@article{9243, abstract = {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.}, author = {Hernández-Rocamora, Víctor M. and Baranova, Natalia S. and Peters, Katharina and Breukink, Eefjan and Loose, Martin and Vollmer, Waldemar}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Real time monitoring of peptidoglycan synthesis by membrane-reconstituted penicillin binding proteins}}, doi = {10.7554/eLife.61525}, volume = {10}, year = {2021}, } @article{9246, abstract = {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.}, author = {Leopold, Nikolai K and Mitrouskas, David Johannes and Seiringer, Robert}, issn = {14320673}, journal = {Archive for Rational Mechanics and Analysis}, pages = {383--417}, publisher = {Springer Nature}, title = {{Derivation of the Landau–Pekar equations in a many-body mean-field limit}}, doi = {10.1007/s00205-021-01616-9}, volume = {240}, year = {2021}, } @article{9256, abstract = {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.}, author = {Napiórkowski, Marcin M and Seiringer, Robert}, issn = {15730530}, journal = {Letters in Mathematical Physics}, number = {2}, publisher = {Springer Nature}, title = {{Free energy asymptotics of the quantum Heisenberg spin chain}}, doi = {10.1007/s11005-021-01375-4}, volume = {111}, year = {2021}, } @article{9242, abstract = {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.}, author = {Rueda Sanchez, Alfredo R}, issn = {2469-9934}, journal = {Physical Review A}, number = {2}, publisher = {American Physical Society}, title = {{Frequency-multiplexed hybrid optical entangled source based on the Pockels effect}}, doi = {10.1103/PhysRevA.103.023708}, volume = {103}, year = {2021}, } @article{9257, abstract = {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.}, author = {Goodrich, Carl Peter and King, Ella M. and Schoenholz, Samuel S. and Cubuk, Ekin D. and Brenner, Michael P.}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {10}, publisher = {National Academy of Sciences}, title = {{Designing self-assembling kinetics with differentiable statistical physics models}}, doi = {10.1073/pnas.2024083118}, volume = {118}, year = {2021}, } @article{9262, abstract = {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.}, author = {Mbianda, Johanne and Bakail, May M and André, Christophe and Moal, Gwenaëlle and Perrin, Marie E. and Pinna, Guillaume and Guerois, Raphaël and Becher, Francois and Legrand, Pierre and Traoré, Seydou and Douat, Céline and Guichard, Gilles and Ochsenbein, Françoise}, issn = {2375-2548}, journal = {Science Advances}, number = {12}, publisher = {American Association for the Advancement of Science}, title = {{Optimal anchoring of a foldamer inhibitor of ASF1 histone chaperone through backbone plasticity}}, doi = {10.1126/sciadv.abd9153}, volume = {7}, year = {2021}, } @article{9259, abstract = {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.}, author = {Vaahtomeri, Kari and Moussion, Christine and Hauschild, Robert and Sixt, Michael K}, issn = {1664-3224}, journal = {Frontiers in Immunology}, publisher = {Frontiers}, title = {{Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium}}, doi = {10.3389/fimmu.2021.630002}, volume = {12}, year = {2021}, } @article{9254, abstract = {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.}, author = {Hu, Yangjie and Omary, Moutasem and Hu, Yun and Doron, Ohad and Hörmayer, Lukas and Chen, Qingguo and Megides, Or and Chekli, Ori and Ding, Zhaojun and Friml, Jiří and Zhao, Yunde and Tsarfaty, Ilan and Shani, Eilon}, issn = {20411723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Cell kinetics of auxin transport and activity in Arabidopsis root growth and skewing}}, doi = {10.1038/s41467-021-21802-3}, volume = {12}, year = {2021}, } @article{9255, abstract = {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.}, author = {Pivoluska, Matej and Plesch, Martin and Farkas, Máté and Ruzickova, Natalia and Flegel, Clara and Valencia, Natalia Herrera and Mccutcheon, Will and Malik, Mehul and Aguilar, Edgar A.}, issn = {2056-6387}, journal = {npj Quantum Information}, publisher = {Springer Nature}, title = {{Semi-device-independent random number generation with flexible assumptions}}, doi = {10.1038/s41534-021-00387-1}, volume = {7}, year = {2021}, } @article{9260, abstract = {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.}, author = {Browning, Timothy D and Yamagishi, Shuntaro}, issn = {1432-1823}, journal = {Mathematische Zeitschrift}, pages = {1071–1101}, publisher = {Springer Nature}, title = {{Arithmetic of higher-dimensional orbifolds and a mixed Waring problem}}, doi = {10.1007/s00209-021-02695-w}, volume = {299}, year = {2021}, } @article{9258, author = {Pinkard, Henry and Stuurman, Nico and Ivanov, Ivan E. and Anthony, Nicholas M. and Ouyang, Wei and Li, Bin and Yang, Bin and Tsuchida, Mark A. and Chhun, Bryant and Zhang, Grace and Mei, Ryan and Anderson, Michael and Shepherd, Douglas P. and Hunt-Isaak, Ian and Dunn, Raymond L. and Jahr, Wiebke and Kato, Saul and Royer, Loïc A. and Thiagarajah, Jay R. and Eliceiri, Kevin W. and Lundberg, Emma and Mehta, Shalin B. and Waller, Laura}, issn = {1548-7105}, journal = {Nature Methods}, number = {3}, pages = {226--228}, publisher = {Springer Nature}, title = {{Pycro-Manager: Open-source software for customized and reproducible microscope control}}, doi = {10.1038/s41592-021-01087-6}, volume = {18}, year = {2021}, } @article{9306, abstract = {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.}, author = {Dobramysl, Ulrich and Jarsch, Iris Katharina and Inoue, Yoshiko and Shimo, Hanae and Richier, Benjamin and Gadsby, Jonathan R. and Mason, Julia and Szałapak, Alicja and Ioannou, Pantelis Savvas and Correia, Guilherme Pereira and Walrant, Astrid and Butler, Richard and Hannezo, Edouard B and Simons, Benjamin D. and Gallop, Jennifer L.}, issn = {15408140}, journal = {Journal of Cell Biology}, number = {4}, publisher = {Rockefeller University Press}, title = {{Stochastic combinations of actin regulatory proteins are sufficient to drive filopodia formation}}, doi = {10.1083/jcb.202003052}, volume = {220}, year = {2021}, } @article{9307, abstract = {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.}, author = {Hensel, Sebastian}, issn = {2194-041X}, journal = {Stochastics and Partial Differential Equations: Analysis and Computations}, pages = {892–939}, publisher = {Springer Nature}, title = {{Finite time extinction for the 1D stochastic porous medium equation with transport noise}}, doi = {10.1007/s40072-021-00188-9}, volume = {9}, year = {2021}, } @article{9297, abstract = {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.}, author = {Liu, T. and Semin, B. and Klotz, Lukasz and Godoy-Diana, R. and Wesfreid, J. E. and Mullin, T.}, issn = {1469-7645}, journal = {Journal of Fluid Mechanics}, publisher = {Cambridge University Press}, title = {{Decay of streaks and rolls in plane Couette-Poiseuille flow}}, doi = {10.1017/jfm.2021.89}, volume = {915}, year = {2021}, } @article{9295, abstract = {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.}, author = {Arroyo Guevara, Alan M and Mcquillan, Dan and Richter, R. Bruce and Salazar, Gelasio and Sullivan, Matthew}, issn = {1097-0118}, journal = {Journal of Graph Theory}, number = {3}, pages = {426--440}, publisher = {Wiley}, title = {{Drawings of complete graphs in the projective plane}}, doi = {10.1002/jgt.22665}, volume = {97}, year = {2021}, } @article{9294, abstract = {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.}, author = {Gärtner, Florian R and Sixt, Michael K}, issn = {18781551}, journal = {Developmental Cell}, number = {6}, pages = {723--725}, publisher = {Elsevier}, title = {{Engaging the front wheels to drive through fibrous terrain}}, doi = {10.1016/j.devcel.2021.03.002}, volume = {56}, year = {2021}, } @article{9329, abstract = {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.}, author = {Zhang, Xiaomin and Schlögl, Alois and Vandael, David H and Jonas, Peter M}, issn = {1872-678X}, journal = {Journal of Neuroscience Methods}, number = {6}, publisher = {Elsevier}, title = {{MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo}}, doi = {10.1016/j.jneumeth.2021.109125}, volume = {357}, year = {2021}, } @article{9316, abstract = {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.}, author = {Petridou, Nicoletta and Corominas-Murtra, Bernat and Heisenberg, Carl-Philipp J and Hannezo, Edouard B}, issn = {10974172}, journal = {Cell}, number = {7}, pages = {1914--1928.e19}, publisher = {Elsevier}, title = {{Rigidity percolation uncovers a structural basis for embryonic tissue phase transitions}}, doi = {10.1016/j.cell.2021.02.017}, volume = {184}, year = {2021}, } @article{9317, abstract = {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.}, author = {Edelsbrunner, Herbert and Osang, Georg F}, issn = {1432-0444}, journal = {Discrete and Computational Geometry}, pages = {1296–1313}, publisher = {Springer Nature}, title = {{The multi-cover persistence of Euclidean balls}}, doi = {10.1007/s00454-021-00281-9}, volume = {65}, year = {2021}, } @article{9318, abstract = {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.}, author = {Bossmann, Lea and Petrat, Sören P and Seiringer, Robert}, issn = {20505094}, journal = {Forum of Mathematics, Sigma}, publisher = {Cambridge University Press}, title = {{Asymptotic expansion of low-energy excitations for weakly interacting bosons}}, doi = {10.1017/fms.2021.22}, volume = {9}, year = {2021}, }