TY - JOUR AB - Half a century after Lewis Wolpert's seminal conceptual advance on how cellular fates distribute in space, we provide a brief historical perspective on how the concept of positional information emerged and influenced the field of developmental biology and beyond. We focus on a modern interpretation of this concept in terms of information theory, largely centered on its application to cell specification in the early Drosophila embryo. We argue that a true physical variable (position) is encoded in local concentrations of patterning molecules, that this mapping is stochastic, and that the processes by which positions and corresponding cell fates are determined based on these concentrations need to take such stochasticity into account. With this approach, we shift the focus from biological mechanisms, molecules, genes and pathways to quantitative systems-level questions: where does positional information reside, how it is transformed and accessed during development, and what fundamental limits it is subject to? AU - Tkačik, Gašper AU - Gregor, Thomas ID - 9226 IS - 2 JF - Development TI - The many bits of positional information VL - 148 ER - TY - JOUR AB - A stochastic PDE, describing mesoscopic fluctuations in systems of weakly interacting inertial particles of finite volume, is proposed and analysed in any finite dimension . It is a regularised and inertial version of the Dean–Kawasaki model. A high-probability well-posedness theory for this model is developed. This theory improves significantly on the spatial scaling restrictions imposed in an earlier work of the same authors, which applied only to significantly larger particles in one dimension. The well-posedness theory now applies in d-dimensions when the particle-width ϵ is proportional to for and N is the number of particles. This scaling is optimal in a certain Sobolev norm. Key tools of the analysis are fractional Sobolev spaces, sharp bounds on Bessel functions, separability of the regularisation in the d-spatial dimensions, and use of the Faà di Bruno's formula. AU - Cornalba, Federico AU - Shardlow, Tony AU - Zimmer, Johannes ID - 9240 IS - 5 JF - Journal of Differential Equations SN - 0022-0396 TI - Well-posedness for a regularised inertial Dean–Kawasaki model for slender particles in several space dimensions VL - 284 ER - TY - CONF AB - In March 2020, the Austrian government introduced a widespread lock-down in response to the COVID-19 pandemic. Based on subjective impressions and anecdotal evidence, Austrian public and private life came to a sudden halt. Here we assess the effect of the lock-down quantitatively for all regions in Austria and present an analysis of daily changes of human mobility throughout Austria using near-real-time anonymized mobile phone data. We describe an efficient data aggregation pipeline and analyze the mobility by quantifying mobile-phone traffic at specific point of interests (POIs), analyzing individual trajectories and investigating the cluster structure of the origin-destination graph. We found a reduction of commuters at Viennese metro stations of over 80% and the number of devices with a radius of gyration of less than 500 m almost doubled. The results of studying crowd-movement behavior highlight considerable changes in the structure of mobility networks, revealed by a higher modularity and an increase from 12 to 20 detected communities. We demonstrate the relevance of mobility data for epidemiological studies by showing a significant correlation of the outflow from the town of Ischgl (an early COVID-19 hotspot) and the reported COVID-19 cases with an 8-day time lag. This research indicates that mobile phone usage data permits the moment-by-moment quantification of mobility behavior for a whole country. We emphasize the need to improve the availability of such data in anonymized form to empower rapid response to combat COVID-19 and future pandemics. AU - Heiler, Georg AU - Reisch, Tobias AU - Hurt, Jan AU - Forghani, Mohammad AU - Omani, Aida AU - Hanbury, Allan AU - Karimipour, Farid ID - 9253 SN - 9781728162515 T2 - 2020 IEEE International Conference on Big Data TI - Country-wide mobility changes observed using mobile phone data during COVID-19 pandemic ER - TY - JOUR AB - Legacy conferences are costly and time consuming, and exclude scientists lacking various resources or abilities. During the 2020 pandemic, we created an online conference platform, Neuromatch Conferences (NMC), aimed at developing technological and cultural changes to make conferences more democratic, scalable, and accessible. We discuss the lessons we learned. AU - Achakulvisut, Titipat AU - Ruangrong, Tulakan AU - Mineault, Patrick AU - Vogels, Tim P AU - Peters, Megan A.K. AU - Poirazi, Panayiota AU - Rozell, Christopher AU - Wyble, Brad AU - Goodman, Dan F.M. AU - Kording, Konrad Paul ID - 9228 IS - 4 JF - Trends in Cognitive Sciences SN - 1364-6613 TI - Towards democratizing and automating online conferences: Lessons from the Neuromatch Conferences VL - 25 ER - TY - JOUR AB - We re-examine attempts to study the many-body localization transition using measures that are physically natural on the ergodic/quantum chaotic regime of the phase diagram. Using simple scaling arguments and an analysis of various models for which rigorous results are available, we find that these measures can be particularly adversely affected by the strong finite-size effects observed in nearly all numerical studies of many-body localization. This severely impacts their utility in probing the transition and the localized phase. In light of this analysis, we discuss a recent study (Šuntajs et al., 2020) of the behaviour of the Thouless energy and level repulsion in disordered spin chains, and its implications for the question of whether MBL is a true phase of matter. AU - Abanin, D. A. AU - Bardarson, J. H. AU - De Tomasi, G. AU - Gopalakrishnan, S. AU - Khemani, V. AU - Parameswaran, S. A. AU - Pollmann, F. AU - Potter, A. C. AU - Serbyn, Maksym AU - Vasseur, R. ID - 9224 IS - 4 JF - Annals of Physics SN - 00034916 TI - Distinguishing localization from chaos: Challenges in finite-size systems VL - 427 ER - TY - JOUR AB - A graph game proceeds as follows: two players move a token through a graph to produce a finite or infinite path, which determines the payoff of the game. We study bidding games in which in each turn, an auction determines which player moves the token. Bidding games were largely studied in combination with two variants of first-price auctions called “Richman” and “poorman” bidding. We study taxman bidding, which span the spectrum between the two. The game is parameterized by a constant : portion τ of the winning bid is paid to the other player, and portion to the bank. While finite-duration (reachability) taxman games have been studied before, we present, for the first time, results on infinite-duration taxman games: we unify, generalize, and simplify previous equivalences between bidding games and a class of stochastic games called random-turn games. AU - Avni, Guy AU - Henzinger, Thomas A AU - Žikelić, Đorđe ID - 9239 IS - 8 JF - Journal of Computer and System Sciences SN - 0022-0000 TI - Bidding mechanisms in graph games VL - 119 ER - TY - JOUR AB - Organ function depends on tissues adopting the correct architecture. However, insights into organ architecture are currently hampered by an absence of standardized quantitative 3D analysis. We aimed to develop a robust technology to visualize, digitalize, and segment the architecture of two tubular systems in 3D: double resin casting micro computed tomography (DUCT). As proof of principle, we applied DUCT to a mouse model for Alagille syndrome (Jag1Ndr/Ndr mice), characterized by intrahepatic bile duct paucity, that can spontaneously generate a biliary system in adulthood. DUCT identified increased central biliary branching and peripheral bile duct tortuosity as two compensatory processes occurring in distinct regions of Jag1Ndr/Ndr liver, leading to full reconstitution of wild-type biliary volume and phenotypic recovery. DUCT is thus a powerful new technology for 3D analysis, which can reveal novel phenotypes and provide a standardized method of defining liver architecture in mouse models. AU - Hankeova, Simona AU - Salplachta, Jakub AU - Zikmund, Tomas AU - Kavkova, Michaela AU - Van Hul, Noémi AU - Brinek, Adam AU - Smekalova, Veronika AU - Laznovsky, Jakub AU - Dawit, Feven AU - Jaros, Josef AU - Bryja, Vítězslav AU - Lendahl, Urban AU - Ellis, Ewa AU - Nemeth, Antal AU - Fischler, Björn AU - Hannezo, Edouard B AU - Kaiser, Jozef AU - Andersson, Emma Rachel ID - 9244 JF - eLife TI - DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for alagille syndrome VL - 10 ER - TY - JOUR AB - Volumetric light transport is a pervasive physical phenomenon, and therefore its accurate simulation is important for a broad array of disciplines. While suitable mathematical models for computing the transport are now available, obtaining the necessary material parameters needed to drive such simulations is a challenging task: direct measurements of these parameters from material samples are seldom possible. Building on the inverse scattering paradigm, we present a novel measurement approach which indirectly infers the transport parameters from extrinsic observations of multiple-scattered radiance. The novelty of the proposed approach lies in replacing structured illumination with a structured reflector bonded to the sample, and a robust fitting procedure that largely compensates for potential systematic errors in the calibration of the setup. We show the feasibility of our approach by validating simulations of complex 3D compositions of the measured materials against physical prints, using photo-polymer resins. As presented in this paper, our technique yields colorspace data suitable for accurate appearance reproduction in the area of 3D printing. Beyond that, and without fundamental changes to the basic measurement methodology, it could equally well be used to obtain spectral measurements that are useful for other application areas. AU - Elek, Oskar AU - Zhang, Ran AU - Sumin, Denis AU - Myszkowski, Karol AU - Bickel, Bernd AU - Wilkie, Alexander AU - Křivánek, Jaroslav AU - Weyrich, Tim ID - 9241 IS - 5 JF - Optics Express TI - Robust and practical measurement of volume transport parameters in solid photo-polymer materials for 3D printing VL - 29 ER - TY - JOUR AB - Peptidoglycan is an essential component of the bacterial cell envelope that surrounds the cytoplasmic membrane to protect the cell from osmotic lysis. Important antibiotics such as β-lactams and glycopeptides target peptidoglycan biosynthesis. Class A penicillin-binding proteins (PBPs) are bifunctional membrane-bound peptidoglycan synthases that polymerize glycan chains and connect adjacent stem peptides by transpeptidation. How these enzymes work in their physiological membrane environment is poorly understood. Here, we developed a novel Förster resonance energy transfer-based assay to follow in real time both reactions of class A PBPs reconstituted in liposomes or supported lipid bilayers and applied this assay with PBP1B homologues from Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii in the presence or absence of their cognate lipoprotein activator. Our assay will allow unravelling the mechanisms of peptidoglycan synthesis in a lipid-bilayer environment and can be further developed to be used for high-throughput screening for new antimicrobials. AU - Hernández-Rocamora, Víctor M. AU - Baranova, Natalia S. AU - Peters, Katharina AU - Breukink, Eefjan AU - Loose, Martin AU - Vollmer, Waldemar ID - 9243 JF - eLife TI - Real time monitoring of peptidoglycan synthesis by membrane-reconstituted penicillin binding proteins VL - 10 ER - TY - JOUR AB - We consider the Fröhlich Hamiltonian in a mean-field limit where many bosonic particles weakly couple to the quantized phonon field. For large particle numbers and a suitably small coupling, we show that the dynamics of the system is approximately described by the Landau–Pekar equations. These describe a Bose–Einstein condensate interacting with a classical polarization field, whose dynamics is effected by the condensate, i.e., the back-reaction of the phonons that are created by the particles during the time evolution is of leading order. AU - Leopold, Nikolai K AU - Mitrouskas, David Johannes AU - Seiringer, Robert ID - 9246 JF - Archive for Rational Mechanics and Analysis SN - 00039527 TI - Derivation of the Landau–Pekar equations in a many-body mean-field limit VL - 240 ER - TY - JOUR AB - We consider the ferromagnetic quantum Heisenberg model in one dimension, for any spin S≥1/2. We give upper and lower bounds on the free energy, proving that at low temperature it is asymptotically equal to the one of an ideal Bose gas of magnons, as predicted by the spin-wave approximation. The trial state used in the upper bound yields an analogous estimate also in the case of two spatial dimensions, which is believed to be sharp at low temperature. AU - Napiórkowski, Marcin M AU - Seiringer, Robert ID - 9256 IS - 2 JF - Letters in Mathematical Physics SN - 03779017 TI - Free energy asymptotics of the quantum Heisenberg spin chain VL - 111 ER - TY - JOUR AB - In the recent years important experimental advances in resonant electro-optic modulators as high-efficiency sources for coherent frequency combs and as devices for quantum information transfer have been realized, where strong optical and microwave mode coupling were achieved. These features suggest electro-optic-based devices as candidates for entangled optical frequency comb sources. In the present work, I study the generation of entangled optical frequency combs in millimeter-sized resonant electro-optic modulators. These devices profit from the experimentally proven advantages such as nearly constant optical free spectral ranges over several gigahertz, and high optical and microwave quality factors. The generation of frequency multiplexed quantum channels with spectral bandwidth in the MHz range for conservative parameter values paves the way towards novel uses in long-distance hybrid quantum networks, quantum key distribution, enhanced optical metrology, and quantum computing. AU - Rueda Sanchez, Alfredo R ID - 9242 IS - 2 JF - Physical Review A SN - 2469-9926 TI - Frequency-multiplexed hybrid optical entangled source based on the Pockels effect VL - 103 ER - TY - JOUR AB - The inverse problem of designing component interactions to target emergent structure is fundamental to numerous applications in biotechnology, materials science, and statistical physics. Equally important is the inverse problem of designing emergent kinetics, but this has received considerably less attention. Using recent advances in automatic differentiation, we show how kinetic pathways can be precisely designed by directly differentiating through statistical physics models, namely free energy calculations and molecular dynamics simulations. We consider two systems that are crucial to our understanding of structural self-assembly: bulk crystallization and small nanoclusters. In each case, we are able to assemble precise dynamical features. Using gradient information, we manipulate interactions among constituent particles to tune the rate at which these systems yield specific structures of interest. Moreover, we use this approach to learn nontrivial features about the high-dimensional design space, allowing us to accurately predict when multiple kinetic features can be simultaneously and independently controlled. These results provide a concrete and generalizable foundation for studying nonstructural self-assembly, including kinetic properties as well as other complex emergent properties, in a vast array of systems. AU - Goodrich, Carl Peter AU - King, Ella M. AU - Schoenholz, Samuel S. AU - Cubuk, Ekin D. AU - Brenner, Michael P. ID - 9257 IS - 10 JF - Proceedings of the National Academy of Sciences SN - 0027-8424 TI - Designing self-assembling kinetics with differentiable statistical physics models VL - 118 ER - TY - JOUR AB - Sequence-specific oligomers with predictable folding patterns, i.e., foldamers, provide new opportunities to mimic α-helical peptides and design inhibitors of protein-protein interactions. One major hurdle of this strategy is to retain the correct orientation of key side chains involved in protein surface recognition. Here, we show that the structural plasticity of a foldamer backbone may notably contribute to the required spatial adjustment for optimal interaction with the protein surface. By using oligoureas as α helix mimics, we designed a foldamer/peptide hybrid inhibitor of histone chaperone ASF1, a key regulator of chromatin dynamics. The crystal structure of its complex with ASF1 reveals a notable plasticity of the urea backbone, which adapts to the ASF1 surface to maintain the same binding interface. One additional benefit of generating ASF1 ligands with nonpeptide oligourea segments is the resistance to proteolysis in human plasma, which was highly improved compared to the cognate α-helical peptide. AU - Mbianda, Johanne AU - Bakail, May M AU - André, Christophe AU - Moal, Gwenaëlle AU - Perrin, Marie E. AU - Pinna, Guillaume AU - Guerois, Raphaël AU - Becher, Francois AU - Legrand, Pierre AU - Traoré, Seydou AU - Douat, Céline AU - Guichard, Gilles AU - Ochsenbein, Françoise ID - 9262 IS - 12 JF - Science Advances SN - 2375-2548 TI - Optimal anchoring of a foldamer inhibitor of ASF1 histone chaperone through backbone plasticity VL - 7 ER - TY - JOUR AB - Gradients of chemokines and growth factors guide migrating cells and morphogenetic processes. Migration of antigen-presenting dendritic cells from the interstitium into the lymphatic system is dependent on chemokine CCL21, which is secreted by endothelial cells of the lymphatic capillary, binds heparan sulfates and forms gradients decaying into the interstitium. Despite the importance of CCL21 gradients, and chemokine gradients in general, the mechanisms of gradient formation are unclear. Studies on fibroblast growth factors have shown that limited diffusion is crucial for gradient formation. Here, we used the mouse dermis as a model tissue to address the necessity of CCL21 anchoring to lymphatic capillary heparan sulfates in the formation of interstitial CCL21 gradients. Surprisingly, the absence of lymphatic endothelial heparan sulfates resulted only in a modest decrease of CCL21 levels at the lymphatic capillaries and did neither affect interstitial CCL21 gradient shape nor dendritic cell migration toward lymphatic capillaries. Thus, heparan sulfates at the level of the lymphatic endothelium are dispensable for the formation of a functional CCL21 gradient. AU - Vaahtomeri, Kari AU - Moussion, Christine AU - Hauschild, Robert AU - Sixt, Michael K ID - 9259 JF - Frontiers in Immunology TI - Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium VL - 12 ER - TY - JOUR AB - Auxin is a key regulator of plant growth and development. Local auxin biosynthesis and intercellular transport generates regional gradients in the root that are instructive for processes such as specification of developmental zones that maintain root growth and tropic responses. Here we present a toolbox to study auxin-mediated root development that features: (i) the ability to control auxin synthesis with high spatio-temporal resolution and (ii) single-cell nucleus tracking and morphokinetic analysis infrastructure. Integration of these two features enables cutting-edge analysis of root development at single-cell resolution based on morphokinetic parameters under normal growth conditions and during cell-type-specific induction of auxin biosynthesis. We show directional auxin flow in the root and refine the contributions of key players in this process. In addition, we determine the quantitative kinetics of Arabidopsis root meristem skewing, which depends on local auxin gradients but does not require PIN2 and AUX1 auxin transporter activities. Beyond the mechanistic insights into root development, the tools developed here will enable biologists to study kinetics and morphology of various critical processes at the single cell-level in whole organisms. AU - Hu, Yangjie AU - Omary, Moutasem AU - Hu, Yun AU - Doron, Ohad AU - Hörmayer, Lukas AU - Chen, Qingguo AU - Megides, Or AU - Chekli, Ori AU - Ding, Zhaojun AU - Friml, Jiří AU - Zhao, Yunde AU - Tsarfaty, Ilan AU - Shani, Eilon ID - 9254 JF - Nature Communications TI - Cell kinetics of auxin transport and activity in Arabidopsis root growth and skewing VL - 12 ER - TY - JOUR AB - Our ability to trust that a random number is truly random is essential for fields as diverse as cryptography and fundamental tests of quantum mechanics. Existing solutions both come with drawbacks—device-independent quantum random number generators (QRNGs) are highly impractical and standard semi-device-independent QRNGs are limited to a specific physical implementation and level of trust. Here we propose a framework for semi-device-independent randomness certification, using a source of trusted vacuum in the form of a signal shutter. It employs a flexible set of assumptions and levels of trust, allowing it to be applied in a wide range of physical scenarios involving both quantum and classical entropy sources. We experimentally demonstrate our protocol with a photonic setup and generate secure random bits under three different assumptions with varying degrees of security and resulting data rates. AU - Pivoluska, Matej AU - Plesch, Martin AU - Farkas, Máté AU - Ruzickova, Natalia AU - Flegel, Clara AU - Valencia, Natalia Herrera AU - Mccutcheon, Will AU - Malik, Mehul AU - Aguilar, Edgar A. ID - 9255 JF - npj Quantum Information TI - Semi-device-independent random number generation with flexible assumptions VL - 7 ER - TY - JOUR AB - We study the density of rational points on a higher-dimensional orbifold (Pn−1,Δ) when Δ is a Q-divisor involving hyperplanes. This allows us to address a question of Tanimoto about whether the set of rational points on such an orbifold constitutes a thin set. Our approach relies on the Hardy–Littlewood circle method to first study an asymptotic version of Waring’s problem for mixed powers. In doing so we make crucial use of the recent resolution of the main conjecture in Vinogradov’s mean value theorem, due to Bourgain–Demeter–Guth and Wooley. AU - Browning, Timothy D AU - Yamagishi, Shuntaro ID - 9260 JF - Mathematische Zeitschrift SN - 0025-5874 TI - Arithmetic of higher-dimensional orbifolds and a mixed Waring problem VL - 299 ER - TY - JOUR AU - Pinkard, Henry AU - Stuurman, Nico AU - Ivanov, Ivan E. AU - Anthony, Nicholas M. AU - Ouyang, Wei AU - Li, Bin AU - Yang, Bin AU - Tsuchida, Mark A. AU - Chhun, Bryant AU - Zhang, Grace AU - Mei, Ryan AU - Anderson, Michael AU - Shepherd, Douglas P. AU - Hunt-Isaak, Ian AU - Dunn, Raymond L. AU - Jahr, Wiebke AU - Kato, Saul AU - Royer, Loïc A. AU - Thiagarajah, Jay R. AU - Eliceiri, Kevin W. AU - Lundberg, Emma AU - Mehta, Shalin B. AU - Waller, Laura ID - 9258 IS - 3 JF - Nature Methods SN - 1548-7091 TI - Pycro-Manager: Open-source software for customized and reproducible microscope control VL - 18 ER - TY - JOUR AB - Assemblies of actin and its regulators underlie the dynamic morphology of all eukaryotic cells. To understand how actin regulatory proteins work together to generate actin-rich structures such as filopodia, we analyzed the localization of diverse actin regulators within filopodia in Drosophila embryos and in a complementary in vitro system of filopodia-like structures (FLSs). We found that the composition of the regulatory protein complex where actin is incorporated (the filopodial tip complex) is remarkably heterogeneous both in vivo and in vitro. Our data reveal that different pairs of proteins correlate with each other and with actin bundle length, suggesting the presence of functional subcomplexes. This is consistent with a theoretical framework where three or more redundant subcomplexes join the tip complex stochastically, with any two being sufficient to drive filopodia formation. We provide an explanation for the observed heterogeneity and suggest that a mechanism based on multiple components allows stereotypical filopodial dynamics to arise from diverse upstream signaling pathways. AU - Dobramysl, Ulrich AU - Jarsch, Iris Katharina AU - Inoue, Yoshiko AU - Shimo, Hanae AU - Richier, Benjamin AU - Gadsby, Jonathan R. AU - Mason, Julia AU - Szałapak, Alicja AU - Ioannou, Pantelis Savvas AU - Correia, Guilherme Pereira AU - Walrant, Astrid AU - Butler, Richard AU - Hannezo, Edouard B AU - Simons, Benjamin D. AU - Gallop, Jennifer L. ID - 9306 IS - 4 JF - Journal of Cell Biology TI - Stochastic combinations of actin regulatory proteins are sufficient to drive filopodia formation VL - 220 ER - TY - JOUR AB - We establish finite time extinction with probability one for weak solutions of the Cauchy–Dirichlet problem for the 1D stochastic porous medium equation with Stratonovich transport noise and compactly supported smooth initial datum. Heuristically, this is expected to hold because Brownian motion has average spread rate O(t12) whereas the support of solutions to the deterministic PME grows only with rate O(t1m+1). The rigorous proof relies on a contraction principle up to time-dependent shift for Wong–Zakai type approximations, the transformation to a deterministic PME with two copies of a Brownian path as the lateral boundary, and techniques from the theory of viscosity solutions. AU - Hensel, Sebastian ID - 9307 JF - Stochastics and Partial Differential Equations: Analysis and Computations SN - 2194-0401 TI - Finite time extinction for the 1D stochastic porous medium equation with transport noise VL - 9 ER - TY - JOUR AB - We report the results of an experimental investigation into the decay of turbulence in plane Couette–Poiseuille flow using ‘quench’ experiments where the flow laminarises after a sudden reduction in Reynolds number Re. Specifically, we study the velocity field in the streamwise–spanwise plane. We show that the spanwise velocity containing rolls decays faster than the streamwise velocity, which displays elongated regions of higher or lower velocity called streaks. At final Reynolds numbers above 425, the decay of streaks displays two stages: first a slow decay when rolls are present and secondly a more rapid decay of streaks alone. The difference in behaviour results from the regeneration of streaks by rolls, called the lift-up effect. We define the turbulent fraction as the portion of the flow containing turbulence and this is estimated by thresholding the spanwise velocity component. It decreases linearly with time in the whole range of final Re. The corresponding decay slope increases linearly with final Re. The extrapolated value at which this decay slope vanishes is Reaz≈656±10, close to Reg≈670 at which turbulence is self-sustained. The decay of the energy computed from the spanwise velocity component is found to be exponential. The corresponding decay rate increases linearly with Re, with an extrapolated vanishing value at ReAz≈688±10. This value is also close to the value at which the turbulence is self-sustained, showing that valuable information on the transition can be obtained over a wide range of Re. AU - Liu, T. AU - Semin, B. AU - Klotz, Lukasz AU - Godoy-Diana, R. AU - Wesfreid, J. E. AU - Mullin, T. ID - 9297 JF - Journal of Fluid Mechanics SN - 0022-1120 TI - Decay of streaks and rolls in plane Couette-Poiseuille flow VL - 915 ER - TY - JOUR AB - Hill's Conjecture states that the crossing number cr(𝐾𝑛) of the complete graph 𝐾𝑛 in the plane (equivalently, the sphere) is 14⌊𝑛2⌋⌊𝑛−12⌋⌊𝑛−22⌋⌊𝑛−32⌋=𝑛4/64+𝑂(𝑛3) . Moon proved that the expected number of crossings in a spherical drawing in which the points are randomly distributed and joined by geodesics is precisely 𝑛4/64+𝑂(𝑛3) , thus matching asymptotically the conjectured value of cr(𝐾𝑛) . Let cr𝑃(𝐺) denote the crossing number of a graph 𝐺 in the projective plane. Recently, Elkies proved that the expected number of crossings in a naturally defined random projective plane drawing of 𝐾𝑛 is (𝑛4/8𝜋2)+𝑂(𝑛3) . In analogy with the relation of Moon's result to Hill's conjecture, Elkies asked if lim𝑛→∞ cr𝑃(𝐾𝑛)/𝑛4=1/8𝜋2 . We construct drawings of 𝐾𝑛 in the projective plane that disprove this. AU - Arroyo Guevara, Alan M AU - Mcquillan, Dan AU - Richter, R. Bruce AU - Salazar, Gelasio AU - Sullivan, Matthew ID - 9295 IS - 3 JF - Journal of Graph Theory SN - 0364-9024 TI - Drawings of complete graphs in the projective plane VL - 97 ER - TY - JOUR AB - In this issue of Developmental Cell, Doyle and colleagues identify periodic anterior contraction as a characteristic feature of fibroblasts and mesenchymal cancer cells embedded in 3D collagen gels. This contractile mechanism generates a matrix prestrain required for crawling in fibrous 3D environments. AU - Gärtner, Florian R AU - Sixt, Michael K ID - 9294 IS - 6 JF - Developmental Cell SN - 15345807 TI - Engaging the front wheels to drive through fibrous terrain VL - 56 ER - TY - JOUR AB - Background: To understand information coding in single neurons, it is necessary to analyze subthreshold synaptic events, action potentials (APs), and their interrelation in different behavioral states. However, detecting excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) in behaving animals remains challenging, because of unfavorable signal-to-noise ratio, high frequency, fluctuating amplitude, and variable time course of synaptic events. New method: We developed a method for synaptic event detection, termed MOD (Machine-learning Optimal-filtering Detection-procedure), which combines concepts of supervised machine learning and optimal Wiener filtering. Experts were asked to manually score short epochs of data. The algorithm was trained to obtain the optimal filter coefficients of a Wiener filter and the optimal detection threshold. Scored and unscored data were then processed with the optimal filter, and events were detected as peaks above threshold. Results: We challenged MOD with EPSP traces in vivo in mice during spatial navigation and EPSC traces in vitro in slices under conditions of enhanced transmitter release. The area under the curve (AUC) of the receiver operating characteristics (ROC) curve was, on average, 0.894 for in vivo and 0.969 for in vitro data sets, indicating high detection accuracy and efficiency. Comparison with existing methods: When benchmarked using a (1 − AUC)−1 metric, MOD outperformed previous methods (template-fit, deconvolution, and Bayesian methods) by an average factor of 3.13 for in vivo data sets, but showed comparable (template-fit, deconvolution) or higher (Bayesian) computational efficacy. Conclusions: MOD may become an important new tool for large-scale, real-time analysis of synaptic activity. AU - Zhang, Xiaomin AU - Schlögl, Alois AU - Vandael, David H AU - Jonas, Peter M ID - 9329 IS - 6 JF - Journal of Neuroscience Methods SN - 0165-0270 TI - MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo VL - 357 ER - TY - JOUR AB - Embryo morphogenesis is impacted by dynamic changes in tissue material properties, which have been proposed to occur via processes akin to phase transitions (PTs). Here, we show that rigidity percolation provides a simple and robust theoretical framework to predict material/structural PTs of embryonic tissues from local cell connectivity. By using percolation theory, combined with directly monitoring dynamic changes in tissue rheology and cell contact mechanics, we demonstrate that the zebrafish blastoderm undergoes a genuine rigidity PT, brought about by a small reduction in adhesion-dependent cell connectivity below a critical value. We quantitatively predict and experimentally verify hallmarks of PTs, including power-law exponents and associated discontinuities of macroscopic observables. Finally, we show that this uniform PT depends on blastoderm cells undergoing meta-synchronous divisions causing random and, consequently, uniform changes in cell connectivity. Collectively, our theoretical and experimental findings reveal the structural basis of material PTs in an organismal context. AU - Petridou, Nicoletta AU - Corominas-Murtra, Bernat AU - Heisenberg, Carl-Philipp J AU - Hannezo, Edouard B ID - 9316 IS - 7 JF - Cell SN - 00928674 TI - Rigidity percolation uncovers a structural basis for embryonic tissue phase transitions VL - 184 ER - TY - JOUR AB - Given a locally finite X⊆Rd and a radius r≥0, the k-fold cover of X and r consists of all points in Rd that have k or more points of X within distance r. We consider two filtrations—one in scale obtained by fixing k and increasing r, and the other in depth obtained by fixing r and decreasing k—and we compute the persistence diagrams of both. While standard methods suffice for the filtration in scale, we need novel geometric and topological concepts for the filtration in depth. In particular, we introduce a rhomboid tiling in Rd+1 whose horizontal integer slices are the order-k Delaunay mosaics of X, and construct a zigzag module of Delaunay mosaics that is isomorphic to the persistence module of the multi-covers. AU - Edelsbrunner, Herbert AU - Osang, Georg F ID - 9317 JF - Discrete and Computational Geometry SN - 0179-5376 TI - The multi-cover persistence of Euclidean balls VL - 65 ER - TY - JOUR AB - We consider a system of N bosons in the mean-field scaling regime for a class of interactions including the repulsive Coulomb potential. We derive an asymptotic expansion of the low-energy eigenstates and the corresponding energies, which provides corrections to Bogoliubov theory to any order in 1/N. AU - Bossmann, Lea AU - Petrat, Sören P AU - Seiringer, Robert ID - 9318 JF - Forum of Mathematics, Sigma TI - Asymptotic expansion of low-energy excitations for weakly interacting bosons VL - 9 ER - TY - JOUR AB - Quantum entanglement has been generated and verified in cold-atom experiments and used to make atom-interferometric measurements below the shot-noise limit. However, current state-of-the-art cold-atom devices exploit separable (i.e., unentangled) atomic states. This perspective piece asks the question: can entanglement usefully improve cold-atom sensors, in the sense that it gives new sensing capabilities unachievable with current state-of-the-art devices? We briefly review the state-of-the-art in precision cold-atom sensing, focusing on clocks and inertial sensors, identifying the potential benefits entanglement could bring to these devices, and the challenges that need to be overcome to realize these benefits. We survey demonstrated methods of generating metrologically useful entanglement in cold-atom systems, note their relative strengths and weaknesses, and assess their prospects for near-to-medium term quantum-enhanced cold-atom sensing. AU - Szigeti, Stuart S. AU - Hosten, Onur AU - Haine, Simon A. ID - 9331 IS - 14 JF - Applied Physics Letters SN - 00036951 TI - Improving cold-atom sensors with quantum entanglement: Prospects and challenges VL - 118 ER - TY - JOUR AB - In nerve cells the genes encoding for α2δ subunits of voltage-gated calcium channels have been linked to synaptic functions and neurological disease. Here we show that α2δ subunits are essential for the formation and organization of glutamatergic synapses. Using a cellular α2δ subunit triple-knockout/knockdown model, we demonstrate a failure in presynaptic differentiation evidenced by defective presynaptic calcium channel clustering and calcium influx, smaller presynaptic active zones, and a strongly reduced accumulation of presynaptic vesicle-associated proteins (synapsin and vGLUT). The presynaptic defect is associated with the downscaling of postsynaptic AMPA receptors and the postsynaptic density. The role of α2δ isoforms as synaptic organizers is highly redundant, as each individual α2δ isoform can rescue presynaptic calcium channel trafficking and expression of synaptic proteins. Moreover, α2δ-2 and α2δ-3 with mutated metal ion-dependent adhesion sites can fully rescue presynaptic synapsin expression but only partially calcium channel trafficking, suggesting that the regulatory role of α2δ subunits is independent from its role as a calcium channel subunit. Our findings influence the current view on excitatory synapse formation. First, our study suggests that postsynaptic differentiation is secondary to presynaptic differentiation. Second, the dependence of presynaptic differentiation on α2δ implicates α2δ subunits as potential nucleation points for the organization of synapses. Finally, our results suggest that α2δ subunits act as transsynaptic organizers of glutamatergic synapses, thereby aligning the synaptic active zone with the postsynaptic density. AU - Schöpf, Clemens L. AU - Ablinger, Cornelia AU - Geisler, Stefanie M. AU - Stanika, Ruslan I. AU - Campiglio, Marta AU - Kaufmann, Walter AU - Nimmervoll, Benedikt AU - Schlick, Bettina AU - Brockhaus, Johannes AU - Missler, Markus AU - Shigemoto, Ryuichi AU - Obermair, Gerald J. ID - 9330 IS - 14 JF - PNAS TI - Presynaptic α2δ subunits are key organizers of glutamatergic synapses VL - 118 ER - TY - JOUR AB - Lateral root (LR) formation is an example of a plant post-embryonic organogenesis event. LRs are issued from non-dividing cells entering consecutive steps of formative divisions, proliferation and elongation. The chromatin remodeling protein PICKLE (PKL) negatively regulates auxin-mediated LR formation through a mechanism that is not yet known. Here we show that PKL interacts with RETINOBLASTOMA-RELATED 1 (RBR1) to repress the LATERAL ORGAN BOUNDARIES-DOMAIN 16 (LBD16) promoter activity. Since LBD16 function is required for the formative division of LR founder cells, repression mediated by the PKL–RBR1 complex negatively regulates formative division and LR formation. Inhibition of LR formation by PKL–RBR1 is counteracted by auxin, indicating that, in addition to auxin-mediated transcriptional responses, the fine-tuned process of LR formation is also controlled at the chromatin level in an auxin-signaling dependent manner. AU - Ötvös, Krisztina AU - Miskolczi, Pál AU - Marhavý, Peter AU - Cruz-Ramírez, Alfredo AU - Benková, Eva AU - Robert, Stéphanie AU - Bakó, László ID - 9332 IS - 8 JF - International Journal of Molecular Sciences SN - 1661-6596 TI - Pickle recruits retinoblastoma related 1 to control lateral root formation in arabidopsis VL - 22 ER - TY - JOUR AB - We revise a previous result about the Fröhlich dynamics in the strong coupling limit obtained in Griesemer (Rev Math Phys 29(10):1750030, 2017). In the latter it was shown that the Fröhlich time evolution applied to the initial state φ0⊗ξα, where φ0 is the electron ground state of the Pekar energy functional and ξα the associated coherent state of the phonons, can be approximated by a global phase for times small compared to α2. In the present note we prove that a similar approximation holds for t=O(α2) if one includes a nontrivial effective dynamics for the phonons that is generated by an operator proportional to α−2 and quadratic in creation and annihilation operators. Our result implies that the electron ground state remains close to its initial state for times of order α2, while the phonon fluctuations around the coherent state ξα can be described by a time-dependent Bogoliubov transformation. AU - Mitrouskas, David Johannes ID - 9333 JF - Letters in Mathematical Physics SN - 03779017 TI - A note on the Fröhlich dynamics in the strong coupling limit VL - 111 ER - TY - JOUR AB - Various degenerate diffusion equations exhibit a waiting time phenomenon: depending on the “flatness” of the compactly supported initial datum at the boundary of the support, the support of the solution may not expand for a certain amount of time. We show that this phenomenon is captured by particular Lagrangian discretizations of the porous medium and the thin film equations, and we obtain sufficient criteria for the occurrence of waiting times that are consistent with the known ones for the original PDEs. For the spatially discrete solution, the waiting time phenomenon refers to a deviation of the edge of support from its original position by a quantity comparable to the mesh width, over a mesh-independent time interval. Our proof is based on estimates on the fluid velocity in Lagrangian coordinates. Combining weighted entropy estimates with an iteration technique à la Stampacchia leads to upper bounds on free boundary propagation. Numerical simulations show that the phenomenon is already clearly visible for relatively coarse discretizations. AU - Fischer, Julian L AU - Matthes, Daniel ID - 9335 IS - 1 JF - SIAM Journal on Numerical Analysis SN - 0036-1429 TI - The waiting time phenomenon in spatially discretized porous medium and thin film equations VL - 59 ER - TY - JOUR AB - The way in which interactions between mechanics and biochemistry lead to the emergence of complex cell and tissue organization is an old question that has recently attracted renewed interest from biologists, physicists, mathematicians and computer scientists. Rapid advances in optical physics, microscopy and computational image analysis have greatly enhanced our ability to observe and quantify spatiotemporal patterns of signalling, force generation, deformation, and flow in living cells and tissues. Powerful new tools for genetic, biophysical and optogenetic manipulation are allowing us to perturb the underlying machinery that generates these patterns in increasingly sophisticated ways. Rapid advances in theory and computing have made it possible to construct predictive models that describe how cell and tissue organization and dynamics emerge from the local coupling of biochemistry and mechanics. Together, these advances have opened up a wealth of new opportunities to explore how mechanochemical patterning shapes organismal development. In this roadmap, we present a series of forward-looking case studies on mechanochemical patterning in development, written by scientists working at the interface between the physical and biological sciences, and covering a wide range of spatial and temporal scales, organisms, and modes of development. Together, these contributions highlight the many ways in which the dynamic coupling of mechanics and biochemistry shapes biological dynamics: from mechanoenzymes that sense force to tune their activity and motor output, to collectives of cells in tissues that flow and redistribute biochemical signals during development. AU - Lenne, Pierre François AU - Munro, Edwin AU - Heemskerk, Idse AU - Warmflash, Aryeh AU - Bocanegra, Laura AU - Kishi, Kasumi AU - Kicheva, Anna AU - Long, Yuchen AU - Fruleux, Antoine AU - Boudaoud, Arezki AU - Saunders, Timothy E. AU - Caldarelli, Paolo AU - Michaut, Arthur AU - Gros, Jerome AU - Maroudas-Sacks, Yonit AU - Keren, Kinneret AU - Hannezo, Edouard B AU - Gartner, Zev J. AU - Stormo, Benjamin AU - Gladfelter, Amy AU - Rodrigues, Alan AU - Shyer, Amy AU - Minc, Nicolas AU - Maître, Jean Léon AU - Di Talia, Stefano AU - Khamaisi, Bassma AU - Sprinzak, David AU - Tlili, Sham ID - 9349 IS - 4 JF - Physical biology TI - Roadmap for the multiscale coupling of biochemical and mechanical signals during development VL - 18 ER - TY - JOUR AB - Polaritons with directional in-plane propagation and ultralow losses in van der Waals (vdW) crystals promise unprecedented manipulation of light at the nanoscale. However, these polaritons present a crucial limitation: their directional propagation is intrinsically determined by the crystal structure of the host material, imposing forbidden directions of propagation. Here, we demonstrate that directional polaritons (in-plane hyperbolic phonon polaritons) in a vdW crystal (α-phase molybdenum trioxide) can be directed along forbidden directions by inducing an optical topological transition, which emerges when the slab is placed on a substrate with a given negative permittivity (4H–silicon carbide). By visualizing the transition in real space, we observe exotic polaritonic states between mutually orthogonal hyperbolic regimes, which unveil the topological origin of the transition: a gap opening in the dispersion. This work provides insights into optical topological transitions in vdW crystals, which introduce a route to direct light at the nanoscale. AU - Duan, J. AU - Álvarez-Pérez, G. AU - Voronin, K. V. AU - Prieto Gonzalez, Ivan AU - Taboada-Gutiérrez, J. AU - Volkov, V. S. AU - Martín-Sánchez, J. AU - Nikitin, A. Y. AU - Alonso-González, P. ID - 9334 IS - 14 JF - Science Advances TI - Enabling propagation of anisotropic polaritons along forbidden directions via a topological transition VL - 7 ER - TY - JOUR AB - We consider the many-body quantum evolution of a factorized initial data, in the mean-field regime. We show that fluctuations around the limiting Hartree dynamics satisfy large deviation estimates that are consistent with central limit theorems that have been established in the last years. AU - Kirkpatrick, Kay AU - Rademacher, Simone Anna Elvira AU - Schlein, Benjamin ID - 9351 JF - Annales Henri Poincare SN - 1424-0637 TI - A large deviation principle in many-body quantum dynamics VL - 22 ER - TY - JOUR AB - Mentorship is experience and/or knowledge‐based guidance. Mentors support, sponsor and advocate for mentees. Having one or more mentors when you seek advice can significantly influence and improve your research endeavours, well‐being and career development. Positive mentee–mentor relationships are vital for maintaining work–life balance and success in careers. Early‐career researchers (ECRs), in particular, can benefit from mentorship to navigate challenges in academic and nonacademic life and careers. Yet, strategies for selecting mentors and maintaining interactions with them are often underdiscussed within research environments. In this Words of Advice, we provide recommendations for ECRs to seek and manage mentorship interactions. Our article draws from our experiences as ECRs and published work, to provide suggestions for mentees to proactively promote beneficial mentorship interactions. The recommended practices highlight the importance of identifying mentorship needs, planning and selecting multiple and diverse mentors, setting goals, and maintaining constructive, and mutually beneficial working relationships with mentors. AU - Sarabipour, Sarvenaz AU - Hainer, Sarah J. AU - Arslan, Feyza N AU - De Winde, Charlotte M. AU - Furlong, Emily AU - Bielczyk, Natalia AU - Jadavji, Nafisa M. AU - Shah, Aparna P. AU - Davla, Sejal ID - 9336 JF - FEBS Journal SN - 1742-464X TI - Building and sustaining mentor interactions as a mentee ER - TY - JOUR AB - Intercellular adhesion is the key to multicellularity, and its malfunction plays an important role in various developmental and disease-related processes. Although it has been intensively studied by both biologists and physicists, a commonly accepted definition of cell-cell adhesion is still being debated. Cell-cell adhesion has been described at the molecular scale as a function of adhesion receptors controlling binding affinity, at the cellular scale as resistance to detachment forces or modulation of surface tension, and at the tissue scale as a regulator of cellular rearrangements and morphogenesis. In this review, we aim to summarize and discuss recent advances in the molecular, cellular, and theoretical description of cell-cell adhesion, ranging from biomimetic models to the complexity of cells and tissues in an organismal context. In particular, we will focus on cadherin-mediated cell-cell adhesion and the role of adhesion signaling and mechanosensation therein, two processes central for understanding the biological and physical basis of cell-cell adhesion. AU - Arslan, Feyza N AU - Eckert, Julia AU - Schmidt, Thomas AU - Heisenberg, Carl-Philipp J ID - 9350 JF - Biophysical Journal SN - 0006-3495 TI - Holding it together: when cadherin meets cadherin VL - 120 ER - TY - JOUR AB - We consider the stochastic quantization of a quartic double-well energy functional in the semiclassical regime and derive optimal asymptotics for the exponentially small splitting of the ground state energy. Our result provides an infinite-dimensional version of some sharp tunneling estimates known in finite dimensions for semiclassical Witten Laplacians in degree zero. From a stochastic point of view it proves that the L2 spectral gap of the stochastic one-dimensional Allen-Cahn equation in finite volume satisfies a Kramers-type formula in the limit of vanishing noise. We work with finite-dimensional lattice approximations and establish semiclassical estimates which are uniform in the dimension. Our key estimate shows that the constant separating the two exponentially small eigenvalues from the rest of the spectrum can be taken independently of the dimension. AU - Brooks, Morris AU - Di Gesù, Giacomo ID - 9348 IS - 3 JF - Journal of Functional Analysis SN - 0022-1236 TI - Sharp tunneling estimates for a double-well model in infinite dimension VL - 281 ER - TY - JOUR AB - This paper provides an a priori error analysis of a localized orthogonal decomposition method for the numerical stochastic homogenization of a model random diffusion problem. If the uniformly elliptic and bounded random coefficient field of the model problem is stationary and satisfies a quantitative decorrelation assumption in the form of the spectral gap inequality, then the expected $L^2$ error of the method can be estimated, up to logarithmic factors, by $H+(\varepsilon/H)^{d/2}$, $\varepsilon$ being the small correlation length of the random coefficient and $H$ the width of the coarse finite element mesh that determines the spatial resolution. The proof bridges recent results of numerical homogenization and quantitative stochastic homogenization. AU - Fischer, Julian L AU - Gallistl, Dietmar AU - Peterseim, Dietmar ID - 9352 IS - 2 JF - SIAM Journal on Numerical Analysis SN - 0036-1429 TI - A priori error analysis of a numerical stochastic homogenization method VL - 59 ER - TY - JOUR AB - Optogenetics has been harnessed to shed new mechanistic light on current and future therapeutic strategies. This has been to date achieved by the regulation of ion flow and electrical signals in neuronal cells and neural circuits that are known to be affected by disease. In contrast, the optogenetic delivery of trophic biochemical signals, which support cell survival and are implicated in degenerative disorders, has never been demonstrated in an animal model of disease. Here, we reengineered the human and Drosophila melanogaster REarranged during Transfection (hRET and dRET) receptors to be activated by light, creating one-component optogenetic tools termed Opto-hRET and Opto-dRET. Upon blue light stimulation, these receptors robustly induced the MAPK/ERK proliferative signaling pathway in cultured cells. In PINK1B9 flies that exhibit loss of PTEN-induced putative kinase 1 (PINK1), a kinase associated with familial Parkinson’s disease (PD), light activation of Opto-dRET suppressed mitochondrial defects, tissue degeneration and behavioral deficits. In human cells with PINK1 loss-of-function, mitochondrial fragmentation was rescued using Opto-dRET via the PI3K/NF-кB pathway. Our results demonstrate that a light-activated receptor can ameliorate disease hallmarks in a genetic model of PD. The optogenetic delivery of trophic signals is cell type-specific and reversible and thus has the potential to inspire novel strategies towards a spatio-temporal regulation of tissue repair. AU - Inglés Prieto, Álvaro AU - Furthmann, Nikolas AU - Crossman, Samuel H. AU - Tichy, Alexandra Madelaine AU - Hoyer, Nina AU - Petersen, Meike AU - Zheden, Vanessa AU - Bicher, Julia AU - Gschaider-Reichhart, Eva AU - György, Attila AU - Siekhaus, Daria E AU - Soba, Peter AU - Winklhofer, Konstanze F. AU - Janovjak, Harald L ID - 9363 IS - 4 JF - PLoS genetics TI - Optogenetic delivery of trophic signals in a genetic model of Parkinson's disease VL - 17 ER - TY - JOUR AB - Shigella are pathogens originating within the Escherichia lineage but frequently classified as a separate genus. Shigella genomes contain numerous insertion sequences (ISs) that lead to pseudogenisation of affected genes and an increase of non-homologous recombination. Here, we study 414 genomes of E. coli and Shigella strains to assess the contribution of genomic rearrangements to Shigella evolution. We found that Shigella experienced exceptionally high rates of intragenomic rearrangements and had a decreased rate of homologous recombination compared to pathogenic and non-pathogenic E. coli. The high rearrangement rate resulted in independent disruption of syntenic regions and parallel rearrangements in different Shigella lineages. Specifically, we identified two types of chromosomally encoded E3 ubiquitin-protein ligases acquired independently by all Shigella strains that also showed a high level of sequence conservation in the promoter and further in the 5′-intergenic region. In the only available enteroinvasive E. coli (EIEC) strain, which is a pathogenic E. coli with a phenotype intermediate between Shigella and non-pathogenic E. coli, we found a rate of genome rearrangements comparable to those in other E. coli and no functional copies of the two Shigella-specific E3 ubiquitin ligases. These data indicate that the accumulation of ISs influenced many aspects of genome evolution and played an important role in the evolution of intracellular pathogens. Our research demonstrates the power of comparative genomics-based on synteny block composition and an important role of non-coding regions in the evolution of genomic islands. AU - Seferbekova, Zaira AU - Zabelkin, Alexey AU - Yakovleva, Yulia AU - Afasizhev, Robert AU - Dranenko, Natalia O. AU - Alexeev, Nikita AU - Gelfand, Mikhail S. AU - Bochkareva, Olga ID - 9380 JF - Frontiers in Microbiology TI - High rates of genome rearrangements and pathogenicity of Shigella spp VL - 12 ER - TY - JOUR AB - We prove that the factorization homologies of a scheme with coefficients in truncated polynomial algebras compute the cohomologies of its generalized configuration spaces. Using Koszul duality between commutative algebras and Lie algebras, we obtain new expressions for the cohomologies of the latter. As a consequence, we obtain a uniform and conceptual approach for treating homological stability, homological densities, and arithmetic densities of generalized configuration spaces. Our results categorify, generalize, and in fact provide a conceptual understanding of the coincidences appearing in the work of Farb--Wolfson--Wood. Our computation of the stable homological densities also yields rational homotopy types, answering a question posed by Vakil--Wood. Our approach hinges on the study of homological stability of cohomological Chevalley complexes, which is of independent interest. AU - Ho, Quoc P ID - 9359 IS - 2 JF - Geometry & Topology KW - Generalized configuration spaces KW - homological stability KW - homological densities KW - chiral algebras KW - chiral homology KW - factorization algebras KW - Koszul duality KW - Ran space SN - 1364-0380 TI - Homological stability and densities of generalized configuration spaces VL - 25 ER - TY - JOUR AB - The multimeric matrix (M) protein of clinically relevant paramyxoviruses orchestrates assembly and budding activity of viral particles at the plasma membrane (PM). We identified within the canine distemper virus (CDV) M protein two microdomains, potentially assuming α-helix structures, which are essential for membrane budding activity. Remarkably, while two rationally designed microdomain M mutants (E89R, microdomain 1 and L239D, microdomain 2) preserved proper folding, dimerization, interaction with the nucleocapsid protein, localization at and deformation of the PM, the virus-like particle formation, as well as production of infectious virions (as monitored using a membrane budding-complementation system), were, in sharp contrast, strongly impaired. Of major importance, raster image correlation spectroscopy (RICS) revealed that both microdomains contributed to finely tune M protein mobility specifically at the PM. Collectively, our data highlighted the cornerstone membrane budding-priming activity of two spatially discrete M microdomains, potentially by coordinating the assembly of productive higher oligomers at the PM. AU - Gast, Matthieu AU - Kadzioch, Nicole P. AU - Milius, Doreen AU - Origgi, Francesco AU - Plattet, Philippe ID - 9361 IS - 2 JF - mSphere TI - Oligomerization and cell egress controlled by two microdomains of canine distemper virus matrix protein VL - 6 ER - TY - JOUR AB - This paper presents a method for designing planar multistable compliant structures. Given a sequence of desired stable states and the corresponding poses of the structure, we identify the topology and geometric realization of a mechanism—consisting of bars and joints—that is able to physically reproduce the desired multistable behavior. In order to solve this problem efficiently, we build on insights from minimally rigid graph theory to identify simple but effective topologies for the mechanism. We then optimize its geometric parameters, such as joint positions and bar lengths, to obtain correct transitions between the given poses. Simultaneously, we ensure adequate stability of each pose based on an effective approximate error metric related to the elastic energy Hessian of the bars in the mechanism. As demonstrated by our results, we obtain functional multistable mechanisms of manageable complexity that can be fabricated using 3D printing. Further, we evaluated the effectiveness of our method on a large number of examples in the simulation and fabricated several physical prototypes. AU - Zhang, Ran AU - Auzinger, Thomas AU - Bickel, Bernd ID - 9376 IS - 5 JF - ACM Transactions on Graphics KW - multistability KW - mechanism KW - computational design KW - rigidity SN - 0730-0301 TI - Computational design of planar multistable compliant structures VL - 40 ER - TY - JOUR AB - Genetic variation segregates as linked sets of variants, or haplotypes. Haplotypes and linkage are central to genetics and underpin virtually all genetic and selection analysis. And yet, genomic data often lack haplotype information, due to constraints in sequencing technologies. Here we present “haplotagging”, a simple, low-cost linked-read sequencing technique that allows sequencing of hundreds of individuals while retaining linkage information. We apply haplotagging to construct megabase-size haplotypes for over 600 individual butterflies (Heliconius erato and H. melpomene), which form overlapping hybrid zones across an elevational gradient in Ecuador. Haplotagging identifies loci controlling distinctive high- and lowland wing color patterns. Divergent haplotypes are found at the same major loci in both species, while chromosome rearrangements show no parallelism. Remarkably, in both species the geographic clines for the major wing pattern loci are displaced by 18 km, leading to the rise of a novel hybrid morph in the centre of the hybrid zone. We propose that shared warning signalling (Müllerian mimicry) may couple the cline shifts seen in both species, and facilitate the parallel co-emergence of a novel hybrid morph in both co-mimetic species. Our results show the power of efficient haplotyping methods when combined with large-scale sequencing data from natural populations. AU - Meier, Joana I. AU - Salazar, Patricio A. AU - Kučka, Marek AU - Davies, Robert William AU - Dréau, Andreea AU - Aldás, Ismael AU - Power, Olivia Box AU - Nadeau, Nicola J. AU - Bridle, Jon R. AU - Rolian, Campbell AU - Barton, Nicholas H AU - McMillan, W. Owen AU - Jiggins, Chris D. AU - Chan, Yingguang Frank ID - 9375 IS - 25 JF - PNAS TI - Haplotype tagging reveals parallel formation of hybrid races in two butterfly species VL - 118 ER - TY - JOUR AB - Chromosomal inversions have long been recognized for their role in local adaptation. By suppressing recombination in heterozygous individuals, they can maintain coadapted gene complexes and protect them from homogenizing effects of gene flow. However, to fully understand their importance for local adaptation we need to know their influence on phenotypes under divergent selection. For this, the marine snail Littorina saxatilis provides an ideal study system. Divergent ecotypes adapted to wave action and crab predation occur in close proximity on intertidal shores with gene flow between them. Here, we used F2 individuals obtained from crosses between the ecotypes to test for associations between genomic regions and traits distinguishing the Crab‐/Wave‐adapted ecotypes including size, shape, shell thickness, and behavior. We show that most of these traits are influenced by two previously detected inversion regions that are divergent between ecotypes. We thus gain a better understanding of one important underlying mechanism responsible for the rapid and repeated formation of ecotypes: divergent selection acting on inversions. We also found that some inversions contributed to more than one trait suggesting that they may contain several loci involved in adaptation, consistent with the hypothesis that suppression of recombination within inversions facilitates differentiation in the presence of gene flow. AU - Koch, Eva L. AU - Morales, Hernán E. AU - Larsson, Jenny AU - Westram, Anja M AU - Faria, Rui AU - Lemmon, Alan R. AU - Lemmon, E. Moriarty AU - Johannesson, Kerstin AU - Butlin, Roger K. ID - 9394 IS - 3 JF - Evolution Letters TI - Genetic variation for adaptive traits is associated with polymorphic inversions in Littorina saxatilis VL - 5 ER - TY - JOUR AB - A game of rock-paper-scissors is an interesting example of an interaction where none of the pure strategies strictly dominates all others, leading to a cyclic pattern. In this work, we consider an unstable version of rock-paper-scissors dynamics and allow individuals to make behavioural mistakes during the strategy execution. We show that such an assumption can break a cyclic relationship leading to a stable equilibrium emerging with only one strategy surviving. We consider two cases: completely random mistakes when individuals have no bias towards any strategy and a general form of mistakes. Then, we determine conditions for a strategy to dominate all other strategies. However, given that individuals who adopt a dominating strategy are still prone to behavioural mistakes in the observed behaviour, we may still observe extinct strategies. That is, behavioural mistakes in strategy execution stabilise evolutionary dynamics leading to an evolutionary stable and, potentially, mixed co-existence equilibrium. AU - Kleshnina, Maria AU - Streipert, Sabrina S. AU - Filar, Jerzy A. AU - Chatterjee, Krishnendu ID - 9381 IS - 4 JF - PLoS Computational Biology SN - 1553734X TI - Mistakes can stabilise the dynamics of rock-paper-scissors games VL - 17 ER - TY - JOUR AB - Humans conceptualize the diversity of life by classifying individuals into types we call ‘species’1. The species we recognize influence political and financial decisions and guide our understanding of how units of diversity evolve and interact. Although the idea of species may seem intuitive, a debate about the best way to define them has raged even before Darwin2. So much energy has been devoted to the so-called ‘species problem’ that no amount of discourse will ever likely solve it2,3. Dozens of species concepts are currently recognized3, but we lack a concrete understanding of how much researchers actually disagree and the factors that cause them to think differently1,2. To address this, we used a survey to quantify the species problem for the first time. The results indicate that the disagreement is extensive: two randomly chosen respondents will most likely disagree on the nature of species. The probability of disagreement is not predicted by researcher experience or broad study system, but tended to be lower among researchers with similar focus, training and who study the same organism. Should we see this diversity of perspectives as a problem? We argue that we should not. AU - Stankowski, Sean AU - Ravinet, Mark ID - 9392 IS - 9 JF - Current Biology SN - 09609822 TI - Quantifying the use of species concepts VL - 31 ER - TY - JOUR AB - We report the complete analysis of a deterministic model of deleterious mutations and negative selection against them at two haploid loci without recombination. As long as mutation is a weaker force than selection, mutant alleles remain rare at the only stable equilibrium, and otherwise, a variety of dynamics are possible. If the mutation-free genotype is absent, generally the only stable equilibrium is the one that corresponds to fixation of the mutant allele at the locus where it is less deleterious. This result suggests that fixation of a deleterious allele that follows a click of the Muller’s ratchet is governed by natural selection, instead of random drift. AU - Khudiakova, Kseniia AU - Neretina, Tatiana Yu. AU - Kondrashov, Alexey S. ID - 9387 JF - Journal of Theoretical Biology KW - General Biochemistry KW - Genetics and Molecular Biology KW - Modelling and Simulation KW - Statistics and Probability KW - General Immunology and Microbiology KW - Applied Mathematics KW - General Agricultural and Biological Sciences KW - General Medicine SN - 0022-5193 TI - Two linked loci under mutation-selection balance and Muller’s ratchet VL - 524 ER -