@article{17183, abstract = {The photon blockade breakdown in a continuously driven cavity QED system has been proposed as a prime example for a first-order driven-dissipative quantum phase transition. However, the predicted scaling from a microscopic behavior—dominated by quantum fluctuations—to a macroscopic one—characterized by stable phases—and the associated exponents and phase diagram have not been observed so far. In this work we couple a single transmon qubit with a fixed coupling strength 𝑔 to a superconducting cavity that is in situ bandwidth 𝜅 tunable to controllably approach this thermodynamic limit. Even though the system remains microscopic, we observe its behavior becoming increasingly macroscopic as a function of 𝑔/𝜅. For the highest realized 𝑔/𝜅 of approximately 287, the system switches with a characteristic timescale as long as 6 s between a bright coherent state with approximately 8×103 intracavity photons and the vacuum state. This exceeds the microscopic timescales by 6 orders of magnitude and approaches the perfect hysteresis expected between two macroscopic attractors in the thermodynamic limit. These findings and interpretation are qualitatively supported by neoclassical theory and large-scale quantum-jump Monte Carlo simulations. Besides shedding more light on driven-dissipative physics in the limit of strong light-matter coupling, this system might also find applications in quantum sensing and metrology.}, author = {Sett, Riya and Hassani, Farid and Phan, Duc T and Barzanjeh, Shabir and Vukics, Andras and Fink, Johannes M}, issn = {2691-3399}, journal = {PRX Quantum}, number = {1}, publisher = {American Physical Society}, title = {{Emergent macroscopic bistability induced by a single superconducting qubit}}, doi = {10.1103/prxquantum.5.010327}, volume = {5}, year = {2024}, } @article{18063, abstract = {The developmental plasticity of the root system plays an essential role in the adaptation of plants to the environment. Among many other signals, auxin and its directional, intercellular transport are critical in regulating root growth and development. In particular, the PIN-FORMED2 (PIN2) auxin exporter acts as a key regulator of root gravitropic growth. Multiple regulators have been reported to be involved in PIN2-mediated root growth; however, our information remains incomplete. Here, we identified ROWY Bro1-domain proteins as important regulators of PIN2 sorting control. Genetic analysis revealed that Arabidopsis rowy1 single mutants and higher-order rowy1 rowy2 rowy3 triple mutants presented a wavy root growth phenotype. Cell biological experiments revealed that ROWY1 and PIN2 colocalized to the apical side of the plasma membrane in the root epidermis and that ROWYs are required for correct PM targeting of PIN2. In addition, ROWYs also affected PIN3 protein abundance in the stele, suggesting the potential involvement of additional PIN transporters as well as other proteins. A global transcriptome analysis revealed that ROWY genes are involved in the Fe2+ availability perception pathway. This work establishes ROWYs as important novel regulators of root gravitropic growth by connecting micronutrient availability to the proper subcellular targeting of PIN auxin transporters.}, author = {Peng, Yakun and Ji, Kangkang and Mao, Yanbo and Wang, Yiqun and Korbei, Barbara and Luschnig, Christian and Shen, Jinbo and Benková, Eva and Friml, Jiří and Tan, Shutang}, issn = {2399-3642}, journal = {Communications Biology}, publisher = {Springer Nature}, title = {{Polarly localized Bro1 domain proteins regulate PIN-FORMED abundance and root gravitropic growth in Arabidopsis}}, doi = {10.1038/s42003-024-06747-9}, volume = {7}, year = {2024}, } @inbook{17425, abstract = {Mosaic Analysis with Double Markers (MADM) is a powerful genetic method typically used for lineage tracing and to disentangle cell autonomous and tissue-wide roles of candidate genes with single cell resolution. Given the relatively sparse labeling, depending on which of the 19 MADM chromosomes one chooses, the MADM approach represents the perfect opportunity for cell morphology analysis. Various MADM studies include reports of morphological anomalies and phenotypes in the central nervous system (CNS). MADM for any candidate gene can easily incorporate morphological analysis within the experimental workflow. Here, we describe the methods of morphological cell analysis which we developed in the course of diverse recent MADM studies. This chapter will specifically focus on methods to quantify aspects of the morphology of neurons and astrocytes within the CNS, but these methods can broadly be applied to any MADM-labeled cells throughout the entire organism. We will cover two analyses—soma volume and dendrite characterization—of physical characteristics of pyramidal neurons in the somatosensory cortex, and two analyses—volume and Sholl analysis—of astrocyte morphology.}, author = {Miranda, Osvaldo and Cheung, Giselle T and Hippenmeyer, Simon}, booktitle = {Neuronal Morphogenesis}, editor = {Toyooka, Kazuhito}, isbn = {9781071639689}, issn = {1940-6029}, pages = {283--299}, publisher = {Springer Nature}, title = {{Morphological Analysis of Neurons and Glia Using Mosaic Analysis with Double Markers}}, doi = {10.1007/978-1-0716-3969-6_19}, volume = {2831}, year = {2024}, } @misc{18978, abstract = {Data analysis files for the manuscript "Emergent Macroscopic Bistability Induced by a Single Superconducting Qubit". This contains the raw data and the data analysis files for generating the figures in the manuscript. Figure1 file - The raw data of cavity transmission spectra for 6 different kappas are there. They are fitted with input-output theory in the python file. Figure2 file - The raw data at 8 MHz kappa are included. all hte figures in figure 2 are generated in the python file Figure3 file - The raw data of PBB single shot measurements at all kappas are included. The detailed analysis and the Figure3 generated for the paper are all in the python analysis file. Also, thefiles containing the time-evolution of the intensity from Master Equation solution are included. Figure4 file - The raw data at 2.6 MHz for different drive detunings and the corresponding analyses are included. And the python file includes the analysis of the experimental data as well as approximate neoclassical equations solutions for 2-level and 3-level transmons are included. }, author = {Sett, Riya and Hassani, Farid and Phan, Duc T and Barzanjeh, Shabir and Vukics, Andras and Fink, Johannes M}, publisher = {Zenodo}, title = {{Data Analysis files for "Emergent Macroscopic Bistability Induced by a Single Superconducting Qubit"}}, doi = {10.5281/ZENODO.10518320}, year = {2024}, } @phdthesis{17319, abstract = {This thesis comprises two distinct projects, each offering unique insights into fundamental cellular processes. While distinct in their focus, these different perspectives have a common theme: chemiosmotic theory and utilisation of the proton gradient for driving the essential processes like auxin efflux and ATP synthesis, effectively bridging the membrane protein structure and function from the realms of plant biology and cellular bioenergetics. The first project of this thesis centres on the characterisation of PIN proteins, a class of transmembrane transporters pivotal in the regulation of auxin transport and distribution in plants. PINs form a conserved and phylogenetically abundant group of transporters present in land plants and certain algae. Despite their great importance, they were one of the few elusive proteins essential for plant development not to be structurally and mechanistically characterised since their discovery almost 30 years ago. This work aimed to uncover the structural and functional dynamics of the PIN protein-mediated auxin transport using an array of experimental techniques, including protein purification, biochemical assays and structural analysis. Through an exhaustive screening process that took several years and included testing different PIN homologues, expression systems, constructs, and purification conditions, we developed a robust protocol for isolating the pure, stable, and monodisperse PIN8 protein. Moreover, utilising biophysical methods and buffer screening, we demonstrated that PIN8 exhibits detergent and pH-dependent stability, with mild detergents and lower pH (5.0 and 6.0) being optimal for the stability of the protein. Using SEC-MALS and crosslinking, we determined that PIN8 forms dimers, which was confirmed by our structural studies. We obtained a cryo-EM map of PIN8 at pH 6.0, and, compared to recently published structures, our map implies major pH-dependent conformational changes and possibly utilisation of the proton gradient in the transport mechanism. The subject of the second project was F1Fo-ATP synthase, an enzyme complex fundamental to cellular energy metabolism. Through an approach integrating biochemical assays and structural analysis, this research aimed to unveil the molecular mechanism of inhibition of ATP synthase by yaku´amide, a bioactive compound with potential therapeutic implications. Using submitochondrial particles and purified F1Fo-ATP synthase, we demonstrated that, contrary to published data, yaku´amide inhibits both ATP hydrolysis and ATP synthesis reactions. Moreover, we found that yaku´amide inhibitory activity is proton motive force (pmf) dependent, with lower inhibition in a more coupled system. Utilising cryo-EM, we obtained maps and models for the three main rotational states of murine ATP synthase (State 1 at 3.0 Å, 8 State 2 at 3.1 Å, and State 3 at 3.2 Å, overall). We observed several new features in our maps; however, we cannot definitively determine the exact mechanism of yaku amide’s inhibition on the protein due to either resolution limits or suboptimal binding of the inhibitor.}, author = {Lukic, Kristina}, issn = {2663-337X}, pages = {224}, publisher = {Institute of Science and Technology Austria}, title = {{Membrane proteins in plant physiology and bioenergetics : Investigating auxin efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor Yaku'amide B}}, doi = {10.15479/at:ista:17319}, year = {2024}, } @article{15323, abstract = {Supercomplexes of the respiratory chain are established constituents of the oxidative phosphorylation system, but their role in mammalian metabolism has been hotly debated. Although recent studies have shown that different tissues/organs are equipped with specific sets of supercomplexes, depending on their metabolic needs, the notion that supercomplexes have a role in the regulation of metabolism has been challenged. However, irrespective of the mechanistic conclusions, the composition of various high molecular weight supercomplexes remains uncertain. Here, using cryogenic electron microscopy, we demonstrate that mammalian (mouse) tissues contain three defined types of ‘respirasome’, supercomplexes made of CI, CIII2 and CIV. The stoichiometry and position of CIV differs in the three respirasomes, of which only one contains the supercomplex-associated factor SCAF1, whose involvement in respirasome formation has long been contended. Our structures confirm that the ‘canonical’ respirasome (the C-respirasome, CICIII2CIV) does not contain SCAF1, which is instead associated to a different respirasome (the CS-respirasome), containing a second copy of CIV. We also identify an alternative respirasome (A-respirasome), with CIV bound to the ‘back’ of CI, instead of the ‘toe’. This structural characterization of mouse mitochondrial supercomplexes allows us to hypothesize a mechanistic basis for their specific role in different metabolic conditions.}, author = {Vercellino, Irene and Sazanov, Leonid A}, issn = {1545-9985}, journal = {Nature Structural and Molecular Biology}, pages = {1061--1071}, publisher = {Springer Nature}, title = {{SCAF1 drives the compositional diversity of mammalian respirasomes}}, doi = {10.1038/s41594-024-01255-0}, volume = {31}, year = {2024}, } @article{18481, abstract = {A tight regulation of morphogen production is key for morphogen gradient formation and thereby for reproducible and organised organ development. Although many genetic interactions involved in the establishment of morphogen production domains are known, the biophysical mechanisms of morphogen source formation are poorly understood. Here we addressed this by focusing on the morphogen Sonic hedgehog (Shh) in the vertebrate neural tube. Shh is produced by the adjacently located notochord and by the floor plate of the neural tube. Using a data-constrained computational screen, we identified different possible mechanisms by which floor plate formation can occur, only one of which is consistent with experimental data. In this mechanism, the floor plate is established rapidly in response to Shh from the notochord and the dynamics of regulatory interactions within the neural tube. In this process, uniform activators and Shh-dependent repressors are key for establishing the floor plate size. Subsequently, the floor plate becomes insensitive to Shh and increases in size due to tissue growth, leading to scaling of the floor plate with neural tube size. In turn, this results in scaling of the Shh amplitude with tissue growth. Thus, this mechanism ensures a separation of time scales in floor plate formation, so that the floor plate domain becomes growth-dependent after an initial rapid establishment phase. Our study raises the possibility that the time scale separation between specification and growth might be a common strategy for scaling the morphogen gradient amplitude in growing organs. The model that we developed provides a new opportunity for quantitative studies of morphogen source formation in growing tissues.}, author = {Ho, Richard D.J.G. and Kishi, Kasumi and Majka, Maciej and Kicheva, Anna and Zagórski, Marcin P}, issn = {1553-7358}, journal = {PLoS Computational Biology}, publisher = {Public Library of Science}, title = {{Dynamics of morphogen source formation in a growing tissue}}, doi = {10.1371/journal.pcbi.1012508}, volume = {20}, year = {2024}, } @article{15357, abstract = {There is a growing interest in cost-effective polycrystalline SnSe-based thermoelectric (TE) materials, which are able to replace the high performance but mechanically fragile and costly single-crystalline SnSe. In this study, we present a low-temperature solution-based approach to produce SnSe-PbSe nanocomposites with outstanding TE performance. Our method involves combining surfactant-free SnSe particles with oleate-capped PbSe nanocrystals in specific ratios, followed by thermal annealing and consolidation using spark plasma sintering. These nanocomposites are characterized by distinct compositional and structural properties that significantly impact their transport properties. In particular, the addition of oleate-capped PbSe nanocrystals results in: i) a reduction in the electrostatically adsorbed Na at the surface of the SnSe particles; ii) a reduction of Sn vacancies due to alloying with Pb; iii) an increase in grain boundary density; and iv) the formation of PbSnSe secondary phases. Notably, the SnSe-2.5 %PbSe nanocomposites demonstrate a 30 % decrease in thermal conductivity compared to that of the SnSe matrix. This reduction contributes to a maximum figure of merit (zT) of 1.75 at 788 K with a high average zT value of ca. 1.2 in the medium temperature range of 573–773 K. These values represent one of the highest reported in polycrystalline SnSe materials, showcasing the potential of our fabricated SnSe-PbSe nanocomposites for cost-effective TE applications.}, author = {Liu, Yu and Lee, Seungho and Fiedler, Christine and Spadaro, Maria Chiara and Chang, Cheng and Li, Mingquan and Hong, Min and Arbiol, Jordi and Ibáñez, Maria}, issn = {1385-8947}, journal = {Chemical Engineering Journal}, publisher = {Elsevier}, title = {{Enhancing thermoelectric performance of solutionpProcessed polycrystalline SnSe with PbSe nanocrystals}}, doi = {10.1016/j.cej.2024.151405}, volume = {490}, year = {2024}, } @article{17148, abstract = {During neural tube (NT) development, the notochord induces an organizer, the floorplate, which secretes Sonic Hedgehog (SHH) to pattern neural progenitors. Conversely, NT organoids (NTOs) from embryonic stem cells (ESCs) spontaneously form floorplates without the notochord, demonstrating that stem cells can self-organize without embryonic inducers. Here, we investigated floorplate self-organization in clonal mouse NTOs. Expression of the floorplate marker FOXA2 was initially spatially scattered before resolving into multiple clusters, which underwent competition and sorting, resulting in a stable “winning” floorplate. We identified that BMP signaling governed long-range cluster competition. FOXA2+ clusters expressed BMP4, suppressing FOXA2 in receiving cells while simultaneously expressing the BMP-inhibitor NOGGIN, promoting cluster persistence. Noggin mutation perturbed floorplate formation in NTOs and in the NT in vivo at mid/hindbrain regions, demonstrating how the floorplate can form autonomously without the notochord. Identifying the pathways governing organizer self-organization is critical for harnessing the developmental plasticity of stem cells in tissue engineering.}, author = {Krammer, Teresa and Stuart, Hannah T. and Gromberg, Elena and Ishihara, Keisuke and Cislo, Dillon and Melchionda, Manuela and Becerril Perez, Fernando and Wang, Jingkui and Costantini, Elena and Rus, Stefanie and Arbanas, Laura and Hörmann, Alexandra and Neumüller, Ralph A. and Elvassore, Nicola and Siggia, Eric and Briscoe, James and Kicheva, Anna and Tanaka, Elly M.}, issn = {1878-1551}, journal = {Developmental Cell}, number = {15}, pages = {1940--1953.e10}, publisher = {Elsevier}, title = {{Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition}}, doi = {10.1016/j.devcel.2024.04.021}, volume = {59}, year = {2024}, } @phdthesis{18642, abstract = {This thesis consists of two pieces of work in the broader field of computational biology, both of which are methods for the analysis of large scale biological data, implemented in efficient software. Chapter 2 introduces a statistical software for causal discovery and inference from observed genetic marker and phenotypic trait data. We explore in simulation how well the method can fine-map genetic effects, find the correct causal structure among tens of traits and millions of genetic markers, and infer the causal effect size for the discovered causal relations. We then apply the method to 8 million markers and 17 traits from the UK Biobank and show that many relationships found with other methods are likely due to the effects of hidden confounders. Chapter 3 describes how this method can be applied to longitudinal data. I show how one can incorporate the background knowledge present in the known order of measurements to improve the accuracy of the causal discovery process, and explore the method’s ability to identify age specific genetic effects, and how the error rates of this recovery are influenced by missing data due to different censoring mechanisms. Chapter 4 introduces a statistical software for the comparison of chromatin contact maps based on the structural similarity index. We explore the robustness of the method to noise and size differences of the compared maps, show how it can measure evolutionary conservation of topological features by providing a similarity ranking of syntenic regions, and finally how it can detect alterations in 3D genome structure due to genetic mutations in samples of medical relevance. }, author = {Machnik, Nick N}, issn = {2663-337X}, pages = {138}, publisher = {Institute of Science and Technology Austria}, title = {{Algorithms for causal learning and comparative analysis for genomic data}}, doi = {10.15479/at:ista:18642}, year = {2024}, } @article{18601, abstract = {Geometrically controlled stem cell differentiation promotes reproducible pattern formation. Here, we present a protocol to fabricate elastomeric stencils for patterned stem cell differentiation. We describe procedures for using photolithography to produce molds, followed by molding polydimethylsiloxane (PDMS) to obtain stencils with through holes. We then provide instructions for culturing cells on stencils and, finally, removing stencils to allow colony growth and cell migration. This approach yields reproducible two-dimensional organoids tailored for quantitative studies of growth and pattern formation. For complete details on the use and execution of this protocol, please refer to Lehr et al.1}, author = {Rus, Stefanie and Merrin, Jack and Kulig, Monika Aleksandra and Minchington, Thomas and Kicheva, Anna}, issn = {2666-1667}, journal = {STAR Protocols}, number = {4}, publisher = {Elsevier}, title = {{Protocol for fabricating elastomeric stencils for patterned stem cell differentiation}}, doi = {10.1016/j.xpro.2024.103187}, volume = {5}, year = {2024}, } @unpublished{18648, abstract = {Statistical causal learning in genomics relies on the instrumental variable method of Mendelian Randomization (MR). Currently, an overwhelming number of MR studies purport to show causal relationships among a wide range of risk factors and outcomes. Here, we show that selecting instrument variables from genome-wide association study estimates leads to high false discovery rates for many MR approaches, which can be greatly reduced by employing a graphical inference approach which: (i) explicitly tests instrumental variable assumptions; (ii) distinguishes direct from indirect factors in very high-dimensional data; (iii) discriminates pleiotropic from trait-specific markers, controlling for LD genome-wide; (iv) accommodates rare variants and binary outcomes in a principled way; and (v) identifies potential unobserved latent confounding. For 17 traits and 8.4M variants recorded for 458,747 individuals in the UK Biobank, we show that standard MR analysis gives an abundance of findings that disappear under stringent assumption checks, with many relationships reflecting potential unmeasured confounding. This implies that mixtures of temporal precedence and potential for reverse-causality prohibit understanding the underlying nature of phenotypic and genetic correlations in biobank data. We propose that well-curated longitudinal records are likely needed and that our approach provides a first-step toward robust principled screening for potential causal links. }, author = {Machnik, Nick N and Mahmoudi, Seyed Mahdi and Borczyk, Malgorzata and Krätschmer, Ilse and Bauer, Markus J. and Robinson, Matthew Richard}, booktitle = {bioRxiv}, title = {{Causal inference for multiple risk factors and diseases from genomics data}}, doi = {10.1101/2023.12.06.570392}, year = {2024}, } @article{17233, abstract = {CRISPR-Cas9 technology has become an essential tool for plant genome editing. Recent advancements have significantly improved the ability to target multiple genes simultaneously within the same genetic background through various strategies. Additionally, there has been significant progress in developing methods for inducible or tissue-specific editing. These advancements offer numerous possibilities for tailored genome modifications. Building upon existing research, we have developed an optimized and modular strategy allowing the targeting of several genes simultaneously in combination with the synchronized expression of the Cas9 endonuclease in the egg cell. This system allows significant editing efficiency while avoiding mosaicism. In addition, the versatile system we propose allows adaptation to inducible and/or tissue-specific edition according to the promoter chosen to drive the expression of the Cas9 gene. Here, we describe a step-by-step protocol for generating the binary vector necessary for establishing Arabidopsis edited lines using a versatile cloning strategy that combines Gateway® and Golden Gate technologies. We describe a versatile system that allows the cloning of as many guides as needed to target DNA, which can be multiplexed into a polycistronic gene and combined in the same construct with sequences for the expression of the Cas9 endonuclease. The expression of Cas9 is controlled by selecting from among a collection of promoters, including constitutive, inducible, ubiquitous, or tissue-specific promoters. Only one vector containing the polycistronic gene (tRNA-sgRNA) needs to be constructed. For that, sgRNA (composed of protospacers chosen to target the gene of interest and sgRNA scaffold) is cloned in tandem with the pre-tRNA sequence. Then, a single recombination reaction is required to assemble the promoter, the zCas9 coding sequence, and the tRNA-gRNA polycistronic gene. Each element is cloned in an entry vector and finally assembled according to the Multisite Gateway® Technology. Here, we detail the process to express zCas9 under the control of egg cell promoter fused to enhancer sequence (EC1.2en-EC1.1p) and to simultaneously target two multiple C2 domains and transmembrane region protein genes (MCTP3 and MCTP4, respectively at3g57880 and at1g51570), using one or two sgRNA per gene.}, author = {Li, Ziqiang and Huard, Jennifer and Bayer, Emmanuelle M. and Wattelet-Boyer, Valérie}, issn = {2331-8325}, journal = {Bio-protocol}, number = {13}, publisher = {Bio-Protocol}, title = {{Versatile cloning strategy for efficient multigene editing in Arabidopsis}}, doi = {10.21769/BioProtoc.5029}, volume = {14}, year = {2024}, } @article{17191, abstract = {Dendritic cells migrate to and from lymph nodes in response to chemokine gradients.Data now show that steady-state migration of these cells can be triggered by a mechanosensitive pathway.}, author = {Lembo, Sergio and Sixt, Michael K}, issn = {1529-2916}, journal = {Nature Immunology}, pages = {1131–1132 }, publisher = {Springer Nature}, title = {{Nuclear squeezing wakes up dendritic cells}}, doi = {10.1038/s41590-024-01881-2}, volume = {25}, year = {2024}, } @misc{18716, abstract = {Data for publication 10.1039/d4cp03727h}, author = {Hrast, Mateja}, publisher = {Zenodo}, title = {{Data for: Ab initio Auger spectrum of the ultrafast dissociating 2p3/2−1σ* resonance in HCl}}, doi = {10.5281/ZENODO.13833474}, year = {2024}, } @misc{22866, author = {Hrast, Mateja}, publisher = {Repository}, title = {{Data for: Ab initio Auger spectrum of the ultrafast dissociating 2p3/2−1σ* resonance in HCl}}, doi = {10.5281/zenodo.13833474}, year = {2024}, } @article{18109, abstract = {Venous thromboembolism (VTE) is a common, deadly disease with an increasing incidence despite preventive efforts. Clinical observations have associated elevated antibody concentrations or antibody-based therapies with thrombotic events. However, how antibodies contribute to thrombosis is unknown. Here, we show that reduced blood flow enabled immunoglobulin M (IgM) to bind to FcμR and the polymeric immunoglobulin receptor (pIgR), initiating endothelial activation and platelet recruitment. Subsequently, the procoagulant surface of activated platelets accommodated antigen- and FcγR-independent IgG deposition. This leads to classical complement activation, setting in motion a prothrombotic vicious circle. Key elements of this mechanism were present in humans in the setting of venous stasis as well as in the dysregulated immunothrombosis of COVID-19. This antibody-driven thrombosis can be prevented by pharmacologically targeting complement. Hence, our results uncover antibodies as previously unrecognized central regulators of thrombosis. These findings carry relevance for therapeutic application of antibodies and open innovative avenues to target thrombosis without compromising hemostasis.}, author = {Stark, Konstantin and Kilani, Badr and Stockhausen, Sven and Busse, Johanna and Schubert, Irene and Tran, Thuy Duong and Gärtner, Florian R and Leunig, Alexander and Pekayvaz, Kami and Nicolai, Leo and Fumagalli, Valeria and Stermann, Julia and Stephan, Felix and David, Christian and Müller, Martin B. and Heyman, Birgitta and Lux, Anja and Da Palma Guerreiro, Alexandra and Frenzel, Lukas P. and Schmidt, Christoph Q. and Dopler, Arthur and Moser, Markus and Chandraratne, Sue and Von Brühl, Marie Luise and Lorenz, Michael and Korff, Thomas and Rudelius, Martina and Popp, Oliver and Kirchner, Marieluise and Mertins, Philipp and Nimmerjahn, Falk and Iannacone, Matteo and Sperandio, Markus and Engelmann, Bernd and Verschoor, Admar and Massberg, Steffen}, issn = {1097-4180}, journal = {Immunity}, number = {9}, pages = {2140--2156}, publisher = {Elsevier}, title = {{Antibodies and complement are key drivers of thrombosis}}, doi = {10.1016/j.immuni.2024.08.007}, volume = {57}, year = {2024}, } @inproceedings{15008, abstract = {Oblivious routing is a well-studied paradigm that uses static precomputed routing tables for selecting routing paths within a network. Existing oblivious routing schemes with polylogarithmic competitive ratio for general networks are tree-based, in the sense that routing is performed according to a convex combination of trees. However, this restriction to trees leads to a construction that has time quadratic in the size of the network and does not parallelize well. In this paper we study oblivious routing schemes based on electrical routing. In particular, we show that general networks with n vertices and m edges admit a routing scheme that has competitive ratio O(log² n) and consists of a convex combination of only O(√m) electrical routings. This immediately leads to an improved construction algorithm with time Õ(m^{3/2}) that can also be implemented in parallel with Õ(√m) depth.}, author = {Goranci, Gramoz and Henzinger, Monika H and Räcke, Harald and Sachdeva, Sushant and Sricharan, A. R.}, booktitle = {15th Innovations in Theoretical Computer Science Conference}, isbn = {9783959773096}, issn = {1868-8969}, location = {Berkeley, CA, United States}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Electrical flows for polylogarithmic competitive oblivious routing}}, doi = {10.4230/LIPIcs.ITCS.2024.55}, volume = {287}, year = {2024}, } @article{15408, abstract = {Background: IgE-mediated degranulation of mast cells (MCs) provides rapid protection against environmental hazards, including animal venoms. A fraction of tissue-resident MCs intimately associates with blood vessels. These perivascular MCs were reported to extend projections into the vessel lumen and to be the first MCs to acquire intravenously injected IgE, suggesting that IgE loading of MCs depends on their vascular association. Objective: We sought to elucidate the molecular basis of the MC–blood vessel interaction and to determine its relevance for IgE-mediated immune responses. Methods: We selectively inactivated the Itgb1 gene, encoding the β1 chain of integrin adhesion molecules (ITGB1), in MCs by conditional gene targeting in mice. We analyzed skin MCs for blood vessel association, surface IgE density, and capability to bind circulating antibody specific for MC surface molecules, as well as in vivo responses to antigen administered via different routes. Results: Lack of ITGB1 expression severely compromised MC–blood vessel association. ITGB1-deficient MCs showed normal densities of surface IgE but reduced binding of intravenously injected antibodies. While their capacity to degranulate in response to IgE ligation in vivo was unimpaired, anaphylactic responses to antigen circulating in the vasculature were largely abolished. Conclusions: ITGB1-mediated association of MCs with blood vessels is key for MC immune surveillance of blood vessel content, but is dispensable for slow steady-state loading of endogenous IgE onto tissue-resident MCs.}, author = {Link, Kristina and Muhandes, Lina and Polikarpova, Anastasia and Lämmermann, Tim and Sixt, Michael K and Fässler, Reinhard and Roers, Axel}, issn = {1097-6825}, journal = {Journal of Allergy and Clinical Immunology}, number = {3}, pages = {745--753}, publisher = {Elsevier}, title = {{Integrin β1–mediated mast cell immune-surveillance of blood vessel content}}, doi = {10.1016/j.jaci.2024.03.022}, volume = {154}, year = {2024}, } @article{14933, abstract = {Centrioles are part of centrosomes and cilia, which are microtubule organising centres (MTOC) with diverse functions. Despite their stability, centrioles can disappear during differentiation, such as in oocytes, but little is known about the regulation of their structural integrity. Our previous research revealed that the pericentriolar material (PCM) that surrounds centrioles and its recruiter, Polo kinase, are downregulated in oogenesis and sufficient for maintaining both centrosome structural integrity and MTOC activity. We now show that the expression of specific components of the centriole cartwheel and wall, including ANA1/CEP295, is essential for maintaining centrosome integrity. We find that Polo kinase requires ANA1 to promote centriole stability in cultured cells and eggs. In addition, ANA1 expression prevents the loss of centrioles observed upon PCM-downregulation. However, the centrioles maintained by overexpressing and tethering ANA1 are inactive, unlike the MTOCs observed upon tethering Polo kinase. These findings demonstrate that several centriole components are needed to maintain centrosome structure. Our study also highlights that centrioles are more dynamic than previously believed, with their structural stability relying on the continuous expression of multiple components.}, author = {Pimenta-Marques, Ana and Perestrelo, Tania and Dos Reis Rodrigues, Patricia and Duarte, Paulo and Ferreira-Silva, Ana and Lince-Faria, Mariana and Bettencourt-Dias, Mónica}, issn = {1469-3178}, journal = {EMBO Reports}, number = {1}, pages = {102--127}, publisher = {Embo Press}, title = {{Ana1/CEP295 is an essential player in the centrosome maintenance program regulated by Polo kinase and the PCM}}, doi = {10.1038/s44319-023-00020-6}, volume = {25}, year = {2024}, }