@article{617, abstract = {Insects are exposed to a variety of potential pathogens in their environment, many of which can severely impact fitness and health. Consequently, hosts have evolved resistance and tolerance strategies to suppress or cope with infections. Hosts utilizing resistance improve fitness by clearing or reducing pathogen loads, and hosts utilizing tolerance reduce harmful fitness effects per pathogen load. To understand variation in, and selective pressures on, resistance and tolerance, we asked to what degree they are shaped by host genetic background, whether plasticity in these responses depends upon dietary environment, and whether there are interactions between these two factors. Females from ten wild-type Drosophila melanogaster genotypes were kept on high- or low-protein (yeast) diets and infected with one of two opportunistic bacterial pathogens, Lactococcus lactis or Pseudomonas entomophila. We measured host resistance as the inverse of bacterial load in the early infection phase. The relationship (slope) between fly fecundity and individual-level bacteria load provided our fecundity tolerance measure. Genotype and dietary yeast determined host fecundity and strongly affected survival after infection with pathogenic P. entomophila. There was considerable genetic variation in host resistance, a commonly found phenomenon resulting from for example varying resistance costs or frequency-dependent selection. Despite this variation and the reproductive cost of higher P. entomophila loads, fecundity tolerance did not vary across genotypes. The absence of genetic variation in tolerance may suggest that at this early infection stage, fecundity tolerance is fixed or that any evolved tolerance mechanisms are not expressed under these infection conditions.}, author = {Kutzer, Megan and Kurtz, Joachim and Armitage, Sophie}, issn = {1420-9101}, journal = {Journal of Evolutionary Biology}, number = {1}, pages = {159 -- 171}, publisher = {Wiley}, title = {{Genotype and diet affect resistance, survival, and fecundity but not fecundity tolerance}}, doi = {10.1111/jeb.13211}, volume = {31}, year = {2018}, } @article{608, abstract = {Synthesis is the automated construction of a system from its specification. In real life, hardware and software systems are rarely constructed from scratch. Rather, a system is typically constructed from a library of components. Lustig and Vardi formalized this intuition and studied LTL synthesis from component libraries. In real life, designers seek optimal systems. In this paper we add optimality considerations to the setting. We distinguish between quality considerations (for example, size - the smaller a system is, the better it is), and pricing (for example, the payment to the company who manufactured the component). We study the problem of designing systems with minimal quality-cost and price. A key point is that while the quality cost is individual - the choices of a designer are independent of choices made by other designers that use the same library, pricing gives rise to a resource-allocation game - designers that use the same component share its price, with the share being proportional to the number of uses (a component can be used several times in a design). We study both closed and open settings, and in both we solve the problem of finding an optimal design. In a setting with multiple designers, we also study the game-theoretic problems of the induced resource-allocation game.}, author = {Avni, Guy and Kupferman, Orna}, journal = {Theoretical Computer Science}, pages = {50 -- 72}, publisher = {Elsevier}, title = {{Synthesis from component libraries with costs}}, doi = {10.1016/j.tcs.2017.11.001}, volume = {712}, year = {2018}, } @article{620, abstract = {Clathrin-mediated endocytosis requires the coordinated assembly of various endocytic proteins and lipids at the plasma membrane. Accumulating evidence demonstrates a crucial role for phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) in endocytosis, but specific roles for PtdIns(4)P other than as the biosynthetic precursor of PtdIns(4,5)P2 have not been clarified. In this study we investigated the role of PtdIns(4)P or PtdIns(4,5)P2 in receptor-mediated endocytosis through the construction of temperature-sensitive (ts) mutants for the PI 4-kinases Stt4p and Pik1p and the PtdIns(4) 5-kinase Mss4p. Quantitative analyses of endocytosis revealed that both the stt4(ts)pik1(ts) and mss4(ts) mutants have a severe defect in endocytic internalization. Live-cell imaging of endocytic protein dynamics in stt4(ts)pik1(ts) and mss4(ts) mutants revealed that PtdIns(4)P is required for the recruitment of the alpha-factor receptor Ste2p to clathrin-coated pits whereas PtdIns(4,5)P2 is required for membrane internalization. We also found that the localization to endocytic sites of the ENTH/ANTH domain-bearing clathrin adaptors, Ent1p/Ent2p and Yap1801p/Yap1802p, is significantly impaired in the stt4(ts)pik1(ts) mutant, but not in the mss4(ts) mutant. These results suggest distinct roles in successive steps for PtdIns(4)P and PtdIns(4,5)P2 during receptor-mediated endocytosis.}, author = {Yamamoto, Wataru and Wada, Suguru and Nagano, Makoto and Aoshima, Kaito and Siekhaus, Daria E and Toshima, Junko and Toshima, Jiro}, journal = {Journal of Cell Science}, number = {1}, publisher = {Company of Biologists}, title = {{Distinct roles for plasma membrane PtdIns 4 P and PtdIns 4 5 P2 during yeast receptor mediated endocytosis}}, doi = {10.1242/jcs.207696}, volume = {131}, year = {2018}, } @inproceedings{6558, abstract = {This paper studies the problem of distributed stochastic optimization in an adversarial setting where, out of m machines which allegedly compute stochastic gradients every iteration, an α-fraction are Byzantine, and may behave adversarially. Our main result is a variant of stochastic gradient descent (SGD) which finds ε-approximate minimizers of convex functions in T=O~(1/ε²m+α²/ε²) iterations. In contrast, traditional mini-batch SGD needs T=O(1/ε²m) iterations, but cannot tolerate Byzantine failures. Further, we provide a lower bound showing that, up to logarithmic factors, our algorithm is information-theoretically optimal both in terms of sample complexity and time complexity.}, author = {Alistarh, Dan-Adrian and Allen-Zhu, Zeyuan and Li, Jerry}, booktitle = {Advances in Neural Information Processing Systems}, location = {Montreal, Canada}, pages = {4613--4623}, publisher = {Neural Information Processing Systems Foundation}, title = {{Byzantine stochastic gradient descent}}, volume = {2018}, year = {2018}, } @article{7, abstract = {Animal social networks are shaped by multiple selection pressures, including the need to ensure efficient communication and functioning while simultaneously limiting disease transmission. Social animals could potentially further reduce epidemic risk by altering their social networks in the presence of pathogens, yet there is currently no evidence for such pathogen-triggered responses. We tested this hypothesis experimentally in the ant Lasius niger using a combination of automated tracking, controlled pathogen exposure, transmission quantification, and temporally explicit simulations. Pathogen exposure induced behavioral changes in both exposed ants and their nestmates, which helped contain the disease by reinforcing key transmission-inhibitory properties of the colony's contact network. This suggests that social network plasticity in response to pathogens is an effective strategy for mitigating the effects of disease in social groups.}, author = {Stroeymeyt, Nathalie and Grasse, Anna V and Crespi, Alessandro and Mersch, Danielle and Cremer, Sylvia and Keller, Laurent}, issn = {1095-9203}, journal = {Science}, number = {6417}, pages = {941 -- 945}, publisher = {AAAS}, title = {{Social network plasticity decreases disease transmission in a eusocial insect}}, doi = {10.1126/science.aat4793}, volume = {362}, year = {2018}, } @misc{13055, abstract = {Dataset for manuscript 'Social network plasticity decreases disease transmission in a eusocial insect' Compared to previous versions: - raw image files added - correction of URLs within README.txt file }, author = {Stroeymeyt, Nathalie and Grasse, Anna V and Crespi, Alessandro and Mersch, Danielle and Cremer, Sylvia and Keller, Laurent}, publisher = {Zenodo}, title = {{Social network plasticity decreases disease transmission in a eusocial insect}}, doi = {10.5281/ZENODO.1322669}, year = {2018}, } @article{9229, author = {Danzl, Johann G}, issn = {2500-2295}, journal = {Opera Medica et Physiologica}, number = {S1}, pages = {11}, publisher = {Lobachevsky State University of Nizhny Novgorod}, title = {{Diffraction-unlimited optical imaging for synaptic physiology}}, doi = {10.20388/omp2018.00s1.001}, volume = {4}, year = {2018}, } @article{542, abstract = {The t-haplotype, a mouse meiotic driver found on chromosome 17, has been a model for autosomal segregation distortion for close to a century, but several questions remain regarding its biology and evolutionary history. A recently published set of population genomics resources for wild mice includes several individuals heterozygous for the t-haplotype, which we use to characterize this selfish element at the genomic and transcriptomic level. Our results show that large sections of the t-haplotype have been replaced by standard homologous sequences, possibly due to occasional events of recombination, and that this complicates the inference of its history. As expected for a long genomic segment of very low recombination, the t-haplotype carries an excess of fixed nonsynonymous mutations compared to the standard chromosome. This excess is stronger for regions that have not undergone recent recombination, suggesting that occasional gene flow between the t and the standard chromosome may provide a mechanism to regenerate coding sequences that have accumulated deleterious mutations. Finally, we find that t-complex genes with altered expression largely overlap with deleted or amplified regions, and that carrying a t-haplotype alters the testis expression of genes outside of the t-complex, providing new leads into the pathways involved in the biology of this segregation distorter.}, author = {Kelemen, Réka K and Vicoso, Beatriz}, journal = {Genetics}, number = {1}, pages = {365 -- 375}, publisher = {Genetics Society of America}, title = {{Complex history and differentiation patterns of the t-haplotype, a mouse meiotic driver}}, doi = {10.1534/genetics.117.300513}, volume = {208}, year = {2018}, } @phdthesis{323, abstract = {In the here presented thesis, we explore the role of branched actin networks in cell migration and antigen presentation, the two most relevant processes in dendritic cell biology. Branched actin networks construct lamellipodial protrusions at the leading edge of migrating cells. These are typically seen as adhesive structures, which mediate force transduction to the extracellular matrix that leads to forward locomotion. We ablated Arp2/3 nucleation promoting factor WAVE in DCs and found that the resulting cells lack lamellipodial protrusions. Instead, depending on the maturation state, one or multiple filopodia were formed. By challenging these cells in a variety of migration assays we found that lamellipodial protrusions are dispensable for the locomotion of leukocytes and actually dampen the speed of migration. However, lamellipodia are critically required to negotiate complex environments that DCs experience while they travel to the next draining lymph node. Taken together our results suggest that leukocyte lamellipodia have rather a sensory- than a force transducing function. Furthermore, we show for the first time structure and dynamics of dendritic cell F-actin at the immunological synapse with naïve T cells. Dendritic cell F-actin appears as dynamic foci that are nucleated by the Arp2/3 complex. WAVE ablated dendritic cells show increased membrane tension, leading to an altered ultrastructure of the immunological synapse and severe T cell priming defects. These results point towards a previously unappreciated role of the cellular mechanics of dendritic cells in T cell activation. Additionally, we present a novel cell culture based system for the differentiation of dendritic cells from conditionally immortalized hematopoietic precursors. These precursor cells are genetically tractable via the CRISPR/Cas9 system while they retain their ability to differentiate into highly migratory dendritic cells and other immune cells. This will foster the study of all aspects of dendritic cell biology and beyond. }, author = {Leithner, Alexander F}, issn = {2663-337X}, pages = {99}, publisher = {Institute of Science and Technology Austria}, title = {{Branched actin networks in dendritic cell biology}}, doi = {10.15479/AT:ISTA:th_998}, year = {2018}, } @article{3, abstract = {SETD5 gene mutations have been identified as a frequent cause of idiopathic intellectual disability. Here we show that Setd5-haploinsufficient mice present developmental defects such as abnormal brain-to-body weight ratios and neural crest defect-associated phenotypes. Furthermore, Setd5-mutant mice show impairments in cognitive tasks, enhanced long-term potentiation, delayed ontogenetic profile of ultrasonic vocalization, and behavioral inflexibility. Behavioral issues are accompanied by abnormal expression of postsynaptic density proteins previously associated with cognition. Our data additionally indicate that Setd5 regulates RNA polymerase II dynamics and gene transcription via its interaction with the Hdac3 and Paf1 complexes, findings potentially explaining the gene expression defects observed in Setd5-haploinsufficient mice. Our results emphasize the decisive role of Setd5 in a biological pathway found to be disrupted in humans with intellectual disability and autism spectrum disorder.}, author = {Deliu, Elena and Arecco, Niccoló and Morandell, Jasmin and Dotter, Christoph and Contreras, Ximena and Girardot, Charles and Käsper, Eva and Kozlova, Alena and Kishi, Kasumi and Chiaradia, Ilaria and Noh, Kyung and Novarino, Gaia}, journal = {Nature Neuroscience}, number = {12}, pages = {1717 -- 1727}, publisher = {Nature Publishing Group}, title = {{Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition}}, doi = {10.1038/s41593-018-0266-2}, volume = {21}, year = {2018}, } @article{2, abstract = {Indirect reciprocity explores how humans act when their reputation is at stake, and which social norms they use to assess the actions of others. A crucial question in indirect reciprocity is which social norms can maintain stable cooperation in a society. Past research has highlighted eight such norms, called “leading-eight” strategies. This past research, however, is based on the assumption that all relevant information about other population members is publicly available and that everyone agrees on who is good or bad. Instead, here we explore the reputation dynamics when information is private and noisy. We show that under these conditions, most leading-eight strategies fail to evolve. Those leading-eight strategies that do evolve are unable to sustain full cooperation.Indirect reciprocity is a mechanism for cooperation based on shared moral systems and individual reputations. It assumes that members of a community routinely observe and assess each other and that they use this information to decide who is good or bad, and who deserves cooperation. When information is transmitted publicly, such that all community members agree on each other’s reputation, previous research has highlighted eight crucial moral systems. These “leading-eight” strategies can maintain cooperation and resist invasion by defectors. However, in real populations individuals often hold their own private views of others. Once two individuals disagree about their opinion of some third party, they may also see its subsequent actions in a different light. Their opinions may further diverge over time. Herein, we explore indirect reciprocity when information transmission is private and noisy. We find that in the presence of perception errors, most leading-eight strategies cease to be stable. Even if a leading-eight strategy evolves, cooperation rates may drop considerably when errors are common. Our research highlights the role of reliable information and synchronized reputations to maintain stable moral systems.}, author = {Hilbe, Christian and Schmid, Laura and Tkadlec, Josef and Chatterjee, Krishnendu and Nowak, Martin}, journal = {PNAS}, number = {48}, pages = {12241--12246}, publisher = {National Academy of Sciences}, title = {{Indirect reciprocity with private, noisy, and incomplete information}}, doi = {10.1073/pnas.1810565115}, volume = {115}, year = {2018}, } @article{5816, abstract = {Solid-state qubit manipulation and read-out fidelities are reaching fault-tolerance, but quantum error correction requires millions of physical qubits and therefore a scalable quantum computer architecture. To solve signal-line bandwidth and fan-out problems, microwave sources required for qubit manipulation might be embedded close to the qubit chip, typically operating at temperatures below 4 K. Here, we perform the first low temperature measurements of a 130 nm BiCMOS based SiGe voltage controlled oscillator at cryogenic temperature. We determined the frequency and output power dependence on temperature and magnetic field up to 5 T and measured the temperature influence on its noise performance. The device maintains its full functionality from 300 K to 4 K. The carrier frequency at 4 K increases by 3% with respect to the carrier frequency at 300 K, and the output power at 4 K increases by 10 dB relative to the output power at 300 K. The frequency tuning range of approximately 20% remains unchanged between 300 K and 4 K. In an in-plane magnetic field of 5 T, the carrier frequency shifts by only 0.02% compared to the frequency at zero magnetic field.}, author = {Hollmann, Arne and Jirovec, Daniel and Kucharski, Maciej and Kissinger, Dietmar and Fischer, Gunter and Schreiber, Lars R.}, issn = {0034-6748}, journal = {Review of Scientific Instruments}, number = {11}, publisher = {AIP Publishing}, title = {{30 GHz-voltage controlled oscillator operating at 4 K}}, doi = {10.1063/1.5038258}, volume = {89}, year = {2018}, } @article{612, abstract = {Metabotropic GABAB receptors mediate slow inhibitory effects presynaptically and postsynaptically through the modulation of different effector signalling pathways. Here, we analysed the distribution of GABAB receptors using highly sensitive SDS-digested freeze-fracture replica labelling in mouse cerebellar Purkinje cells. Immunoreactivity for GABAB1 was observed on presynaptic and, more abundantly, on postsynaptic compartments, showing both scattered and clustered distribution patterns. Quantitative analysis of immunoparticles revealed a somato-dendritic gradient, with the density of immunoparticles increasing 26-fold from somata to dendritic spines. To understand the spatial relationship of GABAB receptors with two key effector ion channels, the G protein-gated inwardly rectifying K+ (GIRK/Kir3) channel and the voltage-dependent Ca2+ channel, biochemical and immunohistochemical approaches were performed. Co-immunoprecipitation analysis demonstrated that GABAB receptors co-assembled with GIRK and CaV2.1 channels in the cerebellum. Using double-labelling immunoelectron microscopic techniques, co-clustering between GABAB1 and GIRK2 was detected in dendritic spines, whereas they were mainly segregated in the dendritic shafts. In contrast, co-clustering of GABAB1 and CaV2.1 was detected in dendritic shafts but not spines. Presynaptically, although no significant co-clustering of GABAB1 and GIRK2 or CaV2.1 channels was detected, inter-cluster distance for GABAB1 and GIRK2 was significantly smaller in the active zone than in the dendritic shafts, and that for GABAB1 and CaV2.1 was significantly smaller in the active zone than in the dendritic shafts and spines. Thus, GABAB receptors are associated with GIRK and CaV2.1 channels in different subcellular compartments. These data provide a better framework for understanding the different roles played by GABAB receptors and their effector ion channels in the cerebellar network.}, author = {Luján, Rafael and Aguado, Carolina and Ciruela, Francisco and Cózar, Javier and Kleindienst, David and De La Ossa, Luis and Bettler, Bernhard and Wickman, Kevin and Watanabe, Masahiko and Shigemoto, Ryuichi and Fukazawa, Yugo}, journal = {Brain Structure and Function}, number = {3}, pages = {1565 -- 1587}, publisher = {Springer}, title = {{Differential association of GABAB receptors with their effector ion channels in Purkinje cells}}, doi = {10.1007/s00429-017-1568-y}, volume = {223}, year = {2018}, } @article{422, abstract = {We show that a rather simple, steady modification of the streamwise velocity profile in a pipe can lead to a complete collapse of turbulence and the flow fully relaminarizes. Two different devices, a stationary obstacle (inset) and a device which injects fluid through an annular gap close to the wall, are used to control the flow. Both devices modify the streamwise velocity profile such that the flow in the center of the pipe is decelerated and the flow in the near wall region is accelerated. We present measurements with stereoscopic particle image velocimetry to investigate and capture the development of the relaminarizing flow downstream these devices and the specific circumstances responsible for relaminarization. We find total relaminarization up to Reynolds numbers of 6000, where the skin friction in the far downstream distance is reduced by a factor of 3.4 due to relaminarization. In a smooth straight pipe the flow remains completely laminar downstream of the control. Furthermore, we show that transient (temporary) relaminarization in a spatially confined region right downstream the devices occurs also at much higher Reynolds numbers, accompanied by a significant local skin friction drag reduction. The underlying physical mechanism of relaminarization is attributed to a weakening of the near-wall turbulence production cycle.}, author = {Kühnen, Jakob and Scarselli, Davide and Schaner, Markus and Hof, Björn}, journal = {Flow Turbulence and Combustion}, number = {4}, pages = {919 -- 942}, publisher = {Springer}, title = {{Relaminarization by steady modification of the streamwise velocity profile in a pipe}}, doi = {10.1007/s10494-018-9896-4}, volume = {100}, year = {2018}, } @article{461, abstract = {Turbulence is the major cause of friction losses in transport processes and it is responsible for a drastic drag increase in flows over bounding surfaces. While much effort is invested into developing ways to control and reduce turbulence intensities, so far no methods exist to altogether eliminate turbulence if velocities are sufficiently large. We demonstrate for pipe flow that appropriate distortions to the velocity profile lead to a complete collapse of turbulence and subsequently friction losses are reduced by as much as 90%. Counterintuitively, the return to laminar motion is accomplished by initially increasing turbulence intensities or by transiently amplifying wall shear. Since neither the Reynolds number nor the shear stresses decrease (the latter often increase), these measures are not indicative of turbulence collapse. Instead, an amplification mechanism measuring the interaction between eddies and the mean shear is found to set a threshold below which turbulence is suppressed beyond recovery.}, author = {Kühnen, Jakob and Song, Baofang and Scarselli, Davide and Budanur, Nazmi B and Riedl, Michael and Willis, Ashley and Avila, Marc and Hof, Björn}, journal = {Nature Physics}, pages = {386--390}, publisher = {Nature Publishing Group}, title = {{Destabilizing turbulence in pipe flow}}, doi = {10.1038/s41567-017-0018-3}, volume = {14}, year = {2018}, } @article{47, abstract = {Plant hormones as signalling molecules play an essential role in the control of plant growth and development. Typically, sites of hormonal action are usually distant from the site of biosynthesis thus relying on efficient transport mechanisms. Over the last decades, molecular identification of proteins and protein complexes involved in hormonal transport has started. Advanced screens for genes involved in hormonal transport in combination with transport assays using heterologous systems such as yeast, insect, or tobacco BY2 cells or Xenopus oocytes provided important insights into mechanisms underlying distribution of hormones in plant body and led to identification of principal transporters for each hormone. This review gives a short overview of the mechanisms of hormonal transport and transporters identified in Arabidopsis thaliana.}, author = {Abualia, Rashed and Benková, Eva and Lacombe, Benoît}, journal = {Advances in Botanical Research}, pages = {115 -- 138}, publisher = {Elsevier}, title = {{Transporters and mechanisms of hormone transport in arabidopsis}}, doi = {10.1016/bs.abr.2018.09.007}, volume = {87}, year = {2018}, } @article{5914, abstract = {With the advent of optogenetics, it became possible to change the activity of a targeted population of neurons in a temporally controlled manner. To combine the advantages of 60-channel in vivo tetrode recording and laser-based optogenetics, we have developed a closed-loop recording system that allows for the actual electrophysiological signal to be used as a trigger for the laser light mediating the optogenetic intervention. We have optimized the weight, size, and shape of the corresponding implant to make it compatible with the size, force, and movements of a behaving mouse, and we have shown that the system can efficiently block sharp wave ripple (SWR) events using those events themselves as a trigger. To demonstrate the full potential of the optogenetic recording system we present a pilot study addressing the contribution of SWR events to learning in a complex behavioral task.}, author = {Rangel Guerrero, Dámaris K and Donnett, James G. and Csicsvari, Jozsef L and Kovács, Krisztián}, journal = {eNeuro}, number = {4}, publisher = {Society for Neuroscience}, title = {{Tetrode recording from the hippocampus of behaving mice coupled with four-point-irradiation closed-loop optogenetics: A technique to study the contribution of Hippocampal SWR events to learning}}, doi = {10.1523/ENEURO.0087-18.2018}, volume = {5}, year = {2018}, } @article{412, abstract = {Clathrin-mediated endocytosis (CME) is a cellular trafficking process in which cargoes and lipids are internalized from the plasma membrane into vesicles coated with clathrin and adaptor proteins. CME is essential for many developmental and physiological processes in plants, but its underlying mechanism is not well characterised compared to that in yeast and animal systems. Here, we searched for new factors involved in CME in Arabidopsis thaliana by performing Tandem Affinity Purification of proteins that interact with clathrin light chain, a principal component of the clathrin coat. Among the confirmed interactors, we found two putative homologues of the clathrin-coat uncoating factor auxilin previously described in non-plant systems. Overexpression of AUXILIN-LIKE1 and AUXILIN-LIKE2 in A. thaliana caused an arrest of seedling growth and development. This was concomitant with inhibited endocytosis due to blocking of clathrin recruitment after the initial step of adaptor protein binding to the plasma membrane. By contrast, auxilin-like(1/2) loss-of-function lines did not present endocytosis-related developmental or cellular phenotypes under normal growth conditions. This work contributes to the on-going characterization of the endocytotic machinery in plants and provides a robust tool for conditionally and specifically interfering with CME in A. thaliana.}, author = {Adamowski, Maciek and Narasimhan, Madhumitha and Kania, Urszula and Glanc, Matous and De Jaeger, Geert and Friml, Jirí}, issn = {1532-298X}, journal = {The Plant Cell}, number = {3}, pages = {700 -- 716}, publisher = {American Society of Plant Biologists}, title = {{A functional study of AUXILIN LIKE1 and 2 two putative clathrin uncoating factors in Arabidopsis}}, doi = {10.1105/tpc.17.00785}, volume = {30}, year = {2018}, } @article{67, abstract = {Gene regulatory networks evolve through rewiring of individual components—that is, through changes in regulatory connections. However, the mechanistic basis of regulatory rewiring is poorly understood. Using a canonical gene regulatory system, we quantify the properties of transcription factors that determine the evolutionary potential for rewiring of regulatory connections: robustness, tunability and evolvability. In vivo repression measurements of two repressors at mutated operator sites reveal their contrasting evolutionary potential: while robustness and evolvability were positively correlated, both were in trade-off with tunability. Epistatic interactions between adjacent operators alleviated this trade-off. A thermodynamic model explains how the differences in robustness, tunability and evolvability arise from biophysical characteristics of repressor–DNA binding. The model also uncovers that the energy matrix, which describes how mutations affect repressor–DNA binding, encodes crucial information about the evolutionary potential of a repressor. The biophysical determinants of evolutionary potential for regulatory rewiring constitute a mechanistic framework for understanding network evolution.}, author = {Igler, Claudia and Lagator, Mato and Tkacik, Gasper and Bollback, Jonathan P and Guet, Calin C}, journal = {Nature Ecology and Evolution}, number = {10}, pages = {1633 -- 1643}, publisher = {Nature Publishing Group}, title = {{Evolutionary potential of transcription factors for gene regulatory rewiring}}, doi = {10.1038/s41559-018-0651-y}, volume = {2}, year = {2018}, } @misc{5585, abstract = {Mean repression values and standard error of the mean are given for all operator mutant libraries.}, author = {Igler, Claudia and Lagator, Mato and Tkacik, Gasper and Bollback, Jonathan P and Guet, Calin C}, publisher = {Institute of Science and Technology Austria}, title = {{Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring}}, doi = {10.15479/AT:ISTA:108}, year = {2018}, }