@article{10548, abstract = {Consider a linear elliptic partial differential equation in divergence form with a random coefficient field. The solution operator displays fluctuations around its expectation. The recently developed pathwise theory of fluctuations in stochastic homogenization reduces the characterization of these fluctuations to those of the so-called standard homogenization commutator. In this contribution, we investigate the scaling limit of this key quantity: starting from a Gaussian-like coefficient field with possibly strong correlations, we establish the convergence of the rescaled commutator to a fractional Gaussian field, depending on the decay of correlations of the coefficient field, and we investigate the (non)degeneracy of the limit. This extends to general dimension $d\ge1$ previous results so far limited to dimension $d=1$, and to the continuum setting with strong correlations recent results in the discrete iid case.}, author = {Duerinckx, Mitia and Fischer, Julian L and Gloria, Antoine}, issn = {1050-5164}, journal = {Annals of Applied Probability}, number = {2}, pages = {1179--1209}, publisher = {Institute of Mathematical Statistics}, title = {{Scaling limit of the homogenization commutator for Gaussian coefficient fields}}, doi = {10.1214/21-AAP1705}, volume = {32}, year = {2022}, } @unpublished{14597, abstract = {Phase-field models such as the Allen-Cahn equation may give rise to the formation and evolution of geometric shapes, a phenomenon that may be analyzed rigorously in suitable scaling regimes. In its sharp-interface limit, the vectorial Allen-Cahn equation with a potential with N≥3 distinct minima has been conjectured to describe the evolution of branched interfaces by multiphase mean curvature flow. In the present work, we give a rigorous proof for this statement in two and three ambient dimensions and for a suitable class of potentials: As long as a strong solution to multiphase mean curvature flow exists, solutions to the vectorial Allen-Cahn equation with well-prepared initial data converge towards multiphase mean curvature flow in the limit of vanishing interface width parameter ε↘0. We even establish the rate of convergence O(ε1/2). Our approach is based on the gradient flow structure of the Allen-Cahn equation and its limiting motion: Building on the recent concept of "gradient flow calibrations" for multiphase mean curvature flow, we introduce a notion of relative entropy for the vectorial Allen-Cahn equation with multi-well potential. This enables us to overcome the limitations of other approaches, e.g. avoiding the need for a stability analysis of the Allen-Cahn operator or additional convergence hypotheses for the energy at positive times.}, author = {Fischer, Julian L and Marveggio, Alice}, booktitle = {arXiv}, title = {{Quantitative convergence of the vectorial Allen-Cahn equation towards multiphase mean curvature flow}}, doi = {10.48550/ARXIV.2203.17143}, year = {2022}, } @article{12231, abstract = {Ventral tail bending, which is transient but pronounced, is found in many chordate embryos and constitutes an interesting model of how tissue interactions control embryo shape. Here, we identify one key upstream regulator of ventral tail bending in embryos of the ascidian Ciona. We show that during the early tailbud stages, ventral epidermal cells exhibit a boat-shaped morphology (boat cell) with a narrow apical surface where phosphorylated myosin light chain (pMLC) accumulates. We further show that interfering with the function of the BMP ligand Admp led to pMLC localizing to the basal instead of the apical side of ventral epidermal cells and a reduced number of boat cells. Finally, we show that cutting ventral epidermal midline cells at their apex using an ultraviolet laser relaxed ventral tail bending. Based on these results, we propose a previously unreported function for Admp in localizing pMLC to the apical side of ventral epidermal cells, which causes the tail to bend ventrally by resisting antero-posterior notochord extension at the ventral side of the tail.}, author = {Kogure, Yuki S. and Muraoka, Hiromochi and Koizumi, Wataru C. and Gelin-alessi, Raphaël and Godard, Benoit G and Oka, Kotaro and Heisenberg, Carl-Philipp J and Hotta, Kohji}, issn = {1477-9129}, journal = {Development}, keywords = {Developmental Biology, Molecular Biology}, number = {21}, publisher = {Company of Biologists}, title = {{Admp regulates tail bending by controlling ventral epidermal cell polarity via phosphorylated myosin localization in Ciona}}, doi = {10.1242/dev.200215}, volume = {149}, year = {2022}, } @article{12245, abstract = {MicroRNAs (miRs) have an important role in tuning dynamic gene expression. However, the mechanism by which they are quantitatively controlled is unknown. We show that the amount of mature miR-9, a key regulator of neuronal development, increases during zebrafish neurogenesis in a sharp stepwise manner. We characterize the spatiotemporal profile of seven distinct microRNA primary transcripts (pri-mir)-9s that produce the same mature miR-9 and show that they are sequentially expressed during hindbrain neurogenesis. Expression of late-onset pri-mir-9-1 is added on to, rather than replacing, the expression of early onset pri-mir-9-4 and -9-5 in single cells. CRISPR/Cas9 mutation of the late-onset pri-mir-9-1 prevents the developmental increase of mature miR-9, reduces late neuronal differentiation and fails to downregulate Her6 at late stages. Mathematical modelling shows that an adaptive network containing Her6 is insensitive to linear increases in miR-9 but responds to stepwise increases of miR-9. We suggest that a sharp stepwise increase of mature miR-9 is created by sequential and additive temporal activation of distinct loci. This may be a strategy to overcome adaptation and facilitate a transition of Her6 to a new dynamic regime or steady state.}, author = {Soto, Ximena and Burton, Joshua and Manning, Cerys S. and Minchington, Thomas and Lea, Robert and Lee, Jessica and Kursawe, Jochen and Rattray, Magnus and Papalopulu, Nancy}, issn = {1477-9129}, journal = {Development}, keywords = {Developmental Biology, Molecular Biology}, number = {19}, publisher = {Company of Biologists}, title = {{Sequential and additive expression of miR-9 precursors control timing of neurogenesis}}, doi = {10.1242/dev.200474}, volume = {149}, year = {2022}, } @article{10735, abstract = {Magnetic anisotropy in strontium iridate (Sr2IrO4) is essential because of its strong spin–orbit coupling and crystal field effect. In this paper, we present a detailed mapping of the out-of-plane (OOP) magnetic anisotropy in Sr2IrO4 for different sample orientations using torque magnetometry measurements in the low-magnetic-field region before the isospins are completely ordered. Dominant in-plane anisotropy was identified at low fields, confirming the b axis as an easy magnetization axis. Based on the fitting analysis of the strong uniaxial magnetic anisotropy, we observed that the main anisotropic effect arises from a spin–orbit-coupled magnetic exchange interaction affecting the OOP interaction. The effect of interlayer exchange interaction results in additional anisotropic terms owing to the tilting of the isospins. The results are relevant for understanding OOP magnetic anisotropy and provide a new way to analyze the effects of spin–orbit-coupling and interlayer magnetic exchange interactions. This study provides insight into the understanding of bulk magnetic, magnetotransport, and spintronic behavior on Sr2IrO4 for future studies.}, author = {Nauman, Muhammad and Hussain, Tayyaba and Choi, Joonyoung and Lee, Nara and Choi, Young Jai and Kang, Woun and Jo, Younjung}, issn = {1361-648X}, journal = {Journal of Physics: Condensed Matter}, number = {13}, publisher = {IOP Publishing}, title = {{Low-field magnetic anisotropy of Sr2IrO4}}, doi = {10.1088/1361-648X/ac484d}, volume = {34}, year = {2022}, } @article{11660, abstract = {We characterize critical points of 1-dimensional maps paired in persistent homology geometrically and this way get elementary proofs of theorems about the symmetry of persistence diagrams and the variation of such maps. In particular, we identify branching points and endpoints of networks as the sole source of asymmetry and relate the cycle basis in persistent homology with a version of the stable marriage problem. Our analysis provides the foundations of fast algorithms for maintaining collections of interrelated sorted lists together with their persistence diagrams. }, author = {Biswas, Ranita and Cultrera di Montesano, Sebastiano and Edelsbrunner, Herbert and Saghafian, Morteza}, journal = {LIPIcs}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{A window to the persistence of 1D maps. I: Geometric characterization of critical point pairs}}, year = {2022}, } @article{12291, abstract = {The phytohormone auxin triggers transcriptional reprogramming through a well-characterized perception machinery in the nucleus. By contrast, mechanisms that underlie fast effects of auxin, such as the regulation of ion fluxes, rapid phosphorylation of proteins or auxin feedback on its transport, remain unclear1,2,3. Whether auxin-binding protein 1 (ABP1) is an auxin receptor has been a source of debate for decades1,4. Here we show that a fraction of Arabidopsis thaliana ABP1 is secreted and binds auxin specifically at an acidic pH that is typical of the apoplast. ABP1 and its plasma-membrane-localized partner, transmembrane kinase 1 (TMK1), are required for the auxin-induced ultrafast global phospho-response and for downstream processes that include the activation of H+-ATPase and accelerated cytoplasmic streaming. abp1 and tmk mutants cannot establish auxin-transporting channels and show defective auxin-induced vasculature formation and regeneration. An ABP1(M2X) variant that lacks the capacity to bind auxin is unable to complement these defects in abp1 mutants. These data indicate that ABP1 is the auxin receptor for TMK1-based cell-surface signalling, which mediates the global phospho-response and auxin canalization.}, author = {Friml, Jiří and Gallei, Michelle C and Gelová, Zuzana and Johnson, Alexander J and Mazur, Ewa and Monzer, Aline and Rodriguez Solovey, Lesia and Roosjen, Mark and Verstraeten, Inge and Živanović, Branka D. and Zou, Minxia and Fiedler, Lukas and Giannini, Caterina and Grones, Peter and Hrtyan, Mónika and Kaufmann, Walter and Kuhn, Andre and Narasimhan, Madhumitha and Randuch, Marek and Rýdza, Nikola and Takahashi, Koji and Tan, Shutang and Teplova, Anastasiia and Kinoshita, Toshinori and Weijers, Dolf and Rakusová, Hana}, issn = {1476-4687}, journal = {Nature}, number = {7927}, pages = {575--581}, publisher = {Springer Nature}, title = {{ABP1–TMK auxin perception for global phosphorylation and auxin canalization}}, doi = {10.1038/s41586-022-05187-x}, volume = {609}, year = {2022}, } @phdthesis{11362, abstract = {Deep learning has enabled breakthroughs in challenging computing problems and has emerged as the standard problem-solving tool for computer vision and natural language processing tasks. One exception to this trend is safety-critical tasks where robustness and resilience requirements contradict the black-box nature of neural networks. To deploy deep learning methods for these tasks, it is vital to provide guarantees on neural network agents' safety and robustness criteria. This can be achieved by developing formal verification methods to verify the safety and robustness properties of neural networks. Our goal is to design, develop and assess safety verification methods for neural networks to improve their reliability and trustworthiness in real-world applications. This thesis establishes techniques for the verification of compressed and adversarially trained models as well as the design of novel neural networks for verifiably safe decision-making. First, we establish the problem of verifying quantized neural networks. Quantization is a technique that trades numerical precision for the computational efficiency of running a neural network and is widely adopted in industry. We show that neglecting the reduced precision when verifying a neural network can lead to wrong conclusions about the robustness and safety of the network, highlighting that novel techniques for quantized network verification are necessary. We introduce several bit-exact verification methods explicitly designed for quantized neural networks and experimentally confirm on realistic networks that the network's robustness and other formal properties are affected by the quantization. Furthermore, we perform a case study providing evidence that adversarial training, a standard technique for making neural networks more robust, has detrimental effects on the network's performance. This robustness-accuracy tradeoff has been studied before regarding the accuracy obtained on classification datasets where each data point is independent of all other data points. On the other hand, we investigate the tradeoff empirically in robot learning settings where a both, a high accuracy and a high robustness, are desirable. Our results suggest that the negative side-effects of adversarial training outweigh its robustness benefits in practice. Finally, we consider the problem of verifying safety when running a Bayesian neural network policy in a feedback loop with systems over the infinite time horizon. Bayesian neural networks are probabilistic models for learning uncertainties in the data and are therefore often used on robotic and healthcare applications where data is inherently stochastic. We introduce a method for recalibrating Bayesian neural networks so that they yield probability distributions over safe decisions only. Our method learns a safety certificate that guarantees safety over the infinite time horizon to determine which decisions are safe in every possible state of the system. We demonstrate the effectiveness of our approach on a series of reinforcement learning benchmarks.}, author = {Lechner, Mathias}, isbn = {978-3-99078-017-6}, keywords = {neural networks, verification, machine learning}, pages = {124}, publisher = {Institute of Science and Technology Austria}, title = {{Learning verifiable representations}}, doi = {10.15479/at:ista:11362}, year = {2022}, } @article{10765, abstract = {We establish the Hardy-Littlewood property (à la Borovoi-Rudnick) for Zariski open subsets in affine quadrics of the form q(x1,...,xn)=m, where q is a non-degenerate integral quadratic form in n>3 variables and m is a non-zero integer. This gives asymptotic formulas for the density of integral points taking coprime polynomial values, which is a quantitative version of the arithmetic purity of strong approximation property off infinity for affine quadrics.}, author = {Cao, Yang and Huang, Zhizhong}, issn = {1090-2082}, journal = {Advances in Mathematics}, number = {3}, publisher = {Elsevier}, title = {{Arithmetic purity of the Hardy-Littlewood property and geometric sieve for affine quadrics}}, doi = {10.1016/j.aim.2022.108236}, volume = {398}, year = {2022}, } @article{17058, abstract = {We compare the Manin-type conjecture for Campana points recently formulated by Pieropan, Smeets, Tanimoto and Várilly-Alvarado with an alternative prediction of Browning and Van Valckenborgh in the special case of the orbifold (P1,D), where D=1/2[0]+1/2[1]+1/2[∞]. We find that the two predicted leading constants do not agree, and we discuss whether thin sets could explain this discrepancy. Motivated by this, we provide a counterexample to the Manin-type conjecture for Campana points, by considering orbifolds corresponding to squareful values of binary quadratic forms.}, author = {Shute, Alec L}, issn = {1730-6264}, journal = {Acta Arithmetica}, number = {4}, pages = {317--346}, publisher = {Institute of Mathematics}, title = {{On the leading constant in the Manin-type conjecture for Campana points}}, doi = {10.4064/aa210430-1-7}, volume = {204}, year = {2022}, } @article{12109, abstract = {Kelvin probe force microscopy (KPFM) is a powerful tool for studying contact electrification (CE) at the nanoscale, but converting KPFM voltage maps to charge density maps is nontrivial due to long-range forces and complex system geometry. Here we present a strategy using finite-element method (FEM) simulations to determine the Green's function of the KPFM probe/insulator/ground system, which allows us to quantitatively extract surface charge. Testing our approach with synthetic data, we find that accounting for the atomic force microscope (AFM) tip, cone, and cantilever is necessary to recover a known input and that existing methods lead to gross miscalculation or even the incorrect sign of the underlying charge. Applying it to experimental data, we demonstrate its capacity to extract realistic surface charge densities and fine details from contact-charged surfaces. Our method gives a straightforward recipe to convert qualitative KPFM voltage data into quantitative charge data over a range of experimental conditions, enabling quantitative CE at the nanoscale.}, author = {Pertl, Felix and Sobarzo Ponce, Juan Carlos A and Shafeek, Lubuna B and Cramer, Tobias and Waitukaitis, Scott R}, issn = {2475-9953}, journal = {Physical Review Materials}, number = {12}, publisher = {American Physical Society}, title = {{Quantifying nanoscale charge density features of contact-charged surfaces with an FEM/KPFM-hybrid approach}}, doi = {10.1103/PhysRevMaterials.6.125605}, volume = {6}, year = {2022}, } @inproceedings{11476, abstract = {Messaging platforms like Signal are widely deployed and provide strong security in an asynchronous setting. It is a challenging problem to construct a protocol with similar security guarantees that can efficiently scale to large groups. A major bottleneck are the frequent key rotations users need to perform to achieve post compromise forward security. In current proposals – most notably in TreeKEM (which is part of the IETF’s Messaging Layer Security (MLS) protocol draft) – for users in a group of size n to rotate their keys, they must each craft a message of size log(n) to be broadcast to the group using an (untrusted) delivery server. In larger groups, having users sequentially rotate their keys requires too much bandwidth (or takes too long), so variants allowing any T≤n users to simultaneously rotate their keys in just 2 communication rounds have been suggested (e.g. “Propose and Commit” by MLS). Unfortunately, 2-round concurrent updates are either damaging or expensive (or both); i.e. they either result in future operations being more costly (e.g. via “blanking” or “tainting”) or are costly themselves requiring Ω(T) communication for each user [Bienstock et al., TCC’20]. In this paper we propose CoCoA; a new scheme that allows for T concurrent updates that are neither damaging nor costly. That is, they add no cost to future operations yet they only require Ω(log2(n)) communication per user. To circumvent the [Bienstock et al.] lower bound, CoCoA increases the number of rounds needed to complete all updates from 2 up to (at most) log(n); though typically fewer rounds are needed. The key insight of our protocol is the following: in the (non-concurrent version of) TreeKEM, a delivery server which gets T concurrent update requests will approve one and reject the remaining T−1. In contrast, our server attempts to apply all of them. If more than one user requests to rotate the same key during a round, the server arbitrarily picks a winner. Surprisingly, we prove that regardless of how the server chooses the winners, all previously compromised users will recover after at most log(n) such update rounds. To keep the communication complexity low, CoCoA is a server-aided CGKA. That is, the delivery server no longer blindly forwards packets, but instead actively computes individualized packets tailored to each user. As the server is untrusted, this change requires us to develop new mechanisms ensuring robustness of the protocol.}, author = {Alwen, Joël and Auerbach, Benedikt and Cueto Noval, Miguel and Klein, Karen and Pascual Perez, Guillermo and Pietrzak, Krzysztof Z and Walter, Michael}, booktitle = {Advances in Cryptology – EUROCRYPT 2022}, isbn = {9783031070846}, issn = {1611-3349}, location = {Trondheim, Norway}, pages = {815–844}, publisher = {Springer Nature}, title = {{CoCoA: Concurrent continuous group key agreement}}, doi = {10.1007/978-3-031-07085-3_28}, volume = {13276}, year = {2022}, } @inproceedings{12101, abstract = {Spatial games form a widely-studied class of games from biology and physics modeling the evolution of social behavior. Formally, such a game is defined by a square (d by d) payoff matrix M and an undirected graph G. Each vertex of G represents an individual, that initially follows some strategy i ∈ {1,2,…,d}. In each round of the game, every individual plays the matrix game with each of its neighbors: An individual following strategy i meeting a neighbor following strategy j receives a payoff equal to the entry (i,j) of M. Then, each individual updates its strategy to its neighbors' strategy with the highest sum of payoffs, and the next round starts. The basic computational problems consist of reachability between configurations and the average frequency of a strategy. For general spatial games and graphs, these problems are in PSPACE. In this paper, we examine restricted setting: the game is a prisoner’s dilemma; and G is a subgraph of grid. We prove that basic computational problems for spatial games with prisoner’s dilemma on a subgraph of a grid are PSPACE-hard.}, author = {Chatterjee, Krishnendu and Ibsen-Jensen, Rasmus and Jecker, Ismael R and Svoboda, Jakub}, booktitle = {42nd IARCS Annual Conference on Foundations of Software Technology and Theoretical Computer Science}, isbn = {9783959772617}, issn = {1868-8969}, location = {Madras, India}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Complexity of spatial games}}, doi = {10.4230/LIPIcs.FSTTCS.2022.11}, volume = {250}, year = {2022}, } @article{12257, abstract = {Structural balance theory is an established framework for studying social relationships of friendship and enmity. These relationships are modeled by a signed network whose energy potential measures the level of imbalance, while stochastic dynamics drives the network toward a state of minimum energy that captures social balance. It is known that this energy landscape has local minima that can trap socially aware dynamics, preventing it from reaching balance. Here we first study the robustness and attractor properties of these local minima. We show that a stochastic process can reach them from an abundance of initial states and that some local minima cannot be escaped by mild perturbations of the network. Motivated by these anomalies, we introduce best-edge dynamics (BED), a new plausible stochastic process. We prove that BED always reaches balance and that it does so fast in various interesting settings.}, author = {Chatterjee, Krishnendu and Svoboda, Jakub and Zikelic, Dorde and Pavlogiannis, Andreas and Tkadlec, Josef}, issn = {2470-0053}, journal = {Physical Review E}, number = {3}, publisher = {American Physical Society}, title = {{Social balance on networks: Local minima and best-edge dynamics}}, doi = {10.1103/physreve.106.034321}, volume = {106}, year = {2022}, } @article{9311, abstract = {Partially observable Markov decision processes (POMDPs) are standard models for dynamic systems with probabilistic and nondeterministic behaviour in uncertain environments. We prove that in POMDPs with long-run average objective, the decision maker has approximately optimal strategies with finite memory. This implies notably that approximating the long-run value is recursively enumerable, as well as a weak continuity property of the value with respect to the transition function. }, author = {Chatterjee, Krishnendu and Saona Urmeneta, Raimundo J and Ziliotto, Bruno}, issn = {1526-5471}, journal = {Mathematics of Operations Research}, keywords = {Management Science and Operations Research, General Mathematics, Computer Science Applications}, number = {1}, pages = {100--119}, publisher = {Institute for Operations Research and the Management Sciences}, title = {{Finite-memory strategies in POMDPs with long-run average objectives}}, doi = {10.1287/moor.2020.1116}, volume = {47}, year = {2022}, } @article{12065, abstract = {Capacity, rate performance, and cycle life of aprotic Li–O2 batteries critically depend on reversible electrodeposition of Li2O2. Current understanding states surface-adsorbed versus solvated LiO2 controls Li2O2 growth as surface film or as large particles. Herein, we show that Li2O2 forms across a wide range of electrolytes, carbons, and current densities as particles via solution-mediated LiO2 disproportionation, bringing into question the prevalence of any surface growth under practical conditions. We describe a unified O2 reduction mechanism, which can explain all found capacity relations and Li2O2 morphologies with exclusive solution discharge. Determining particle morphology and achievable capacities are species mobilities, true areal rate, and the degree of LiO2 association in solution. Capacity is conclusively limited by mass transport through the tortuous Li2O2 rather than electron transport through a passivating Li2O2 film. Provided that species mobilities and surface growth are high, high capacities are also achieved with weakly solvating electrolytes, which were previously considered prototypical for low capacity via surface growth.}, author = {Prehal, Christian and Mondal, Soumyadip and Lovicar, Ludek and Freunberger, Stefan Alexander}, issn = {2380-8195}, journal = {ACS Energy Letters}, number = {9}, pages = {3112--3119}, publisher = {American Chemical Society}, title = {{Exclusive solution discharge in Li-O₂ batteries?}}, doi = {10.1021/acsenergylett.2c01711}, volume = {7}, year = {2022}, } @inproceedings{12537, abstract = {The Neural Tangent Kernel (NTK) has emerged as a powerful tool to provide memorization, optimization and generalization guarantees in deep neural networks. A line of work has studied the NTK spectrum for two-layer and deep networks with at least a layer with Ω(N) neurons, N being the number of training samples. Furthermore, there is increasing evidence suggesting that deep networks with sub-linear layer widths are powerful memorizers and optimizers, as long as the number of parameters exceeds the number of samples. Thus, a natural open question is whether the NTK is well conditioned in such a challenging sub-linear setup. In this paper, we answer this question in the affirmative. Our key technical contribution is a lower bound on the smallest NTK eigenvalue for deep networks with the minimum possible over-parameterization: the number of parameters is roughly Ω(N) and, hence, the number of neurons is as little as Ω(N−−√). To showcase the applicability of our NTK bounds, we provide two results concerning memorization capacity and optimization guarantees for gradient descent training.}, author = {Bombari, Simone and Amani, Mohammad Hossein and Mondelli, Marco}, booktitle = {36th Conference on Neural Information Processing Systems}, isbn = {9781713871088}, issn = {1049-5258}, location = {New Orleans, LA, United States}, pages = {7628--7640}, publisher = {Neural Information Processing Systems Foundation}, title = {{Memorization and optimization in deep neural networks with minimum over-parameterization}}, volume = {35}, year = {2022}, } @phdthesis{11196, abstract = {One of the fundamental questions in Neuroscience is how the structure of synapses and their physiological properties are related. While synaptic transmission remains a dynamic process, electron microscopy provides images with comparably low temporal resolution (Studer et al., 2014). The current work overcomes this challenge and describes an improved “Flash and Freeze” technique (Watanabe et al., 2013a; Watanabe et al., 2013b) to study synaptic transmission at the hippocampal mossy fiber-CA3 pyramidal neuron synapses, using mouse acute brain slices and organotypic slices culture. The improved method allowed for selective stimulation of presynaptic mossy fiber boutons and the observation of synaptic vesicle pool dynamics at the active zones. Our results uncovered several intriguing morphological features of mossy fiber boutons. First, the docked vesicle pool was largely depleted (more than 70%) after stimulation, implying that the docked synaptic vesicles pool and readily releasable pool are vastly overlapping in mossy fiber boutons. Second, the synaptic vesicles are skewed towards larger diameters, displaying a wide range of sizes. An increase in the mean diameter of synaptic vesicles, after single and repetitive stimulation, suggests that smaller vesicles have a higher release probability. Third, we observed putative endocytotic structures after moderate light stimulation, matching the timing of previously described ultrafast endocytosis (Watanabe et al., 2013a; Delvendahl et al., 2016). In addition, synaptic transmission depends on a sophisticated system of protein machinery and calcium channels (Südhof, 2013b), which amplifies the challenge in studying synaptic communication as these interactions can be potentially modified during synaptic plasticity. And although recent study elucidated the potential correlation between physiological and morphological properties of synapses during synaptic plasticity (Vandael et al., 2020), the molecular underpinning of it remains unknown. Thus, the presented work tries to overcome this challenge and aims to pinpoint changes in the molecular architecture at hippocampal mossy fiber bouton synapses during short- and long-term potentiation (STP and LTP), we combined chemical potentiation, with the application of a cyclic adenosine monophosphate agonist (i.e. forskolin) and freeze-fracture replica immunolabelling. This method allowed the localization of membrane-bound proteins with nanometer precision within the active zone, in particular, P/Q-type calcium channels and synaptic vesicle priming proteins Munc13-1/2. First, we found that the number of clusters of Munc13-1 in the mossy fiber bouton active zone increased significantly during STP, but decreased to lower than the control value during LTP. Secondly, although the distance between the calcium channels and Munc13-1s did not change after induction of STP, it shortened during the LTP phase. Additionally, forskolin did not affect Munc13-2 distribution during STP and LTP. These results indicate the existence of two distinct mechanisms that govern STP and LTP at mossy fiber bouton synapses: an increase in the readily realizable pool in the case of STP and a potential increase in release probability during LTP. “Flash and freeze” and functional electron microscopy, are versatile methods that can be successfully applied to intact brain circuits to study synaptic transmission even at the molecular level. }, author = {Kim, Olena}, issn = {2663-337X}, pages = {132}, publisher = {Institute of Science and Technology Austria}, title = {{Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses}}, doi = {10.15479/at:ista:11196}, year = {2022}, } @phdthesis{11879, abstract = {As the overall global mean surface temperature is increasing due to climate change, plant adaptation to those stressful conditions is of utmost importance for their survival. Plants are sessile organisms, thus to compensate for their lack of mobility, they evolved a variety of mechanisms enabling them to flexibly adjust their physiological, growth and developmental processes to fluctuating temperatures and to survive in harsh environments. While these unique adaptation abilities provide an important evolutionary advantage, overall modulation of plant growth and developmental program due to non-optimal temperature negatively affects biomass production, crop productivity or sensitivity to pathogens. Thus, understanding molecular processes underlying plant adaptation to increased temperature can provide important resources for breeding strategies to ensure sufficient agricultural food production. An increase in ambient temperature by a few degrees leads to profound changes in organ growth including enhanced hypocotyl elongation, expansion of petioles, hyponastic growth of leaves and cotyledons, collectively named thermomorphogenesis (Casal & Balasubramanian, 2019). Auxin, one of the best-studied growth hormones, plays an essential role in this process by direct activation of transcriptional and non-transcriptional processes resulting in elongation growth (Majda & Robert, 2018).To modulate hypocotyl growth in response to high ambient temperature (hAT), auxin needs to be redistributed accordingly. PINs, auxin efflux transporters, are key components of the polar auxin transport (PAT) machinery, which controls the amount and direction of auxin translocated in the plant tissues and organs(Adamowski & Friml, 2015). Hence, PIN-mediated transport is tightly linked with thermo-morphogenesis, and interference with PAT through either chemical or genetic means dramatically affecting the adaptive responses to hAT. Intriguingly, despite the key role of PIN mediated transport in growth response to hAT, whether and how PINs at the level of expression adapt to fluctuation in temperature is scarcely understood. With genetic, molecular and advanced bio-imaging approaches, we demonstrate the role of PIN auxin transporters in the regulation of hypocotyl growth in response to hAT. We show that via adjustment of PIN3, PIN4 and PIN7 expression in cotyledons and hypocotyls, auxin distribution is modulated thereby determining elongation pattern of epidermal cells at hAT. Furthermore, we identified three Zinc-Finger (ZF) transcription factors as novel molecular components of the thermo-regulatory network, which through negative regulation of PIN transcription adjust the transport of auxin at hAT. Our results suggest that the ZF-PIN module might be a part of the negative feedback loop attenuating the activity of the thermo-sensing pathway to restrain exaggerated growth and developmental responses to hAT.}, author = {Artner, Christina}, isbn = {978-3-99078-022-0}, issn = {2663-337X}, keywords = {high ambient temperature, auxin, PINs, Zinc-Finger proteins, thermomorphogenesis, stress}, pages = {128}, publisher = {Institute of Science and Technology Austria}, title = {{Modulation of auxin transport via ZF proteins adjust plant response to high ambient temperature}}, doi = {10.15479/at:ista:11879}, year = {2022}, } @article{11160, abstract = {Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency affects neurodevelopmental is unclear. Here, employing human cerebral organoids, we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories with an accelerated and delayed generation of, respectively, inhibitory and excitatory neurons that yields, at days 60 and 120, symmetrically opposite expansions in their proportions. This imbalance is consistent with an enlargement of cerebral organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic design of patient-specific mutations and mosaic organoids, we define genotype-phenotype relationships and uncover their cell-autonomous nature. Our results define cell-type-specific CHD8-dependent molecular defects related to an abnormal program of proliferation and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations, our study uncovers reproducible developmental alterations that may be employed for neurodevelopmental disease modeling.}, author = {Villa, Carlo Emanuele and Cheroni, Cristina and Dotter, Christoph and López-Tóbon, Alejandro and Oliveira, Bárbara and Sacco, Roberto and Yahya, Aysan Çerağ and Morandell, Jasmin and Gabriele, Michele and Tavakoli, Mojtaba and Lyudchik, Julia and Sommer, Christoph M and Gabitto, Mariano and Danzl, Johann G and Testa, Giuseppe and Novarino, Gaia}, issn = {2211-1247}, journal = {Cell Reports}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {1}, publisher = {Elsevier}, title = {{CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories}}, doi = {10.1016/j.celrep.2022.110615}, volume = {39}, year = {2022}, }