@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}, }