[{"volume":6,"ec_funded":1,"publication_status":"published","file":[{"date_created":"2018-12-12T10:09:32Z","file_name":"IST-2017-744-v1+1_srep36440.pdf","date_updated":"2018-12-12T10:09:32Z","file_size":2353456,"creator":"system","file_id":"4756","content_type":"application/pdf","access_level":"open_access","relation":"main_file"}],"language":[{"iso":"eng"}],"scopus_import":1,"month":"11","intvolume":" 6","abstract":[{"lang":"eng","text":"Cellular locomotion is a central hallmark of eukaryotic life. It is governed by cell-extrinsic molecular factors, which can either emerge in the soluble phase or as immobilized, often adhesive ligands. To encode for direction, every cue must be present as a spatial or temporal gradient. Here, we developed a microfluidic chamber that allows measurement of cell migration in combined response to surface immobilized and soluble molecular gradients. As a proof of principle we study the response of dendritic cells to their major guidance cues, chemokines. The majority of data on chemokine gradient sensing is based on in vitro studies employing soluble gradients. Despite evidence suggesting that in vivo chemokines are often immobilized to sugar residues, limited information is available how cells respond to immobilized chemokines. We tracked migration of dendritic cells towards immobilized gradients of the chemokine CCL21 and varying superimposed soluble gradients of CCL19. Differential migratory patterns illustrate the potential of our setup to quantitatively study the competitive response to both types of gradients. Beyond chemokines our approach is broadly applicable to alternative systems of chemo- and haptotaxis such as cells migrating along gradients of adhesion receptor ligands vs. any soluble cue. \r\n"}],"oa_version":"Published Version","department":[{"_id":"MiSi"},{"_id":"NanoFab"},{"_id":"Bio"},{"_id":"ToBo"}],"file_date_updated":"2018-12-12T10:09:32Z","date_updated":"2021-01-12T06:48:41Z","ddc":["579"],"type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","pubrep_id":"744","_id":"1154","date_published":"2016-11-07T00:00:00Z","doi":"10.1038/srep36440","date_created":"2018-12-11T11:50:27Z","has_accepted_license":"1","year":"2016","day":"07","publication":"Scientific Reports","publisher":"Nature Publishing Group","quality_controlled":"1","oa":1,"acknowledgement":"This work was supported by the Swiss National Science Foundation (Ambizione fellowship; PZ00P3-154733 to M.M.), the Swiss Multiple Sclerosis Society (research support to M.M.), a fellowship from the Boehringer Ingelheim Fonds (BIF) to J.S., the European Research Council (grant ERC GA 281556) and a START award from the Austrian Science Foundation (FWF) to M.S. #BioimagingFacility","author":[{"last_name":"Schwarz","full_name":"Schwarz, Jan","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","first_name":"Jan"},{"last_name":"Bierbaum","full_name":"Bierbaum, Veronika","first_name":"Veronika","id":"3FD04378-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87","full_name":"Merrin, Jack","orcid":"0000-0001-5145-4609","last_name":"Merrin"},{"full_name":"Frank, Tino","last_name":"Frank","first_name":"Tino"},{"id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","first_name":"Robert","full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522","last_name":"Hauschild"},{"first_name":"Mark Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4398-476X","full_name":"Bollenbach, Mark Tobias","last_name":"Bollenbach"},{"last_name":"Tay","full_name":"Tay, Savaş","first_name":"Savaş"},{"first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179"},{"first_name":"Matthias","id":"3C23B994-F248-11E8-B48F-1D18A9856A87","last_name":"Mehling","orcid":"0000-0001-8599-1226","full_name":"Mehling, Matthias"}],"publist_id":"6204","title":"A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients","citation":{"ista":"Schwarz J, Bierbaum V, Merrin J, Frank T, Hauschild R, Bollenbach MT, Tay S, Sixt MK, Mehling M. 2016. A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients. Scientific Reports. 6, 36440.","chicago":"Schwarz, Jan, Veronika Bierbaum, Jack Merrin, Tino Frank, Robert Hauschild, Mark Tobias Bollenbach, Savaş Tay, Michael K Sixt, and Matthias Mehling. “A Microfluidic Device for Measuring Cell Migration towards Substrate Bound and Soluble Chemokine Gradients.” Scientific Reports. Nature Publishing Group, 2016. https://doi.org/10.1038/srep36440.","ieee":"J. Schwarz et al., “A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients,” Scientific Reports, vol. 6. Nature Publishing Group, 2016.","short":"J. Schwarz, V. Bierbaum, J. Merrin, T. Frank, R. Hauschild, M.T. Bollenbach, S. Tay, M.K. Sixt, M. Mehling, Scientific Reports 6 (2016).","ama":"Schwarz J, Bierbaum V, Merrin J, et al. A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients. Scientific Reports. 2016;6. doi:10.1038/srep36440","apa":"Schwarz, J., Bierbaum, V., Merrin, J., Frank, T., Hauschild, R., Bollenbach, M. T., … Mehling, M. (2016). A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients. Scientific Reports. Nature Publishing Group. https://doi.org/10.1038/srep36440","mla":"Schwarz, Jan, et al. “A Microfluidic Device for Measuring Cell Migration towards Substrate Bound and Soluble Chemokine Gradients.” Scientific Reports, vol. 6, 36440, Nature Publishing Group, 2016, doi:10.1038/srep36440."},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","project":[{"call_identifier":"FP7","_id":"25A603A2-B435-11E9-9278-68D0E5697425","grant_number":"281556","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)"},{"call_identifier":"FWF","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and transduction of leukocytes (FWF)","grant_number":"Y 564-B12"}],"article_number":"36440"},{"year":"2016","publication":"Applied and Environmental Microbiology","day":"01","page":"4180 - 4189","date_created":"2018-12-11T11:50:46Z","date_published":"2016-07-01T00:00:00Z","doi":"10.1128/AEM.00256-16","acknowledgement":"Dutch Ministry of Economic Affairs, Agriculture, and Innovation through the program BioSolar CellsS. Andreas Angermayr,Pascal van Alphen, Klaas J. Hellingwerf\r\nWe thank Naira Quintana (presently at Rousselot, Belgium) for the ini-\r\ntiative at the 10th Cyanobacterial Molecular Biology Workshop\r\n(CMBW), June 2010, Lake Arrowhead, Los Angeles, CA, USA, to start the\r\ncollaborative endeavor reported here. We thank Timo Maarleveld from\r\nCWI/VU (Amsterdam) for a custom-made Python script handling the output from the NMR analysis and for evaluating and visualizing the\r\nseparate metabolites for their evaluation. We thank Rob Verpoorte from\r\nLeiden University (metabolome analysis) and Hans Aerts from the AMC\r\n(proteome analysis) for lab space and equipment. We thank Robert Leh-\r\nmann (Humboldt University Berlin) and Ilka Axmann (University of\r\nDüsseldorf) for sharing the R-code for the LOS transformation of the\r\ntranscript data. We thank Hans C. P. Matthijs from IBED for inspiring\r\ndialogues and insightful thoughts on continuous culturing of cyanobac-\r\nteria. We thank Sandra Waaijenborg for performing the transcript nor-\r\nmalization and Johan Westerhuis from BDA, Jeroen van der Steen and\r\nFilipe Branco dos Santos from MMP, and Lucas Stal from IBED/NIOZ for\r\nhelpful discussions. We thank Milou Schuurmans from MMP for help\r\nwith sampling and glycogen determination. We thank the members of the\r\nRNA Biology & Applied Bioinformatics group at SILS, in particular Selina\r\nvan Leeuwen, Elisa Hoekstra, and Martijs Jonker, for the microarray anal-\r\nysis. We thank the reviewers of this work for their insightful comments\r\nwhich improved the quality of the manuscript. This work, including the efforts of S. Andreas Angermayr, Pascal van\r\nAlphen, and Klaas J. Hellingwerf, was funded by Dutch Ministry of Eco-\r\nnomic Affairs, Agriculture, and Innovation through the program BioSolar\r\nCells.","oa":1,"publisher":"American Society for Microbiology","quality_controlled":"1","citation":{"mla":"Angermayr, Andreas, et al. “Culturing Synechocystis Sp. Strain Pcc 6803 with N2 and CO2 in a Diel Regime Reveals Multiphase Glycogen Dynamics with Low Maintenance Costs.” Applied and Environmental Microbiology, vol. 82, no. 14, American Society for Microbiology, 2016, pp. 4180–89, doi:10.1128/AEM.00256-16.","ieee":"A. Angermayr et al., “Culturing synechocystis sp. Strain pcc 6803 with N2 and CO2 in a diel regime reveals multiphase glycogen dynamics with low maintenance costs,” Applied and Environmental Microbiology, vol. 82, no. 14. American Society for Microbiology, pp. 4180–4189, 2016.","short":"A. Angermayr, P. Van Alphen, D. Hasdemir, G. Kramer, M. Iqbal, W. Van Grondelle, H. Hoefsloot, Y. Choi, K. Hellingwerf, Applied and Environmental Microbiology 82 (2016) 4180–4189.","apa":"Angermayr, A., Van Alphen, P., Hasdemir, D., Kramer, G., Iqbal, M., Van Grondelle, W., … Hellingwerf, K. (2016). Culturing synechocystis sp. Strain pcc 6803 with N2 and CO2 in a diel regime reveals multiphase glycogen dynamics with low maintenance costs. Applied and Environmental Microbiology. American Society for Microbiology. https://doi.org/10.1128/AEM.00256-16","ama":"Angermayr A, Van Alphen P, Hasdemir D, et al. Culturing synechocystis sp. Strain pcc 6803 with N2 and CO2 in a diel regime reveals multiphase glycogen dynamics with low maintenance costs. Applied and Environmental Microbiology. 2016;82(14):4180-4189. doi:10.1128/AEM.00256-16","chicago":"Angermayr, Andreas, Pascal Van Alphen, Dicle Hasdemir, Gertjan Kramer, Muzamal Iqbal, Wilmar Van Grondelle, Huub Hoefsloot, Younghae Choi, and Klaas Hellingwerf. “Culturing Synechocystis Sp. Strain Pcc 6803 with N2 and CO2 in a Diel Regime Reveals Multiphase Glycogen Dynamics with Low Maintenance Costs.” Applied and Environmental Microbiology. American Society for Microbiology, 2016. https://doi.org/10.1128/AEM.00256-16.","ista":"Angermayr A, Van Alphen P, Hasdemir D, Kramer G, Iqbal M, Van Grondelle W, Hoefsloot H, Choi Y, Hellingwerf K. 2016. Culturing synechocystis sp. Strain pcc 6803 with N2 and CO2 in a diel regime reveals multiphase glycogen dynamics with low maintenance costs. Applied and Environmental Microbiology. 82(14), 4180–4189."},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","author":[{"last_name":"Angermayr","full_name":"Angermayr, Andreas","orcid":"0000-0001-8619-2223","id":"4677C796-F248-11E8-B48F-1D18A9856A87","first_name":"Andreas"},{"full_name":"Van Alphen, Pascal","last_name":"Van Alphen","first_name":"Pascal"},{"full_name":"Hasdemir, Dicle","last_name":"Hasdemir","first_name":"Dicle"},{"full_name":"Kramer, Gertjan","last_name":"Kramer","first_name":"Gertjan"},{"full_name":"Iqbal, Muzamal","last_name":"Iqbal","first_name":"Muzamal"},{"full_name":"Van Grondelle, Wilmar","last_name":"Van Grondelle","first_name":"Wilmar"},{"last_name":"Hoefsloot","full_name":"Hoefsloot, Huub","first_name":"Huub"},{"first_name":"Younghae","last_name":"Choi","full_name":"Choi, Younghae"},{"first_name":"Klaas","last_name":"Hellingwerf","full_name":"Hellingwerf, Klaas"}],"publist_id":"6117","title":"Culturing synechocystis sp. Strain pcc 6803 with N2 and CO2 in a diel regime reveals multiphase glycogen dynamics with low maintenance costs","publication_status":"published","language":[{"iso":"eng"}],"volume":82,"issue":"14","abstract":[{"text":"Investigating the physiology of cyanobacteria cultured under a diel light regime is relevant for a better understanding of the resulting growth characteristics and for specific biotechnological applications that are foreseen for these photosynthetic organisms. Here, we present the results of a multiomics study of the model cyanobacterium Synechocystis sp. strain PCC 6803, cultured in a lab-scale photobioreactor in physiological conditions relevant for large-scale culturing. The culture was sparged withN2 andCO2, leading to an anoxic environment during the dark period. Growth followed the availability of light. Metabolite analysis performed with 1Hnuclear magnetic resonance analysis showed that amino acids involved in nitrogen and sulfur assimilation showed elevated levels in the light. Most protein levels, analyzed through mass spectrometry, remained rather stable. However, several high-light-response proteins and stress-response proteins showed distinct changes at the onset of the light period. Microarray-based transcript analysis found common patterns of~56% of the transcriptome following the diel regime. These oscillating transcripts could be grouped coarsely into genes that were upregulated and downregulated in the dark period. The accumulated glycogen was degraded in the anaerobic environment in the dark. A small part was degraded gradually, reflecting basic maintenance requirements of the cells in darkness. Surprisingly, the largest part was degraded rapidly in a short time span at the end of the dark period. This degradation could allow rapid formation of metabolic intermediates at the end of the dark period, preparing the cells for the resumption of growth at the start of the light period.","lang":"eng"}],"oa_version":"Submitted Version","main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959195/"}],"scopus_import":1,"intvolume":" 82","month":"07","date_updated":"2021-01-12T06:49:10Z","department":[{"_id":"ToBo"}],"_id":"1218","type":"journal_article","status":"public"},{"publication_status":"published","file":[{"checksum":"78ffe70c1c88af3856d31ca6b7195a27","file_id":"4899","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"IST-2016-488-v1+1_20152452.full.pdf","date_created":"2018-12-12T10:11:43Z","creator":"system","file_size":626804,"date_updated":"2020-07-14T12:45:02Z"}],"language":[{"iso":"eng"}],"issue":"1822","volume":283,"abstract":[{"text":"Antibiotic resistance carries a fitness cost that must be overcome in order for resistance to persist over the long term. Compensatory mutations that recover the functional defects associated with resistance mutations have been argued to play a key role in overcoming the cost of resistance, but compensatory mutations are expected to be rare relative to generally beneficial mutations that increase fitness, irrespective of antibiotic resistance. Given this asymmetry, population genetics theory predicts that populations should adapt by compensatory mutations when the cost of resistance is large, whereas generally beneficial mutations should drive adaptation when the cost of resistance is small. We tested this prediction by determining the genomic mechanisms underpinning adaptation to antibiotic-free conditions in populations of the pathogenic bacterium Pseudomonas aeruginosa that carry costly antibiotic resistance mutations. Whole-genome sequencing revealed that populations founded by high-cost rifampicin-resistant mutants adapted via compensatory mutations in three genes of the RNA polymerase core enzyme, whereas populations founded by low-cost mutants adapted by generally beneficial mutations, predominantly in the quorum-sensing transcriptional regulator gene lasR. Even though the importance of compensatory evolution in maintaining resistance has been widely recognized, our study shows that the roles of general adaptation in maintaining resistance should not be underestimated and highlights the need to understand how selection at other sites in the genome influences the dynamics of resistance alleles in clinical settings.","lang":"eng"}],"oa_version":"Published Version","scopus_import":1,"month":"01","intvolume":" 283","date_updated":"2021-01-12T06:51:33Z","ddc":["570"],"file_date_updated":"2020-07-14T12:45:02Z","department":[{"_id":"ToBo"}],"_id":"1552","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","pubrep_id":"488","has_accepted_license":"1","year":"2016","day":"13","publication":"Proceedings of the Royal Society of London Series B Biological Sciences","doi":"10.1098/rspb.2015.2452","date_published":"2016-01-13T00:00:00Z","date_created":"2018-12-11T11:52:40Z","acknowledgement":"We thank the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics funded by Wellcome\r\nTrust grant reference 090532/Z/09/Z and Medical Research Council Hub grant no. G0900747 91070 for generation of the high-throughput sequencing data. We thank Wook Kim and two anonymous reviewers for their constructive feedback on previous versions of our manuscript.","quality_controlled":"1","publisher":"Royal Society, The","oa":1,"citation":{"ista":"Qi Q, Toll Riera M, Heilbron K, Preston G, Maclean RC. 2016. The genomic basis of adaptation to the fitness cost of rifampicin resistance in Pseudomonas aeruginosa. Proceedings of the Royal Society of London Series B Biological Sciences. 283(1822), 20152452.","chicago":"Qi, Qin, Macarena Toll Riera, Karl Heilbron, Gail Preston, and R Craig Maclean. “The Genomic Basis of Adaptation to the Fitness Cost of Rifampicin Resistance in Pseudomonas Aeruginosa.” Proceedings of the Royal Society of London Series B Biological Sciences. Royal Society, The, 2016. https://doi.org/10.1098/rspb.2015.2452.","short":"Q. Qi, M. Toll Riera, K. Heilbron, G. Preston, R.C. Maclean, Proceedings of the Royal Society of London Series B Biological Sciences 283 (2016).","ieee":"Q. Qi, M. Toll Riera, K. Heilbron, G. Preston, and R. C. Maclean, “The genomic basis of adaptation to the fitness cost of rifampicin resistance in Pseudomonas aeruginosa,” Proceedings of the Royal Society of London Series B Biological Sciences, vol. 283, no. 1822. Royal Society, The, 2016.","apa":"Qi, Q., Toll Riera, M., Heilbron, K., Preston, G., & Maclean, R. C. (2016). The genomic basis of adaptation to the fitness cost of rifampicin resistance in Pseudomonas aeruginosa. Proceedings of the Royal Society of London Series B Biological Sciences. Royal Society, The. https://doi.org/10.1098/rspb.2015.2452","ama":"Qi Q, Toll Riera M, Heilbron K, Preston G, Maclean RC. The genomic basis of adaptation to the fitness cost of rifampicin resistance in Pseudomonas aeruginosa. Proceedings of the Royal Society of London Series B Biological Sciences. 2016;283(1822). doi:10.1098/rspb.2015.2452","mla":"Qi, Qin, et al. “The Genomic Basis of Adaptation to the Fitness Cost of Rifampicin Resistance in Pseudomonas Aeruginosa.” Proceedings of the Royal Society of London Series B Biological Sciences, vol. 283, no. 1822, 20152452, Royal Society, The, 2016, doi:10.1098/rspb.2015.2452."},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","publist_id":"5619","author":[{"id":"3B22D412-F248-11E8-B48F-1D18A9856A87","first_name":"Qin","orcid":"0000-0002-6148-2416","full_name":"Qi, Qin","last_name":"Qi"},{"first_name":"Macarena","full_name":"Toll Riera, Macarena","last_name":"Toll Riera"},{"first_name":"Karl","full_name":"Heilbron, Karl","last_name":"Heilbron"},{"full_name":"Preston, Gail","last_name":"Preston","first_name":"Gail"},{"full_name":"Maclean, R Craig","last_name":"Maclean","first_name":"R Craig"}],"title":"The genomic basis of adaptation to the fitness cost of rifampicin resistance in Pseudomonas aeruginosa","article_number":"20152452"},{"citation":{"ista":"de Vos M, Dawid A, Šunderlíková V, Tans S. 2015. Breaking evolutionary constraint with a tradeoff ratchet. PNAS. 112(48), 14906–14911.","chicago":"Vos, Marjon de, Alexandre Dawid, Vanda Šunderlíková, and Sander Tans. “Breaking Evolutionary Constraint with a Tradeoff Ratchet.” PNAS. National Academy of Sciences, 2015. https://doi.org/10.1073/pnas.1510282112.","apa":"de Vos, M., Dawid, A., Šunderlíková, V., & Tans, S. (2015). Breaking evolutionary constraint with a tradeoff ratchet. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.1510282112","ama":"de Vos M, Dawid A, Šunderlíková V, Tans S. Breaking evolutionary constraint with a tradeoff ratchet. PNAS. 2015;112(48):14906-14911. doi:10.1073/pnas.1510282112","ieee":"M. de Vos, A. Dawid, V. Šunderlíková, and S. Tans, “Breaking evolutionary constraint with a tradeoff ratchet,” PNAS, vol. 112, no. 48. National Academy of Sciences, pp. 14906–14911, 2015.","short":"M. de Vos, A. Dawid, V. Šunderlíková, S. Tans, PNAS 112 (2015) 14906–14911.","mla":"de Vos, Marjon, et al. “Breaking Evolutionary Constraint with a Tradeoff Ratchet.” PNAS, vol. 112, no. 48, National Academy of Sciences, 2015, pp. 14906–11, doi:10.1073/pnas.1510282112."},"date_updated":"2021-01-12T06:51:40Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publist_id":"5600","author":[{"full_name":"De Vos, Marjon","last_name":"De Vos","first_name":"Marjon","id":"3111FFAC-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Alexandre","last_name":"Dawid","full_name":"Dawid, Alexandre"},{"first_name":"Vanda","full_name":"Šunderlíková, Vanda","last_name":"Šunderlíková"},{"first_name":"Sander","full_name":"Tans, Sander","last_name":"Tans"}],"title":"Breaking evolutionary constraint with a tradeoff ratchet","department":[{"_id":"ToBo"}],"_id":"1571","type":"journal_article","status":"public","year":"2015","publication_status":"published","language":[{"iso":"eng"}],"publication":"PNAS","day":"01","page":"14906 - 14911","date_created":"2018-12-11T11:52:47Z","date_published":"2015-12-01T00:00:00Z","volume":112,"doi":"10.1073/pnas.1510282112","issue":"48","abstract":[{"lang":"eng","text":"Epistatic interactions can frustrate and shape evolutionary change. Indeed, phenotypes may fail to evolve when essential mutations are only accessible through positive selection if they are fixed simultaneously. How environmental variability affects such constraints is poorly understood. Here, we studied genetic constraints in fixed and fluctuating environments using the Escherichia coli lac operon as a model system for genotype-environment interactions. We found that, in different fixed environments, all trajectories that were reconstructed by applying point mutations within the transcription factor-operator interface became trapped at suboptima, where no additional improvements were possible. Paradoxically, repeated switching between these same environments allows unconstrained adaptation by continuous improvements. This evolutionary mode is explained by pervasive cross-environmental tradeoffs that reposition the peaks in such a way that trapped genotypes can repeatedly climb ascending slopes and hence, escape adaptive stasis. Using a Markov approach, we developed a mathematical framework to quantify the landscape-crossing rates and show that this ratchet-like adaptive mechanism is robust in a wide spectrum of fluctuating environments. Overall, this study shows that genetic constraints can be overcome by environmental change and that crossenvironmental tradeoffs do not necessarily impede but also, can facilitate adaptive evolution. Because tradeoffs and environmental variability are ubiquitous in nature, we speculate this evolutionary mode to be of general relevance."}],"acknowledgement":"This work is part of the research program of the Foundation for Fundamental Research on Matter, which is part of the Netherlands Organization for Scientific Research (NWO). M.G.J.d.V. was (partially) funded by NWO Earth and Life Sciences (ALW), project 863.14.015. We thank D. M. Weinreich, J. A. G. M. de Visser, T. Paixão, J. Polechová, T. Friedlander, and A. E. Mayo for reading and commenting on earlier versions of the manuscript and B. Houchmandzadeh, O. Rivoire, and M. Hemery for discussions and suggestions on the Markov computation. Furthermore, we thank F. J. Poelwijk for sharing plasmid pCascade5 and pRD007 and Y. Yokobayashi for sharing plasmid pINV-110. We also thank the anonymous reviewers for remarks on the initial version of the manuscript.","oa_version":"None","publisher":"National Academy of Sciences","quality_controlled":"1","scopus_import":1,"intvolume":" 112","month":"12"},{"month":"04","intvolume":" 161","quality_controlled":"1","scopus_import":"1","publisher":"Cell Press","oa_version":"None","abstract":[{"lang":"eng","text":"In animal embryos, morphogen gradients determine tissue patterning and morphogenesis. Shyer et al. provide evidence that, during vertebrate gut formation, tissue folding generates graded activity of signals required for subsequent steps of gut growth and differentiation, thereby revealing an intriguing link between tissue morphogenesis and morphogen gradient formation."}],"doi":"10.1016/j.cell.2015.04.009","date_published":"2015-04-23T00:00:00Z","issue":"3","volume":161,"date_created":"2018-12-11T11:52:50Z","page":"431 - 432","day":"23","language":[{"iso":"eng"}],"publication":"Cell","year":"2015","publication_status":"published","status":"public","type":"journal_article","_id":"1581","title":"Gradients are shaping up","department":[{"_id":"ToBo"},{"_id":"CaHe"}],"author":[{"first_name":"Mark Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","full_name":"Bollenbach, Mark Tobias","orcid":"0000-0003-4398-476X","last_name":"Bollenbach"},{"first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","last_name":"Heisenberg","orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J"}],"publist_id":"5590","article_processing_charge":"No","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"mla":"Bollenbach, Mark Tobias, and Carl-Philipp J. Heisenberg. “Gradients Are Shaping Up.” Cell, vol. 161, no. 3, Cell Press, 2015, pp. 431–32, doi:10.1016/j.cell.2015.04.009.","ieee":"M. T. Bollenbach and C.-P. J. Heisenberg, “Gradients are shaping up,” Cell, vol. 161, no. 3. Cell Press, pp. 431–432, 2015.","short":"M.T. Bollenbach, C.-P.J. Heisenberg, Cell 161 (2015) 431–432.","apa":"Bollenbach, M. T., & Heisenberg, C.-P. J. (2015). Gradients are shaping up. Cell. Cell Press. https://doi.org/10.1016/j.cell.2015.04.009","ama":"Bollenbach MT, Heisenberg C-PJ. Gradients are shaping up. Cell. 2015;161(3):431-432. doi:10.1016/j.cell.2015.04.009","chicago":"Bollenbach, Mark Tobias, and Carl-Philipp J Heisenberg. “Gradients Are Shaping Up.” Cell. Cell Press, 2015. https://doi.org/10.1016/j.cell.2015.04.009.","ista":"Bollenbach MT, Heisenberg C-PJ. 2015. Gradients are shaping up. Cell. 161(3), 431–432."},"date_updated":"2022-08-25T13:56:10Z"}]