@article{9392, abstract = {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.}, author = {Stankowski, Sean and Ravinet, Mark}, issn = {18790445}, journal = {Current Biology}, number = {9}, pages = {R428--R429}, publisher = {Cell Press}, title = {{Quantifying the use of species concepts}}, doi = {10.1016/j.cub.2021.03.060}, volume = {31}, year = {2021}, } @article{9387, abstract = {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.}, author = {Khudiakova, Kseniia and Neretina, Tatiana Yu. and Kondrashov, Alexey S.}, issn = {0022-5193}, journal = {Journal of Theoretical Biology}, keywords = {General Biochemistry, Genetics and Molecular Biology, Modelling and Simulation, Statistics and Probability, General Immunology and Microbiology, Applied Mathematics, General Agricultural and Biological Sciences, General Medicine}, publisher = {Elsevier }, title = {{Two linked loci under mutation-selection balance and Muller’s ratchet}}, doi = {10.1016/j.jtbi.2021.110729}, volume = {524}, year = {2021}, } @misc{12987, abstract = {Chromosomal inversion polymorphisms, segments of chromosomes that are flipped in orientation and occur in reversed order in some individuals, have long been recognized to play an important role in local adaptation. They can reduce recombination in heterozygous individuals and thus help to maintain sets of locally adapted alleles. In a wide range of organisms, populations adapted to different habitats differ in frequency of inversion arrangements. However, getting a full understanding of the importance of inversions for adaptation requires confirmation of their influence on traits under divergent selection. Here, we studied a marine snail, Littorina saxatilis, that has evolved ecotypes adapted to wave exposure or crab predation. These two types occur in close proximity on different parts of the shore. Gene flow between them exists in contact zones. However, they exhibit strong phenotypic divergence in several traits under habitat-specific selection, including size, shape and behaviour. We used crosses between these ecotypes to identify genomic regions that explain variation in these traits by using QTL analysis and variance partitioning across linkage groups. We could show that previously detected inversion regions contribute to adaptive divergence. Some inversions influenced multiple traits suggesting that they contain sets of locally adaptive alleles. Our study also identified regions without known inversions that are important for phenotypic divergence. Thus, we provide a more complete overview of the importance of inversions in relation to the remaining genome.}, author = {Koch, Eva and Morales, Hernán E. and Larsson, Jenny and Westram, Anja M and Faria, Rui and Lemmon, Alan R. and Lemmon, E. Moriarty and Johannesson, Kerstin and Butlin, Roger K.}, publisher = {Dryad}, title = {{Data from: Genetic variation for adaptive traits is associated with polymorphic inversions in Littorina saxatilis}}, doi = {10.5061/DRYAD.ZGMSBCCB4}, year = {2021}, } @article{9408, abstract = {We present a computational design system that assists users to model, optimize, and fabricate quad-robots with soft skins. Our system addresses the challenging task of predicting their physical behavior by fully integrating the multibody dynamics of the mechanical skeleton and the elastic behavior of the soft skin. The developed motion control strategy uses an alternating optimization scheme to avoid expensive full space time-optimization, interleaving space-time optimization for the skeleton, and frame-by-frame optimization for the full dynamics. The output are motor torques to drive the robot to achieve a user prescribed motion trajectory. We also provide a collection of convenient engineering tools and empirical manufacturing guidance to support the fabrication of the designed quad-robot. We validate the feasibility of designs generated with our system through physics simulations and with a physically-fabricated prototype.}, author = {Feng, Xudong and Liu, Jiafeng and Wang, Huamin and Yang, Yin and Bao, Hujun and Bickel, Bernd and Xu, Weiwei}, issn = {10772626}, journal = {IEEE Transactions on Visualization and Computer Graphics}, number = {6}, publisher = {IEEE}, title = {{Computational design of skinned Quad-Robots}}, doi = {10.1109/TVCG.2019.2957218}, volume = {27}, year = {2021}, } @article{9410, abstract = {Antibiotic concentrations vary dramatically in the body and the environment. Hence, understanding the dynamics of resistance evolution along antibiotic concentration gradients is critical for predicting and slowing the emergence and spread of resistance. While it has been shown that increasing the concentration of an antibiotic slows resistance evolution, how adaptation to one antibiotic concentration correlates with fitness at other points along the gradient has not received much attention. Here, we selected populations of Escherichia coli at several points along a concentration gradient for three different antibiotics, asking how rapidly resistance evolved and whether populations became specialized to the antibiotic concentration they were selected on. Populations selected at higher concentrations evolved resistance more slowly but exhibited equal or higher fitness across the whole gradient. Populations selected at lower concentrations evolved resistance rapidly, but overall fitness in the presence of antibiotics was lower. However, these populations readily adapted to higher concentrations upon subsequent selection. Our results indicate that resistance management strategies must account not only for the rates of resistance evolution but also for the fitness of evolved strains.}, author = {Lagator, Mato and Uecker, Hildegard and Neve, Paul}, issn = {1744957X}, journal = {Biology letters}, number = {5}, publisher = {Royal Society of London}, title = {{Adaptation at different points along antibiotic concentration gradients}}, doi = {10.1098/rsbl.2020.0913}, volume = {17}, year = {2021}, } @article{9412, abstract = {We extend our recent result [22] on the central limit theorem for the linear eigenvalue statistics of non-Hermitian matrices X with independent, identically distributed complex entries to the real symmetry class. We find that the expectation and variance substantially differ from their complex counterparts, reflecting (i) the special spectral symmetry of real matrices onto the real axis; and (ii) the fact that real i.i.d. matrices have many real eigenvalues. Our result generalizes the previously known special cases where either the test function is analytic [49] or the first four moments of the matrix elements match the real Gaussian [59, 44]. The key element of the proof is the analysis of several weakly dependent Dyson Brownian motions (DBMs). The conceptual novelty of the real case compared with [22] is that the correlation structure of the stochastic differentials in each individual DBM is non-trivial, potentially even jeopardising its well-posedness.}, author = {Cipolloni, Giorgio and Erdös, László and Schröder, Dominik J}, issn = {10836489}, journal = {Electronic Journal of Probability}, publisher = {Institute of Mathematical Statistics}, title = {{Fluctuation around the circular law for random matrices with real entries}}, doi = {10.1214/21-EJP591}, volume = {26}, year = {2021}, } @article{9407, abstract = {High impact epidemics constitute one of the largest threats humanity is facing in the 21st century. In the absence of pharmaceutical interventions, physical distancing together with testing, contact tracing and quarantining are crucial in slowing down epidemic dynamics. Yet, here we show that if testing capacities are limited, containment may fail dramatically because such combined countermeasures drastically change the rules of the epidemic transition: Instead of continuous, the response to countermeasures becomes discontinuous. Rather than following the conventional exponential growth, the outbreak that is initially strongly suppressed eventually accelerates and scales faster than exponential during an explosive growth period. As a consequence, containment measures either suffice to stop the outbreak at low total case numbers or fail catastrophically if marginally too weak, thus implying large uncertainties in reliably estimating overall epidemic dynamics, both during initial phases and during second wave scenarios.}, author = {Scarselli, Davide and Budanur, Nazmi B and Timme, Marc and Hof, Björn}, issn = {20411723}, journal = {Nature Communications}, number = {1}, publisher = {Springer Nature}, title = {{Discontinuous epidemic transition due to limited testing}}, doi = {10.1038/s41467-021-22725-9}, volume = {12}, year = {2021}, } @article{9411, abstract = {The dynamics of a triangular magnetocapillary swimmer is studied using the lattice Boltzmann method. We extend on our previous work, which deals with the self-assembly and a specific type of the swimmer motion characterized by the swimmer’s maximum velocity centred around the particle’s inverse viscous time. Here, we identify additional regimes of motion. First, modifying the ratio of surface tension and magnetic forces allows to study the swimmer propagation in the regime of significantly lower frequencies mainly defined by the strength of the magnetocapillary potential. Second, introducing a constant magnetic contribution in each of the particles in addition to their magnetic moment induced by external fields leads to another regime characterized by strong in-plane swimmer reorientations that resemble experimental observations.}, author = {Sukhov, Alexander and Hubert, Maxime and Grosjean, Galien M and Trosman, Oleg and Ziegler, Sebastian and Collard, Ylona and Vandewalle, Nicolas and Smith, Ana Sunčana and Harting, Jens}, issn = {1292895X}, journal = {European Physical Journal E}, number = {4}, publisher = {Springer}, title = {{Regimes of motion of magnetocapillary swimmers}}, doi = {10.1140/epje/s10189-021-00065-2}, volume = {44}, year = {2021}, } @article{9414, abstract = {Microtubule plus-end depolymerization rate is a potentially important target of physiological regulation, but it has been challenging to measure, so its role in spatial organization is poorly understood. Here we apply a method for tracking plus ends based on time difference imaging to measure depolymerization rates in large interphase asters growing in Xenopus egg extract. We observed strong spatial regulation of depolymerization rates, which were higher in the aster interior compared with the periphery, and much less regulation of polymerization or catastrophe rates. We interpret these data in terms of a limiting component model, where aster growth results in lower levels of soluble tubulin and microtubule-associated proteins (MAPs) in the interior cytosol compared with that at the periphery. The steady-state polymer fraction of tubulin was ∼30%, so tubulin is not strongly depleted in the aster interior. We propose that the limiting component for microtubule assembly is a MAP that inhibits depolymerization, and that egg asters are tuned to low microtubule density.}, author = {Ishihara, Keisuke and Decker, Franziska and Dos Santos Caldas, Paulo R and Pelletier, James F. and Loose, Martin and Brugués, Jan and Mitchison, Timothy J.}, issn = {1939-4586}, journal = {Molecular Biology of the Cell}, number = {9}, pages = {869--879}, publisher = {American Society for Cell Biology}, title = {{Spatial variation of microtubule depolymerization in large asters}}, doi = {10.1091/MBC.E20-11-0723}, volume = {32}, year = {2021}, } @inproceedings{9356, abstract = {In runtime verification, a monitor watches a trace of a system and, if possible, decides after observing each finite prefix whether or not the unknown infinite trace satisfies a given specification. We generalize the theory of runtime verification to monitors that attempt to estimate numerical values of quantitative trace properties (instead of attempting to conclude boolean values of trace specifications), such as maximal or average response time along a trace. Quantitative monitors are approximate: with every finite prefix, they can improve their estimate of the infinite trace's unknown property value. Consequently, quantitative monitors can be compared with regard to a precision-cost trade-off: better approximations of the property value require more monitor resources, such as states (in the case of finite-state monitors) or registers, and additional resources yield better approximations. We introduce a formal framework for quantitative and approximate monitoring, show how it conservatively generalizes the classical boolean setting for monitoring, and give several precision-cost trade-offs for monitors. For example, we prove that there are quantitative properties for which every additional register improves monitoring precision.}, author = {Henzinger, Thomas A and Sarac, Naci E}, booktitle = {Proceedings of the 36th Annual ACM/IEEE Symposium on Logic in Computer Science}, location = {Online}, publisher = {Institute of Electrical and Electronics Engineers}, title = {{Quantitative and approximate monitoring}}, doi = {10.1109/LICS52264.2021.9470547}, year = {2021}, } @article{9439, abstract = {The ability to adapt to changes in stimulus statistics is a hallmark of sensory systems. Here, we developed a theoretical framework that can account for the dynamics of adaptation from an information processing perspective. We use this framework to optimize and analyze adaptive sensory codes, and we show that codes optimized for stationary environments can suffer from prolonged periods of poor performance when the environment changes. To mitigate the adversarial effects of these environmental changes, sensory systems must navigate tradeoffs between the ability to accurately encode incoming stimuli and the ability to rapidly detect and adapt to changes in the distribution of these stimuli. We derive families of codes that balance these objectives, and we demonstrate their close match to experimentally observed neural dynamics during mean and variance adaptation. Our results provide a unifying perspective on adaptation across a range of sensory systems, environments, and sensory tasks.}, author = {Mlynarski, Wiktor F and Hermundstad, Ann M.}, issn = {1546-1726}, journal = {Nature Neuroscience}, pages = {998--1009}, publisher = {Springer Nature}, title = {{Efficient and adaptive sensory codes}}, doi = {10.1038/s41593-021-00846-0}, volume = {24}, year = {2021}, } @article{9443, abstract = {Endoplasmic reticulum–plasma membrane contact sites (ER–PM CS) play fundamental roles in all eukaryotic cells. Arabidopsis thaliana mutants lacking the ER–PM protein tether synaptotagmin1 (SYT1) exhibit decreased PM integrity under multiple abiotic stresses, such as freezing, high salt, osmotic stress, and mechanical damage. Here, we show that, together with SYT1, the stress-induced SYT3 is an ER–PM tether that also functions in maintaining PM integrity. The ER–PM CS localization of SYT1 and SYT3 is dependent on PM phosphatidylinositol-4-phosphate and is regulated by abiotic stress. Lipidomic analysis revealed that cold stress increased the accumulation of diacylglycerol at the PM in a syt1/3 double mutant relative to wild-type while the levels of most glycerolipid species remain unchanged. In addition, the SYT1-green fluorescent protein fusion preferentially binds diacylglycerol in vivo with little affinity for polar glycerolipids. Our work uncovers a SYT-dependent mechanism of stress adaptation counteracting the detrimental accumulation of diacylglycerol at the PM produced during episodes of abiotic stress.}, author = {Ruiz-Lopez, N and Pérez-Sancho, J and Esteban Del Valle, A and Haslam, RP and Vanneste, S and Catalá, R and Perea-Resa, C and Van Damme, D and García-Hernández, S and Albert, A and Vallarino, J and Lin, J and Friml, Jiří and Macho, AP and Salinas, J and Rosado, A and Napier, JA and Amorim-Silva, V and Botella, MA}, issn = {1532-298x}, journal = {Plant Cell}, number = {7}, pages = {2431--2453}, publisher = {American Society of Plant Biologists}, title = {{Synaptotagmins at the endoplasmic reticulum-plasma membrane contact sites maintain diacylglycerol homeostasis during abiotic stress}}, doi = {10.1093/plcell/koab122}, volume = {33}, year = {2021}, } @article{9431, abstract = {Inositol hexakisphosphate (IP6) is an assembly cofactor for HIV-1. We report here that IP6 is also used for assembly of Rous sarcoma virus (RSV), a retrovirus from a different genus. IP6 is ~100-fold more potent at promoting RSV mature capsid protein (CA) assembly than observed for HIV-1 and removal of IP6 in cells reduces infectivity by 100-fold. Here, visualized by cryo-electron tomography and subtomogram averaging, mature capsid-like particles show an IP6-like density in the CA hexamer, coordinated by rings of six lysines and six arginines. Phosphate and IP6 have opposing effects on CA in vitro assembly, inducing formation of T = 1 icosahedrons and tubes, respectively, implying that phosphate promotes pentamer and IP6 hexamer formation. Subtomogram averaging and classification optimized for analysis of pleomorphic retrovirus particles reveal that the heterogeneity of mature RSV CA polyhedrons results from an unexpected, intrinsic CA hexamer flexibility. In contrast, the CA pentamer forms rigid units organizing the local architecture. These different features of hexamers and pentamers determine the structural mechanism to form CA polyhedrons of variable shape in mature RSV particles.}, author = {Obr, Martin and Ricana, Clifton L. and Nikulin, Nadia and Feathers, Jon-Philip R. and Klanschnig, Marco and Thader, Andreas and Johnson, Marc C. and Vogt, Volker M. and Schur, Florian KM and Dick, Robert A.}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry}, number = {1}, publisher = {Nature Research}, title = {{Structure of the mature Rous sarcoma virus lattice reveals a role for IP6 in the formation of the capsid hexamer}}, doi = {10.1038/s41467-021-23506-0}, volume = {12}, year = {2021}, } @article{9467, abstract = {Turbulence in the flow of fluid through a pipe can be suppressed by buoyancy forces. As the suppression of turbulence leads to severe heat transfer deterioration, this is an important and undesirable phenomenon in both heating and cooling applications. Vertical flow is often considered, as the axial buoyancy force can help drive the flow. With heating measured by the buoyancy parameter 𝐶, our direct numerical simulations show that shear-driven turbulence may either be completely laminarised or it transitions to a relatively quiescent convection-driven state. Buoyancy forces cause a flattening of the base flow profile, which in isothermal pipe flow has recently been linked to complete suppression of turbulence (Kühnen et al., Nat. Phys., vol. 14, 2018, pp. 386–390), and the flattened laminar base profile has enhanced nonlinear stability (Marensi et al., J. Fluid Mech., vol. 863, 2019, pp. 50–875). In agreement with these findings, the nonlinear lower-branch travelling-wave solution analysed here, which is believed to mediate transition to turbulence in isothermal pipe flow, is shown to be suppressed by buoyancy. A linear instability of the laminar base flow is responsible for the appearance of the relatively quiescent convection driven state for 𝐶≳4 across the range of Reynolds numbers considered. In the suppression of turbulence, however, i.e. in the transition from turbulence, we find clearer association with the analysis of He et al. (J. Fluid Mech., vol. 809, 2016, pp. 31–71) than with the above dynamical systems approach, which describes better the transition to turbulence. The laminarisation criterion He et al. propose, based on an apparent Reynolds number of the flow as measured by its driving pressure gradient, is found to capture the critical 𝐶=𝐶𝑐𝑟(𝑅𝑒) above which the flow will be laminarised or switch to the convection-driven type. Our analysis suggests that it is the weakened rolls, rather than the streaks, which appear to be critical for laminarisation.}, author = {Marensi, Elena and He, Shuisheng and Willis, Ashley P.}, issn = {14697645}, journal = {Journal of Fluid Mechanics}, publisher = {Cambridge University Press}, title = {{Suppression of turbulence and travelling waves in a vertical heated pipe}}, doi = {10.1017/jfm.2021.371}, volume = {919}, year = {2021}, } @article{9470, abstract = {A key step in understanding the genetic basis of different evolutionary outcomes (e.g., adaptation) is to determine the roles played by different mutation types (e.g., SNPs, translocations and inversions). To do this we must simultaneously consider different mutation types in an evolutionary framework. Here, we propose a research framework that directly utilizes the most important characteristics of mutations, their population genetic effects, to determine their relative evolutionary significance in a given scenario. We review known population genetic effects of different mutation types and show how these may be connected to different evolutionary outcomes. We provide examples of how to implement this framework and pinpoint areas where more data, theory and synthesis are needed. Linking experimental and theoretical approaches to examine different mutation types simultaneously is a critical step towards understanding their evolutionary significance.}, author = {Berdan, Emma L. and Blanckaert, Alexandre and Slotte, Tanja and Suh, Alexander and Westram, Anja M and Fragata, Inês}, issn = {1365294X}, journal = {Molecular Ecology}, number = {12}, pages = {2710--2723}, publisher = {Wiley}, title = {{Unboxing mutations: Connecting mutation types with evolutionary consequences}}, doi = {10.1111/mec.15936}, volume = {30}, year = {2021}, } @article{9468, abstract = {Motivated by the successful application of geometry to proving the Harary--Hill conjecture for “pseudolinear” drawings of $K_n$, we introduce “pseudospherical” drawings of graphs. A spherical drawing of a graph $G$ is a drawing in the unit sphere $\mathbb{S}^2$ in which the vertices of $G$ are represented as points---no three on a great circle---and the edges of $G$ are shortest-arcs in $\mathbb{S}^2$ connecting pairs of vertices. Such a drawing has three properties: (1) every edge $e$ is contained in a simple closed curve $\gamma_e$ such that the only vertices in $\gamma_e$ are the ends of $e$; (2) if $e\ne f$, then $\gamma_e\cap\gamma_f$ has precisely two crossings; and (3) if $e\ne f$, then $e$ intersects $\gamma_f$ at most once, in either a crossing or an end of $e$. We use properties (1)--(3) to define a pseudospherical drawing of $G$. Our main result is that for the complete graph, properties (1)--(3) are equivalent to the same three properties but with “precisely two crossings” in (2) replaced by “at most two crossings.” The proof requires a result in the geometric transversal theory of arrangements of pseudocircles. This is proved using the surprising result that the absence of special arcs (coherent spirals) in an arrangement of simple closed curves characterizes the fact that any two curves in the arrangement have at most two crossings. Our studies provide the necessary ideas for exhibiting a drawing of $K_{10}$ that has no extension to an arrangement of pseudocircles and a drawing of $K_9$ that does extend to an arrangement of pseudocircles, but no such extension has all pairs of pseudocircles crossing twice. }, author = {Arroyo Guevara, Alan M and Richter, R. Bruce and Sunohara, Matthew}, issn = {08954801}, journal = {SIAM Journal on Discrete Mathematics}, number = {2}, pages = {1050--1076}, publisher = {Society for Industrial and Applied Mathematics}, title = {{Extending drawings of complete graphs into arrangements of pseudocircles}}, doi = {10.1137/20M1313234}, volume = {35}, year = {2021}, } @article{9462, abstract = {We consider a system of N trapped bosons with repulsive interactions in a combined semiclassical mean-field limit at positive temperature. We show that the free energy is well approximated by the minimum of the Hartree free energy functional – a natural extension of the Hartree energy functional to positive temperatures. The Hartree free energy functional converges in the same limit to a semiclassical free energy functional, and we show that the system displays Bose–Einstein condensation if and only if it occurs in the semiclassical free energy functional. This allows us to show that for weak coupling the critical temperature decreases due to the repulsive interactions.}, author = {Deuchert, Andreas and Seiringer, Robert}, issn = {1096-0783}, journal = {Journal of Functional Analysis}, number = {6}, publisher = {Elsevier}, title = {{Semiclassical approximation and critical temperature shift for weakly interacting trapped bosons}}, doi = {10.1016/j.jfa.2021.109096}, volume = {281}, year = {2021}, } @article{9469, abstract = {In this paper, we consider reflected three-operator splitting methods for monotone inclusion problems in real Hilbert spaces. To do this, we first obtain weak convergence analysis and nonasymptotic O(1/n) convergence rate of the reflected Krasnosel'skiĭ-Mann iteration for finding a fixed point of nonexpansive mapping in real Hilbert spaces under some seemingly easy to implement conditions on the iterative parameters. We then apply our results to three-operator splitting for the monotone inclusion problem and consequently obtain the corresponding convergence analysis. Furthermore, we derive reflected primal-dual algorithms for highly structured monotone inclusion problems. Some numerical implementations are drawn from splitting methods to support the theoretical analysis.}, author = {Iyiola, Olaniyi S. and Enyi, Cyril D. and Shehu, Yekini}, issn = {1029-4937}, journal = {Optimization Methods and Software}, publisher = {Taylor and Francis}, title = {{Reflected three-operator splitting method for monotone inclusion problem}}, doi = {10.1080/10556788.2021.1924715}, year = {2021}, } @article{9540, abstract = {The hexameric AAA-ATPase Drg1 is a key factor in eukaryotic ribosome biogenesis and initiates cytoplasmic maturation of the large ribosomal subunit by releasing the shuttling maturation factor Rlp24. Drg1 monomers contain two AAA-domains (D1 and D2) that act in a concerted manner. Rlp24 release is inhibited by the drug diazaborine which blocks ATP hydrolysis in D2. The mode of inhibition was unknown. Here we show the first cryo-EM structure of Drg1 revealing the inhibitory mechanism. Diazaborine forms a covalent bond to the 2′-OH of the nucleotide in D2, explaining its specificity for this site. As a consequence, the D2 domain is locked in a rigid, inactive state, stalling the whole Drg1 hexamer. Resistance mechanisms identified include abolished drug binding and altered positioning of the nucleotide. Our results suggest nucleotide-modifying compounds as potential novel inhibitors for AAA-ATPases.}, author = {Prattes, Michael and Grishkovskaya, Irina and Hodirnau, Victor-Valentin and Rössler, Ingrid and Klein, Isabella and Hetzmannseder, Christina and Zisser, Gertrude and Gruber, Christian C. and Gruber, Karl and Haselbach, David and Bergler, Helmut}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry}, number = {1}, publisher = {Springer Nature}, title = {{Structural basis for inhibition of the AAA-ATPase Drg1 by diazaborine}}, doi = {10.1038/s41467-021-23854-x}, volume = {12}, year = {2021}, } @article{9549, abstract = {AMPA receptors (AMPARs) mediate the majority of excitatory transmission in the brain and enable the synaptic plasticity that underlies learning1. A diverse array of AMPAR signalling complexes are established by receptor auxiliary subunits, which associate with the AMPAR in various combinations to modulate trafficking, gating and synaptic strength2. However, their mechanisms of action are poorly understood. Here we determine cryo-electron microscopy structures of the heteromeric GluA1–GluA2 receptor assembled with both TARP-γ8 and CNIH2, the predominant AMPAR complex in the forebrain, in both resting and active states. Two TARP-γ8 and two CNIH2 subunits insert at distinct sites beneath the ligand-binding domains of the receptor, with site-specific lipids shaping each interaction and affecting the gating regulation of the AMPARs. Activation of the receptor leads to asymmetry between GluA1 and GluA2 along the ion conduction path and an outward expansion of the channel triggers counter-rotations of both auxiliary subunit pairs, promoting the active-state conformation. In addition, both TARP-γ8 and CNIH2 pivot towards the pore exit upon activation, extending their reach for cytoplasmic receptor elements. CNIH2 achieves this through its uniquely extended M2 helix, which has transformed this endoplasmic reticulum-export factor into a powerful AMPAR modulator that is capable of providing hippocampal pyramidal neurons with their integrative synaptic properties. }, author = {Zhang, Danyang and Watson, Jake and Matthews, Peter M. and Cais, Ondrej and Greger, Ingo H.}, issn = {1476-4687}, journal = {Nature}, pages = {454--458}, publisher = {Springer Nature}, title = {{Gating and modulation of a hetero-octameric AMPA glutamate receptor}}, doi = {10.1038/s41586-021-03613-0}, volume = {594}, year = {2021}, } @article{9550, abstract = {We prove that the energy of any eigenvector of a sum of several independent large Wigner matrices is equally distributed among these matrices with very high precision. This shows a particularly strong microcanonical form of the equipartition principle for quantum systems whose components are modelled by Wigner matrices. }, author = {Bao, Zhigang and Erdös, László and Schnelli, Kevin}, issn = {20505094}, journal = {Forum of Mathematics, Sigma}, publisher = {Cambridge University Press}, title = {{Equipartition principle for Wigner matrices}}, doi = {10.1017/fms.2021.38}, volume = {9}, year = {2021}, } @article{9570, abstract = {We present conductance-matrix measurements in long, three-terminal hybrid superconductor-semiconductor nanowires, and compare with theoretical predictions of a magnetic-field-driven, topological quantum phase transition. By examining the nonlocal conductance, we identify the closure of the excitation gap in the bulk of the semiconductor before the emergence of zero-bias peaks, ruling out spurious gap-closure signatures from localized states. We observe that after the gap closes, nonlocal signals and zero-bias peaks fluctuate strongly at both ends, inconsistent with a simple picture of clean topological superconductivity.}, author = {Puglia, Denise and Martinez, E. A. and Ménard, G. C. and Pöschl, A. and Gronin, S. and Gardner, G. C. and Kallaher, R. and Manfra, M. J. and Marcus, C. M. and Higginbotham, Andrew P and Casparis, L.}, issn = {24699969}, journal = {Physical Review B}, number = {23}, publisher = {American Physical Society}, title = {{Closing of the induced gap in a hybrid superconductor-semiconductor nanowire}}, doi = {10.1103/PhysRevB.103.235201}, volume = {103}, year = {2021}, } @article{9548, abstract = {We extend the notion of the minimal volume ellipsoid containing a convex body in Rd to the setting of logarithmically concave functions. We consider a vast class of logarithmically concave functions whose superlevel sets are concentric ellipsoids. For a fixed function from this class, we consider the set of all its “affine” positions. For any log-concave function f on Rd, we consider functions belonging to this set of “affine” positions, and find the one with the minimal integral under the condition that it is pointwise greater than or equal to f. We study the properties of existence and uniqueness of the solution to this problem. For any s∈[0,+∞), we consider the construction dual to the recently defined John s-function (Ivanov and Naszódi in Functional John ellipsoids. arXiv preprint: arXiv:2006.09934, 2020). We prove that such a construction determines a unique function and call it the Löwner s-function of f. We study the Löwner s-functions as s tends to zero and to infinity. Finally, extending the notion of the outer volume ratio, we define the outer integral ratio of a log-concave function and give an asymptotically tight bound on it.}, author = {Ivanov, Grigory and Tsiutsiurupa, Igor}, issn = {1559-002X}, journal = {Journal of Geometric Analysis}, pages = {11493--11528}, publisher = {Springer}, title = {{Functional Löwner ellipsoids}}, doi = {10.1007/s12220-021-00691-4}, volume = {31}, year = {2021}, } @misc{13080, abstract = {Data for the manuscript 'Closing of the Induced Gap in a Hybrid Superconductor-Semiconductor Nanowire' ([2006.01275] Closing of the Induced Gap in a Hybrid Superconductor-Semiconductor Nanowire (arxiv.org)) We upload a pdf with extended data sets, and the raw data for these extended datasets as well.}, author = {Puglia, Denise and Martinez, Esteban and Menard, Gerbold and Pöschl, Andreas and Gronin, Sergei and Gardner, Geoffrey and Kallaher, Ray and Manfra, Michael and Marcus, Charles and Higginbotham, Andrew P and Casparis, Lucas}, publisher = {Zenodo}, title = {{Data for 'Closing of the Induced Gap in a Hybrid Superconductor-Semiconductor Nanowire}}, doi = {10.5281/ZENODO.4592435}, year = {2021}, } @article{9569, abstract = {We report the synthesis and characterization of graphene functionalized with iron (Fe3+) oxide (G-Fe3O4) nanohybrids for radio-frequency magnetic hyperthermia application. We adopted the wet chemical procedure, using various contents of Fe3O4 (magnetite) from 0–100% for making two-dimensional graphene–Fe3O4 nanohybrids. The homogeneous dispersal of Fe3O4 nanoparticles decorated on the graphene surface combined with their biocompatibility and high thermal conductivity make them an excellent material for magnetic hyperthermia. The morphological and magnetic properties of the nanohybrids were studied using scanning electron microscopy (SEM) and a vibrating sample magnetometer (VSM), respectively. The smart magnetic platforms were exposed to an alternating current (AC) magnetic field of 633 kHz and of strength 9.1 mT for studying their hyperthermic performance. The localized antitumor effects were investigated with artificial neural network modeling. A neural net time-series model was developed for the assessment of the best nanohybrid composition to serve the purpose with an accuracy close to 100%. Six Nonlinear Autoregressive with External Input (NARX) models were obtained, one for each of the components. The assessment of the accuracy of the predicted results has been done on the basis of Mean Squared Error (MSE). The highest Mean Squared Error value was obtained for the nanohybrid containing 45% magnetite and 55% graphene (F45G55) in the training phase i.e., 0.44703, which is where the model achieved optimal results after 71 epochs. The F45G55 nanohybrid was found to be the best for hyperthermia applications in low dosage with the highest specific absorption rate (SAR) and mean squared error values.}, author = {Dar, M. S. and Akram, Khush Bakhat and Sohail, Ayesha and Arif, Fatima and Zabihi, Fatemeh and Yang, Shengyuan and Munir, Shamsa and Zhu, Meifang and Abid, M. and Nauman, Muhammad}, issn = {2046-2069}, journal = {RSC Advances}, number = {35}, pages = {21702--21715}, publisher = {Royal Society of Chemistry}, title = {{Heat induction in two-dimensional graphene–Fe3O4 nanohybrids for magnetic hyperthermia applications with artificial neural network modeling}}, doi = {10.1039/d1ra03428f}, volume = {11}, year = {2021}, } @article{9558, abstract = {We show that turbulent dynamics that arise in simulations of the three-dimensional Navier--Stokes equations in a triply-periodic domain under sinusoidal forcing can be described as transient visits to the neighborhoods of unstable time-periodic solutions. Based on this description, we reduce the original system with more than 10^5 degrees of freedom to a 17-node Markov chain where each node corresponds to the neighborhood of a periodic orbit. The model accurately reproduces long-term averages of the system's observables as weighted sums over the periodic orbits. }, author = {Yalniz, Gökhan and Hof, Björn and Budanur, Nazmi B}, issn = {1079-7114}, journal = {Physical Review Letters}, number = {24}, publisher = {American Physical Society}, title = {{Coarse graining the state space of a turbulent flow using periodic orbits}}, doi = {10.1103/PhysRevLett.126.244502}, volume = {126}, year = {2021}, } @article{9607, abstract = {While high risk of failure is an inherent part of developing innovative therapies, it can be reduced by adherence to evidence-based rigorous research practices. Numerous analyses conducted to date have clearly identified measures that need to be taken to improve research rigor. Supported through the European Union's Innovative Medicines Initiative, the EQIPD consortium has developed a novel preclinical research quality system that can be applied in both public and private sectors and is free for anyone to use. The EQIPD Quality System was designed to be suited to boost innovation by ensuring the generation of robust and reliable preclinical data while being lean, effective and not becoming a burden that could negatively impact the freedom to explore scientific questions. EQIPD defines research quality as the extent to which research data are fit for their intended use. Fitness, in this context, is defined by the stakeholders, who are the scientists directly involved in the research, but also their funders, sponsors, publishers, research tool manufacturers and collaboration partners such as peers in a multi-site research project. The essence of the EQIPD Quality System is the set of 18 core requirements that can be addressed flexibly, according to user-specific needs and following a user-defined trajectory. The EQIPD Quality System proposes guidance on expectations for quality-related measures, defines criteria for adequate processes (i.e., performance standards) and provides examples of how such measures can be developed and implemented. However, it does not prescribe any pre-determined solutions. EQIPD has also developed tools (for optional use) to support users in implementing the system and assessment services for those research units that successfully implement the quality system and seek formal accreditation. Building upon the feedback from users and continuous improvement, a sustainable EQIPD Quality System will ultimately serve the entire community of scientists conducting non-regulated preclinical research, by helping them generate reliable data that are fit for their intended use.}, author = {Bespalov, Anton and Bernard, René and Gilis, Anja and Gerlach, Björn and Guillén, Javier and Castagné, Vincent and Lefevre, Isabel A. and Ducrey, Fiona and Monk, Lee and Bongiovanni, Sandrine and Altevogt, Bruce and Arroyo-Araujo, María and Bikovski, Lior and De Bruin, Natasja and Castaños-Vélez, Esmeralda and Dityatev, Alexander and Emmerich, Christoph H. and Fares, Raafat and Ferland-Beckham, Chantelle and Froger-Colléaux, Christelle and Gailus-Durner, Valerie and Hölter, Sabine M. and Hofmann, Martine Cj and Kabitzke, Patricia and Kas, Martien Jh and Kurreck, Claudia and Moser, Paul and Pietraszek, Malgorzata and Popik, Piotr and Potschka, Heidrun and Prado Montes De Oca, Ernesto and Restivo, Leonardo and Riedel, Gernot and Ritskes-Hoitinga, Merel and Samardzic, Janko and Schunn, Michael and Stöger, Claudia and Voikar, Vootele and Vollert, Jan and Wever, Kimberley E. and Wuyts, Kathleen and Macleod, Malcolm R. and Dirnagl, Ulrich and Steckler, Thomas}, issn = {2050084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Introduction to the EQIPD quality system}}, doi = {10.7554/eLife.63294}, volume = {10}, year = {2021}, } @article{9601, abstract = {In mammalian genomes, differentially methylated regions (DMRs) and histone marks including trimethylation of histone 3 lysine 27 (H3K27me3) at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. However, neither parent-of-origin-specific transcription nor imprints have been comprehensively mapped at the blastocyst stage of preimplantation development. Here, we address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos. We find that seventy-one genes exhibit previously unreported parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expressed). Uniparental expression of nBiX genes disappears soon after implantation. Micro-whole-genome bisulfite sequencing (µWGBS) of individual uniparental blastocysts detects 859 DMRs. We further find that 16% of nBiX genes are associated with a DMR, whereas most are associated with parentally-biased H3K27me3, suggesting a role for Polycomb-mediated imprinting in blastocysts. nBiX genes are clustered: five clusters contained at least one published imprinted gene, and five clusters exclusively contained nBiX genes. These data suggest that early development undergoes a complex program of stage-specific imprinting involving different tiers of regulation.}, author = {Santini, Laura and Halbritter, Florian and Titz-Teixeira, Fabian and Suzuki, Toru and Asami, Maki and Ma, Xiaoyan and Ramesmayer, Julia and Lackner, Andreas and Warr, Nick and Pauler, Florian and Hippenmeyer, Simon and Laue, Ernest and Farlik, Matthias and Bock, Christoph and Beyer, Andreas and Perry, Anthony C.F. and Leeb, Martin}, issn = {20411723}, journal = {Nature Communications}, number = {1}, publisher = {Springer Nature}, title = {{Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3}}, doi = {10.1038/s41467-021-23510-4}, volume = {12}, year = {2021}, } @article{9602, abstract = {An ordered graph is a graph with a linear ordering on its vertex set. We prove that for every positive integer k, there exists a constant ck > 0 such that any ordered graph G on n vertices with the property that neither G nor its complement contains an induced monotone path of size k, has either a clique or an independent set of size at least n^ck . This strengthens a result of Bousquet, Lagoutte, and Thomassé, who proved the analogous result for unordered graphs. A key idea of the above paper was to show that any unordered graph on n vertices that does not contain an induced path of size k, and whose maximum degree is at most c(k)n for some small c(k) > 0, contains two disjoint linear size subsets with no edge between them. This approach fails for ordered graphs, because the analogous statement is false for k ≥ 3, by a construction of Fox. We provide some further examples showing that this statement also fails for ordered graphs avoiding other ordered trees.}, author = {Pach, János and Tomon, István}, issn = {0095-8956}, journal = {Journal of Combinatorial Theory. Series B}, pages = {21--37}, publisher = {Elsevier}, title = {{Erdős-Hajnal-type results for monotone paths}}, doi = {10.1016/j.jctb.2021.05.004}, volume = {151}, year = {2021}, } @article{9606, abstract = {Sound propagation is a macroscopic manifestation of the interplay between the equilibrium thermodynamics and the dynamical transport properties of fluids. Here, for a two-dimensional system of ultracold fermions, we calculate the first and second sound velocities across the whole BCS-BEC crossover, and we analyze the system response to an external perturbation. In the low-temperature regime we reproduce the recent measurements [Phys. Rev. Lett. 124, 240403 (2020)] of the first sound velocity, which, due to the decoupling of density and entropy fluctuations, is the sole mode excited by a density probe. Conversely, a heat perturbation excites only the second sound, which, being sensitive to the superfluid depletion, vanishes in the deep BCS regime and jumps discontinuously to zero at the Berezinskii-Kosterlitz-Thouless superfluid transition. A mixing between the modes occurs only in the finite-temperature BEC regime, where our theory converges to the purely bosonic results.}, author = {Tononi, A. and Cappellaro, Alberto and Bighin, Giacomo and Salasnich, L.}, issn = {24699934}, journal = {Physical Review A}, number = {6}, publisher = {American Physical Society}, title = {{Propagation of first and second sound in a two-dimensional Fermi superfluid}}, doi = {10.1103/PhysRevA.103.L061303}, volume = {103}, year = {2021}, } @article{9642, abstract = {Perineuronal nets (PNNs), components of the extracellular matrix, preferentially coat parvalbumin-positive interneurons and constrain critical-period plasticity in the adult cerebral cortex. Current strategies to remove PNN are long-lasting, invasive, and trigger neuropsychiatric symptoms. Here, we apply repeated anesthetic ketamine as a method with minimal behavioral effect. We find that this paradigm strongly reduces PNN coating in the healthy adult brain and promotes juvenile-like plasticity. Microglia are critically involved in PNN loss because they engage with parvalbumin-positive neurons in their defined cortical layer. We identify external 60-Hz light-flickering entrainment to recapitulate microglia-mediated PNN removal. Importantly, 40-Hz frequency, which is known to remove amyloid plaques, does not induce PNN loss, suggesting microglia might functionally tune to distinct brain frequencies. Thus, our 60-Hz light-entrainment strategy provides an alternative form of PNN intervention in the healthy adult brain.}, author = {Venturino, Alessandro and Schulz, Rouven and De Jesús-Cortés, Héctor and Maes, Margaret E and Nagy, Balint and Reilly-Andújar, Francis and Colombo, Gloria and Cubero, Ryan J and Schoot Uiterkamp, Florianne E and Bear, Mark F. and Siegert, Sandra}, issn = {22111247}, journal = {Cell Reports}, number = {1}, publisher = {Elsevier}, title = {{Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain}}, doi = {10.1016/j.celrep.2021.109313}, volume = {36}, year = {2021}, } @article{9603, abstract = {Mosaic analysis with double markers (MADM) offers one approach to visualize and concomitantly manipulate genetically defined cells in mice with single-cell resolution. MADM applications include the analysis of lineage, single-cell morphology and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous gene functions in vivo in health and disease. Yet, MADM can only be applied to <25% of all mouse genes on select chromosomes to date. To overcome this limitation, we generate transgenic mice with knocked-in MADM cassettes near the centromeres of all 19 autosomes and validate their use across organs. With this resource, >96% of the entire mouse genome can now be subjected to single-cell genetic mosaic analysis. Beyond a proof of principle, we apply our MADM library to systematically trace sister chromatid segregation in distinct mitotic cell lineages. We find striking chromosome-specific biases in segregation patterns, reflecting a putative mechanism for the asymmetric segregation of genetic determinants in somatic stem cell division.}, author = {Contreras, Ximena and Amberg, Nicole and Davaatseren, Amarbayasgalan and Hansen, Andi H and Sonntag, Johanna and Andersen, Lill and Bernthaler, Tina and Streicher, Carmen and Heger, Anna-Magdalena and Johnson, Randy L. and Schwarz, Lindsay A. and Luo, Liqun and Rülicke, Thomas and Hippenmeyer, Simon}, issn = {22111247}, journal = {Cell Reports}, number = {12}, publisher = {Cell Press}, title = {{A genome-wide library of MADM mice for single-cell genetic mosaic analysis}}, doi = {10.1016/j.celrep.2021.109274}, volume = {35}, year = {2021}, } @article{9618, abstract = {The control of nonequilibrium quantum dynamics in many-body systems is challenging because interactions typically lead to thermalization and a chaotic spreading throughout Hilbert space. We investigate nonequilibrium dynamics after rapid quenches in a many-body system composed of 3 to 200 strongly interacting qubits in one and two spatial dimensions. Using a programmable quantum simulator based on Rydberg atom arrays, we show that coherent revivals associated with so-called quantum many-body scars can be stabilized by periodic driving, which generates a robust subharmonic response akin to discrete time-crystalline order. We map Hilbert space dynamics, geometry dependence, phase diagrams, and system-size dependence of this emergent phenomenon, demonstrating new ways to steer complex dynamics in many-body systems and enabling potential applications in quantum information science.}, author = {Bluvstein, D. and Omran, A. and Levine, H. and Keesling, A. and Semeghini, G. and Ebadi, S. and Wang, T. T. and Michailidis, Alexios and Maskara, N. and Ho, W. W. and Choi, S. and Serbyn, Maksym and Greiner, M. and Vuletić, V. and Lukin, M. D.}, issn = {1095-9203}, journal = {Science}, keywords = {Multidisciplinary}, number = {6536}, pages = {1355--1359}, publisher = {AAAS}, title = {{Controlling quantum many-body dynamics in driven Rydberg atom arrays}}, doi = {10.1126/science.abg2530}, volume = {371}, year = {2021}, } @article{9657, abstract = {To overcome nitrogen deficiency, legume roots establish symbiotic interactions with nitrogen-fixing rhizobia that is fostered in specialized organs (nodules). Similar to other organs, nodule formation is determined by a local maximum of the phytohormone auxin at the primordium site. However, how auxin regulates nodule development remains poorly understood. Here, we found that in soybean, (Glycine max), dynamic auxin transport driven by PIN-FORMED (PIN) transporter GmPIN1 is involved in nodule primordium formation. GmPIN1 was specifically expressed in nodule primordium cells and GmPIN1 was polarly localized in these cells. Two nodulation regulators, (iso)flavonoids trigger expanded distribution of GmPIN1b to root cortical cells, and cytokinin rearranges GmPIN1b polarity. Gmpin1abc triple mutants generated with CRISPR-Cas9 showed impaired establishment of auxin maxima in nodule meristems and aberrant divisions in the nodule primordium cells. Moreover, overexpression of GmPIN1 suppressed nodule primordium initiation. GmPIN9d, an ortholog of Arabidopsis thaliana PIN2, acts together with GmPIN1 later in nodule development to acropetally transport auxin in vascular bundles, fine-tuning the auxin supply for nodule enlargement. Our findings reveal how PIN-dependent auxin transport modulates different aspects of soybean nodule development and suggest that establishment of auxin gradient is a prerequisite for the proper interaction between legumes and rhizobia.}, author = {Gao, Z and Chen, Z and Cui, Y and Ke, M and Xu, H and Xu, Q and Chen, J and Li, Y and Huang, L and Zhao, H and Huang, D and Mai, S and Xu, T and Liu, X and Li, S and Guan, Y and Yang, W and Friml, Jiří and Petrášek, J and Zhang, J and Chen, X}, issn = {1532-298x}, journal = {Plant Cell}, number = {9}, pages = {2981–3003}, publisher = {American Society of Plant Biologists}, title = {{GmPIN-dependent polar auxin transport is involved in soybean nodule development}}, doi = {10.1093/plcell/koab183}, volume = {33}, year = {2021}, } @article{9640, abstract = {Selection and random drift determine the probability that novel mutations fixate in a population. Population structure is known to affect the dynamics of the evolutionary process. Amplifiers of selection are population structures that increase the fixation probability of beneficial mutants compared to well-mixed populations. Over the past 15 years, extensive research has produced remarkable structures called strong amplifiers which guarantee that every beneficial mutation fixates with high probability. But strong amplification has come at the cost of considerably delaying the fixation event, which can slow down the overall rate of evolution. However, the precise relationship between fixation probability and time has remained elusive. Here we characterize the slowdown effect of strong amplification. First, we prove that all strong amplifiers must delay the fixation event at least to some extent. Second, we construct strong amplifiers that delay the fixation event only marginally as compared to the well-mixed populations. Our results thus establish a tight relationship between fixation probability and time: Strong amplification always comes at a cost of a slowdown, but more than a marginal slowdown is not needed.}, author = {Tkadlec, Josef and Pavlogiannis, Andreas and Chatterjee, Krishnendu and Nowak, Martin A.}, issn = {20411723}, journal = {Nature Communications}, number = {1}, publisher = {Springer Nature}, title = {{Fast and strong amplifiers of natural selection}}, doi = {10.1038/s41467-021-24271-w}, volume = {12}, year = {2021}, } @article{9656, abstract = {Tropisms, growth responses to environmental stimuli such as light or gravity, are spectacular examples of adaptive plant development. The plant hormone auxin serves as a major coordinative signal. The PIN auxin exporters, through their dynamic polar subcellular localizations, redirect auxin fluxes in response to environmental stimuli and the resulting auxin gradients across organs underly differential cell elongation and bending. In this review, we discuss recent advances concerning regulations of PIN polarity during tropisms, focusing on PIN phosphorylation and trafficking. We also cover how environmental cues regulate PIN actions during tropisms, and a crucial role of auxin feedback on PIN polarity during bending termination. Finally, the interactions between different tropisms are reviewed to understand plant adaptive growth in the natural environment.}, author = {Han, Huibin and Adamowski, Maciek and Qi, Linlin and Alotaibi, SS and Friml, Jiří}, issn = {1469-8137}, journal = {New Phytologist}, number = {2}, pages = {510--522}, publisher = {Wiley}, title = {{PIN-mediated polar auxin transport regulations in plant tropic responses}}, doi = {10.1111/nph.17617}, volume = {232}, year = {2021}, } @article{9679, abstract = {The relative motion of three impenetrable particles on a ring, in our case two identical fermions and one impurity, is isomorphic to a triangular quantum billiard. Depending on the ratio κ of the impurity and fermion masses, the billiards can be integrable or non-integrable (also referred to in the main text as chaotic). To set the stage, we first investigate the energy level distributions of the billiards as a function of 1/κ ∈ [0, 1] and find no evidence of integrable cases beyond the limiting values 1/κ = 1 and 1/κ = 0. Then, we use machine learning tools to analyze properties of probability distributions of individual quantum states. We find that convolutional neural networks can correctly classify integrable and non-integrable states. The decisive features of the wave functions are the normalization and a large number of zero elements, corresponding to the existence of a nodal line. The network achieves typical accuracies of 97%, suggesting that machine learning tools can be used to analyze and classify the morphology of probability densities obtained in theory or experiment.}, author = {Huber, David and Marchukov, Oleksandr V. and Hammer, Hans Werner and Volosniev, Artem}, issn = {13672630}, journal = {New Journal of Physics}, number = {6}, publisher = {IOP Publishing}, title = {{Morphology of three-body quantum states from machine learning}}, doi = {10.1088/1367-2630/ac0576}, volume = {23}, year = {2021}, } @article{9629, abstract = {Intestinal organoids derived from single cells undergo complex crypt–villus patterning and morphogenesis. However, the nature and coordination of the underlying forces remains poorly characterized. Here, using light-sheet microscopy and large-scale imaging quantification, we demonstrate that crypt formation coincides with a stark reduction in lumen volume. We develop a 3D biophysical model to computationally screen different mechanical scenarios of crypt morphogenesis. Combining this with live-imaging data and multiple mechanical perturbations, we show that actomyosin-driven crypt apical contraction and villus basal tension work synergistically with lumen volume reduction to drive crypt morphogenesis, and demonstrate the existence of a critical point in differential tensions above which crypt morphology becomes robust to volume changes. Finally, we identified a sodium/glucose cotransporter that is specific to differentiated enterocytes that modulates lumen volume reduction through cell swelling in the villus region. Together, our study uncovers the cellular basis of how cell fate modulates osmotic and actomyosin forces to coordinate robust morphogenesis.}, author = {Yang, Qiutan and Xue, Shi-lei and Chan, Chii Jou and Rempfler, Markus and Vischi, Dario and Maurer-Gutierrez, Francisca and Hiiragi, Takashi and Hannezo, Edouard B and Liberali, Prisca}, issn = {1476-4679}, journal = {Nature Cell Biology}, pages = {733–744}, publisher = {Springer Nature}, title = {{Cell fate coordinates mechano-osmotic forces in intestinal crypt formation}}, doi = {10.1038/s41556-021-00700-2}, volume = {23}, year = {2021}, } @article{9626, abstract = {SnSe, a wide-bandgap semiconductor, has attracted significant attention from the thermoelectric (TE) community due to its outstanding TE performance deriving from the ultralow thermal conductivity and advantageous electronic structures. Here, we promoted the TE performance of n-type SnSe polycrystals through bandgap engineering and vacancy compensation. We found that PbTe can significantly reduce the wide bandgap of SnSe to reduce the impurity transition energy, largely enhancing the carrier concentration. Also, PbTe-induced crystal symmetry promotion increases the carrier mobility, preserving large Seebeck coefficient. Consequently, a maximum ZT of ∼1.4 at 793 K is obtained in Br doped SnSe–13%PbTe. Furthermore, we found that extra Sn in n-type SnSe can compensate for the intrinsic Sn vacancies and form electron donor-like metallic Sn nanophases. The Sn nanophases near the grain boundary could also reduce the intergrain energy barrier which largely enhances the carrier mobility. As a result, a maximum ZT value of ∼1.7 at 793 K and an average ZT (ZTave) of ∼0.58 in 300–793 K are achieved in Br doped Sn1.08Se–13%PbTe. Our findings provide a novel strategy to promote the TE performance in wide-bandgap semiconductors.}, author = {Su, Lizhong and Hong, Tao and Wang, Dongyang and Wang, Sining and Qin, Bingchao and Zhang, Mengmeng and Gao, Xiang and Chang, Cheng and Zhao, Li Dong}, issn = {2542-5293}, journal = {Materials Today Physics}, publisher = {Elsevier}, title = {{Realizing high doping efficiency and thermoelectric performance in n-type SnSe polycrystals via bandgap engineering and vacancy compensation}}, doi = {10.1016/j.mtphys.2021.100452}, volume = {20}, year = {2021}, } @article{9778, abstract = {The hippocampal mossy fiber synapse is a key synapse of the trisynaptic circuit. Post-tetanic potentiation (PTP) is the most powerful form of plasticity at this synaptic connection. It is widely believed that mossy fiber PTP is an entirely presynaptic phenomenon, implying that PTP induction is input-specific, and requires neither activity of multiple inputs nor stimulation of postsynaptic neurons. To directly test cooperativity and associativity, we made paired recordings between single mossy fiber terminals and postsynaptic CA3 pyramidal neurons in rat brain slices. By stimulating non-overlapping mossy fiber inputs converging onto single CA3 neurons, we confirm that PTP is input-specific and non-cooperative. Unexpectedly, mossy fiber PTP exhibits anti-associative induction properties. EPSCs show only minimal PTP after combined pre- and postsynaptic high-frequency stimulation with intact postsynaptic Ca2+ signaling, but marked PTP in the absence of postsynaptic spiking and after suppression of postsynaptic Ca2+ signaling (10 mM EGTA). PTP is largely recovered by inhibitors of voltage-gated R- and L-type Ca2+ channels, group II mGluRs, and vacuolar-type H+-ATPase, suggesting the involvement of retrograde vesicular glutamate signaling. Transsynaptic regulation of PTP extends the repertoire of synaptic computations, implementing a brake on mossy fiber detonation and a “smart teacher” function of hippocampal mossy fiber synapses.}, author = {Vandael, David H and Okamoto, Yuji and Jonas, Peter M}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {general physics and astronomy, general biochemistry, genetics and molecular biology, general chemistry}, number = {1}, publisher = {Springer}, title = {{Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses}}, doi = {10.1038/s41467-021-23153-5}, volume = {12}, year = {2021}, } @article{9647, abstract = {Gene expression is regulated by the set of transcription factors (TFs) that bind to the promoter. The ensuing regulating function is often represented as a combinational logic circuit, where output (gene expression) is determined by current input values (promoter bound TFs) only. However, the simultaneous arrival of TFs is a strong assumption, since transcription and translation of genes introduce intrinsic time delays and there is no global synchronisation among the arrival times of different molecular species at their targets. We present an experimentally implementable genetic circuit with two inputs and one output, which in the presence of small delays in input arrival, exhibits qualitatively distinct population-level phenotypes, over timescales that are longer than typical cell doubling times. From a dynamical systems point of view, these phenotypes represent long-lived transients: although they converge to the same value eventually, they do so after a very long time span. The key feature of this toy model genetic circuit is that, despite having only two inputs and one output, it is regulated by twenty-three distinct DNA-TF configurations, two of which are more stable than others (DNA looped states), one promoting and another blocking the expression of the output gene. Small delays in input arrival time result in a majority of cells in the population quickly reaching the stable state associated with the first input, while exiting of this stable state occurs at a slow timescale. In order to mechanistically model the behaviour of this genetic circuit, we used a rule-based modelling language, and implemented a grid-search to find parameter combinations giving rise to long-lived transients. Our analysis shows that in the absence of feedback, there exist path-dependent gene regulatory mechanisms based on the long timescale of transients. The behaviour of this toy model circuit suggests that gene regulatory networks can exploit event timing to create phenotypes, and it opens the possibility that they could use event timing to memorise events, without regulatory feedback. The model reveals the importance of (i) mechanistically modelling the transitions between the different DNA-TF states, and (ii) employing transient analysis thereof.}, author = {Petrov, Tatjana and Igler, Claudia and Sezgin, Ali and Henzinger, Thomas A and Guet, Calin C}, issn = {0304-3975}, journal = {Theoretical Computer Science}, pages = {1--16}, publisher = {Elsevier}, title = {{Long lived transients in gene regulation}}, doi = {10.1016/j.tcs.2021.05.023}, volume = {893}, year = {2021}, } @article{9761, abstract = {The important roles of mitochondrial function and dysfunction in the process of neurodegeneration are widely acknowledged. Retinal ganglion cells (RGCs) appear to be a highly vulnerable neuronal cell type in the central nervous system with respect to mitochondrial dysfunction but the actual reasons for this are still incompletely understood. These cells have a unique circumstance where unmyelinated axons must bend nearly 90° to exit the eye and then cross a translaminar pressure gradient before becoming myelinated in the optic nerve. This region, the optic nerve head, contains some of the highest density of mitochondria present in these cells. Glaucoma represents a perfect storm of events occurring at this location, with a combination of changes in the translaminar pressure gradient and reassignment of the metabolic support functions of supporting glia, which appears to apply increased metabolic stress to the RGC axons leading to a failure of axonal transport mechanisms. However, RGCs themselves are also extremely sensitive to genetic mutations, particularly in genes affecting mitochondrial dynamics and mitochondrial clearance. These mutations, which systemically affect the mitochondria in every cell, often lead to an optic neuropathy as the sole pathologic defect in affected patients. This review summarizes knowledge of mitochondrial structure and function, the known energy demands of neurons in general, and places these in the context of normal and pathological characteristics of mitochondria attributed to RGCs. }, author = {Muench, Nicole A. and Patel, Sonia and Maes, Margaret E and Donahue, Ryan J. and Ikeda, Akihiro and Nickells, Robert W.}, issn = {20734409}, journal = {Cells}, number = {7}, publisher = {MDPI}, title = {{The influence of mitochondrial dynamics and function on retinal ganglion cell susceptibility in optic nerve disease}}, doi = {10.3390/cells10071593}, volume = {10}, year = {2021}, } @article{9641, abstract = {At the encounter with a novel environment, contextual memory formation is greatly enhanced, accompanied with increased arousal and active exploration. Although this phenomenon has been widely observed in animal and human daily life, how the novelty in the environment is detected and contributes to contextual memory formation has lately started to be unveiled. The hippocampus has been studied for many decades for its largely known roles in encoding spatial memory, and a growing body of evidence indicates a differential involvement of dorsal and ventral hippocampal divisions in novelty detection. In this brief review article, we discuss the recent findings of the role of mossy cells in the ventral hippocampal moiety in novelty detection and put them in perspective with other novelty-related pathways in the hippocampus. We propose a mechanism for novelty-driven memory acquisition in the dentate gyrus by the direct projection of ventral mossy cells to dorsal dentate granule cells. By this projection, the ventral hippocampus sends novelty signals to the dorsal hippocampus, opening a gate for memory encoding in dentate granule cells based on information coming from the entorhinal cortex. We conclude that, contrary to the presently accepted functional independence, the dorsal and ventral hippocampi cooperate to link the novelty and contextual information, and this dorso-ventral interaction is crucial for the novelty-dependent memory formation.}, author = {Fredes, Felipe and Shigemoto, Ryuichi}, issn = {10959564}, journal = {Neurobiology of Learning and Memory}, publisher = {Elsevier}, title = {{The role of hippocampal mossy cells in novelty detection}}, doi = {10.1016/j.nlm.2021.107486}, volume = {183}, year = {2021}, } @inproceedings{9646, abstract = {We consider the fundamental problem of deriving quantitative bounds on the probability that a given assertion is violated in a probabilistic program. We provide automated algorithms that obtain both lower and upper bounds on the assertion violation probability. The main novelty of our approach is that we prove new and dedicated fixed-point theorems which serve as the theoretical basis of our algorithms and enable us to reason about assertion violation bounds in terms of pre and post fixed-point functions. To synthesize such fixed-points, we devise algorithms that utilize a wide range of mathematical tools, including repulsing ranking supermartingales, Hoeffding's lemma, Minkowski decompositions, Jensen's inequality, and convex optimization. On the theoretical side, we provide (i) the first automated algorithm for lower-bounds on assertion violation probabilities, (ii) the first complete algorithm for upper-bounds of exponential form in affine programs, and (iii) provably and significantly tighter upper-bounds than the previous approaches. On the practical side, we show our algorithms can handle a wide variety of programs from the literature and synthesize bounds that are remarkably tighter than previous results, in some cases by thousands of orders of magnitude.}, author = {Wang, Jinyi and Sun, Yican and Fu, Hongfei and Chatterjee, Krishnendu and Goharshady, Amir Kafshdar}, booktitle = {Proceedings of the 42nd ACM SIGPLAN International Conference on Programming Language Design and Implementation}, isbn = {9781450383912}, location = {Online}, pages = {1171--1186}, publisher = {Association for Computing Machinery}, title = {{Quantitative analysis of assertion violations in probabilistic programs}}, doi = {10.1145/3453483.3454102}, year = {2021}, } @inproceedings{9645, abstract = {We consider the fundamental problem of reachability analysis over imperative programs with real variables. Previous works that tackle reachability are either unable to handle programs consisting of general loops (e.g. symbolic execution), or lack completeness guarantees (e.g. abstract interpretation), or are not automated (e.g. incorrectness logic). In contrast, we propose a novel approach for reachability analysis that can handle general and complex loops, is complete, and can be entirely automated for a wide family of programs. Through the notion of Inductive Reachability Witnesses (IRWs), our approach extends ideas from both invariant generation and termination to reachability analysis. We first show that our IRW-based approach is sound and complete for reachability analysis of imperative programs. Then, we focus on linear and polynomial programs and develop automated methods for synthesizing linear and polynomial IRWs. In the linear case, we follow the well-known approaches using Farkas' Lemma. Our main contribution is in the polynomial case, where we present a push-button semi-complete algorithm. We achieve this using a novel combination of classical theorems in real algebraic geometry, such as Putinar's Positivstellensatz and Hilbert's Strong Nullstellensatz. Finally, our experimental results show we can prove complex reachability objectives over various benchmarks that were beyond the reach of previous methods.}, author = {Asadi, Ali and Chatterjee, Krishnendu and Fu, Hongfei and Goharshady, Amir Kafshdar and Mahdavi, Mohammad}, booktitle = {Proceedings of the 42nd ACM SIGPLAN International Conference on Programming Language Design and Implementation}, isbn = {9781450383912}, location = {Online}, pages = {772--787}, publisher = {Association for Computing Machinery}, title = {{Polynomial reachability witnesses via Stellensätze}}, doi = {10.1145/3453483.3454076}, year = {2021}, } @article{9759, author = {Bartlett, Michael John and Arslan, Feyza N and Bankston, Adriana and Sarabipour, Sarvenaz}, issn = {15537358}, journal = {PLoS Computational Biology}, number = {7}, publisher = {Public Library of Science}, title = {{Ten simple rules to improve academic work- life balance}}, doi = {10.1371/journal.pcbi.1009124}, volume = {17}, year = {2021}, } @article{9822, abstract = {Attachment of adhesive molecules on cell culture surfaces to restrict cell adhesion to defined areas and shapes has been vital for the progress of in vitro research. In currently existing patterning methods, a combination of pattern properties such as stability, precision, specificity, high-throughput outcome, and spatiotemporal control is highly desirable but challenging to achieve. Here, we introduce a versatile and high-throughput covalent photoimmobilization technique, comprising a light-dose-dependent patterning step and a subsequent functionalization of the pattern via click chemistry. This two-step process is feasible on arbitrary surfaces and allows for generation of sustainable patterns and gradients. The method is validated in different biological systems by patterning adhesive ligands on cell-repellent surfaces, thereby constraining the growth and migration of cells to the designated areas. We then implement a sequential photopatterning approach by adding a second switchable patterning step, allowing for spatiotemporal control over two distinct surface patterns. As a proof of concept, we reconstruct the dynamics of the tip/stalk cell switch during angiogenesis. Our results show that the spatiotemporal control provided by our “sequential photopatterning” system is essential for mimicking dynamic biological processes and that our innovative approach has great potential for further applications in cell science.}, author = {Zisis, Themistoklis and Schwarz, Jan and Balles, Miriam and Kretschmer, Maibritt and Nemethova, Maria and Chait, Remy P and Hauschild, Robert and Lange, Janina and Guet, Calin C and Sixt, Michael K and Zahler, Stefan}, issn = {19448252}, journal = {ACS Applied Materials and Interfaces}, number = {30}, pages = {35545–35560}, publisher = {American Chemical Society}, title = {{Sequential and switchable patterning for studying cellular processes under spatiotemporal control}}, doi = {10.1021/acsami.1c09850}, volume = {13}, year = {2021}, } @article{9819, abstract = {Photorealistic editing of head portraits is a challenging task as humans are very sensitive to inconsistencies in faces. We present an approach for high-quality intuitive editing of the camera viewpoint and scene illumination (parameterised with an environment map) in a portrait image. This requires our method to capture and control the full reflectance field of the person in the image. Most editing approaches rely on supervised learning using training data captured with setups such as light and camera stages. Such datasets are expensive to acquire, not readily available and do not capture all the rich variations of in-the-wild portrait images. In addition, most supervised approaches only focus on relighting, and do not allow camera viewpoint editing. Thus, they only capture and control a subset of the reflectance field. Recently, portrait editing has been demonstrated by operating in the generative model space of StyleGAN. While such approaches do not require direct supervision, there is a significant loss of quality when compared to the supervised approaches. In this paper, we present a method which learns from limited supervised training data. The training images only include people in a fixed neutral expression with eyes closed, without much hair or background variations. Each person is captured under 150 one-light-at-a-time conditions and under 8 camera poses. Instead of training directly in the image space, we design a supervised problem which learns transformations in the latent space of StyleGAN. This combines the best of supervised learning and generative adversarial modeling. We show that the StyleGAN prior allows for generalisation to different expressions, hairstyles and backgrounds. This produces high-quality photorealistic results for in-the-wild images and significantly outperforms existing methods. Our approach can edit the illumination and pose simultaneously, and runs at interactive rates.}, author = {Mallikarjun, B. R. and Tewari, Ayush and Dib, Abdallah and Weyrich, Tim and Bickel, Bernd and Seidel, Hans Peter and Pfister, Hanspeter and Matusik, Wojciech and Chevallier, Louis and Elgharib, Mohamed A. and Theobalt, Christian}, issn = {15577368}, journal = {ACM Transactions on Graphics}, number = {4}, publisher = {Association for Computing Machinery}, title = {{PhotoApp: Photorealistic appearance editing of head portraits}}, doi = {10.1145/3450626.3459765}, volume = {40}, year = {2021}, } @article{9816, abstract = {Aims: Mass antigen testing programs have been challenged because of an alleged insufficient specificity, leading to a large number of false positives. The objective of this study is to derive a lower bound of the specificity of the SD Biosensor Standard Q Ag-Test in large scale practical use. Methods: Based on county data from the nationwide tests for SARS-CoV-2 in Slovakia between 31.10.–1.11. 2020 we calculate a lower confidence bound for the specificity. As positive test results were not systematically verified by PCR tests, we base the lower bound on a worst case assumption, assuming all positives to be false positives. Results: 3,625,332 persons from 79 counties were tested. The lowest positivity rate was observed in the county of Rožňava where 100 out of 34307 (0.29%) tests were positive. This implies a test specificity of at least 99.6% (97.5% one-sided lower confidence bound, adjusted for multiplicity). Conclusion: The obtained lower bound suggests a higher specificity compared to earlier studies in spite of the underlying worst case assumption and the application in a mass testing setting. The actual specificity is expected to exceed 99.6% if the prevalence in the respective regions was non-negligible at the time of testing. To our knowledge, this estimate constitutes the first bound obtained from large scale practical use of an antigen test.}, author = {Hledik, Michal and Polechova, Jitka and Beiglböck, Mathias and Herdina, Anna Nele and Strassl, Robert and Posch, Martin}, issn = {1932-6203}, journal = {PLoS ONE}, number = {7}, publisher = {Public Library of Science}, title = {{Analysis of the specificity of a COVID-19 antigen test in the Slovak mass testing program}}, doi = {10.1371/journal.pone.0255267}, volume = {16}, year = {2021}, } @article{9821, abstract = {Heart rate variability (hrv) is a physiological phenomenon of the variation in the length of the time interval between consecutive heartbeats. In many cases it could be an indicator of the development of pathological states. The classical approach to the analysis of hrv includes time domain methods and frequency domain methods. However, attempts are still being made to define new and more effective hrv assessment tools. Persistent homology is a novel data analysis tool developed in the recent decades that is rooted at algebraic topology. The Topological Data Analysis (TDA) approach focuses on examining the shape of the data in terms of connectedness and holes, and has recently proved to be very effective in various fields of research. In this paper we propose the use of persistent homology to the hrv analysis. We recall selected topological descriptors used in the literature and we introduce some new topological descriptors that reflect the specificity of hrv, and we discuss their relation to the standard hrv measures. In particular, we show that this novel approach provides a collection of indices that might be at least as useful as the classical parameters in differentiating between series of beat-to-beat intervals (RR-intervals) in healthy subjects and patients suffering from a stroke episode.}, author = {Graff, Grzegorz and Graff, Beata and Pilarczyk, Pawel and Jablonski, Grzegorz and Gąsecki, Dariusz and Narkiewicz, Krzysztof}, issn = {19326203}, journal = {PLoS ONE}, number = {7}, publisher = {Public Library of Science}, title = {{Persistent homology as a new method of the assessment of heart rate variability}}, doi = {10.1371/journal.pone.0253851}, volume = {16}, year = {2021}, }