@article{14517, abstract = {State-of-the-art transmon qubits rely on large capacitors, which systematically improve their coherence due to reduced surface-loss participation. However, this approach increases both the footprint and the parasitic cross-coupling and is ultimately limited by radiation losses—a potential roadblock for scaling up quantum processors to millions of qubits. In this work we present transmon qubits with sizes as low as 36 × 39 µm2 with 100-nm-wide vacuum-gap capacitors that are micromachined from commercial silicon-on-insulator wafers and shadow evaporated with aluminum. We achieve a vacuum participation ratio up to 99.6% in an in-plane design that is compatible with standard coplanar circuits. Qubit relaxationtime measurements for small gaps with high zero-point electric field variance of up to 22 V/m reveal a double exponential decay indicating comparably strong qubit interaction with long-lived two-level systems. The exceptionally high selectivity of up to 20 dB to the superconductor-vacuum interface allows us to precisely back out the sub-single-photon dielectric loss tangent of aluminum oxide previously exposed to ambient conditions. In terms of future scaling potential, we achieve a ratio of qubit quality factor to a footprint area equal to 20 µm−2, which is comparable with the highest T1 devices relying on larger geometries, a value that could improve substantially for lower surface-loss superconductors. }, author = {Zemlicka, Martin and Redchenko, Elena and Peruzzo, Matilda and Hassani, Farid and Trioni, Andrea and Barzanjeh, Shabir and Fink, Johannes M}, issn = {2331-7019}, journal = {Physical Review Applied}, number = {4}, publisher = {American Physical Society}, title = {{Compact vacuum-gap transmon qubits: Selective and sensitive probes for superconductor surface losses}}, doi = {10.1103/PhysRevApplied.20.044054}, volume = {20}, year = {2023}, } @article{14515, abstract = {Most natural and engineered information-processing systems transmit information via signals that vary in time. Computing the information transmission rate or the information encoded in the temporal characteristics of these signals requires the mutual information between the input and output signals as a function of time, i.e., between the input and output trajectories. Yet, this is notoriously difficult because of the high-dimensional nature of the trajectory space, and all existing techniques require approximations. We present an exact Monte Carlo technique called path weight sampling (PWS) that, for the first time, makes it possible to compute the mutual information between input and output trajectories for any stochastic system that is described by a master equation. The principal idea is to use the master equation to evaluate the exact conditional probability of an individual output trajectory for a given input trajectory and average this via Monte Carlo sampling in trajectory space to obtain the mutual information. We present three variants of PWS, which all generate the trajectories using the standard stochastic simulation algorithm. While direct PWS is a brute-force method, Rosenbluth-Rosenbluth PWS exploits the analogy between signal trajectory sampling and polymer sampling, and thermodynamic integration PWS is based on a reversible work calculation in trajectory space. PWS also makes it possible to compute the mutual information between input and output trajectories for systems with hidden internal states as well as systems with feedback from output to input. Applying PWS to the bacterial chemotaxis system, consisting of 182 coupled chemical reactions, demonstrates not only that the scheme is highly efficient but also that the number of receptor clusters is much smaller than hitherto believed, while their size is much larger.}, author = {Reinhardt, Manuel and Tkačik, Gašper and Ten Wolde, Pieter Rein}, issn = {2160-3308}, journal = {Physical Review X}, number = {4}, publisher = {American Physical Society}, title = {{Path weight sampling: Exact Monte Carlo computation of the mutual information between stochastic trajectories}}, doi = {10.1103/PhysRevX.13.041017}, volume = {13}, year = {2023}, } @article{14514, abstract = {The elastic Leidenfrost effect occurs when a vaporizable soft solid is lowered onto a hot surface. Evaporative flow couples to elastic deformation, giving spontaneous bouncing or steady-state floating. The effect embodies an unexplored interplay between thermodynamics, elasticity, and lubrication: despite being observed, its basic theoretical description remains a challenge. Here, we provide a theory of elastic Leidenfrost floating. As weight increases, a rigid solid sits closer to the hot surface. By contrast, we discover an elasticity-dominated regime where the heavier the solid, the higher it floats. This geometry-governed behavior is reminiscent of the dynamics of large liquid Leidenfrost drops. We show that this elastic regime is characterized by Hertzian behavior of the solid’s underbelly and derive how the float height scales with materials parameters. Introducing a dimensionless elastic Leidenfrost number, we capture the crossover between rigid and Hertzian behavior. Our results provide theoretical underpinning for recent experiments, and point to the design of novel soft machines.}, author = {Binysh, Jack and Chakraborty, Indrajit and Chubynsky, Mykyta V. and Diaz Melian, Vicente L and Waitukaitis, Scott R and Sprittles, James E. and Souslov, Anton}, issn = {1079-7114}, journal = {Physical Review Letters}, number = {16}, publisher = {American Physical Society}, title = {{Modeling Leidenfrost levitation of soft elastic solids}}, doi = {10.1103/PhysRevLett.131.168201}, volume = {131}, year = {2023}, } @misc{14523, abstract = {see Readme file}, author = {Binysh, Jack and Chakraborty, Indrajit and Chubynsky, Mykyta and Diaz Melian, Vicente L and Waitukaitis, Scott R and Sprittles, James and Souslov, Anton}, publisher = {Zenodo}, title = {{SouslovLab/PRL2023-ModellingLeidenfrostLevitationofSoftElasticSolids: v1.0.1}}, doi = {10.5281/ZENODO.8329143}, year = {2023}, } @inproceedings{14518, abstract = {We consider bidding games, a class of two-player zero-sum graph games. The game proceeds as follows. Both players have bounded budgets. A token is placed on a vertex of a graph, in each turn the players simultaneously submit bids, and the higher bidder moves the token, where we break bidding ties in favor of Player 1. Player 1 wins the game iff the token visits a designated target vertex. We consider, for the first time, poorman discrete-bidding in which the granularity of the bids is restricted and the higher bid is paid to the bank. Previous work either did not impose granularity restrictions or considered Richman bidding (bids are paid to the opponent). While the latter mechanisms are technically more accessible, the former is more appealing from a practical standpoint. Our study focuses on threshold budgets, which is the necessary and sufficient initial budget required for Player 1 to ensure winning against a given Player 2 budget. We first show existence of thresholds. In DAGs, we show that threshold budgets can be approximated with error bounds by thresholds under continuous-bidding and that they exhibit a periodic behavior. We identify closed-form solutions in special cases. We implement and experiment with an algorithm to find threshold budgets.}, author = {Avni, Guy and Meggendorfer, Tobias and Sadhukhan, Suman and Tkadlec, Josef and Zikelic, Dorde}, booktitle = {Frontiers in Artificial Intelligence and Applications}, isbn = {9781643684369}, issn = {0922-6389}, location = {Krakow, Poland}, pages = {141--148}, publisher = {IOS Press}, title = {{Reachability poorman discrete-bidding games}}, doi = {10.3233/FAIA230264}, volume = {372}, year = {2023}, } @article{13096, abstract = {Eukaryotic cells can undergo different forms of programmed cell death, many of which culminate in plasma membrane rupture as the defining terminal event1,2,3,4,5,6,7. Plasma membrane rupture was long thought to be driven by osmotic pressure, but it has recently been shown to be in many cases an active process, mediated by the protein ninjurin-18 (NINJ1). Here we resolve the structure of NINJ1 and the mechanism by which it ruptures membranes. Super-resolution microscopy reveals that NINJ1 clusters into structurally diverse assemblies in the membranes of dying cells, in particular large, filamentous assemblies with branched morphology. A cryo-electron microscopy structure of NINJ1 filaments shows a tightly packed fence-like array of transmembrane α-helices. Filament directionality and stability is defined by two amphipathic α-helices that interlink adjacent filament subunits. The NINJ1 filament features a hydrophilic side and a hydrophobic side, and molecular dynamics simulations show that it can stably cap membrane edges. The function of the resulting supramolecular arrangement was validated by site-directed mutagenesis. Our data thus suggest that, during lytic cell death, the extracellular α-helices of NINJ1 insert into the plasma membrane to polymerize NINJ1 monomers into amphipathic filaments that rupture the plasma membrane. The membrane protein NINJ1 is therefore an interactive component of the eukaryotic cell membrane that functions as an in-built breaking point in response to activation of cell death.}, author = {Degen, Morris and Santos, José Carlos and Pluhackova, Kristyna and Cebrero, Gonzalo and Ramos, Saray and Jankevicius, Gytis and Hartenian, Ella and Guillerm, Undina and Mari, Stefania A. and Kohl, Bastian and Müller, Daniel J. and Schanda, Paul and Maier, Timm and Perez, Camilo and Sieben, Christian and Broz, Petr and Hiller, Sebastian}, issn = {1476-4687}, journal = {Nature}, pages = {1065--1071}, publisher = {Springer Nature}, title = {{Structural basis of NINJ1-mediated plasma membrane rupture in cell death}}, doi = {10.1038/s41586-023-05991-z}, volume = {618}, year = {2023}, } @article{13041, abstract = {A series of triarylamines was synthesised and screened for their suitability as catholytes in redox flow batteries using cyclic voltammetry (CV). Tris(4-aminophenyl)amine was found to be the strongest candidate. Solubility and initial electrochemical performance were promising; however, polymerisation was observed during electrochemical cycling leading to rapid capacity fade prescribed to a loss of accessible active material and the limitation of ion transport processes within the cell. A mixed electrolyte system of H3PO4 and HCl was found to inhibit polymerisation producing oligomers that consumed less active material reducing rates of degradation in the redox flow battery. Under these conditions Coulombic efficiency improved by over 4 %, the maximum number of cycles more than quadrupled and an additional theoretical capacity of 20 % was accessed. This paper is, to our knowledge, the first example of triarylamines as catholytes in all-aqueous redox flow batteries and emphasises the impact supporting electrolytes can have on electrochemical performance.}, author = {Farag, Nadia L. and Jethwa, Rajesh B and Beardmore, Alice E. and Insinna, Teresa and O'Keefe, Christopher A. and Klusener, Peter A.A. and Grey, Clare P. and Wright, Dominic S.}, issn = {1864-564X}, journal = {ChemSusChem}, number = {13}, publisher = {Wiley}, title = {{Triarylamines as catholytes in aqueous organic redox flow batteries}}, doi = {10.1002/cssc.202300128}, volume = {16}, year = {2023}, } @article{13118, abstract = {Under high pressures and temperatures, molecular systems with substantial polarization charges, such as ammonia and water, are predicted to form superionic phases and dense fluid states with dissociating molecules and high electrical conductivity. This behaviour potentially plays a role in explaining the origin of the multipolar magnetic fields of Uranus and Neptune, whose mantles are thought to result from a mixture of H2O, NH3 and CH4 ices. Determining the stability domain, melting curve and electrical conductivity of these superionic phases is therefore crucial for modelling planetary interiors and dynamos. Here we report the melting curve of superionic ammonia up to 300 GPa from laser-driven shock compression of pre-compressed samples and atomistic calculations. We show that ammonia melts at lower temperatures than water above 100 GPa and that fluid ammonia’s electrical conductivity exceeds that of water at conditions predicted by hot, super-adiabatic models for Uranus and Neptune, and enhances the conductivity in their fluid water-rich dynamo layers.}, author = {Hernandez, J.-A. and Bethkenhagen, Mandy and Ninet, S. and French, M. and Benuzzi-Mounaix, A. and Datchi, F. and Guarguaglini, M. and Lefevre, F. and Occelli, F. and Redmer, R. and Vinci, T. and Ravasio, A.}, issn = {1745-2481}, journal = {Nature Physics}, pages = {1280--1285}, publisher = {Springer Nature}, title = {{Melting curve of superionic ammonia at planetary interior conditions}}, doi = {10.1038/s41567-023-02074-8}, volume = {19}, year = {2023}, } @article{13119, abstract = {A density wave (DW) is a fundamental type of long-range order in quantum matter tied to self-organization into a crystalline structure. The interplay of DW order with superfluidity can lead to complex scenarios that pose a great challenge to theoretical analysis. In the past decades, tunable quantum Fermi gases have served as model systems for exploring the physics of strongly interacting fermions, including most notably magnetic ordering1, pairing and superfluidity2, and the crossover from a Bardeen–Cooper–Schrieffer superfluid to a Bose–Einstein condensate3. Here, we realize a Fermi gas featuring both strong, tunable contact interactions and photon-mediated, spatially structured long-range interactions in a transversely driven high-finesse optical cavity. Above a critical long-range interaction strength, DW order is stabilized in the system, which we identify via its superradiant light-scattering properties. We quantitatively measure the variation of the onset of DW order as the contact interaction is varied across the Bardeen–Cooper–Schrieffer superfluid and Bose–Einstein condensate crossover, in qualitative agreement with a mean-field theory. The atomic DW susceptibility varies over an order of magnitude upon tuning the strength and the sign of the long-range interactions below the self-ordering threshold, demonstrating independent and simultaneous control over the contact and long-range interactions. Therefore, our experimental setup provides a fully tunable and microscopically controllable platform for the experimental study of the interplay of superfluidity and DW order.}, author = {Helson, Victor and Zwettler, Timo and Mivehvar, Farokh and Colella, Elvia and Roux, Kevin Etienne Robert and Konishi, Hideki and Ritsch, Helmut and Brantut, Jean Philippe}, issn = {1476-4687}, journal = {Nature}, pages = {716--720}, publisher = {Springer Nature}, title = {{Density-wave ordering in a unitary Fermi gas with photon-mediated interactions}}, doi = {10.1038/s41586-023-06018-3}, volume = {618}, year = {2023}, } @article{12911, abstract = {This paper establishes new connections between many-body quantum systems, One-body Reduced Density Matrices Functional Theory (1RDMFT) and Optimal Transport (OT), by interpreting the problem of computing the ground-state energy of a finite-dimensional composite quantum system at positive temperature as a non-commutative entropy regularized Optimal Transport problem. We develop a new approach to fully characterize the dual-primal solutions in such non-commutative setting. The mathematical formalism is particularly relevant in quantum chemistry: numerical realizations of the many-electron ground-state energy can be computed via a non-commutative version of Sinkhorn algorithm. Our approach allows to prove convergence and robustness of this algorithm, which, to our best knowledge, were unknown even in the two marginal case. Our methods are based on a priori estimates in the dual problem, which we believe to be of independent interest. Finally, the above results are extended in 1RDMFT setting, where bosonic or fermionic symmetry conditions are enforced on the problem.}, author = {Feliciangeli, Dario and Gerolin, Augusto and Portinale, Lorenzo}, issn = {1096-0783}, journal = {Journal of Functional Analysis}, number = {4}, publisher = {Elsevier}, title = {{A non-commutative entropic optimal transport approach to quantum composite systems at positive temperature}}, doi = {10.1016/j.jfa.2023.109963}, volume = {285}, year = {2023}, } @article{13177, abstract = {In this note we study the eigenvalue growth of infinite graphs with discrete spectrum. We assume that the corresponding Dirichlet forms satisfy certain Sobolev-type inequalities and that the total measure is finite. In this sense, the associated operators on these graphs display similarities to elliptic operators on bounded domains in the continuum. Specifically, we prove lower bounds on the eigenvalue growth and show by examples that corresponding upper bounds cannot be established.}, author = {Hua, Bobo and Keller, Matthias and Schwarz, Michael and Wirth, Melchior}, issn = {1088-6826}, journal = {Proceedings of the American Mathematical Society}, number = {8}, pages = {3401--3414}, publisher = {American Mathematical Society}, title = {{Sobolev-type inequalities and eigenvalue growth on graphs with finite measure}}, doi = {10.1090/proc/14361}, volume = {151}, year = {2023}, } @article{14558, abstract = {n the dynamic minimum set cover problem, the challenge is to minimize the update time while guaranteeing a close-to-optimal min{O(log n), f} approximation factor. (Throughout, n, m, f , and C are parameters denoting the maximum number of elements, the number of sets, the frequency, and the cost range.) In the high-frequency range, when f = Ω(log n) , this was achieved by a deterministic O(log n) -approximation algorithm with O(f log n) amortized update time by Gupta et al. [Online and dynamic algorithms for set cover, in Proceedings STOC 2017, ACM, pp. 537–550]. In this paper we consider the low-frequency range, when f = O(log n) , and obtain deterministic algorithms with a (1 + ∈)f -approximation ratio and the following guarantees on the update time. (1) O ((f/∈)-log(Cn)) amortized update time: Prior to our work, the best approximation ratio guaranteed by deterministic algorithms was O(f2) of Bhattacharya, Henzinger, and Italiano [Design of dynamic algorithms via primal-dual method, in Proceedings ICALP 2015, Springer, pp. 206–218]. In contrast, the only result with O(f) -approximation was that of Abboud et al. [Dynamic set cover: Improved algorithms and lower bounds, in Proceedings STOC 2019, ACM, pp. 114–125], who designed a randomized (1+∈)f -approximation algorithm with amortized update time. (2) O(f2/∈3 + (f/∈2).logC) amortized update time: This result improves the above update time bound for most values of f in the low-frequency range, i.e., f=o(log n) . It is also the first result that is independent of m and n. It subsumes the constant amortized update time of Bhattacharya and Kulkarni [Deterministically maintaining a (2 + ∈) -approximate minimum vertex cover in O(1/∈2) amortized update time, in Proceedings SODA 2019, SIAM, pp. 1872–1885] for unweighted dynamic vertex cover (i.e., when f = 2 and C = 1). (3) O((f/∈3).log2(Cn)) worst-case update time: No nontrivial worst-case update time was previously known for the dynamic set cover problem. Our bound subsumes and improves by a logarithmic factor the O(log3n/poly (∈)) worst-case update time for the unweighted dynamic vertex cover problem (i.e., when f = 2 and C =1) of Bhattacharya, Henzinger, and Nanongkai [Fully dynamic approximate maximum matching and minimum vertex cover in O(log3)n worst case update time, in Proceedings SODA 2017, SIAM, pp. 470–489]. We achieve our results via the primal-dual approach, by maintaining a fractional packing solution as a dual certificate. Prior work in dynamic algorithms that employs the primal-dual approach uses a local update scheme that maintains relaxed complementary slackness conditions for every set. For our first result we use instead a global update scheme that does not always maintain complementary slackness conditions. For our second result we combine the global and the local update schema. To achieve our third result we use a hierarchy of background schedulers. It is an interesting open question whether this background scheduler technique can also be used to transform algorithms with amortized running time bounds into algorithms with worst-case running time bounds.}, author = {Bhattacharya, Sayan and Henzinger, Monika H and Nanongkai, Danupon and Wu, Xiaowei}, issn = {1095-7111}, journal = {SIAM Journal on Computing}, number = {5}, pages = {1132--1192}, publisher = {Society for Industrial and Applied Mathematics}, title = {{Deterministic near-optimal approximation algorithms for dynamic set cover}}, doi = {10.1137/21M1428649}, volume = {52}, year = {2023}, } @inproceedings{14559, abstract = {We consider the problem of learning control policies in discrete-time stochastic systems which guarantee that the system stabilizes within some specified stabilization region with probability 1. Our approach is based on the novel notion of stabilizing ranking supermartingales (sRSMs) that we introduce in this work. Our sRSMs overcome the limitation of methods proposed in previous works whose applicability is restricted to systems in which the stabilizing region cannot be left once entered under any control policy. We present a learning procedure that learns a control policy together with an sRSM that formally certifies probability 1 stability, both learned as neural networks. We show that this procedure can also be adapted to formally verifying that, under a given Lipschitz continuous control policy, the stochastic system stabilizes within some stabilizing region with probability 1. Our experimental evaluation shows that our learning procedure can successfully learn provably stabilizing policies in practice.}, author = {Ansaripour, Matin and Chatterjee, Krishnendu and Henzinger, Thomas A and Lechner, Mathias and Zikelic, Dorde}, booktitle = {21st International Symposium on Automated Technology for Verification and Analysis}, isbn = {9783031453281}, issn = {1611-3349}, location = {Singapore, Singapore}, pages = {357--379}, publisher = {Springer Nature}, title = {{Learning provably stabilizing neural controllers for discrete-time stochastic systems}}, doi = {10.1007/978-3-031-45329-8_17}, volume = {14215}, year = {2023}, } @article{14554, abstract = {The Regularised Inertial Dean–Kawasaki model (RIDK) – introduced by the authors and J. Zimmer in earlier works – is a nonlinear stochastic PDE capturing fluctuations around the meanfield limit for large-scale particle systems in both particle density and momentum density. We focus on the following two aspects. Firstly, we set up a Discontinuous Galerkin (DG) discretisation scheme for the RIDK model: we provide suitable definitions of numerical fluxes at the interface of the mesh elements which are consistent with the wave-type nature of the RIDK model and grant stability of the simulations, and we quantify the rate of convergence in mean square to the continuous RIDK model. Secondly, we introduce modifications of the RIDK model in order to preserve positivity of the density (such a feature only holds in a “high-probability sense” for the original RIDK model). By means of numerical simulations, we show that the modifications lead to physically realistic and positive density profiles. In one case, subject to additional regularity constraints, we also prove positivity. Finally, we present an application of our methodology to a system of diffusing and reacting particles. Our Python code is available in open-source format.}, author = {Cornalba, Federico and Shardlow, Tony}, issn = {2804-7214}, journal = {ESAIM: Mathematical Modelling and Numerical Analysis}, number = {5}, pages = {3061--3090}, publisher = {EDP Sciences}, title = {{The regularised inertial Dean' Kawasaki equation: Discontinuous Galerkin approximation and modelling for low-density regime}}, doi = {10.1051/m2an/2023077}, volume = {57}, year = {2023}, } @article{14556, abstract = {Inversions are structural mutations that reverse the sequence of a chromosome segment and reduce the effective rate of recombination in the heterozygous state. They play a major role in adaptation, as well as in other evolutionary processes such as speciation. Although inversions have been studied since the 1920s, they remain difficult to investigate because the reduced recombination conferred by them strengthens the effects of drift and hitchhiking, which in turn can obscure signatures of selection. Nonetheless, numerous inversions have been found to be under selection. Given recent advances in population genetic theory and empirical study, here we review how different mechanisms of selection affect the evolution of inversions. A key difference between inversions and other mutations, such as single nucleotide variants, is that the fitness of an inversion may be affected by a larger number of frequently interacting processes. This considerably complicates the analysis of the causes underlying the evolution of inversions. We discuss the extent to which these mechanisms can be disentangled, and by which approach.}, author = {Berdan, Emma L. and Barton, Nicholas H and Butlin, Roger and Charlesworth, Brian and Faria, Rui and Fragata, Inês and Gilbert, Kimberly J. and Jay, Paul and Kapun, Martin and Lotterhos, Katie E. and Mérot, Claire and Durmaz Mitchell, Esra and Pascual, Marta and Peichel, Catherine L. and Rafajlović, Marina and Westram, Anja M and Schaeffer, Stephen W. and Johannesson, Kerstin and Flatt, Thomas}, issn = {1420-9101}, journal = {Journal of Evolutionary Biology}, publisher = {Wiley}, title = {{How chromosomal inversions reorient the evolutionary process}}, doi = {10.1111/jeb.14242}, year = {2023}, } @article{14555, abstract = {The intricate regulatory processes behind actin polymerization play a crucial role in cellular biology, including essential mechanisms such as cell migration or cell division. However, the self-organizing principles governing actin polymerization are still poorly understood. In this perspective article, we compare the Belousov-Zhabotinsky (BZ) reaction, a classic and well understood chemical oscillator known for its self-organizing spatiotemporal dynamics, with the excitable dynamics of polymerizing actin. While the BZ reaction originates from the domain of inorganic chemistry, it shares remarkable similarities with actin polymerization, including the characteristic propagating waves, which are influenced by geometry and external fields, and the emergent collective behavior. Starting with a general description of emerging patterns, we elaborate on single droplets or cell-level dynamics, the influence of geometric confinements and conclude with collective interactions. Comparing these two systems sheds light on the universal nature of self-organization principles in both living and inanimate systems.}, author = {Riedl, Michael and Sixt, Michael K}, issn = {2296-634X}, journal = {Frontiers in Cell and Developmental Biology}, publisher = {Frontiers}, title = {{The excitable nature of polymerizing actin and the Belousov-Zhabotinsky reaction}}, doi = {10.3389/fcell.2023.1287420}, volume = {11}, year = {2023}, } @article{14543, abstract = {The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins, and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Utilizing exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with YnMyr chemical proteomics in the model organisms and human cells, with the latter also being subjected further to ACBD6 peroxisomal localization studies. The affected individuals (23 males and 22 females), with ages ranging from 1 to 50 years old, typically present with a complex and progressive disease involving moderate-to-severe global developmental delay/intellectual disability (100%) with significant expressive language impairment (98%), movement disorders (97%), facial dysmorphism (95%), and mild cerebellar ataxia (85%) associated with gait impairment (94%), limb spasticity/hypertonia (76%), oculomotor (71%) and behavioural abnormalities (65%), overweight (59%), microcephaly (39%) and epilepsy (33%). The most conspicuous and common movement disorder was dystonia (94%), frequently leading to early-onset progressive postural deformities (97%), limb dystonia (55%), and cervical dystonia (31%). A jerky tremor in the upper limbs (63%), a mild head tremor (59%), parkinsonism/hypokinesia developing with advancing age (32%), and simple motor and vocal tics were among other frequent movement disorders. Midline brain malformations including corpus callosum abnormalities (70%), hypoplasia/agenesis of the anterior commissure (66%), short midbrain and small inferior cerebellar vermis (38% each), as well as hypertrophy of the clava (24%) were common neuroimaging findings. acbd6-deficient zebrafish and Xenopus models effectively recapitulated many clinical phenotypes reported in patients including movement disorders, progressive neuromotor impairment, seizures, microcephaly, craniofacial dysmorphism, and midbrain defects accompanied by developmental delay with increased mortality over time. Unlike ACBD5, ACBD6 did not show a peroxisomal localisation and ACBD6-deficiency was not associated with altered peroxisomal parameters in patient fibroblasts. Significant differences in YnMyr-labelling were observed for 68 co- and 18 post-translationally N-myristoylated proteins in patient-derived fibroblasts. N-Myristoylation was similarly affected in acbd6-deficient zebrafish and Xenopus tropicalis models, including Fus, Marcks, and Chchd-related proteins implicated in neurological diseases. The present study provides evidence that bi-allelic pathogenic variants in ACBD6 lead to a distinct neurodevelopmental syndrome accompanied by complex and progressive cognitive and movement disorders.}, author = {Kaiyrzhanov, Rauan and Rad, Aboulfazl and Lin, Sheng-Jia and Bertoli-Avella, Aida and Kallemeijn, Wouter W and Godwin, Annie and Zaki, Maha S and Huang, Kevin and Lau, Tracy and Petree, Cassidy and Efthymiou, Stephanie and Ghayoor Karimiani, Ehsan and Hempel, Maja and Normand, Elizabeth A and Rudnik-Schöneborn, Sabine and Schatz, Ulrich A and Baggelaar, Marc P and Ilyas, Muhammad and Sultan, Tipu and Alvi, Javeria Raza and Ganieva, Manizha and Fowler, Ben and Aanicai, Ruxandra and Akay Tayfun, Gulsen and Al Saman, Abdulaziz and Alswaid, Abdulrahman and Amiri, Nafise and Asilova, Nilufar and Shotelersuk, Vorasuk and Yeetong, Patra and Azam, Matloob and Babaei, Meisam and Bahrami Monajemi, Gholamreza and Mohammadi, Pouria and Samie, Saeed and Banu, Selina Husna and Basto, Jorge Pinto and Kortüm, Fanny and Bauer, Mislen and Bauer, Peter and Beetz, Christian and Garshasbi, Masoud and Hameed Issa, Awatif and Eyaid, Wafaa and Ahmed, Hind and Hashemi, Narges and Hassanpour, Kazem and Herman, Isabella and Ibrohimov, Sherozjon and Abdul-Majeed, Ban A and Imdad, Maria and Isrofilov, Maksudjon and Kaiyal, Qassem and Khan, Suliman and Kirmse, Brian and Koster, Janet and Lourenço, Charles Marques and Mitani, Tadahiro and Moldovan, Oana and Murphy, David and Najafi, Maryam and Pehlivan, Davut and Rocha, Maria Eugenia and Salpietro, Vincenzo and Schmidts, Miriam and Shalata, Adel and Mahroum, Mohammad and Talbeya, Jawabreh Kassem and Taylor, Robert W and Vazquez, Dayana and Vetro, Annalisa and Waterham, Hans R and Zaman, Mashaya and Schrader, Tina A and Chung, Wendy K and Guerrini, Renzo and Lupski, James R and Gleeson, Joseph and Suri, Mohnish and Jamshidi, Yalda and Bhatia, Kailash P and Vona, Barbara and Schrader, Michael and Severino, Mariasavina and Guille, Matthew and Tate, Edward W and Varshney, Gaurav K and Houlden, Henry and Maroofian, Reza}, issn = {1460-2156}, journal = {Brain}, keywords = {Neurology (clinical)}, publisher = {Oxford University Press}, title = {{Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders}}, doi = {10.1093/brain/awad380}, year = {2023}, } @article{14542, abstract = {It is a remarkable property of BCS theory that the ratio of the energy gap at zero temperature Ξ and the critical temperature Tc is (approximately) given by a universal constant, independent of the microscopic details of the fermionic interaction. This universality has rigorously been proven quite recently in three spatial dimensions and three different limiting regimes: weak coupling, low density and high density. The goal of this short note is to extend the universal behavior to lower dimensions d=1,2 and give an exemplary proof in the weak coupling limit.}, author = {Henheik, Sven Joscha and Lauritsen, Asbjørn Bækgaard and Roos, Barbara}, issn = {1793-6659}, journal = {Reviews in Mathematical Physics}, publisher = {World Scientific Publishing}, title = {{Universality in low-dimensional BCS theory}}, doi = {10.1142/s0129055x2360005x}, year = {2023}, } @article{14553, abstract = {Quantum state tomography is an essential component of modern quantum technology. In application to continuous-variable harmonic-oscillator systems, such as the electromagnetic field, existing tomography methods typically reconstruct the state in discrete bases, and are hence limited to states with relatively low amplitudes and energies. Here, we overcome this limitation by utilizing a feed-forward neural network to obtain the density matrix directly in the continuous position basis. An important benefit of our approach is the ability to choose specific regions in the phase space for detailed reconstruction. This results in a relatively slow scaling of the amount of resources required for the reconstruction with the state amplitude, and hence allows us to dramatically increase the range of amplitudes accessible with our method.}, author = {Fedotova, Ekaterina and Kuznetsov, Nikolai and Tiunov, Egor and Ulanov, A. E. and Lvovsky, A. I.}, issn = {2469-9934}, journal = {Physical Review A}, number = {4}, publisher = {American Physical Society}, title = {{Continuous-variable quantum tomography of high-amplitude states}}, doi = {10.1103/PhysRevA.108.042430}, volume = {108}, year = {2023}, } @article{14557, abstract = {Motivated by a problem posed in [10], we investigate the closure operators of the category SLatt of join semilattices and its subcategory SLattO of join semilattices with bottom element. In particular, we show that there are only finitely many closure operators of both categories, and provide a complete classification. We use this result to deduce the known fact that epimorphisms of SLatt and SLattO are surjective. We complement the paper with two different proofs of this result using either generators or Isbell’s zigzag theorem.}, author = {Dikranjan, D. and Giordano Bruno, A. and Zava, Nicolò}, issn = {1727-933X}, journal = {Quaestiones Mathematicae}, number = {S1}, pages = {191--221}, publisher = {Taylor & Francis}, title = {{Epimorphisms and closure operators of categories of semilattices}}, doi = {10.2989/16073606.2023.2247731}, volume = {46}, year = {2023}, } @article{14552, abstract = {Interactions between plants and herbivores are central in most ecosystems, but their strength is highly variable. The amount of variability within a system is thought to influence most aspects of plant-herbivore biology, from ecological stability to plant defense evolution. Our understanding of what influences variability, however, is limited by sparse data. We collected standardized surveys of herbivory for 503 plant species at 790 sites across 116° of latitude. With these data, we show that within-population variability in herbivory increases with latitude, decreases with plant size, and is phylogenetically structured. Differences in the magnitude of variability are thus central to how plant-herbivore biology varies across macroscale gradients. We argue that increased focus on interaction variability will advance understanding of patterns of life on Earth.}, author = {Robinson, M. L. and Hahn, P. G. and Inouye, B. D. and Underwood, N. and Whitehead, S. R. and Abbott, K. C. and Bruna, E. M. and Cacho, N. I. and Dyer, L. A. and Abdala-Roberts, L. and Allen, W. J. and Andrade, J. F. and Angulo, D. F. and Anjos, D. and Anstett, D. N. and Bagchi, R. and Bagchi, S. and Barbosa, M. and Barrett, S. and Baskett, Carina and Ben-Simchon, E. and Bloodworth, K. J. and Bronstein, J. L. and Buckley, Y. M. and Burghardt, K. T. and Bustos-Segura, C. and Calixto, E. S. and Carvalho, R. L. and Castagneyrol, B. and Chiuffo, M. C. and Cinoğlu, D. and Cinto Mejía, E. and Cock, M. C. and Cogni, R. and Cope, O. L. and Cornelissen, T. and Cortez, D. R. and Crowder, D. W. and Dallstream, C. and Dáttilo, W. and Davis, J. K. and Dimarco, R. D. and Dole, H. E. and Egbon, I. N. and Eisenring, M. and Ejomah, A. and Elderd, B. D. and Endara, M. J. and Eubanks, M. D. and Everingham, S. E. and Farah, K. N. and Farias, R. P. and Fernandes, A. P. and Fernandes, G. W. and Ferrante, M. and Finn, A. and Florjancic, G. A. and Forister, M. L. and Fox, Q. N. and Frago, E. and França, F. M. and Getman-Pickering, A. S. and Getman-Pickering, Z. and Gianoli, E. and Gooden, B. and Gossner, M. M. and Greig, K. A. and Gripenberg, S. and Groenteman, R. and Grof-Tisza, P. and Haack, N. and Hahn, L. and Haq, S. M. and Helms, A. M. and Hennecke, J. and Hermann, S. L. and Holeski, L. M. and Holm, S. and Hutchinson, M. C. and Jackson, E. E. and Kagiya, S. and Kalske, A. and Kalwajtys, M. and Karban, R. and Kariyat, R. and Keasar, T. and Kersch-Becker, M. F. and Kharouba, H. M. and Kim, T. N. and Kimuyu, D. M. and Kluse, J. and Koerner, S. E. and Komatsu, K. J. and Krishnan, S. and Laihonen, M. and Lamelas-López, L. and Lascaleia, M. C. and Lecomte, N. and Lehn, C. R. and Li, X. and Lindroth, R. L. and Lopresti, E. F. and Losada, M. and Louthan, A. M. and Luizzi, V. J. and Lynch, S. C. and Lynn, J. S. and Lyon, N. J. and Maia, L. F. and Maia, R. A. and Mannall, T. L. and Martin, B. S. and Massad, T. J. and Mccall, A. C. and Mcgurrin, K. and Merwin, A. C. and Mijango-Ramos, Z. and Mills, C. H. and Moles, A. T. and Moore, C. M. and Moreira, X. and Morrison, C. R. and Moshobane, M. C. and Muola, A. and Nakadai, R. and Nakajima, K. and Novais, S. and Ogbebor, C. O. and Ohsaki, H. and Pan, V. S. and Pardikes, N. A. and Pareja, M. and Parthasarathy, N. and Pawar, R. R. and Paynter, Q. and Pearse, I. S. and Penczykowski, R. M. and Pepi, A. A. and Pereira, C. C. and Phartyal, S. S. and Piper, F. I. and Poveda, K. and Pringle, E. G. and Puy, J. and Quijano, T. and Quintero, C. and Rasmann, S. and Rosche, C. and Rosenheim, L. Y. and Rosenheim, J. A. and Runyon, J. B. and Sadeh, A. and Sakata, Y. and Salcido, D. M. and Salgado-Luarte, C. and Santos, B. A. and Sapir, Y. and Sasal, Y. and Sato, Y. and Sawant, M. and Schroeder, H. and Schumann, I. and Segoli, M. and Segre, H. and Shelef, O. and Shinohara, N. and Singh, R. P. and Smith, D. S. and Sobral, M. and Stotz, G. C. and Tack, A. J.M. and Tayal, M. and Tooker, J. F. and Torrico-Bazoberry, D. and Tougeron, K. and Trowbridge, A. M. and Utsumi, S. and Uyi, O. and Vaca-Uribe, J. L. and Valtonen, A. and Van Dijk, L. J.A. and Vandvik, V. and Villellas, J. and Waller, L. P. and Weber, M. G. and Yamawo, A. and Yim, S. and Zarnetske, P. L. and Zehr, L. N. and Zhong, Z. and Wetzel, W. C.}, issn = {1095-9203}, journal = {Science}, number = {6671}, pages = {679--683}, publisher = {AAAS}, title = {{Plant size, latitude, and phylogeny explain within-population variability in herbivory}}, doi = {10.1126/science.adh8830}, volume = {382}, year = {2023}, } @article{14551, abstract = {Methylation of CG dinucleotides (mCGs), which regulates eukaryotic genome functions, is epigenetically propagated by Dnmt1/MET1 methyltransferases. How mCG is established and transmitted across generations despite imperfect enzyme fidelity is unclear. Whether mCG variation in natural populations is governed by genetic or epigenetic inheritance also remains mysterious. Here, we show that MET1 de novo activity, which is enhanced by existing proximate methylation, seeds and stabilizes mCG in Arabidopsis thaliana genes. MET1 activity is restricted by active demethylation and suppressed by histone variant H2A.Z, producing localized mCG patterns. Based on these observations, we develop a stochastic mathematical model that precisely recapitulates mCG inheritance dynamics and predicts intragenic mCG patterns and their population-scale variation given only CG site spacing. Our results demonstrate that intragenic mCG establishment, inheritance, and variance constitute a unified epigenetic process, revealing that intragenic mCG undergoes large, millennia-long epigenetic fluctuations and can therefore mediate evolution on this timescale.}, author = {Briffa, Amy and Hollwey, Elizabeth and Shahzad, Zaigham and Moore, Jonathan D. and Lyons, David B. and Howard, Martin and Zilberman, Daniel}, issn = {2405-4720}, journal = {Cell Systems}, number = {11}, pages = {953--967}, publisher = {Elsevier}, title = {{Millennia-long epigenetic fluctuations generate intragenic DNA methylation variance in Arabidopsis populations}}, doi = {10.1016/j.cels.2023.10.007}, volume = {14}, year = {2023}, } @misc{14579, abstract = {This is associated with our paper "Plant size, latitude, and phylogeny explain within-population variability in herbivory" published in Science. }, author = {Wetzel, William}, publisher = {Zenodo}, title = {{HerbVar-Network/HV-Large-Patterns-MS-public: v1.0.0}}, doi = {10.5281/ZENODO.8133117}, year = {2023}, } @article{12334, abstract = {Regulation of the Arp2/3 complex is required for productive nucleation of branched actin networks. An emerging aspect of regulation is the incorporation of subunit isoforms into the Arp2/3 complex. Specifically, both ArpC5 subunit isoforms, ArpC5 and ArpC5L, have been reported to fine-tune nucleation activity and branch junction stability. We have combined reverse genetics and cellular structural biology to describe how ArpC5 and ArpC5L differentially affect cell migration. Both define the structural stability of ArpC1 in branch junctions and, in turn, by determining protrusion characteristics, affect protein dynamics and actin network ultrastructure. ArpC5 isoforms also affect the positioning of members of the Ena/Vasodilator-stimulated phosphoprotein (VASP) family of actin filament elongators, which mediate ArpC5 isoform–specific effects on the actin assembly level. Our results suggest that ArpC5 and Ena/VASP proteins are part of a signaling pathway enhancing cell migration.}, author = {Fäßler, Florian and Javoor, Manjunath and Datler, Julia and Döring, Hermann and Hofer, Florian and Dimchev, Georgi A and Hodirnau, Victor-Valentin and Faix, Jan and Rottner, Klemens and Schur, Florian KM}, issn = {2375-2548}, journal = {Science Advances}, keywords = {Multidisciplinary}, number = {3}, publisher = {American Association for the Advancement of Science}, title = {{ArpC5 isoforms regulate Arp2/3 complex–dependent protrusion through differential Ena/VASP positioning}}, doi = {10.1126/sciadv.add6495}, volume = {9}, year = {2023}, } @misc{14562, abstract = {Regulation of the Arp2/3 complex is required for productive nucleation of branched actin networks. An emerging aspect of regulation is the incorporation of subunit isoforms into the Arp2/3 complex. Specifically, both ArpC5 subunit isoforms, ArpC5 and ArpC5L, have been reported to fine-tune nucleation activity and branch junction stability. We have combined reverse genetics and cellular structural biology to describe how ArpC5 and ArpC5L differentially affect cell migration. Both define the structural stability of ArpC1 in branch junctions and, in turn, by determining protrusion characteristics, affect protein dynamics and actin network ultrastructure. ArpC5 isoforms also affect the positioning of members of the Ena/Vasodilator-stimulated phosphoprotein (VASP) family of actin filament elongators, which mediate ArpC5 isoform–specific effects on the actin assembly level. Our results suggest that ArpC5 and Ena/VASP proteins are part of a signaling pathway enhancing cell migration. }, author = {Schur, Florian KM}, publisher = {Institute of Science and Technology Austria}, title = {{Research data of the publication "ArpC5 isoforms regulate Arp2/3 complex-dependent protrusion through differential Ena/VASP positioning"}}, doi = {10.15479/AT:ISTA:14562}, year = {2023}, } @misc{14502, abstract = {A precise quantitative description of the ultrastructural characteristics underlying biological mechanisms is often key to their understanding. This is particularly true for dynamic extra- and intracellular filamentous assemblies, playing a role in cell motility, cell integrity, cytokinesis, tissue formation and maintenance. For example, genetic manipulation or modulation of actin regulatory proteins frequently manifests in changes of the morphology, dynamics, and ultrastructural architecture of actin filament-rich cell peripheral structures, such as lamellipodia or filopodia. However, the observed ultrastructural effects often remain subtle and require sufficiently large datasets for appropriate quantitative analysis. The acquisition of such large datasets has been enabled by recent advances in high-throughput cryo-electron tomography (cryo-ET) methods. This also necessitates the development of complementary approaches to maximize the extraction of relevant biological information. We have developed a computational toolbox for the semi-automatic quantification of segmented and vectorized fila- mentous networks from pre-processed cryo-electron tomograms, facilitating the analysis and cross-comparison of multiple experimental conditions. GUI-based components simplify the processing of data and allow users to obtain a large number of ultrastructural parameters describing filamentous assemblies. We demonstrate the feasibility of this workflow by analyzing cryo-ET data of untreated and chemically perturbed branched actin filament networks and that of parallel actin filament arrays. In principle, the computational toolbox presented here is applicable for data analysis comprising any type of filaments in regular (i.e. parallel) or random arrangement. We show that it can ease the identification of key differences between experimental groups and facilitate the in-depth analysis of ultrastructural data in a time-efficient manner.}, author = {Dimchev, Georgi A and Amiri, Behnam and Fäßler, Florian and Falcke, Martin and Schur, Florian KM}, keywords = {cryo-electron tomography, actin cytoskeleton, toolbox}, publisher = {Institute of Science and Technology Austria}, title = {{Computational toolbox for ultrastructural quantitative analysis of filament networks in cryo-ET data}}, doi = {10.15479/AT:ISTA:14502}, year = {2023}, } @article{13342, abstract = {Motile cells moving in multicellular organisms encounter microenvironments of locally heterogeneous mechanochemical composition. Individual compositional parameters like chemotactic signals, adhesiveness, and pore sizes are well known to be sensed by motile cells, providing individual guidance cues for cellular pathfinding. However, motile cells encounter diverse mechanochemical signals at the same time, raising the question of how cells respond to locally diverse and potentially competing signals on their migration routes. Here, we reveal that motile amoeboid cells require nuclear repositioning, termed nucleokinesis, for adaptive pathfinding in heterogeneous mechanochemical microenvironments. Using mammalian immune cells and the amoebaDictyostelium discoideum, we discover that frequent, rapid and long-distance nucleokinesis is a basic component of amoeboid pathfinding, enabling cells to reorientate quickly between locally competing cues. Amoeboid nucleokinesis comprises a two-step cell polarity switch and is driven by myosin II-forces, sliding the nucleus from a ‘losing’ to the ‘winning’ leading edge to re-adjust the nuclear to the cellular path. Impaired nucleokinesis distorts fast path adaptions and causes cellular arrest in the microenvironment. Our findings establish that nucleokinesis is required for amoeboid cell navigation. Given that motile single-cell amoebae, many immune cells, and some cancer cells utilize an amoeboid migration strategy, these results suggest that amoeboid nucleokinesis underlies cellular navigation during unicellular biology, immunity, and disease.}, author = {Kroll, Janina and Hauschild, Robert and Kuznetcov, Arthur and Stefanowski, Kasia and Hermann, Monika D. and Merrin, Jack and Shafeek, Lubuna B and Müller-Taubenberger, Annette and Renkawitz, Jörg}, issn = {1460-2075}, journal = {EMBO Journal}, publisher = {Embo Press}, title = {{Adaptive pathfinding by nucleokinesis during amoeboid migration}}, doi = {10.15252/embj.2023114557}, year = {2023}, } @article{14610, abstract = {AbstractEndomembrane damage represents a form of stress that is detrimental for eukaryotic cells1,2. To cope with this threat, cells possess mechanisms that repair the damage and restore cellular homeostasis3–7. Endomembrane damage also results in organelle instability and the mechanisms by which cells stabilize damaged endomembranes to enable membrane repair remains unknown. Here, by combining in vitro and in cellulo studies with computational modelling we uncover a biological function for stress granules whereby these biomolecular condensates form rapidly at endomembrane damage sites and act as a plug that stabilizes the ruptured membrane. Functionally, we demonstrate that stress granule formation and membrane stabilization enable efficient repair of damaged endolysosomes, through both ESCRT (endosomal sorting complex required for transport)-dependent and independent mechanisms. We also show that blocking stress granule formation in human macrophages creates a permissive environment for Mycobacterium tuberculosis, a human pathogen that exploits endomembrane damage to survive within the host.}, author = {Bussi, Claudio and Mangiarotti, Agustín and Vanhille-Campos, Christian Eduardo and Aylan, Beren and Pellegrino, Enrica and Athanasiadi, Natalia and Fearns, Antony and Rodgers, Angela and Franzmann, Titus M. and Šarić, Anđela and Dimova, Rumiana and Gutierrez, Maximiliano G.}, issn = {1476-4687}, journal = {Nature}, keywords = {Multidisciplinary}, publisher = {Springer Nature}, title = {{Stress granules plug and stabilize damaged endolysosomal membranes}}, doi = {10.1038/s41586-023-06726-w}, year = {2023}, } @misc{14472, abstract = {Data related to the following paper: "Stress granules plug and stabilize damaged endolysosomal membranes" (https://doi.org/10.1038/s41586-023-06726-w) Abstract: Endomembrane damage represents a form of stress that is detrimental for eukaryotic cells. To cope with this threat, cells possess mechanisms that repair the damage and restore cellular homeostasis. Endomembrane damage also results in organelle instability and the mechanisms by which cells stabilize damaged endomembranes to enable membrane repair remains unknown. In this work we use a minimal coarse-grained molecular dynamics system to explore how lipid vesicles undergoing poration in a protein-rich medium can be plugged and stabilised by condensate formation. The solution of proteins in and out of the vesicle is described by beads dispersed in implicit solvent. The membrane is described as a one-bead-thick fluid elastic layer of mechanical properties that mimic biological membranes. We tune the interactions between solution beads in the different compartments to capture the differences between the cytoplasmic and endosomal protein solutions and explore how the system responds to different degrees of membrane poration. We find that, in the right interaction regime, condensates form rapidly at the damage site upon solution mixing and act as a plug that prevents futher mixing and destabilisation of the vesicle. Further, when the condensate can interact with the membrane (wetting interactions) we find that it mediates pore sealing and membrane repair. This research is part of the work published in "Stress granules plug and stabilize damaged endolysosomal membranes", Bussi et al, Nature, 2023 - 10.1038/s41586-023-06726-w.}, author = {Vanhille-Campos, Christian Eduardo and Šarić, Anđela}, publisher = {Institute of Science and Technology Austria}, title = {{Stress granules plug and stabilize damaged endolysosomal membranes}}, doi = {10.15479/AT:ISTA:14472}, year = {2023}, } @article{12747, abstract = {Muscle degeneration is the most prevalent cause for frailty and dependency in inherited diseases and ageing. Elucidation of pathophysiological mechanisms, as well as effective treatments for muscle diseases, represents an important goal in improving human health. Here, we show that the lipid synthesis enzyme phosphatidylethanolamine cytidyltransferase (PCYT2/ECT) is critical to muscle health. Human deficiency in PCYT2 causes a severe disease with failure to thrive and progressive weakness. pcyt2-mutant zebrafish and muscle-specific Pcyt2-knockout mice recapitulate the participant phenotypes, with failure to thrive, progressive muscle weakness and accelerated ageing. Mechanistically, muscle Pcyt2 deficiency affects cellular bioenergetics and membrane lipid bilayer structure and stability. PCYT2 activity declines in ageing muscles of mice and humans, and adeno-associated virus-based delivery of PCYT2 ameliorates muscle weakness in Pcyt2-knockout and old mice, offering a therapy for individuals with a rare disease and muscle ageing. Thus, PCYT2 plays a fundamental and conserved role in vertebrate muscle health, linking PCYT2 and PCYT2-synthesized lipids to severe muscle dystrophy and ageing.}, author = {Cikes, Domagoj and Elsayad, Kareem and Sezgin, Erdinc and Koitai, Erika and Ferenc, Torma and Orthofer, Michael and Yarwood, Rebecca and Heinz, Leonhard X. and Sedlyarov, Vitaly and Darwish-Miranda, Nasser and Taylor, Adrian and Grapentine, Sophie and al-Murshedi, Fathiya and Abot, Anne and Weidinger, Adelheid and Kutchukian, Candice and Sanchez, Colline and Cronin, Shane J. F. and Novatchkova, Maria and Kavirayani, Anoop and Schuetz, Thomas and Haubner, Bernhard and Haas, Lisa and Hagelkruys, Astrid and Jackowski, Suzanne and Kozlov, Andrey and Jacquemond, Vincent and Knauf, Claude and Superti-Furga, Giulio and Rullman, Eric and Gustafsson, Thomas and McDermot, John and Lowe, Martin and Radak, Zsolt and Chamberlain, Jeffrey S. and Bakovic, Marica and Banka, Siddharth and Penninger, Josef M.}, issn = {2522-5812}, journal = {Nature Metabolism}, keywords = {Cell Biology, Physiology (medical), Endocrinology, Diabetes and Metabolism, Internal Medicine}, pages = {495--515}, publisher = {Springer Nature}, title = {{PCYT2-regulated lipid biosynthesis is critical to muscle health and ageing}}, doi = {10.1038/s42255-023-00766-2}, volume = {5}, year = {2023}, } @article{14605, abstract = {The phonon transport mechanisms and ultralow lattice thermal conductivities (κL) in silver halide AgX (X=Cl,Br,I) compounds are not yet well understood. Herein, we study the lattice dynamics and thermal property of AgX under the framework of perturbation theory and the two-channel Wigner thermal transport model based on accurate machine learning potentials. We find that an accurate extraction of the third-order atomic force constants from largely displaced configurations is significant for the calculation of the κL of AgX, and the coherence thermal transport is also non-negligible. In AgI, however, the calculated κL still considerably overestimates the experimental values even including four-phonon scatterings. Molecular dynamics (MD) simulations using machine learning potential suggest an important role of the higher-than-fourth-order lattice anharmonicity in the low-frequency phonon linewidths of AgI at room temperature, which can be related to the simultaneous restrictions of the three- and four-phonon phase spaces. The κL of AgI calculated using MD phonon lifetimes including full-order lattice anharmonicity shows a better agreement with experiments.}, author = {Ouyang, Niuchang and Zeng, Zezhu and Wang, Chen and Wang, Qi and Chen, Yue}, issn = {2469-9969}, journal = {Physical Review B}, number = {17}, publisher = {American Physical Society}, title = {{Role of high-order lattice anharmonicity in the phonon thermal transport of silver halide AgX (X=Cl,Br, I)}}, doi = {10.1103/PhysRevB.108.174302}, volume = {108}, year = {2023}, } @inproceedings{14609, abstract = {Distributed Key Generation (DKG) is a technique to bootstrap threshold cryptosystems without a trusted party. DKG is an essential building block to many decentralized protocols such as randomness beacons, threshold signatures, Byzantine consensus, and multiparty computation. While significant progress has been made recently, existing asynchronous DKG constructions are inefficient when the reconstruction threshold is larger than one-third of the total nodes. In this paper, we present a simple and concretely efficient asynchronous DKG (ADKG) protocol among n = 3t + 1 nodes that can tolerate up to t malicious nodes and support any reconstruction threshold ℓ ≥ t. Our protocol has an expected O(κn3) communication cost, where κ is the security parameter, and only assumes the hardness of the Discrete Logarithm. The core ingredient of our ADKG protocol is an asynchronous protocol to secret share a random polynomial of degree ℓ ≥ t, which has other applications, such as asynchronous proactive secret sharing and asynchronous multiparty computation. We implement our high-threshold ADKG protocol and evaluate it using a network of up to 128 geographically distributed nodes. Our evaluation shows that our high-threshold ADKG protocol reduces the running time by 90% and bandwidth usage by 80% over the state-of-the-art.}, author = {Das, Sourav and Xiang, Zhuolun and Kokoris Kogias, Eleftherios and Ren, Ling}, booktitle = {32nd USENIX Security Symposium}, isbn = {9781713879497}, location = {Anaheim, CA, United States}, pages = {5359--5376}, publisher = {Usenix}, title = {{Practical asynchronous high-threshold distributed key generation and distributed polynomial sampling}}, volume = {8}, year = {2023}, } @article{14603, abstract = {Computing the solubility of crystals in a solvent using atomistic simulations is notoriously challenging due to the complexities and convergence issues associated with free-energy methods, as well as the slow equilibration in direct-coexistence simulations. This paper introduces a molecular-dynamics workflow that simplifies and robustly computes the solubility of molecular or ionic crystals. This method is considerably more straightforward than the state-of-the-art, as we have streamlined and optimised each step of the process. Specifically, we calculate the chemical potential of the crystal using the gas-phase molecule as a reference state, and employ the S0 method to determine the concentration dependence of the chemical potential of the solute. We use this workflow to predict the solubilities of sodium chloride in water, urea polymorphs in water, and paracetamol polymorphs in both water and ethanol. Our findings indicate that the predicted solubility is sensitive to the chosen potential energy surface. Furthermore, we note that the harmonic approximation often fails for both molecular crystals and gas molecules at or above room temperature, and that the assumption of an ideal solution becomes less valid for highly soluble substances.}, author = {Reinhardt, Aleks and Chew, Pin Yu and Cheng, Bingqing}, issn = {1089-7690}, journal = {Journal of Chemical Physics}, number = {18}, publisher = {AIP Publishing}, title = {{A streamlined molecular-dynamics workflow for computing solubilities of molecular and ionic crystals}}, doi = {10.1063/5.0173341}, volume = {159}, year = {2023}, } @article{14604, abstract = {Sex chromosomes have evolved independently multiple times, but why some are conserved for more than 100 million years whereas others turnover rapidly remains an open question. Here, we examine the homology of sex chromosomes across nine orders of insects, plus the outgroup springtails. We find that the X chromosome is likely homologous across insects and springtails; the only exception is in the Lepidoptera, which has lost the X and now has a ZZ/ZW sex-chromosome system. These results suggest the ancestral insect X chromosome has persisted for more than 450 million years—the oldest known sex chromosome to date. Further, we propose that the shrinking of gene content the dipteran X chromosome has allowed for a burst of sex-chromosome turnover that is absent from other speciose insect orders.}, author = {Toups, Melissa A and Vicoso, Beatriz}, issn = {1558-5646}, journal = {Evolution}, number = {11}, pages = {2504--2511}, publisher = {Oxford University Press}, title = {{The X chromosome of insects likely predates the origin of class Insecta}}, doi = {10.1093/evolut/qpad169}, volume = {77}, year = {2023}, } @misc{14616, abstract = {Sex chromosomes have evolved independently multiple times, but why some are conserved for more than 100 million years whereas others turnover rapidly remains an open question. Here, we examine the homology of sex chromosomes across nine orders of insects, plus the outgroup springtails. We find that the X chromosome is likely homologous across insects and springtails; the only exception is in the Lepidoptera, which has lost the X and now has a ZZ/ZW sex chromosome system. These results suggest the ancestral insect X chromosome has persisted for more than 450 million years – the oldest known sex chromosome to date. Further, we propose that the shrinking of gene content of the Dipteran X chromosome has allowed for a burst of sex-chromosome turnover that is absent from other speciose insect orders.}, author = {Toups, Melissa A and Vicoso, Beatriz}, publisher = {Dryad}, title = {{The X chromosome of insects likely predates the origin of Class Insecta}}, doi = {10.5061/DRYAD.HX3FFBGKT}, year = {2023}, } @misc{14617, abstract = {Sex chromosomes have evolved independently multiple times, but why some are conserved for more than 100 million years whereas others turnover rapidly remains an open question. Here, we examine the homology of sex chromosomes across nine orders of insects, plus the outgroup springtails. We find that the X chromosome is likely homologous across insects and springtails; the only exception is in the Lepidoptera, which has lost the X and now has a ZZ/ZW sex chromosome system. These results suggest the ancestral insect X chromosome has persisted for more than 450 million years – the oldest known sex chromosome to date. Further, we propose that the shrinking of gene content of the Dipteran X chromosome has allowed for a burst of sex-chromosome turnover that is absent from other speciose insect orders.}, author = {Toups, Melissa A and Vicoso, Beatriz}, publisher = {Zenodo}, title = {{The X chromosome of insects likely predates the origin of Class Insecta}}, doi = {10.5281/ZENODO.8138705}, year = {2023}, } @misc{14619, abstract = {Data underlying the publication "A streamlined molecular-dynamics workflow for computing solubilities of molecular and ionic crystals" (DOI https://doi.org/10.1063/5.0173341).}, author = {Cheng, Bingqing}, publisher = {Zenodo}, title = {{BingqingCheng/solubility: V1.0}}, doi = {10.5281/ZENODO.8398094}, year = {2023}, } @article{14564, abstract = {Cumulus parameterization (CP) in state‐of‐the‐art global climate models is based on the quasi‐equilibrium assumption (QEA), which views convection as the action of an ensemble of cumulus clouds, in a state of equilibrium with respect to a slowly varying atmospheric state. This view is not compatible with the organization and dynamical interactions across multiple scales of cloud systems in the tropics and progress in this research area was slow over decades despite the widely recognized major shortcomings. Novel ideas on how to represent key physical processes of moist convection‐large‐scale interaction to overcome the QEA have surged recently. The stochastic multicloud model (SMCM) CP in particular mimics the dynamical interactions of multiple cloud types that characterize organized tropical convection. Here, the SMCM is used to modify the Zhang‐McFarlane (ZM) CP by changing the way in which the bulk mass flux and bulk entrainment and detrainment rates are calculated. This is done by introducing a stochastic ensemble of plumes characterized by randomly varying detrainment level distributions based on the cloud area fraction of the SMCM. The SMCM is here extended to include shallow cumulus clouds resulting in a unified shallow‐deep CP. The new stochastic multicloud plume CP is validated against the control ZM scheme in the context of the single column Community Climate Model of the National Center for Atmospheric Research using data from both tropical ocean and midlatitude land convection. Some key features of the SMCM CP such as it capability to represent the tri‐modal nature of organized convection are emphasized.}, author = {Khouider, B. and GOSWAMI, BIDYUT B and Phani, R. and Majda, A. J.}, issn = {1942-2466}, journal = {Journal of Advances in Modeling Earth Systems}, keywords = {General Earth and Planetary Sciences, Environmental Chemistry, Global and Planetary Change}, number = {11}, publisher = {American Geophysical Union}, title = {{A shallow‐deep unified stochastic mass flux cumulus parameterization in the single column community climate model}}, doi = {10.1029/2022ms003391}, volume = {15}, year = {2023}, } @article{12789, abstract = {Experiments have shown that charge distributions of granular materials are non-Gaussian, with broad tails that indicate many particles with high charge. This observation has consequences for the behavior of granular materials in many settings, and may bear relevance to the underlying charge transfer mechanism. However, there is the unaddressed possibility that broad tails arise due to experimental uncertainties, as determining the shapes of tails is nontrivial. Here we show that measurement uncertainties can indeed account for most of the tail broadening previously observed. The clue that reveals this is that distributions are sensitive to the electric field at which they are measured; ones measured at low (high) fields have larger (smaller) tails. Accounting for sources of uncertainty, we reproduce this broadening in silico. Finally, we use our results to back out the true charge distribution without broadening, which we find is still non-Guassian, though with substantially different behavior at the tails and indicating significantly fewer highly charged particles. These results have implications in many natural settings where electrostatic interactions, especially among highly charged particles, strongly affect granular behavior.}, author = {Mujica, Nicolás and Waitukaitis, Scott R}, issn = {2470-0053}, journal = {Physical Review E}, number = {3}, publisher = {American Physical Society}, title = {{Accurate determination of the shapes of granular charge distributions}}, doi = {10.1103/PhysRevE.107.034901}, volume = {107}, year = {2023}, } @inproceedings{13238, abstract = {We consider a natural problem dealing with weighted packet selection across a rechargeable link, which e.g., finds applications in cryptocurrency networks. The capacity of a link (u, v) is determined by how much nodes u and v allocate for this link. Specifically, the input is a finite ordered sequence of packets that arrive in both directions along a link. Given (u, v) and a packet of weight x going from u to v, node u can either accept or reject the packet. If u accepts the packet, the capacity on link (u, v) decreases by x. Correspondingly, v’s capacity on (u, v) increases by x. If a node rejects the packet, this will entail a cost affinely linear in the weight of the packet. A link is “rechargeable” in the sense that the total capacity of the link has to remain constant, but the allocation of capacity at the ends of the link can depend arbitrarily on the nodes’ decisions. The goal is to minimise the sum of the capacity injected into the link and the cost of rejecting packets. We show that the problem is NP-hard, but can be approximated efficiently with a ratio of (1+ε)⋅(1+3–√) for some arbitrary ε>0. .}, author = {Schmid, Stefan and Svoboda, Jakub and Yeo, Michelle X}, booktitle = {SIROCCO 2023: Structural Information and Communication Complexity }, isbn = {9783031327322}, issn = {1611-3349}, location = {Alcala de Henares, Spain}, pages = {576--594}, publisher = {Springer Nature}, title = {{Weighted packet selection for rechargeable links in cryptocurrency networks: Complexity and approximation}}, doi = {10.1007/978-3-031-32733-9_26}, volume = {13892}, year = {2023}, } @phdthesis{14506, abstract = {Payment channel networks are a promising approach to improve the scalability bottleneck of cryptocurrencies. Two design principles behind payment channel networks are efficiency and privacy. Payment channel networks improve efficiency by allowing users to transact in a peer-to-peer fashion along multi-hop routes in the network, avoiding the lengthy process of consensus on the blockchain. Transacting over payment channel networks also improves privacy as these transactions are not broadcast to the blockchain. Despite the influx of recent protocols built on top of payment channel networks and their analysis, a common shortcoming of many of these protocols is that they typically focus only on either improving efficiency or privacy, but not both. Another limitation on the efficiency front is that the models used to model actions, costs and utilities of users are limited or come with unrealistic assumptions. This thesis aims to address some of the shortcomings of recent protocols and algorithms on payment channel networks, particularly in their privacy and efficiency aspects. We first present a payment route discovery protocol based on hub labelling and private information retrieval that hides the route query and is also efficient. We then present a rebalancing protocol that formulates the rebalancing problem as a linear program and solves the linear program using multiparty computation so as to hide the channel balances. The rebalancing solution as output by our protocol is also globally optimal. We go on to develop more realistic models of the action space, costs, and utilities of both existing and new users that want to join the network. In each of these settings, we also develop algorithms to optimise the utility of these users with good guarantees on the approximation and competitive ratios.}, author = {Yeo, Michelle X}, issn = {2663 - 337X}, pages = {162}, publisher = {Institute of Science and Technology Austria}, title = {{Advances in efficiency and privacy in payment channel network analysis}}, doi = {10.15479/14506}, year = {2023}, } @inproceedings{14490, abstract = {Payment channel networks (PCNs) are a promising solution to the scalability problem of cryptocurrencies. Any two users connected by a payment channel in the network can theoretically send an unbounded number of instant, costless transactions between them. Users who are not directly connected can also transact with each other in a multi-hop fashion. In this work, we study the incentive structure behind the creation of payment channel networks, particularly from the point of view of a single user that wants to join the network. We define a utility function for a new user in terms of expected revenue, expected fees, and the cost of creating channels, and then provide constant factor approximation algorithms that optimise the utility function given a certain budget. Additionally, we take a step back from a single user to the whole network and examine the parameter spaces under which simple graph topologies form a Nash equilibrium.}, author = {Avarikioti, Zeta and Lizurej, Tomasz and Michalak, Tomasz and Yeo, Michelle X}, booktitle = {43rd International Conference on Distributed Computing Systems}, isbn = {9798350339864}, issn = {2575-8411}, location = {Hong Kong, China}, pages = {603--613}, publisher = {IEEE}, title = {{Lightning creation games}}, doi = {10.1109/ICDCS57875.2023.00037}, volume = {2023}, year = {2023}, } @phdthesis{12726, abstract = {Most motions of many-body systems at any scale in nature with sufficient degrees of freedom tend to be chaotic; reaching from the orbital motion of planets, the air currents in our atmosphere, down to the water flowing through our pipelines or the movement of a population of bacteria. To the observer it is therefore intriguing when a moving collective exhibits order. Collective motion of flocks of birds, schools of fish or swarms of self-propelled particles or robots have been studied extensively over the past decades but the mechanisms involved in the transition from chaos to order remain unclear. Here, the interactions, that in most systems give rise to chaos, sustain order. In this thesis we investigate mechanisms that preserve, destabilize or lead to the ordered state. We show that endothelial cells migrating in circular confinements transition to a collective rotating state and concomitantly synchronize the frequencies of nucleating actin waves within individual cells. Consequently, the frequency dependent cell migration speed uniformizes across the population. Complementary to the WAVE dependent nucleation of traveling actin waves, we show that in leukocytes the actin polymerization depending on WASp generates pushing forces locally at stationary patches. Next, in pipe flows, we study methods to disrupt the self–sustaining cycle of turbulence and therefore relaminarize the flow. While we find in pulsating flow conditions that turbulence emerges through a helical instability during the decelerating phase. Finally, we show quantitatively in brain slices of mice that wild-type control neurons can compensate the migratory deficits of a genetically modified neuronal sub–population in the developing cortex.}, author = {Riedl, Michael}, issn = {2663-337X}, pages = {260}, publisher = {Institute of Science and Technology Austria}, title = {{Synchronization in collectively moving active matter}}, doi = {10.15479/at:ista:12726}, year = {2023}, } @phdthesis{14530, abstract = {Most motions of many-body systems at any scale in nature with sufficient degrees of freedom tend to be chaotic; reaching from the orbital motion of planets, the air currents in our atmosphere, down to the water flowing through our pipelines or the movement of a population of bacteria. To the observer it is therefore intriguing when a moving collective exhibits order. Collective motion of flocks of birds, schools of fish or swarms of self-propelled particles or robots have been studied extensively over the past decades but the mechanisms involved in the transition from chaos to order remain unclear. Here, the interactions, that in most systems give rise to chaos, sustain order. In this thesis we investigate mechanisms that preserve, destabilize or lead to the ordered state. We show that endothelial cells migrating in circular confinements transition to a collective rotating state and concomitantly synchronize the frequencies of nucleating actin waves within individual cells. Consequently, the frequency dependent cell migration speed uniformizes across the population. Complementary to the WAVE dependent nucleation of traveling actin waves, we show that in leukocytes the actin polymerization depending on WASp generates pushing forces locally at stationary patches. Next, in pipe flows, we study methods to disrupt the self--sustaining cycle of turbulence and therefore relaminarize the flow. While we find in pulsating flow conditions that turbulence emerges through a helical instability during the decelerating phase. Finally, we show quantitatively in brain slices of mice that wild-type control neurons can compensate the migratory deficits of a genetically modified neuronal sub--population in the developing cortex. }, author = {Riedl, Michael}, issn = {2663 - 337X}, keywords = {Synchronization, Collective Movement, Active Matter, Cell Migration, Active Colloids}, pages = {260}, publisher = {Institute of Science and Technology Austria}, title = {{Synchronization in collectively moving active matter}}, doi = {10.15479/14530}, year = {2023}, } @phdthesis{14547, abstract = {Superconductor-semiconductor heterostructures currently capture a significant amount of research interest and they serve as the physical platform in many proposals towards topological quantum computation. Despite being under extensive investigations, historically using transport techniques, the basic properties of the interface between the superconductor and the semiconductor remain to be understood. In this thesis, two separate studies on the Al-InAs heterostructures are reported with the first focusing on the physics of the material motivated by the emergence of a new phase, the Bogoliubov-Fermi surface. The second focuses on a technological application, a gate-tunable Josephson parametric amplifier. In the first study, we investigate the hypothesized unconventional nature of the induced superconductivity at the interface between the Al thin film and the InAs quantum well. We embed a two-dimensional Al-InAs hybrid system in a resonant microwave circuit allowing measurements of change in inductance. The behaviour of the resonance in a range of temperature and in-plane magnetic field has been studied and compared with the theory of conventional s-wave superconductor and a two-component theory that includes both contribution of the $s$-wave pairing in Al and the intraband $p \pm ip$ pairing in InAs. Measuring the temperature dependence of resonant frequency, no discrepancy is found between data and the conventional theory. We observe the breakdown of superconductivity due to an applied magnetic field which contradicts the conventional theory. In contrast, the data can be captured quantitatively by fitting to a two-component model. We find the evidence of the intraband $p \pm ip$ pairing in the InAs and the emergence of the Bogoliubov-Fermi surfaces due to magnetic field with the characteristic value $B^* = 0.33~\mathrm{T}$. From the fits, the sheet resistance of Al, the carrier density and mobility in InAs are determined. By systematically studying the anisotropy of the circuit response, we find weak anisotropy for $B < B^*$ and increasingly strong anisotropy for $B > B^*$ resulting in a pronounced two-lobe structure in polar plot of frequency versus field angle. Strong resemblance between the field dependence of dissipation and superfluid density hints at a hidden signature of the Bogoliubov-Fermi surface that is burried in the dissipation data. In the second study, we realize a parametric amplifier with a Josephson field effect transistor as the active element. The device's modest construction consists of a gated SNS weak link embedded at the center of a coplanar waveguide resonator. By applying a gate voltage, the resonant frequency is field-effect tunable over a range of 2 GHz. Modelling the JoFET minimally as a parallel RL circuit, the dissipation introduced by the JoFET can be quantitatively related to the gate voltage. We observed gate-tunable Kerr nonlinearity qualitatively in line with expectation. The JoFET amplifier has 20 dB of gain, 4 MHz of instantaneous bandwidth, and a 1dB compression point of -125.5 dBm when operated at a fixed resonant frequency. In general, the signal-to-noise ratio is improved by 5-7 dB when the JoFET amplifier is activated compared. The noise of the measurement chain and insertion loss of relevant circuit elements are calibrated to determine the expected and the real noise performance of the JoFET amplifier. As a quantification of the noise performance, the measured total input-referred noise of the JoFET amplifier is in good agreement with the estimated expectation which takes device loss into account. We found that the noise performance of the device reported in this document approaches one photon of total input-referred added noise which is the quantum limit imposed in nondegenerate parametric amplifier.}, author = {Phan, Duc T}, issn = {2663 - 337X}, keywords = {superconductor-semiconductor, superconductivity, Al, InAs, p-wave, superconductivity, JPA, microwave}, pages = {80}, publisher = {Institute of Science and Technology Austria}, title = {{Resonant microwave spectroscopy of Al-InAs}}, doi = {10.15479/14547}, year = {2023}, } @article{13264, abstract = {We build a parametric amplifier with a Josephson field-effect transistor (JoFET) as the active element. The resonant frequency of the device is field-effect tunable over a range of 2 GHz. The JoFET amplifier has 20 dB of gain, 4 MHz of instantaneous bandwidth, and a 1-dB compression point of -125.5 dBm when operated at a fixed resonance frequency. }, author = {Phan, Duc T and Falthansl-Scheinecker, Paul and Mishra, Umang and Strickland, W. M. and Langone, D. and Shabani, J. and Higginbotham, Andrew P}, issn = {2331-7019}, journal = {Physical Review Applied}, number = {6}, publisher = {American Physical Society}, title = {{Gate-tunable superconductor-semiconductor parametric amplifier}}, doi = {10.1103/PhysRevApplied.19.064032}, volume = {19}, year = {2023}, } @unpublished{14591, abstract = {Clathrin-mediated endocytosis (CME) is vital for the regulation of plant growth and development by controlling plasma membrane protein composition and cargo uptake. CME relies on the precise recruitment of regulators for vesicle maturation and release. Homologues of components of mammalian vesicle scission are strong candidates to be part of the scissin machinery in plants, but the precise roles of these proteins in this process is not fully understood. Here, we characterised the roles of Plant Dynamin-Related Proteins 2 (DRP2s) and SH3-domain containing protein 2 (SH3P2), the plant homologue to Dynamins’ recruiters, like Endophilin and Amphiphysin, in the CME by combining high-resolution imaging of endocytic events in vivo and characterisation of the purified proteins in vitro. Although DRP2s and SH3P2 arrive similarly late during CME and physically interact, genetic analysis of the Dsh3p1,2,3 triple-mutant and complementation assays with non-SH3P2-interacting DRP2 variants suggests that SH3P2 does not directly recruit DRP2s to the site of endocytosis. These observations imply that despite the presence of many well-conserved endocytic components, plants have acquired a distinct mechanism for CME. One Sentence Summary In contrast to predictions based on mammalian systems, plant Dynamin-related proteins 2 are recruited to the site of Clathrin-mediated endocytosis independently of BAR-SH3 proteins.}, author = {Gnyliukh, Nataliia and Johnson, Alexander J and Nagel, Marie-Kristin and Monzer, Aline and Hlavata, Annamaria and Isono, Erika and Loose, Martin and Friml, Jiří}, booktitle = {bioRxiv}, title = {{Role of dynamin-related proteins 2 and SH3P2 in clathrin-mediated endocytosis in plants}}, doi = {10.1101/2023.10.09.561523}, year = {2023}, } @article{14639, abstract = {Background: Biallelic variants in OGDHL, encoding part of the α-ketoglutarate dehydrogenase complex, have been associated with highly heterogeneous neurological and neurodevelopmental disorders. However, the validity of this association remains to be confirmed. A second OGDHL patient cohort was recruited to carefully assess the gene-disease relationship. Methods: Using an unbiased genotype-first approach, we screened large, multiethnic aggregated sequencing datasets worldwide for biallelic OGDHL variants. We used CRISPR/Cas9 to generate zebrafish knockouts of ogdhl, ogdh paralogs, and dhtkd1 to investigate functional relationships and impact during development. Functional complementation with patient variant transcripts was conducted to systematically assess protein functionality as a readout for pathogenicity. Results: A cohort of 14 individuals from 12 unrelated families exhibited highly variable clinical phenotypes, with the majority of them presenting at least one additional variant, potentially accounting for a blended phenotype and complicating phenotypic understanding. We also uncovered extreme clinical heterogeneity and high allele frequencies, occasionally incompatible with a fully penetrant recessive disorder. Human cDNA of previously described and new variants were tested in an ogdhl zebrafish knockout model, adding functional evidence for variant reclassification. We disclosed evidence of hypomorphic alleles as well as a loss-of-function variant without deleterious effects in zebrafish variant testing also showing discordant familial segregation, challenging the relationship of OGDHL as a conventional Mendelian gene. Going further, we uncovered evidence for a complex compensatory relationship among OGDH, OGDHL, and DHTKD1 isoenzymes that are associated with neurodevelopmental disorders and exhibit complex transcriptional compensation patterns with partial functional redundancy. Conclusions: Based on the results of genetic, clinical, and functional studies, we formed three hypotheses in which to frame observations: biallelic OGDHL variants lead to a highly variable monogenic disorder, variants in OGDHL are following a complex pattern of inheritance, or they may not be causative at all. Our study further highlights the continuing challenges of assessing the validity of reported disease-gene associations and effects of variants identified in these genes. This is particularly more complicated in making genetic diagnoses based on identification of variants in genes presenting a highly heterogenous phenotype such as “OGDHL-related disorders”.}, author = {Lin, Sheng-Jia and Vona, Barbara and Lau, Tracy and Huang, Kevin and Zaki, Maha S. and Aldeen, Huda Shujaa and Karimiani, Ehsan Ghayoor and Rocca, Clarissa and Noureldeen, Mahmoud M. and Saad, Ahmed K. and Petree, Cassidy and Bartolomaeus, Tobias and Abou Jamra, Rami and Zifarelli, Giovanni and Gotkhindikar, Aditi and Wentzensen, Ingrid M. and Liao, Mingjuan and Cork, Emalyn Elise and Varshney, Pratishtha and Hashemi, Narges and Mohammadi, Mohammad Hasan and Rad, Aboulfazl and Neira, Juanita and Toosi, Mehran Beiraghi and Knopp, Cordula and Kurth, Ingo and Challman, Thomas D. and Smith, Rebecca and Abdalla, Asmahan and Haaf, Thomas and Suri, Mohnish and Joshi, Manali and Chung, Wendy K. and Moreno-De-Luca, Andres and Houlden, Henry and Maroofian, Reza and Varshney, Gaurav K.}, issn = {1756-994X}, journal = {Genome Medicine}, keywords = {Genetics (clinical), Genetics, Molecular Biology, Molecular Medicine}, publisher = {Springer Nature}, title = {{Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity}}, doi = {10.1186/s13073-023-01258-4}, volume = {15}, year = {2023}, } @article{14628, abstract = {We introduce a compact, intuitive procedural graph representation for cellular metamaterials, which are small-scale, tileable structures that can be architected to exhibit many useful material properties. Because the structures’ “architectures” vary widely—with elements such as beams, thin shells, and solid bulks—it is difficult to explore them using existing representations. Generic approaches like voxel grids are versatile, but it is cumbersome to represent and edit individual structures; architecture-specific approaches address these issues, but are incompatible with one another. By contrast, our procedural graph succinctly represents the construction process for any structure using a simple skeleton annotated with spatially varying thickness. To express the highly constrained triply periodic minimal surfaces (TPMS) in this manner, we present the first fully automated version of the conjugate surface construction method, which allows novices to create complex TPMS from intuitive input. We demonstrate our representation’s expressiveness, accuracy, and compactness by constructing a wide range of established structures and hundreds of novel structures with diverse architectures and material properties. We also conduct a user study to verify our representation’s ease-of-use and ability to expand engineers’ capacity for exploration.}, author = {Makatura, Liane and Wang, Bohan and Chen, Yi-Lu and Deng, Bolei and Wojtan, Christopher J and Bickel, Bernd and Matusik, Wojciech}, issn = {0730-0301}, journal = {ACM Transactions on Graphics}, keywords = {Computer Graphics and Computer-Aided Design}, number = {5}, publisher = {Association for Computing Machinery}, title = {{Procedural metamaterials: A unified procedural graph for metamaterial design}}, doi = {10.1145/3605389}, volume = {42}, year = {2023}, } @unpublished{14644, abstract = {Transcription by RNA polymerase II (Pol II) can be repressed by noncoding RNA, including the human RNA Alu. However, the mechanism by which endogenous RNAs repress transcription remains unclear. Here we present cryo-electron microscopy structures of Pol II bound to Alu RNA, which reveal that Alu RNA mimics how DNA and RNA bind to Pol II during transcription elongation. Further, we show how domains of the general transcription factor TFIIF affect complex dynamics and control repressive activity. Together, we reveal how a non-coding RNA can regulate mammalian gene expression.}, author = {Tluckova, Katarina and Testa Salmazo, Anita P and Bernecky, Carrie A}, publisher = {Institute of Science and Technology Austria}, title = {{Mechanism of mammalian transcriptional repression by noncoding RNA}}, doi = {10.15479/AT:ISTA:14644}, year = {2023}, }