738-7</a>.","ista":"Ganguly A, Petrov T, Koeppl H. 2014. Markov chain aggregation and its applications to combinatorial reaction networks. Journal of Mathematical Biology. 69(3), 767–797.","apa":"Ganguly, A., Petrov, T., &#38; Koeppl, H. (2014). Markov chain aggregation and its applications to combinatorial reaction networks. <i>Journal of Mathematical Biology</i>. Springer. <a href=\"https://doi.org/10.1007/s00285-013-0738-7\">https://doi.org/10.1007/s00285-013-0738-7</a>"},"type":"journal_article","acknowledgement":"T. Petrov is supported by SystemsX.ch—the Swiss Inititative for Systems Biology.","doi":"10.1007/s00285-013-0738-7","day":"20","_id":"2056","publist_id":"4990","issue":"3","publication":"Journal of Mathematical Biology","publisher":"Springer","main_file_link":[{"open_access":"1","url":"http://arxiv.org/abs/1303.4532"}],"date_published":"2014-11-20T00:00:00Z","year":"2014","abstract":[{"lang":"eng","text":"We consider a continuous-time Markov chain (CTMC) whose state space is partitioned into aggregates, and each aggregate is assigned a probability measure. A sufficient condition for defining a CTMC over the aggregates is presented as a variant of weak lumpability, which also characterizes that the measure over the original process can be recovered from that of the aggregated one. We show how the applicability of de-aggregation depends on the initial distribution. The application section is devoted to illustrate how the developed theory aids in reducing CTMC models of biochemical systems particularly in connection to protein-protein interactions. We assume that the model is written by a biologist in form of site-graph-rewrite rules. Site-graph-rewrite rules compactly express that, often, only a local context of a protein (instead of a full molecular species) needs to be in a certain configuration in order to trigger a reaction event. This observation leads to suitable aggregate Markov chains with smaller state spaces, thereby providing sufficient reduction in computational complexity. This is further exemplified in two case studies: simple unbounded polymerization and early EGFR/insulin crosstalk."}],"scopus_import":"1","isi":1,"month":"11","date_updated":"2025-09-29T11:50:22Z","arxiv":1,"oa_version":"Submitted Version","publication_status":"published","article_processing_charge":"No"},{"date_created":"2018-12-11T11:54:35Z","ddc":["570"],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","article_number":"e106247","volume":9,"has_accepted_license":"1","quality_controlled":"1","title":"Functional and bioinformatics analysis of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"status":"public","intvolume":"         9","language":[{"iso":"eng"}],"author":[{"first_name":"Anna","full_name":"Grabowska, Anna","last_name":"Grabowska"},{"last_name":"Wywiał","first_name":"Ewa","full_name":"Wywiał, Ewa"},{"full_name":"Dunin Horkawicz, Stanislaw","first_name":"Stanislaw","last_name":"Dunin Horkawicz"},{"first_name":"Anna","full_name":"Łasica, Anna","last_name":"Łasica"},{"last_name":"Wösten","full_name":"Wösten, Marc","first_name":"Marc"},{"last_name":"Nagy-Staron","orcid":"0000-0002-1391-8377","first_name":"Anna A","full_name":"Nagy-Staron, Anna A","id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Godlewska","first_name":"Renata","full_name":"Godlewska, Renata"},{"last_name":"Bocian Ostrzycka","first_name":"Katarzyna","full_name":"Bocian Ostrzycka, Katarzyna"},{"last_name":"Pieńkowska","first_name":"Katarzyna","full_name":"Pieńkowska, Katarzyna"},{"last_name":"Łaniewski","first_name":"Paweł","full_name":"Łaniewski, Paweł"},{"full_name":"Bujnicki, Janusz","first_name":"Janusz","last_name":"Bujnicki"},{"last_name":"Van Putten","first_name":"Jos","full_name":"Van Putten, Jos"},{"first_name":"Elzbieta","full_name":"Jagusztyn Krynicka, Elzbieta","last_name":"Jagusztyn Krynicka"}],"external_id":{"isi":["000341231500064"]},"article_processing_charge":"No","publication_status":"published","oa_version":"Published Version","file":[{"file_name":"IST-2016-438-v1+1_journal.pone.0106247.pdf","checksum":"7d02c3da7f72b82bb5d7932d80c3251f","content_type":"application/pdf","date_updated":"2020-07-14T12:45:20Z","file_size":4248801,"file_id":"5205","date_created":"2018-12-12T10:16:19Z","relation":"main_file","access_level":"open_access","creator":"system"}],"date_updated":"2025-09-29T13:05:10Z","isi":1,"month":"09","abstract":[{"lang":"eng","text":"Background: Bacterial Dsb enzymes are involved in the oxidative folding of many proteins, through the formation of disulfide bonds between their cysteine residues. The Dsb protein network has been well characterized in cells of the model microorganism Escherichia coli. To gain insight into the functioning of the Dsb system in epsilon-Proteobacteria, where it plays an important role in the colonization process, we studied two homologs of the main Escherichia coli Dsb oxidase (EcDsbA) that are present in the cells of the enteric pathogen Campylobacter jejuni, the most frequently reported bacterial cause of human enteritis in the world. Methods and Results: Phylogenetic analysis suggests the horizontal transfer of the epsilon-Proteobacterial DsbAs from a common ancestor to gamma-Proteobacteria, which then gave rise to the DsbL lineage. Phenotype and enzymatic assays suggest that the two C. jejuni DsbAs play different roles in bacterial cells and have divergent substrate spectra. CjDsbA1 is essential for the motility and autoagglutination phenotypes, while CjDsbA2 has no impact on those processes. CjDsbA1 plays a critical role in the oxidative folding that ensures the activity of alkaline phosphatase CjPhoX, whereas CjDsbA2 is crucial for the activity of arylsulfotransferase CjAstA, encoded within the dsbA2-dsbB-astA operon. Conclusions: Our results show that CjDsbA1 is the primary thiol-oxidoreductase affecting life processes associated with bacterial spread and host colonization, as well as ensuring the oxidative folding of particular protein substrates. In contrast, CjDsbA2 activity does not affect the same processes and so far its oxidative folding activity has been demonstrated for one substrate, arylsulfotransferase CjAstA. The results suggest the cooperation between CjDsbA2 and CjDsbB. In the case of the CjDsbA1, this cooperation is not exclusive and there is probably another protein to be identified in C. jejuni cells that acts to re-oxidize CjDsbA1. Altogether the data presented here constitute the considerable insight to the Epsilonproteobacterial Dsb systems, which have been poorly understood so far."}],"year":"2014","scopus_import":"1","pubrep_id":"438","date_published":"2014-09-02T00:00:00Z","publisher":"Public Library of Science","publication":"PLoS One","file_date_updated":"2020-07-14T12:45:20Z","issue":"9","publist_id":"5201","day":"02","_id":"1894","doi":"10.1371/journal.pone.0106247","type":"journal_article","citation":{"ieee":"A. Grabowska <i>et al.</i>, “Functional and bioinformatics analysis of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA,” <i>PLoS One</i>, vol. 9, no. 9. Public Library of Science, 2014.","chicago":"Grabowska, Anna, Ewa Wywiał, Stanislaw Dunin Horkawicz, Anna Łasica, Marc Wösten, Anna A Nagy-Staron, Renata Godlewska, et al. “Functional and Bioinformatics Analysis of Two Campylobacter Jejuni Homologs of the Thiol-Disulfide Oxidoreductase, DsbA.” <i>PLoS One</i>. Public Library of Science, 2014. <a href=\"https://doi.org/10.1371/journal.pone.0106247\">https://doi.org/10.1371/journal.pone.0106247</a>.","short":"A. Grabowska, E. Wywiał, S. Dunin Horkawicz, A. Łasica, M. Wösten, A.A. Nagy-Staron, R. Godlewska, K. Bocian Ostrzycka, K. Pieńkowska, P. Łaniewski, J. Bujnicki, J. Van Putten, E. Jagusztyn Krynicka, PLoS One 9 (2014).","mla":"Grabowska, Anna, et al. “Functional and Bioinformatics Analysis of Two Campylobacter Jejuni Homologs of the Thiol-Disulfide Oxidoreductase, DsbA.” <i>PLoS One</i>, vol. 9, no. 9, e106247, Public Library of Science, 2014, doi:<a href=\"https://doi.org/10.1371/journal.pone.0106247\">10.1371/journal.pone.0106247</a>.","ama":"Grabowska A, Wywiał E, Dunin Horkawicz S, et al. Functional and bioinformatics analysis of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA. <i>PLoS One</i>. 2014;9(9). doi:<a href=\"https://doi.org/10.1371/journal.pone.0106247\">10.1371/journal.pone.0106247</a>","apa":"Grabowska, A., Wywiał, E., Dunin Horkawicz, S., Łasica, A., Wösten, M., Nagy-Staron, A. A., … Jagusztyn Krynicka, E. (2014). Functional and bioinformatics analysis of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA. <i>PLoS One</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pone.0106247\">https://doi.org/10.1371/journal.pone.0106247</a>","ista":"Grabowska A, Wywiał E, Dunin Horkawicz S, Łasica A, Wösten M, Nagy-Staron AA, Godlewska R, Bocian Ostrzycka K, Pieńkowska K, Łaniewski P, Bujnicki J, Van Putten J, Jagusztyn Krynicka E. 2014. Functional and bioinformatics analysis of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA. PLoS One. 9(9), e106247."},"department":[{"_id":"CaGu"}],"oa":1},{"volume":38,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","pmid":1,"article_type":"original","date_created":"2018-12-11T11:54:41Z","author":[{"full_name":"Milenković, Ivan","first_name":"Ivan","last_name":"Milenković"},{"full_name":"Petrov, Tatjana","first_name":"Tatjana","last_name":"Petrov","orcid":"0000-0002-9041-0905","id":"3D5811FC-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Kovács","full_name":"Kovács, Gábor","first_name":"Gábor"}],"external_id":{"pmid":["25195847"],"isi":["000344049900011"]},"language":[{"iso":"eng"}],"intvolume":"        38","status":"public","page":"375 - 388","title":"Patterns of hippocampal tau pathology differentiate neurodegenerative dementias","quality_controlled":"1","publisher":"Karger Publishers","main_file_link":[{"open_access":"1","url":"https://kops.uni-konstanz.de/bitstream/123456789/42127/1/Milenkovic_2-17ivylo2up0798.pdf"}],"date_published":"2014-11-07T00:00:00Z","abstract":[{"text":"Deposits of phosphorylated tau protein and convergence of pathology in the hippocampus are the hallmarks of neurodegenerative tauopathies. Thus we aimed to evaluate whether regional and cellular vulnerability patterns in the hippocampus distinguish tauopathies or are influenced by their concomitant presence. Methods: We created a heat map of phospho-tau (AT8) immunoreactivity patterns in 24 hippocampal subregions/layers in individuals with Alzheimer's disease (AD)-related neurofibrillary degeneration (n = 40), Pick's disease (n = 8), progressive supranuclear palsy (n = 7), corticobasal degeneration (n = 6), argyrophilic grain disease (AGD, n = 18), globular glial tauopathy (n = 5), and tau-astrogliopathy of the elderly (n = 10). AT8 immunoreactivity patterns were compared by mathematical analysis. Results: Our study reveals disease-specific hot spots and regional selective vulnerability for these disorders. The pattern of hippocampal AD-related tau pathology is strongly influenced by concomitant AGD. Mathematical analysis reveals that hippocampal involvement in primary tauopathies is distinguishable from early-stage AD-related neurofibrillary degeneration. Conclusion: Our data demonstrate disease-specific AT8 immunoreactivity patterns and hot spots in the hippocampus even in tauopathies, which primarily do not affect the hippocampus. These hot spots can be shifted to other regions by the co-occurrence of tauopathies like AGD. Our observations support the notion that globular glial tauopathies and tau-astrogliopathy of the elderly are distinct entities.","lang":"eng"}],"year":"2014","scopus_import":"1","isi":1,"month":"11","date_updated":"2025-09-29T12:24:16Z","oa_version":"Published Version","publication_status":"published","article_processing_charge":"No","oa":1,"type":"journal_article","citation":{"chicago":"Milenković, Ivan, Tatjana Petrov, and Gábor Kovács. “Patterns of Hippocampal Tau Pathology Differentiate Neurodegenerative Dementias.” <i>Dementia and Geriatric Cognitive Disorders</i>. Karger Publishers, 2014. <a href=\"https://doi.org/10.1159/000365548\">https://doi.org/10.1159/000365548</a>.","ieee":"I. Milenković, T. Petrov, and G. Kovács, “Patterns of hippocampal tau pathology differentiate neurodegenerative dementias,” <i>Dementia and Geriatric Cognitive Disorders</i>, vol. 38, no. 5–6. Karger Publishers, pp. 375–388, 2014.","apa":"Milenković, I., Petrov, T., &#38; Kovács, G. (2014). Patterns of hippocampal tau pathology differentiate neurodegenerative dementias. <i>Dementia and Geriatric Cognitive Disorders</i>. Karger Publishers. <a href=\"https://doi.org/10.1159/000365548\">https://doi.org/10.1159/000365548</a>","ista":"Milenković I, Petrov T, Kovács G. 2014. Patterns of hippocampal tau pathology differentiate neurodegenerative dementias. Dementia and Geriatric Cognitive Disorders. 38(5–6), 375–388.","ama":"Milenković I, Petrov T, Kovács G. Patterns of hippocampal tau pathology differentiate neurodegenerative dementias. <i>Dementia and Geriatric Cognitive Disorders</i>. 2014;38(5-6):375-388. doi:<a href=\"https://doi.org/10.1159/000365548\">10.1159/000365548</a>","mla":"Milenković, Ivan, et al. “Patterns of Hippocampal Tau Pathology Differentiate Neurodegenerative Dementias.” <i>Dementia and Geriatric Cognitive Disorders</i>, vol. 38, no. 5–6, Karger Publishers, 2014, pp. 375–88, doi:<a href=\"https://doi.org/10.1159/000365548\">10.1159/000365548</a>.","short":"I. Milenković, T. Petrov, G. Kovács, Dementia and Geriatric Cognitive Disorders 38 (2014) 375–388."},"department":[{"_id":"CaGu"}],"publication_identifier":{"issn":["1420-8008"]},"acknowledgement":"This study was supported by the European Commission’s 7th Framework Programme under GA No. 278486, ‘DEVELAGE’.","doi":"10.1159/000365548","_id":"1913","day":"07","publist_id":"5181","issue":"5-6","publication":"Dementia and Geriatric Cognitive Disorders"},{"has_accepted_license":"1","volume":68,"related_material":{"record":[{"id":"9747","relation":"research_data","status":"public"}]},"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","corr_author":"1","article_type":"original","date_created":"2018-12-11T11:55:36Z","ddc":["570"],"language":[{"iso":"eng"}],"external_id":{"isi":["000340470600012"]},"author":[{"first_name":"Mato","full_name":"Lagator, Mato","last_name":"Lagator","id":"345D25EC-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Morgan","first_name":"Andrew","full_name":"Morgan, Andrew"},{"full_name":"Neve, Paul","first_name":"Paul","last_name":"Neve"},{"full_name":"Colegrave, Nick","first_name":"Nick","last_name":"Colegrave"}],"intvolume":"        68","status":"public","page":"2296 - 2305","quality_controlled":"1","title":"Role of sex and migration in adaptation to sink environments","date_published":"2014-04-25T00:00:00Z","publisher":"Wiley","year":"2014","scopus_import":"1","abstract":[{"lang":"eng","text":"Understanding the effects of sex and migration on adaptation to novel environments remains a key problem in evolutionary biology. Using a single-cell alga Chlamydomonas reinhardtii, we investigated how sex and migration affected rates of evolutionary rescue in a sink environment, and subsequent changes in fitness following evolutionary rescue. We show that sex and migration affect both the rate of evolutionary rescue and subsequent adaptation. However, their combined effects change as the populations adapt to a sink habitat. Both sex and migration independently increased rates of evolutionary rescue, but the effect of sex on subsequent fitness improvements, following initial rescue, changed with migration, as sex was beneficial in the absence of migration but constraining adaptation when combined with migration. These results suggest that sex and migration are beneficial during the initial stages of adaptation, but can become detrimental as the population adapts to its environment."}],"date_updated":"2025-09-29T11:46:47Z","month":"04","isi":1,"file":[{"date_created":"2020-05-14T16:40:31Z","relation":"main_file","access_level":"open_access","creator":"dernst","file_id":"7845","date_updated":"2020-07-14T12:45:28Z","file_size":467254,"file_name":"2014_Evolution_Lagator.pdf","checksum":"8d459b07e4a11bb5fde92d969184fe48","content_type":"application/pdf"}],"oa_version":"Published Version","publication_status":"published","article_processing_charge":"No","oa":1,"type":"journal_article","department":[{"_id":"CaGu"}],"citation":{"ista":"Lagator M, Morgan A, Neve P, Colegrave N. 2014. Role of sex and migration in adaptation to sink environments. Evolution. 68(8), 2296–2305.","apa":"Lagator, M., Morgan, A., Neve, P., &#38; Colegrave, N. (2014). Role of sex and migration in adaptation to sink environments. <i>Evolution</i>. Wiley. <a href=\"https://doi.org/10.1111/evo.12440\">https://doi.org/10.1111/evo.12440</a>","short":"M. Lagator, A. Morgan, P. Neve, N. Colegrave, Evolution 68 (2014) 2296–2305.","ama":"Lagator M, Morgan A, Neve P, Colegrave N. Role of sex and migration in adaptation to sink environments. <i>Evolution</i>. 2014;68(8):2296-2305. doi:<a href=\"https://doi.org/10.1111/evo.12440\">10.1111/evo.12440</a>","mla":"Lagator, Mato, et al. “Role of Sex and Migration in Adaptation to Sink Environments.” <i>Evolution</i>, vol. 68, no. 8, Wiley, 2014, pp. 2296–305, doi:<a href=\"https://doi.org/10.1111/evo.12440\">10.1111/evo.12440</a>.","chicago":"Lagator, Mato, Andrew Morgan, Paul Neve, and Nick Colegrave. “Role of Sex and Migration in Adaptation to Sink Environments.” <i>Evolution</i>. Wiley, 2014. <a href=\"https://doi.org/10.1111/evo.12440\">https://doi.org/10.1111/evo.12440</a>.","ieee":"M. Lagator, A. Morgan, P. Neve, and N. Colegrave, “Role of sex and migration in adaptation to sink environments,” <i>Evolution</i>, vol. 68, no. 8. Wiley, pp. 2296–2305, 2014."},"doi":"10.1111/evo.12440","acknowledgement":"The authors are grateful to the Leverhulme Trust (F/00 215/AW) for funding this work.","_id":"2083","day":"25","publist_id":"4954","file_date_updated":"2020-07-14T12:45:28Z","issue":"8","publication":"Evolution"},{"author":[{"id":"345D25EC-F248-11E8-B48F-1D18A9856A87","last_name":"Lagator","full_name":"Lagator, Mato","first_name":"Mato"},{"first_name":"Nick","full_name":"Colegrave, Nick","last_name":"Colegrave"},{"first_name":"Paul","full_name":"Neve, Paul","last_name":"Neve"}],"oa":1,"type":"research_data_reference","citation":{"mla":"Lagator, Mato, et al. <i>Data from: Selection History and Epistatic Interactions Impact Dynamics of Adaptation to Novel Environmental Stresses</i>. Dryad, 2014, doi:<a href=\"https://doi.org/10.5061/dryad.85dn7\">10.5061/dryad.85dn7</a>.","ama":"Lagator M, Colegrave N, Neve P. Data from: Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses. 2014. doi:<a href=\"https://doi.org/10.5061/dryad.85dn7\">10.5061/dryad.85dn7</a>","short":"M. Lagator, N. Colegrave, P. Neve, (2014).","ista":"Lagator M, Colegrave N, Neve P. 2014. Data from: Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses, Dryad, <a href=\"https://doi.org/10.5061/dryad.85dn7\">10.5061/dryad.85dn7</a>.","apa":"Lagator, M., Colegrave, N., &#38; Neve, P. (2014). Data from: Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses. Dryad. <a href=\"https://doi.org/10.5061/dryad.85dn7\">https://doi.org/10.5061/dryad.85dn7</a>","ieee":"M. Lagator, N. Colegrave, and P. Neve, “Data from: Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses.” Dryad, 2014.","chicago":"Lagator, Mato, Nick Colegrave, and Paul Neve. “Data from: Selection History and Epistatic Interactions Impact Dynamics of Adaptation to Novel Environmental Stresses.” Dryad, 2014. <a href=\"https://doi.org/10.5061/dryad.85dn7\">https://doi.org/10.5061/dryad.85dn7</a>."},"department":[{"_id":"CaGu"}],"doi":"10.5061/dryad.85dn7","status":"public","day":"21","_id":"9741","title":"Data from: Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses","publisher":"Dryad","date_published":"2014-08-21T00:00:00Z","main_file_link":[{"open_access":"1","url":"https://doi.org/10.5061/dryad.85dn7"}],"abstract":[{"lang":"eng","text":"In rapidly changing environments, selection history may impact the dynamics of adaptation. Mutations selected in one environment may result in pleiotropic fitness trade-offs in subsequent novel environments, slowing the rates of adaptation. Epistatic interactions between mutations selected in sequential stressful environments may slow or accelerate subsequent rates of adaptation, depending on the nature of that interaction. We explored the dynamics of adaptation during sequential exposure to herbicides with different modes of action in Chlamydomonas reinhardtii. Evolution of resistance to two of the herbicides was largely independent of selection history. For carbetamide, previous adaptation to other herbicide modes of action positively impacted the likelihood of adaptation to this herbicide. Furthermore, while adaptation to all individual herbicides was associated with pleiotropic fitness costs in stress-free environments, we observed that accumulation of resistance mechanisms was accompanied by a reduction in overall fitness costs. We suggest that antagonistic epistasis may be a driving mechanism that enables populations to more readily adapt in novel environments. These findings highlight the potential for sequences of xenobiotics to facilitate the rapid evolution of multiple-drug and -pesticide resistance, as well as the potential for epistatic interactions between adaptive mutations to facilitate evolutionary rescue in rapidly changing environments."}],"year":"2014","related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"2036"}]},"month":"08","date_updated":"2025-09-29T11:54:45Z","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","oa_version":"Published Version","article_processing_charge":"No","date_created":"2021-07-28T08:48:06Z"}]