@article{5886, abstract = {Problems involving quantum impurities, in which one or a few particles are interacting with a macroscopic environment, represent a pervasive paradigm, spanning across atomic, molecular, and condensed-matter physics. In this paper we introduce new variational approaches to quantum impurities and apply them to the Fröhlich polaron–a quasiparticle formed out of an electron (or other point-like impurity) in a polar medium, and to the angulon–a quasiparticle formed out of a rotating molecule in a bosonic bath. We benchmark these approaches against established theories, evaluating their accuracy as a function of the impurity-bath coupling.}, author = {Li, Xiang and Bighin, Giacomo and Yakaboylu, Enderalp and Lemeshko, Mikhail}, issn = {0026-8976}, journal = {Molecular Physics}, publisher = {Taylor and Francis}, title = {{Variational approaches to quantum impurities: from the Fröhlich polaron to the angulon}}, doi = {10.1080/00268976.2019.1567852}, year = {2019}, } @phdthesis{6957, abstract = {In many shear flows like pipe flow, plane Couette flow, plane Poiseuille flow, etc. turbulence emerges subcritically. Here, when subjected to strong enough perturbations, the flow becomes turbulent in spite of the laminar base flow being linearly stable. The nature of this instability has puzzled the scientific community for decades. At onset, turbulence appears in localized patches and flows are spatio-temporally intermittent. In pipe flow the localized turbulent structures are referred to as puffs and in planar flows like plane Couette and channel flow, patches arise in the form of localized oblique bands. In this thesis, we study the onset of turbulence in channel flow in direct numerical simulations from a dynamical system theory perspective, as well as by performing experiments in a large aspect ratio channel. The aim of the experimental work is to determine the critical Reynolds number where turbulence first becomes sustained. Recently, the onset of turbulence has been described in analogy to absorbing state phase transition (i.e. directed percolation). In particular, it has been shown that the critical point can be estimated from the competition between spreading and decay processes. Here, by performing experiments, we identify the mechanisms underlying turbulence proliferation in channel flow and find the critical Reynolds number, above which turbulence becomes sustained. Above the critical point, the continuous growth at the tip of the stripes outweighs the stochastic shedding of turbulent patches at the tail and the stripes expand. For growing stripes, the probability to decay decreases while the probability of stripe splitting increases. Consequently, and unlike for the puffs in pipe flow, neither of these two processes is time-independent i.e. memoryless. Coupling between stripe expansion and creation of new stripes via splitting leads to a significantly lower critical point ($Re_c=670+/-10$) than most earlier studies suggest. While the above approach sheds light on how turbulence first becomes sustained, it provides no insight into the origin of the stripes themselves. In the numerical part of the thesis we investigate how turbulent stripes form from invariant solutions of the Navier-Stokes equations. The origin of these turbulent stripes can be identified by applying concepts from the dynamical system theory. In doing so, we identify the exact coherent structures underlying stripes and their bifurcations and how they give rise to the turbulent attractor in phase space. We first report a family of localized nonlinear traveling wave solutions of the Navier-Stokes equations in channel flow. These solutions show structural similarities with turbulent stripes in experiments like obliqueness, quasi-streamwise streaks and vortices, etc. A parametric study of these traveling wave solution is performed, with parameters like Reynolds number, stripe tilt angle and domain size, including the stability of the solutions. These solutions emerge through saddle-node bifurcations and form a phase space skeleton for the turbulent stripes observed in the experiments. The lower branches of these TW solutions at different tilt angles undergo Hopf bifurcation and new solutions branches of relative periodic orbits emerge. These RPO solutions do not belong to the same family and therefore the routes to chaos for different angles are different. In shear flows, turbulence at onset is transient in nature. Consequently,turbulence can not be tracked to lower Reynolds numbers, where the dynamics may simplify. Before this happens, turbulence becomes short-lived and laminarizes. In the last part of the thesis, we show that using numerical simulations we can continue turbulent stripes in channel flow past the 'relaminarization barrier' all the way to their origin. Here, turbulent stripe dynamics simplifies and the fluctuations are no longer stochastic and the stripe settles down to a relative periodic orbit. This relative periodic orbit originates from the aforementioned traveling wave solutions. Starting from the relative periodic orbit, a small increase in speed i.e. Reynolds number gives rise to chaos and the attractor dimension sharply increases in contrast to the classical transition scenario where the instabilities affect the flow globally and give rise to much more gradual route to turbulence.}, author = {Paranjape, Chaitanya S}, issn = {2663-337X}, keywords = {Instabilities, Turbulence, Nonlinear dynamics}, pages = {138}, publisher = {Institute of Science and Technology Austria}, title = {{Onset of turbulence in plane Poiseuille flow}}, doi = {10.15479/AT:ISTA:6957}, year = {2019}, } @phdthesis{7172, abstract = {The development and growth of Arabidopsis thaliana is regulated by a combination of genetic programing and also by the environmental influences. An important role in these processes play the phytohormones and among them, auxin is crucial as it controls many important functions. It is transported through the whole plant body by creating local and temporal concentration maxima and minima, which have an impact on the cell status, tissue and organ identity. Auxin has the property to undergo a directional and finely regulated cell-to-cell transport, which is enabled by the transport proteins, localized on the plasma membrane. An important role in this process have the PIN auxin efflux proteins, which have an asymmetric/polar subcellular localization and determine the directionality of the auxin transport. During the last years, there were significant advances in understanding how the trafficking molecular machineries function, including studies on molecular interactions, function, subcellular localization and intracellular distribution. However, there is still a lack of detailed characterization on the steps of endocytosis, exocytosis, endocytic recycling and degradation. Due to this fact, I focused on the identification of novel trafficking factors and better characterization of the intracellular trafficking pathways. My PhD thesis consists of an introductory chapter, three experimental chapters, a chapter containing general discussion, conclusions and perspectives and also an appendix chapter with published collaborative papers. The first chapter is separated in two different parts: I start by a general introduction to auxin biology and then I introduce the trafficking pathways in the model plant Arabidopsis thaliana. Then, I explain also the phosphorylation-signals for polar targeting and also the roles of the phytohormone strigolactone. The second chapter includes the characterization of bar1/sacsin mutant, which was identified in a forward genetic screen for novel trafficking components in Arabidopsis thaliana, where by the implementation of an EMS-treated pPIN1::PIN1-GFP marker line and by using the established inhibitor of ARF-GEFs, Brefeldin A (BFA) as a tool to study trafficking processes, we identified a novel factor, which is mediating the adaptation of the plant cell to ARF-GEF inhibition. The mutation is in a previously uncharacterized gene, encoding a very big protein that we, based on its homologies, called SACSIN with domains suggesting roles as a molecular chaperon or as a component of the ubiquitin-proteasome system. Our physiology and imaging studies revealed that SACSIN is a crucial plant cell component of the adaptation to the ARF-GEF inhibition. The third chapter includes six subchapters, where I focus on the role of the phytohormone strigolactone, which interferes with auxin feedback on PIN internalization. Strigolactone moderates the polar auxin transport by increasing the internalization of the PIN auxin efflux carriers, which reduces the canalization related growth responses. In addition, I also studied the role of phosphorylation in the strigolactone regulation of auxin feedback on PIN internalization. In this chapter I also present my results on the MAX2-dependence of strigolactone-mediated root growth inhibition and I also share my results on the auxin metabolomics profiling after application of GR24. In the fourth chapter I studied the effect of two small molecules ES-9 and ES9-17, which were identified from a collection of small molecules with the property to impair the clathrin-mediated endocytosis. In the fifth chapter, I discuss all my observations and experimental findings and suggest alternative hypothesis to interpret my results. In the appendix there are three collaborative published projects. In the first, I participated in the characterization of the role of ES9 as a small molecule, which is inhibitor of clathrin- mediated endocytosis in different model organisms. In the second paper, I contributed to the characterization of another small molecule ES9-17, which is a non-protonophoric analog of ES9 and also impairs the clathrin-mediated endocytosis not only in plant cells, but also in mammalian HeLa cells. Last but not least, I also attach another paper, where I tried to establish the grafting method as a technique in our lab to study canalization related processes.}, author = {Vasileva, Mina K}, issn = {2663-337X}, pages = {192}, publisher = {Institute of Science and Technology Austria}, title = {{Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana}}, doi = {10.15479/AT:ISTA:7172}, year = {2019}, } @phdthesis{6071, abstract = {Transcription factors, by binding to specific sequences on the DNA, control the precise spatio-temporal expression of genes inside a cell. However, this specificity is limited, leading to frequent incorrect binding of transcription factors that might have deleterious consequences on the cell. By constructing a biophysical model of TF-DNA binding in the context of gene regulation, I will first explore how regulatory constraints can strongly shape the distribution of a population in sequence space. Then, by directly linking this to a picture of multiple types of transcription factors performing their functions simultaneously inside the cell, I will explore the extent of regulatory crosstalk -- incorrect binding interactions between transcription factors and binding sites that lead to erroneous regulatory states -- and understand the constraints this places on the design of regulatory systems. I will then develop a generic theoretical framework to investigate the coevolution of multiple transcription factors and multiple binding sites, in the context of a gene regulatory network that performs a certain function. As a particular tractable version of this problem, I will consider the evolution of two transcription factors when they transmit upstream signals to downstream target genes. Specifically, I will describe the evolutionary steady states and the evolutionary pathways involved, along with their timescales, of a system that initially undergoes a transcription factor duplication event. To connect this important theoretical model to the prominent biological event of transcription factor duplication giving rise to paralogous families, I will then describe a bioinformatics analysis of C2H2 Zn-finger transcription factors, a major family in humans, and focus on the patterns of evolution that paralogs have undergone in their various protein domains in the recent past. }, author = {Prizak, Roshan}, issn = {2663-337X}, pages = {189}, publisher = {Institute of Science and Technology Austria}, title = {{Coevolution of transcription factors and their binding sites in sequence space}}, doi = {10.15479/at:ista:th6071}, year = {2019}, } @article{6377, abstract = {Clathrin-mediated endocytosis (CME) is a highly conserved and essential cellular process in eukaryotic cells, but its dynamic and vital nature makes it challenging to study using classical genetics tools. In contrast, although small molecules can acutely and reversibly perturb CME, the few chemical CME inhibitors that have been applied to plants are either ineffective or show undesirable side effects. Here, we identify the previously described endosidin9 (ES9) as an inhibitor of clathrin heavy chain (CHC) function in both Arabidopsis and human cells through affinity-based target isolation, in vitro binding studies and X-ray crystallography. Moreover, we present a chemically improved ES9 analog, ES9-17, which lacks the undesirable side effects of ES9 while retaining the ability to target CHC. ES9 and ES9-17 have expanded the chemical toolbox used to probe CHC function, and present chemical scaffolds for further design of more specific and potent CHC inhibitors across different systems.}, author = {Dejonghe, Wim and Sharma, Isha and Denoo, Bram and De Munck, Steven and Lu, Qing and Mishev, Kiril and Bulut, Haydar and Mylle, Evelien and De Rycke, Riet and Vasileva, Mina K and Savatin, Daniel V. and Nerinckx, Wim and Staes, An and Drozdzecki, Andrzej and Audenaert, Dominique and Yperman, Klaas and Madder, Annemieke and Friml, Jiří and Van Damme, Daniël and Gevaert, Kris and Haucke, Volker and Savvides, Savvas N. and Winne, Johan and Russinova, Eugenia}, issn = {1552-4469}, journal = {Nature Chemical Biology}, number = {6}, pages = {641–649}, publisher = {Springer Nature}, title = {{Disruption of endocytosis through chemical inhibition of clathrin heavy chain function}}, doi = {10.1038/s41589-019-0262-1}, volume = {15}, year = {2019}, } @phdthesis{6179, abstract = {In the first part of this thesis we consider large random matrices with arbitrary expectation and a general slowly decaying correlation among its entries. We prove universality of the local eigenvalue statistics and optimal local laws for the resolvent in the bulk and edge regime. The main novel tool is a systematic diagrammatic control of a multivariate cumulant expansion. In the second part we consider Wigner-type matrices and show that at any cusp singularity of the limiting eigenvalue distribution the local eigenvalue statistics are uni- versal and form a Pearcey process. Since the density of states typically exhibits only square root or cubic root cusp singularities, our work complements previous results on the bulk and edge universality and it thus completes the resolution of the Wigner- Dyson-Mehta universality conjecture for the last remaining universality type. Our analysis holds not only for exact cusps, but approximate cusps as well, where an ex- tended Pearcey process emerges. As a main technical ingredient we prove an optimal local law at the cusp, and extend the fast relaxation to equilibrium of the Dyson Brow- nian motion to the cusp regime. In the third and final part we explore the entrywise linear statistics of Wigner ma- trices and identify the fluctuations for a large class of test functions with little regularity. This enables us to study the rectangular Young diagram obtained from the interlacing eigenvalues of the random matrix and its minor, and we find that, despite having the same limit, the fluctuations differ from those of the algebraic Young tableaux equipped with the Plancharel measure.}, author = {Schröder, Dominik J}, issn = {2663-337X}, pages = {375}, publisher = {Institute of Science and Technology Austria}, title = {{From Dyson to Pearcey: Universal statistics in random matrix theory}}, doi = {10.15479/AT:ISTA:th6179}, year = {2019}, } @article{6182, abstract = {We consider large random matrices with a general slowly decaying correlation among its entries. We prove universality of the local eigenvalue statistics and optimal local laws for the resolvent away from the spectral edges, generalizing the recent result of Ajanki et al. [‘Stability of the matrix Dyson equation and random matrices with correlations’, Probab. Theory Related Fields 173(1–2) (2019), 293–373] to allow slow correlation decay and arbitrary expectation. The main novel tool is a systematic diagrammatic control of a multivariate cumulant expansion.}, author = {Erdös, László and Krüger, Torben H and Schröder, Dominik J}, issn = {2050-5094}, journal = {Forum of Mathematics, Sigma}, publisher = {Cambridge University Press}, title = {{Random matrices with slow correlation decay}}, doi = {10.1017/fms.2019.2}, volume = {7}, year = {2019}, } @article{6186, abstract = {We prove that the local eigenvalue statistics of real symmetric Wigner-type matrices near the cusp points of the eigenvalue density are universal. Together with the companion paper [arXiv:1809.03971], which proves the same result for the complex Hermitian symmetry class, this completes the last remaining case of the Wigner-Dyson-Mehta universality conjecture after bulk and edge universalities have been established in the last years. We extend the recent Dyson Brownian motion analysis at the edge [arXiv:1712.03881] to the cusp regime using the optimal local law from [arXiv:1809.03971] and the accurate local shape analysis of the density from [arXiv:1506.05095, arXiv:1804.07752]. We also present a PDE-based method to improve the estimate on eigenvalue rigidity via the maximum principle of the heat flow related to the Dyson Brownian motion.}, author = {Cipolloni, Giorgio and Erdös, László and Krüger, Torben H and Schröder, Dominik J}, issn = {2578-5885}, journal = {Pure and Applied Analysis }, number = {4}, pages = {615–707}, publisher = {MSP}, title = {{Cusp universality for random matrices, II: The real symmetric case}}, doi = {10.2140/paa.2019.1.615}, volume = {1}, year = {2019}, } @phdthesis{7186, abstract = {Tissue morphogenesis in developmental or physiological processes is regulated by molecular and mechanical signals. While the molecular signaling cascades are increasingly well described, the mechanical signals affecting tissue shape changes have only recently been studied in greater detail. To gain more insight into the mechanochemical and biophysical basis of an epithelial spreading process (epiboly) in early zebrafish development, we studied cell-cell junction formation and actomyosin network dynamics at the boundary between surface layer epithelial cells (EVL) and the yolk syncytial layer (YSL). During zebrafish epiboly, the cell mass sitting on top of the yolk cell spreads to engulf the yolk cell by the end of gastrulation. It has been previously shown that an actomyosin ring residing within the YSL pulls on the EVL tissue through a cable-constriction and a flow-friction motor, thereby dragging the tissue vegetal wards. Pulling forces are likely transmitted from the YSL actomyosin ring to EVL cells; however, the nature and formation of the junctional structure mediating this process has not been well described so far. Therefore, our main aim was to determine the nature, dynamics and potential function of the EVL-YSL junction during this epithelial tissue spreading. Specifically, we show that the EVL-YSL junction is a mechanosensitive structure, predominantly made of tight junction (TJ) proteins. The process of TJ mechanosensation depends on the retrograde flow of non-junctional, phase-separated Zonula Occludens-1 (ZO-1) protein clusters towards the EVL-YSL boundary. Interestingly, we could demonstrate that ZO-1 is present in a non-junctional pool on the surface of the yolk cell, and ZO-1 undergoes a phase separation process that likely renders the protein responsive to flows. These flows are directed towards the junction and mediate proper tension-dependent recruitment of ZO-1. Upon reaching the EVL-YSL junction ZO-1 gets incorporated into the junctional pool mediated through its direct actin-binding domain. When the non-junctional pool and/or ZO-1 direct actin binding is absent, TJs fail in their proper mechanosensitive responses resulting in slower tissue spreading. We could further demonstrate that depletion of ZO proteins within the YSL results in diminished actomyosin ring formation. This suggests that a mechanochemical feedback loop is at work during zebrafish epiboly: ZO proteins help in proper actomyosin ring formation and actomyosin contractility and flows positively influence ZO-1 junctional recruitment. Finally, such a mesoscale polarization process mediated through the flow of phase-separated protein clusters might have implications for other processes such as immunological synapse formation, C. elegans zygote polarization and wound healing.}, author = {Schwayer, Cornelia}, issn = {2663-337X}, pages = {107}, publisher = {Institute of Science and Technology Austria}, title = {{Mechanosensation of tight junctions depends on ZO-1 phase separation and flow}}, doi = {10.15479/AT:ISTA:7186}, year = {2019}, } @article{6240, abstract = {For a general class of large non-Hermitian random block matrices X we prove that there are no eigenvalues away from a deterministic set with very high probability. This set is obtained from the Dyson equation of the Hermitization of X as the self-consistent approximation of the pseudospectrum. We demonstrate that the analysis of the matrix Dyson equation from (Probab. Theory Related Fields (2018)) offers a unified treatment of many structured matrix ensembles.}, author = {Alt, Johannes and Erdös, László and Krüger, Torben H and Nemish, Yuriy}, issn = {0246-0203}, journal = {Annales de l'institut Henri Poincare}, number = {2}, pages = {661--696}, publisher = {Institut Henri Poincaré}, title = {{Location of the spectrum of Kronecker random matrices}}, doi = {10.1214/18-AIHP894}, volume = {55}, year = {2019}, } @article{5856, abstract = {We give a bound on the ground-state energy of a system of N non-interacting fermions in a three-dimensional cubic box interacting with an impurity particle via point interactions. We show that the change in energy compared to the system in the absence of the impurity is bounded in terms of the gas density and the scattering length of the interaction, independently of N. Our bound holds as long as the ratio of the mass of the impurity to the one of the gas particles is larger than a critical value m∗ ∗≈ 0.36 , which is the same regime for which we recently showed stability of the system.}, author = {Moser, Thomas and Seiringer, Robert}, issn = {1424-0637}, journal = {Annales Henri Poincare}, number = {4}, pages = {1325–1365}, publisher = {Springer}, title = {{Energy contribution of a point-interacting impurity in a Fermi gas}}, doi = {10.1007/s00023-018-00757-0}, volume = {20}, year = {2019}, } @article{5828, abstract = {Hippocampus is needed for both spatial working and reference memories. Here, using a radial eight-arm maze, we examined how the combined demand on these memories influenced CA1 place cell assemblies while reference memories were partially updated. This was contrasted with control tasks requiring only working memory or the update of reference memory. Reference memory update led to the reward-directed place field shifts at newly rewarded arms and to the gradual strengthening of firing in passes between newly rewarded arms but not between those passes that included a familiar-rewarded arm. At the maze center, transient network synchronization periods preferentially replayed trajectories of the next chosen arm in reference memory tasks but the previously visited arm in the working memory task. Hence, reference memory demand was uniquely associated with a gradual, goal novelty-related reorganization of place cell assemblies and with trajectory replay that reflected the animal's decision of which arm to visit next.}, author = {Xu, Haibing and Baracskay, Peter and O'Neill, Joseph and Csicsvari, Jozsef L}, issn = {1097-4199}, journal = {Neuron}, number = {1}, pages = {119--132.e4}, publisher = {Elsevier}, title = {{Assembly responses of hippocampal CA1 place cells predict learned behavior in goal-directed spatial tasks on the radial eight-arm maze}}, doi = {10.1016/j.neuron.2018.11.015}, volume = {101}, year = {2019}, } @article{5678, abstract = {The order-k Voronoi tessellation of a locally finite set 𝑋⊆ℝ𝑛 decomposes ℝ𝑛 into convex domains whose points have the same k nearest neighbors in X. Assuming X is a stationary Poisson point process, we give explicit formulas for the expected number and total area of faces of a given dimension per unit volume of space. We also develop a relaxed version of discrete Morse theory and generalize by counting only faces, for which the k nearest points in X are within a given distance threshold.}, author = {Edelsbrunner, Herbert and Nikitenko, Anton}, issn = {14320444}, journal = {Discrete and Computational Geometry}, number = {4}, pages = {865–878}, publisher = {Springer}, title = {{Poisson–Delaunay Mosaics of Order k}}, doi = {10.1007/s00454-018-0049-2}, volume = {62}, year = {2019}, } @article{7406, abstract = {Background Synaptic vesicles (SVs) are an integral part of the neurotransmission machinery, and isolation of SVs from their host neuron is necessary to reveal their most fundamental biochemical and functional properties in in vitro assays. Isolated SVs from neurons that have been genetically engineered, e.g. to introduce genetically encoded indicators, are not readily available but would permit new insights into SV structure and function. Furthermore, it is unclear if cultured neurons can provide sufficient starting material for SV isolation procedures. New method Here, we demonstrate an efficient ex vivo procedure to obtain functional SVs from cultured rat cortical neurons after genetic engineering with a lentivirus. Results We show that ∼108 plated cortical neurons allow isolation of suitable SV amounts for functional analysis and imaging. We found that SVs isolated from cultured neurons have neurotransmitter uptake comparable to that of SVs isolated from intact cortex. Using total internal reflection fluorescence (TIRF) microscopy, we visualized an exogenous SV-targeted marker protein and demonstrated the high efficiency of SV modification. Comparison with existing methods Obtaining SVs from genetically engineered neurons currently generally requires the availability of transgenic animals, which is constrained by technical (e.g. cost and time) and biological (e.g. developmental defects and lethality) limitations. Conclusions These results demonstrate the modification and isolation of functional SVs using cultured neurons and viral transduction. The ability to readily obtain SVs from genetically engineered neurons will permit linking in situ studies to in vitro experiments in a variety of genetic contexts.}, author = {Mckenzie, Catherine and Spanova, Miroslava and Johnson, Alexander J and Kainrath, Stephanie and Zheden, Vanessa and Sitte, Harald H. and Janovjak, Harald L}, issn = {0165-0270}, journal = {Journal of Neuroscience Methods}, pages = {114--121}, publisher = {Elsevier}, title = {{Isolation of synaptic vesicles from genetically engineered cultured neurons}}, doi = {10.1016/j.jneumeth.2018.11.018}, volume = {312}, year = {2019}, } @article{7156, abstract = {We propose an efficient microwave-photonic modulator as a resource for stationary entangled microwave-optical fields and develop the theory for deterministic entanglement generation and quantum state transfer in multi-resonant electro-optic systems. The device is based on a single crystal whispering gallery mode resonator integrated into a 3D-microwave cavity. The specific design relies on a new combination of thin-film technology and conventional machining that is optimized for the lowest dissipation rates in the microwave, optical, and mechanical domains. We extract important device properties from finite-element simulations and predict continuous variable entanglement generation rates on the order of a Mebit/s for optical pump powers of only a few tens of microwatts. We compare the quantum state transfer fidelities of coherent, squeezed, and non-Gaussian cat states for both teleportation and direct conversion protocols under realistic conditions. Combining the unique capabilities of circuit quantum electrodynamics with the resilience of fiber optic communication could facilitate long-distance solid-state qubit networks, new methods for quantum signal synthesis, quantum key distribution, and quantum enhanced detection, as well as more power-efficient classical sensing and modulation.}, author = {Rueda Sanchez, Alfredo R and Hease, William J and Barzanjeh, Shabir and Fink, Johannes M}, issn = {2056-6387}, journal = {npj Quantum Information}, publisher = {Springer Nature}, title = {{Electro-optic entanglement source for microwave to telecom quantum state transfer}}, doi = {10.1038/s41534-019-0220-5}, volume = {5}, year = {2019}, } @article{7182, abstract = {During infection pathogens secrete small molecules, termed effectors, to manipulate and control the interaction with their specific hosts. Both the pathogen and the plant are under high selective pressure to rapidly adapt and co-evolve in what is usually referred to as molecular arms race. Components of the host’s immune system form a network that processes information about molecules with a foreign origin and damage-associated signals, integrating them with developmental and abiotic cues to adapt the plant’s responses. Both in the case of nucleotide-binding leucine-rich repeat receptors and leucine-rich repeat receptor kinases interaction networks have been extensively characterized. However, little is known on whether pathogenic effectors form complexes to overcome plant immunity and promote disease. Ustilago maydis, a biotrophic fungal pathogen that infects maize plants, produces effectors that target hubs in the immune network of the host cell. Here we assess the capability of U. maydis effector candidates to interact with each other, which may play a crucial role during the infection process. Using a systematic yeast-two-hybrid approach and based on a preliminary pooled screen, we selected 63 putative effectors for one-on-one matings with a library of nearly 300 effector candidates. We found that 126 of these effector candidates interacted either with themselves or other predicted effectors. Although the functional relevance of the observed interactions remains elusive, we propose that the observed abundance in complex formation between effectors adds an additional level of complexity to effector research and should be taken into consideration when studying effector evolution and function. Based on this fundamental finding, we suggest various scenarios which could evolutionarily drive the formation and stabilization of an effector interactome.}, author = {Alcântara, André and Bosch, Jason and Nazari, Fahimeh and Hoffmann, Gesa and Gallei, Michelle C and Uhse, Simon and Darino, Martin A. and Olukayode, Toluwase and Reumann, Daniel and Baggaley, Laura and Djamei, Armin}, issn = {1664-462X}, journal = {Frontiers in Plant Science}, number = {11}, publisher = {Frontiers}, title = {{Systematic Y2H screening reveals extensive effector-complex formation}}, doi = {10.3389/fpls.2019.01437}, volume = {10}, year = {2019}, } @article{6466, abstract = {One of the most striking and consistent results in speciation genomics is the heterogeneous divergence observed across the genomes of closely related species. This pattern was initially attributed to different levels of gene exchange—with divergence preserved at loci generating a barrier to gene flow but homogenized at unlinked neutral loci. Although there is evidence to support this model, it is now recognized that interpreting patterns of divergence across genomes is not so straightforward. One problem is that heterogenous divergence between populations can also be generated by other processes (e.g. recurrent selective sweeps or background selection) without any involvement of differential gene flow. Thus, integrated studies that identify which loci are likely subject to divergent selection are required to shed light on the interplay between selection and gene flow during the early phases of speciation. In this issue of Molecular Ecology, Rifkin et al. (2019) confront this challenge using a pair of sister morning glory species. They wisely design their sampling to take the geographic context of individuals into account, including geographically isolated (allopatric) and co‐occurring (sympatric) populations. This enabled them to show that individuals are phenotypically less differentiated in sympatry. They also found that the loci that resist introgression are enriched for those most differentiated in allopatry and loci that exhibit signals of divergent selection. One great strength of the study is the combination of methods from population genetics and molecular evolution, including the development of a model to simultaneously infer admixture proportions and selfing rates.}, author = {Field, David and Fraisse, Christelle}, issn = {1365-294X}, journal = {Molecular ecology}, number = {7}, pages = {1579--1581}, publisher = {Wiley}, title = {{Breaking down barriers in morning glories}}, doi = {10.1111/mec.15048}, volume = {28}, year = {2019}, } @article{6575, abstract = {Motivated by recent experimental observations of coherent many-body revivals in a constrained Rydbergatom chain, we construct a weak quasilocal deformation of the Rydberg-blockaded Hamiltonian, whichmakes the revivals virtually perfect. Our analysis suggests the existence of an underlying nonintegrableHamiltonian which supports an emergent SU(2)-spin dynamics within a small subspace of the many-bodyHilbert space. We show that such perfect dynamics necessitates the existence of atypical, nonergodicenergy eigenstates—quantum many-body scars. Furthermore, using these insights, we construct a toymodel that hosts exact quantum many-body scars, providing an intuitive explanation of their origin. Ourresults offer specific routes to enhancing coherent many-body revivals and provide a step towardestablishing the stability of quantum many-body scars in the thermodynamic limit.}, author = {Choi, Soonwon and Turner, Christopher J. and Pichler, Hannes and Ho, Wen Wei and Michailidis, Alexios and Papić, Zlatko and Serbyn, Maksym and Lukin, Mikhail D. and Abanin, Dmitry A.}, issn = {1079-7114}, journal = {Physical Review Letters}, number = {22}, publisher = {American Physical Society}, title = {{Emergent SU(2) dynamics and perfect quantum many-body scars}}, doi = {10.1103/PhysRevLett.122.220603}, volume = {122}, year = {2019}, } @phdthesis{6473, abstract = {Single cells are constantly interacting with their environment and each other, more importantly, the accurate perception of environmental cues is crucial for growth, survival, and reproduction. This communication between cells and their environment can be formalized in mathematical terms and be quantified as the information flow between them, as prescribed by information theory. The recent availability of real–time dynamical patterns of signaling molecules in single cells has allowed us to identify encoding about the identity of the environment in the time–series. However, efficient estimation of the information transmitted by these signals has been a data–analysis challenge due to the high dimensionality of the trajectories and the limited number of samples. In the first part of this thesis, we develop and evaluate decoding–based estimation methods to lower bound the mutual information and derive model–based precise information estimates for biological reaction networks governed by the chemical master equation. This is followed by applying the decoding-based methods to study the intracellular representation of extracellular changes in budding yeast, by observing the transient dynamics of nuclear translocation of 10 transcription factors in response to 3 stress conditions. Additionally, we apply these estimators to previously published data on ERK and Ca2+ signaling and yeast stress response. We argue that this single cell decoding-based measure of information provides an unbiased, quantitative and interpretable measure for the fidelity of biological signaling processes. Finally, in the last section, we deal with gene regulation which is primarily controlled by transcription factors (TFs) that bind to the DNA to activate gene expression. The possibility that non-cognate TFs activate transcription diminishes the accuracy of regulation with potentially disastrous effects for the cell. This ’crosstalk’ acts as a previously unexplored source of noise in biochemical networks and puts a strong constraint on their performance. To mitigate erroneous initiation we propose an out of equilibrium scheme that implements kinetic proofreading. We show that such architectures are favored over their equilibrium counterparts for complex organisms despite introducing noise in gene expression. }, author = {Cepeda Humerez, Sarah A}, issn = {2663-337X}, keywords = {Information estimation, Time-series, data analysis}, pages = {135}, publisher = {Institute of Science and Technology Austria}, title = {{Estimating information flow in single cells}}, doi = {10.15479/AT:ISTA:6473}, year = {2019}, } @article{6900, abstract = {Across diverse biological systems—ranging from neural networks to intracellular signaling and genetic regulatory networks—the information about changes in the environment is frequently encoded in the full temporal dynamics of the network nodes. A pressing data-analysis challenge has thus been to efficiently estimate the amount of information that these dynamics convey from experimental data. Here we develop and evaluate decoding-based estimation methods to lower bound the mutual information about a finite set of inputs, encoded in single-cell high-dimensional time series data. For biological reaction networks governed by the chemical Master equation, we derive model-based information approximations and analytical upper bounds, against which we benchmark our proposed model-free decoding estimators. In contrast to the frequently-used k-nearest-neighbor estimator, decoding-based estimators robustly extract a large fraction of the available information from high-dimensional trajectories with a realistic number of data samples. We apply these estimators to previously published data on Erk and Ca2+ signaling in mammalian cells and to yeast stress-response, and find that substantial amount of information about environmental state can be encoded by non-trivial response statistics even in stationary signals. We argue that these single-cell, decoding-based information estimates, rather than the commonly-used tests for significant differences between selected population response statistics, provide a proper and unbiased measure for the performance of biological signaling networks.}, author = {Cepeda Humerez, Sarah A and Ruess, Jakob and Tkačik, Gašper}, issn = {1553-7358}, journal = {PLoS computational biology}, number = {9}, pages = {e1007290}, publisher = {Public Library of Science}, title = {{Estimating information in time-varying signals}}, doi = {10.1371/journal.pcbi.1007290}, volume = {15}, year = {2019}, }