@article{7665, abstract = {Acute brain slice preparation is a powerful experimental model for investigating the characteristics of synaptic function in the brain. Although brain tissue is usually cut at ice-cold temperature (CT) to facilitate slicing and avoid neuronal damage, exposure to CT causes molecular and architectural changes of synapses. To address these issues, we investigated ultrastructural and electrophysiological features of synapses in mouse acute cerebellar slices prepared at ice-cold and physiological temperature (PT). In the slices prepared at CT, we found significant spine loss and reconstruction, synaptic vesicle rearrangement and decrease in synaptic proteins, all of which were not detected in slices prepared at PT. Consistent with these structural findings, slices prepared at PT showed higher release probability. Furthermore, preparation at PT allows electrophysiological recording immediately after slicing resulting in higher detectability of long-term depression (LTD) after motor learning compared with that at CT. These results indicate substantial advantages of the slice preparation at PT for investigating synaptic functions in different physiological conditions.}, author = {Eguchi, Kohgaku and Velicky, Philipp and Hollergschwandtner, Elena and Itakura, Makoto and Fukazawa, Yugo and Danzl, Johann G and Shigemoto, Ryuichi}, issn = {16625102}, journal = {Frontiers in Cellular Neuroscience}, publisher = {Frontiers Media}, title = {{Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions}}, doi = {10.3389/fncel.2020.00063}, volume = {14}, year = {2020}, } @article{7666, abstract = {Generalizing the decomposition of a connected planar graph into a tree and a dual tree, we prove a combinatorial analog of the classic Helmholtz–Hodge decomposition of a smooth vector field. Specifically, we show that for every polyhedral complex, K, and every dimension, p, there is a partition of the set of p-cells into a maximal p-tree, a maximal p-cotree, and a collection of p-cells whose cardinality is the p-th reduced Betti number of K. Given an ordering of the p-cells, this tri-partition is unique, and it can be computed by a matrix reduction algorithm that also constructs canonical bases of cycle and boundary groups.}, author = {Edelsbrunner, Herbert and Ölsböck, Katharina}, issn = {14320444}, journal = {Discrete and Computational Geometry}, pages = {759--775}, publisher = {Springer Nature}, title = {{Tri-partitions and bases of an ordered complex}}, doi = {10.1007/s00454-020-00188-x}, volume = {64}, year = {2020}, } @article{7672, abstract = {Large overpotentials upon discharge and charge of Li-O2 cells have motivated extensive research into heterogeneous solid electrocatalysts or non-carbon electrodes with the aim to improve rate capability, round-trip efficiency and cycle life. These features are equally governed by parasitic reactions, which are now recognized to be caused by the highly reactive singlet oxygen (1O2). However, the link between the presence of electrocatalysts and 1O2 formation in metal-O2 cells is unknown. Here, we show that, compared to pristine carbon black electrodes, a representative selection of electrocatalysts or non-carbon electrodes (noble metal, transition metal compounds) may both slightly reduce or severely increase the 1O2 formation. The individual reaction steps, where the surfaces impact the 1O2 yield are deciphered, showing that 1O2 yield from superoxide disproportionation as well as the decomposition of trace H2O2 are sensitive to catalysts. Transition metal compounds in general are prone to increase 1O2.}, author = {Samojlov, Aleksej and Schuster, David and Kahr, Jürgen and Freunberger, Stefan Alexander}, journal = {Electrochimica Acta}, number = {12}, publisher = {Elsevier}, title = {{Surface and catalyst driven singlet oxygen formation in Li-O2 cells}}, doi = {10.1016/j.electacta.2020.137175}, volume = {362}, year = {2020}, } @unpublished{7673, abstract = {Combining drugs can improve the efficacy of treatments. However, predicting the effect of drug combinations is still challenging. The combined potency of drugs determines the drug interaction, which is classified as synergistic, additive, antagonistic, or suppressive. While probabilistic, non-mechanistic models exist, there is currently no biophysical model that can predict antibiotic interactions. Here, we present a physiologically relevant model of the combined action of antibiotics that inhibit protein synthesis by targeting the ribosome. This model captures the kinetics of antibiotic binding and transport, and uses bacterial growth laws to predict growth in the presence of antibiotic combinations. We find that this biophysical model can produce all drug interaction types except suppression. We show analytically that antibiotics which cannot bind to the ribosome simultaneously generally act as substitutes for one another, leading to additive drug interactions. Previously proposed null expectations for higher-order drug interactions follow as a limiting case of our model. We further extend the model to include the effects of direct physical or allosteric interactions between individual drugs on the ribosome. Notably, such direct interactions profoundly change the combined drug effect, depending on the kinetic parameters of the drugs used. The model makes additional predictions for the effects of resistance genes on drug interactions and for interactions between ribosome-targeting antibiotics and antibiotics with other targets. These findings enhance our understanding of the interplay between drug action and cell physiology and are a key step toward a general framework for predicting drug interactions.}, author = {Kavcic, Bor and Tkačik, Gašper and Bollenbach, Tobias}, booktitle = {bioRxiv}, publisher = {Cold Spring Harbor Laboratory}, title = {{A minimal biophysical model of combined antibiotic action}}, doi = {10.1101/2020.04.18.047886}, year = {2020}, } @unpublished{7675, abstract = {In prokaryotes, thermodynamic models of gene regulation provide a highly quantitative mapping from promoter sequences to gene expression levels that is compatible with in vivo and in vitro bio-physical measurements. Such concordance has not been achieved for models of enhancer function in eukaryotes. In equilibrium models, it is difficult to reconcile the reported short transcription factor (TF) residence times on the DNA with the high specificity of regulation. In non-equilibrium models, progress is difficult due to an explosion in the number of parameters. Here, we navigate this complexity by looking for minimal non-equilibrium enhancer models that yield desired regulatory phenotypes: low TF residence time, high specificity and tunable cooperativity. We find that a single extra parameter, interpretable as the “linking rate” by which bound TFs interact with Mediator components, enables our models to escape equilibrium bounds and access optimal regulatory phenotypes, while remaining consistent with the reported phenomenology and simple enough to be inferred from upcoming experiments. We further find that high specificity in non-equilibrium models is in a tradeoff with gene expression noise, predicting bursty dynamics — an experimentally-observed hallmark of eukaryotic transcription. By drastically reducing the vast parameter space to a much smaller subspace that optimally realizes biological function prior to inference from data, our normative approach holds promise for mathematical models in systems biology.}, author = {Grah, Rok and Zoller, Benjamin and Tkačik, Gašper}, booktitle = {bioRxiv}, publisher = {Cold Spring Harbor Laboratory}, title = {{Normative models of enhancer function}}, doi = {10.1101/2020.04.08.029405}, year = {2020}, } @phdthesis{7680, abstract = {Proteins and their complex dynamic interactions regulate cellular mechanisms from sensing and transducing extracellular signals, to mediating genetic responses, and sustaining or changing cell morphology. To manipulate these protein-protein interactions (PPIs) that govern the behavior and fate of cells, synthetically constructed, genetically encoded tools provide the means to precisely target proteins of interest (POIs), and control their subcellular localization and activity in vitro and in vivo. Ideal synthetic tools react to an orthogonal cue, i.e. a trigger that does not activate any other endogenous process, thereby allowing manipulation of the POI alone. In optogenetics, naturally occurring photosensory domain from plants, algae and bacteria are re-purposed and genetically fused to POIs. Illumination with light of a specific wavelength triggers a conformational change that can mediate PPIs, such as dimerization or oligomerization. By using light as a trigger, these tools can be activated with high spatial and temporal precision, on subcellular and millisecond scales. Chemogenetic tools consist of protein domains that recognize and bind small molecules. By genetic fusion to POIs, these domains can mediate PPIs upon addition of their specific ligands, which are often synthetically designed to provide highly specific interactions and exhibit good bioavailability. Most optogenetic tools to mediate PPIs are based on well-studied photoreceptors responding to red, blue or near-UV light, leaving a striking gap in the green band of the visible light spectrum. Among both optogenetic and chemogenetic tools, there is an abundance of methods to induce PPIs, but tools to disrupt them require UV illumination, rely on covalent linkage and subsequent enzymatic cleavage or initially result in protein clustering of unknown stoichiometry. This work describes how the recently structurally and photochemically characterized green-light responsive cobalamin-binding domains (CBDs) from bacterial transcription factors were re-purposed to function as a green-light responsive optogenetic tool. In contrast to previously engineered optogenetic tools, CBDs do not induce PPI, but rather confer a PPI already upon expression, which can be rapidly disrupted by illumination. This was employed to mimic inhibition of constitutive activity of a growth factor receptor, and successfully implement for cell signalling in mammalian cells and in vivo to rescue development in zebrafish. This work further describes the development and application of a chemically induced de-dimerizer (CDD) based on a recently identified and structurally described bacterial oxyreductase. CDD forms a dimer upon expression in absence of its cofactor, the flavin derivative F420. Safety and of domain expression and ligand exposure are demonstrated in vitro and in vivo in zebrafish. The system is further applied to inhibit cell signalling output from a chimeric receptor upon F420 treatment. CBDs and CDD expand the repertoire of synthetic tools by providing novel mechanisms of mediating PPIs, and by recognizing previously not utilized cues. In the future, they can readily be combined with existing synthetic tools to functionally manipulate PPIs in vitro and in vivo.}, author = {Kainrath, Stephanie}, issn = {2663-337X}, pages = {98}, publisher = {Institute of Science and Technology Austria}, title = {{Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals}}, doi = {10.15479/AT:ISTA:7680}, year = {2020}, } @article{7683, abstract = {For any free oriented Borel–Moore homology theory A, we construct an associative product on the A-theory of the stack of Higgs torsion sheaves over a projective curve C. We show that the resulting algebra AHa0C admits a natural shuffle presentation, and prove it is faithful when A is replaced with usual Borel–Moore homology groups. We also introduce moduli spaces of stable triples, heavily inspired by Nakajima quiver varieties, whose A-theory admits an AHa0C-action. These triples can be interpreted as certain sheaves on PC(ωC⊕OC). In particular, we obtain an action of AHa0C on the cohomology of Hilbert schemes of points on T∗C.}, author = {Minets, Sasha}, issn = {14209020}, journal = {Selecta Mathematica, New Series}, number = {2}, publisher = {Springer Nature}, title = {{Cohomological Hall algebras for Higgs torsion sheaves, moduli of triples and sheaves on surfaces}}, doi = {10.1007/s00029-020-00553-x}, volume = {26}, year = {2020}, } @article{7684, author = {Gridchyn, Igor and Schönenberger, Philipp and O'Neill, Joseph and Csicsvari, Jozsef L}, issn = {10974199}, journal = {Neuron}, number = {2}, pages = {291--300.e6}, publisher = {Elsevier}, title = {{Assembly-specific disruption of hippocampal replay leads to selective memory deficit}}, doi = {10.1016/j.neuron.2020.01.021}, volume = {106}, year = {2020}, } @article{7686, abstract = {The agricultural green revolution spectacularly enhanced crop yield and lodging resistance with modified DELLA-mediated gibberellin signaling. However, this was achieved at the expense of reduced nitrogen-use efficiency (NUE). Recently, Wu et al. revealed novel gibberellin signaling that provides a blueprint for improving tillering and NUE in Green Revolution varieties (GRVs). }, author = {Xue, Huidan and Zhang, Yuzhou and Xiao, Guanghui}, issn = {1360-1385}, journal = {Trends in Plant Science}, number = {6}, pages = {520--522}, publisher = {Elsevier}, title = {{Neo-gibberellin signaling: Guiding the next generation of the green revolution}}, doi = {10.1016/j.tplants.2020.04.001}, volume = {25}, year = {2020}, } @article{7687, abstract = {A working group, which was established within the Network of Repository Managers (RepManNet), has dealt with common certifications for repositories. In addition, current requirements of the research funding agencies FWF and EU were also taken into account. The Core Trust Seal was examined in more detail. For this purpose, a questionnaire was sent to those organizations that are already certified with CTS in Austria. The answers were summarized and evaluated anonymously. It is recommended to go for a repository certification. Moreover, the development of a DINI certificate in Austria is strongly suggested.}, author = {Ernst, Doris and Novotny, Gertraud and Schönher, Eva Maria}, issn = {1022-2588}, journal = {Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare}, number = {1}, pages = {46--59}, publisher = {Vereinigung Osterreichischer Bibliothekarinnen und Bibliothekare}, title = {{(Core Trust) Seal your repository!}}, doi = {10.31263/voebm.v73i1.3491}, volume = {73}, year = {2020}, } @misc{7689, abstract = {These are the supplementary research data to the publication "Zero field splitting of heavy-hole states in quantum dots". All matrix files have the same format. Within each column the bias voltage is changed. Each column corresponds to either a different gate voltage or magnetic field. The voltage values are given in mV, the current values in pA. Find a specific description in the included Readme file. }, author = {Katsaros, Georgios}, publisher = {Institute of Science and Technology Austria}, title = {{Supplementary data for "Zero field splitting of heavy-hole states in quantum dots"}}, doi = {10.15479/AT:ISTA:7689}, year = {2020}, } @article{7695, abstract = {The TPLATE complex (TPC) is a key endocytic adaptor protein complex in plants. TPC in Arabidopsis (Arabidopsis thaliana) contains six evolutionarily conserved subunits and two plant-specific subunits, AtEH1/Pan1 and AtEH2/Pan1, although cytoplasmic proteins are not associated with the hexameric subcomplex in the cytoplasm. To investigate the dynamic assembly of the octameric TPC at the plasma membrane (PM), we performed state-of-the-art dual-color live cell imaging at physiological and lowered temperatures. Lowering the temperature slowed down endocytosis, thereby enhancing the temporal resolution of the differential recruitment of endocytic components. Under both normal and lowered temperature conditions, the core TPC subunit TPLATE and the AtEH/Pan1 proteins exhibited simultaneous recruitment at the PM. These results, together with co-localization analysis of different TPC subunits, allow us to conclude that TPC in plant cells is not recruited to the PM sequentially but as an octameric complex.}, author = {Wang, J and Mylle, E and Johnson, Alexander J and Besbrugge, N and De Jaeger, G and Friml, Jiří and Pleskot, R and van Damme, D}, issn = {1532-2548}, journal = {Plant Physiology}, number = {3}, pages = {986--997}, publisher = {American Society of Plant Biologists}, title = {{High temporal resolution reveals simultaneous plasma membrane recruitment of TPLATE complex subunits}}, doi = {10.1104/pp.20.00178}, volume = {183}, year = {2020}, } @article{7697, abstract = {* Morphogenesis and adaptive tropic growth in plants depend on gradients of the phytohormone auxin, mediated by the membrane‐based PIN‐FORMED (PIN) auxin transporters. PINs localize to a particular side of the plasma membrane (PM) or to the endoplasmic reticulum (ER) to directionally transport auxin and maintain intercellular and intracellular auxin homeostasis, respectively. However, the molecular cues that confer their diverse cellular localizations remain largely unknown. * In this study, we systematically swapped the domains between ER‐ and PM‐localized PIN proteins, as well as between apical and basal PM‐localized PINs from Arabidopsis thaliana , to shed light on why PIN family members with similar topological structures reside at different membrane compartments within cells. * Our results show that not only do the N‐ and C‐terminal transmembrane domains (TMDs) and central hydrophilic loop contribute to their differential subcellular localizations and cellular polarity, but that the pairwise‐matched N‐ and C‐terminal TMDs resulting from intramolecular domain–domain coevolution are also crucial for their divergent patterns of localization. * These findings illustrate the complexity of the evolutionary path of PIN proteins in acquiring their plethora of developmental functions and adaptive growth in plants.}, author = {Zhang, Yuzhou and Hartinger, Corinna and Wang, Xiaojuan and Friml, Jiří}, issn = {1469-8137}, journal = {New Phytologist}, number = {5}, pages = {1406--1416}, publisher = {Wiley}, title = {{Directional auxin fluxes in plants by intramolecular domain‐domain co‐evolution of PIN auxin transporters}}, doi = {10.1111/nph.16629}, volume = {227}, year = {2020}, } @article{7707, abstract = {The growing sample size of genome-wide association studies has facilitated the discovery of gene-environment interactions (GxE). Here we propose a maximum likelihood method to estimate the contribution of GxE to continuous traits taking into account all interacting environmental variables, without the need to measure any. Extensive simulations demonstrate that our method provides unbiased interaction estimates and excellent coverage. We also offer strategies to distinguish specific GxE from general scale effects. Applying our method to 32 traits in the UK Biobank reveals that while the genetic risk score (GRS) of 376 variants explains 5.2% of body mass index (BMI) variance, GRSxE explains an additional 1.9%. Nevertheless, this interaction holds for any variable with identical correlation to BMI as the GRS, hence may not be GRS-specific. Still, we observe that the global contribution of specific GRSxE to complex traits is substantial for nine obesity-related measures (including leg impedance and trunk fat-free mass).}, author = {Sulc, Jonathan and Mounier, Ninon and Günther, Felix and Winkler, Thomas and Wood, Andrew R. and Frayling, Timothy M. and Heid, Iris M. and Robinson, Matthew Richard and Kutalik, Zoltán}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Quantification of the overall contribution of gene-environment interaction for obesity-related traits}}, doi = {10.1038/s41467-020-15107-0}, volume = {11}, year = {2020}, } @article{7708, abstract = {We conducted DNA methylation association analyses using Illumina 450K data from whole blood for an Australian amyotrophic lateral sclerosis (ALS) case–control cohort (782 cases and 613 controls). Analyses used mixed linear models as implemented in the OSCA software. We found a significantly higher proportion of neutrophils in cases compared to controls which replicated in an independent cohort from the Netherlands (1159 cases and 637 controls). The OSCA MOMENT linear mixed model has been shown in simulations to best account for confounders. When combined in a methylation profile score, the 25 most-associated probes identified by MOMENT significantly classified case–control status in the Netherlands sample (area under the curve, AUC = 0.65, CI95% = [0.62–0.68], p = 8.3 × 10−22). The maximum AUC achieved was 0.69 (CI95% = [0.66–0.71], p = 4.3 × 10−34) when cell-type proportion was included in the predictor.}, author = {Nabais, Marta F. and Lin, Tian and Benyamin, Beben and Williams, Kelly L. and Garton, Fleur C. and Vinkhuyzen, Anna A. E. and Zhang, Futao and Vallerga, Costanza L. and Restuadi, Restuadi and Freydenzon, Anna and Zwamborn, Ramona A. J. and Hop, Paul J. and Robinson, Matthew Richard and Gratten, Jacob and Visscher, Peter M. and Hannon, Eilis and Mill, Jonathan and Brown, Matthew A. and Laing, Nigel G. and Mather, Karen A. and Sachdev, Perminder S. and Ngo, Shyuan T. and Steyn, Frederik J. and Wallace, Leanne and Henders, Anjali K. and Needham, Merrilee and Veldink, Jan H. and Mathers, Susan and Nicholson, Garth and Rowe, Dominic B. and Henderson, Robert D. and McCombe, Pamela A. and Pamphlett, Roger and Yang, Jian and Blair, Ian P. and McRae, Allan F. and Wray, Naomi R.}, issn = {2056-7944}, journal = {npj Genomic Medicine}, publisher = {Springer Nature}, title = {{Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis}}, doi = {10.1038/s41525-020-0118-3}, volume = {5}, year = {2020}, } @article{5681, abstract = {We introduce dynamically warping grids for adaptive liquid simulation. Our primary contributions are a strategy for dynamically deforming regular grids over the course of a simulation and a method for efficiently utilizing these deforming grids for liquid simulation. Prior work has shown that unstructured grids are very effective for adaptive fluid simulations. However, unstructured grids often lead to complicated implementations and a poor cache hit rate due to inconsistent memory access. Regular grids, on the other hand, provide a fast, fixed memory access pattern and straightforward implementation. Our method combines the advantages of both: we leverage the simplicity of regular grids while still achieving practical and controllable spatial adaptivity. We demonstrate that our method enables adaptive simulations that are fast, flexible, and robust to null-space issues. At the same time, our method is simple to implement and takes advantage of existing highly-tuned algorithms.}, author = {Hikaru, Ibayashi and Wojtan, Christopher J and Thuerey, Nils and Igarashi, Takeo and Ando, Ryoichi}, issn = {19410506}, journal = {IEEE Transactions on Visualization and Computer Graphics}, number = {6}, pages = {2288--2302}, publisher = {IEEE}, title = {{Simulating liquids on dynamically warping grids}}, doi = {10.1109/TVCG.2018.2883628}, volume = {26}, year = {2020}, } @article{6184, abstract = {We prove edge universality for a general class of correlated real symmetric or complex Hermitian Wigner matrices with arbitrary expectation. Our theorem also applies to internal edges of the self-consistent density of states. In particular, we establish a strong form of band rigidity which excludes mismatches between location and label of eigenvalues close to internal edges in these general models.}, author = {Alt, Johannes and Erdös, László and Krüger, Torben H and Schröder, Dominik J}, issn = {0091-1798}, journal = {Annals of Probability}, number = {2}, pages = {963--1001}, publisher = {Institute of Mathematical Statistics}, title = {{Correlated random matrices: Band rigidity and edge universality}}, doi = {10.1214/19-AOP1379}, volume = {48}, year = {2020}, } @article{6185, abstract = {For complex Wigner-type matrices, i.e. Hermitian random matrices with independent, not necessarily identically distributed entries above the diagonal, we show that at any cusp singularity of the limiting eigenvalue distribution the local eigenvalue statistics are universal and form a Pearcey process. Since the density of states typically exhibits only square root or cubic root cusp singularities, our work complements previous results on the bulk and edge universality and it thus completes the resolution of the Wigner–Dyson–Mehta universality conjecture for the last remaining universality type in the complex Hermitian class. Our analysis holds not only for exact cusps, but approximate cusps as well, where an extended Pearcey process emerges. As a main technical ingredient we prove an optimal local law at the cusp for both symmetry classes. This result is also the key input in the companion paper (Cipolloni et al. in Pure Appl Anal, 2018. arXiv:1811.04055) where the cusp universality for real symmetric Wigner-type matrices is proven. The novel cusp fluctuation mechanism is also essential for the recent results on the spectral radius of non-Hermitian random matrices (Alt et al. in Spectral radius of random matrices with independent entries, 2019. arXiv:1907.13631), and the non-Hermitian edge universality (Cipolloni et al. in Edge universality for non-Hermitian random matrices, 2019. arXiv:1908.00969).}, author = {Erdös, László and Krüger, Torben H and Schröder, Dominik J}, issn = {1432-0916}, journal = {Communications in Mathematical Physics}, pages = {1203--1278}, publisher = {Springer Nature}, title = {{Cusp universality for random matrices I: Local law and the complex Hermitian case}}, doi = {10.1007/s00220-019-03657-4}, volume = {378}, year = {2020}, } @article{6358, abstract = {We study dynamical optimal transport metrics between density matricesassociated to symmetric Dirichlet forms on finite-dimensional C∗-algebras. Our settingcovers arbitrary skew-derivations and it provides a unified framework that simultaneously generalizes recently constructed transport metrics for Markov chains, Lindblad equations, and the Fermi Ornstein–Uhlenbeck semigroup. We develop a non-nommutative differential calculus that allows us to obtain non-commutative Ricci curvature bounds, logarithmic Sobolev inequalities, transport-entropy inequalities, andspectral gap estimates.}, author = {Carlen, Eric A. and Maas, Jan}, issn = {15729613}, journal = {Journal of Statistical Physics}, number = {2}, pages = {319--378}, publisher = {Springer Nature}, title = {{Non-commutative calculus, optimal transport and functional inequalities in dissipative quantum systems}}, doi = {10.1007/s10955-019-02434-w}, volume = {178}, year = {2020}, } @article{6359, abstract = {The strong rate of convergence of the Euler-Maruyama scheme for nondegenerate SDEs with irregular drift coefficients is considered. In the case of α-Hölder drift in the recent literature the rate α/2 was proved in many related situations. By exploiting the regularising effect of the noise more efficiently, we show that the rate is in fact arbitrarily close to 1/2 for all α>0. The result extends to Dini continuous coefficients, while in d=1 also to all bounded measurable coefficients.}, author = {Dareiotis, Konstantinos and Gerencser, Mate}, issn = {1083-6489}, journal = {Electronic Journal of Probability}, publisher = {Institute of Mathematical Statistics}, title = {{On the regularisation of the noise for the Euler-Maruyama scheme with irregular drift}}, doi = {10.1214/20-EJP479}, volume = {25}, year = {2020}, }