TY - JOUR AB - Tension of the actomyosin cell cortex plays a key role in determining cell–cell contact growth and size. The level of cortical tension outside of the cell–cell contact, when pulling at the contact edge, scales with the total size to which a cell–cell contact can grow [J.-L. Maître et al., Science 338, 253–256 (2012)]. Here, we show in zebrafish primary germ-layer progenitor cells that this monotonic relationship only applies to a narrow range of cortical tension increase and that above a critical threshold, contact size inversely scales with cortical tension. This switch from cortical tension increasing to decreasing progenitor cell–cell contact size is caused by cortical tension promoting E-cadherin anchoring to the actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin at the contact. After tension-mediated E-cadherin stabilization at the contact exceeds a critical threshold level, the rate by which the contact expands in response to pulling forces from the cortex sharply drops, leading to smaller contacts at physiologically relevant timescales of contact formation. Thus, the activity of cortical tension in expanding cell–cell contact size is limited by tension-stabilizing E-cadherin–actin complexes at the contact. AU - Slovakova, Jana AU - Sikora, Mateusz K AU - Arslan, Feyza N AU - Caballero Mancebo, Silvia AU - Krens, Gabriel AU - Kaufmann, Walter AU - Merrin, Jack AU - Heisenberg, Carl-Philipp J ID - 10766 IS - 8 JF - Proceedings of the National Academy of Sciences of the United States of America TI - Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells VL - 119 ER - TY - JOUR AB - In eukaryotes, clathrin-coated vesicles (CCVs) facilitate the internalization of material from the cell surface as well as the movement of cargo in post-Golgi trafficking pathways. This diversity of functions is partially provided by multiple monomeric and multimeric clathrin adaptor complexes that provide compartment and cargo selectivity. The adaptor-protein assembly polypeptide-1 (AP-1) complex operates as part of the secretory pathway at the trans-Golgi network (TGN), while the AP-2 complex and the TPLATE complex jointly operate at the plasma membrane to execute clathrin-mediated endocytosis. Key to our further understanding of clathrin-mediated trafficking in plants will be the comprehensive identification and characterization of the network of evolutionarily conserved and plant-specific core and accessory machinery involved in the formation and targeting of CCVs. To facilitate these studies, we have analyzed the proteome of enriched TGN/early endosome-derived and endocytic CCVs isolated from dividing and expanding suspension-cultured Arabidopsis (Arabidopsis thaliana) cells. Tandem mass spectrometry analysis results were validated by differential chemical labeling experiments to identify proteins co-enriching with CCVs. Proteins enriched in CCVs included previously characterized CCV components and cargos such as the vacuolar sorting receptors in addition to conserved and plant-specific components whose function in clathrin-mediated trafficking has not been previously defined. Notably, in addition to AP-1 and AP-2, all subunits of the AP-4 complex, but not AP-3 or AP-5, were found to be in high abundance in the CCV proteome. The association of AP-4 with suspension-cultured Arabidopsis CCVs is further supported via additional biochemical data. AU - Dahhan, DA AU - Reynolds, GD AU - Cárdenas, JJ AU - Eeckhout, D AU - Johnson, Alexander J AU - Yperman, K AU - Kaufmann, Walter AU - Vang, N AU - Yan, X AU - Hwang, I AU - Heese, A AU - De Jaeger, G AU - Friml, Jiří AU - Van Damme, D AU - Pan, J AU - Bednarek, SY ID - 10841 IS - 6 JF - Plant Cell SN - 1040-4651 TI - Proteomic characterization of isolated Arabidopsis clathrin-coated vesicles reveals evolutionarily conserved and plant-specific components VL - 34 ER - TY - JOUR AB - The broad implementation of thermoelectricity requires high-performance and low-cost materials. One possibility is employing surfactant-free solution synthesis to produce nanopowders. We propose the strategy of functionalizing “naked” particles’ surface by inorganic molecules to control the nanostructure and, consequently, thermoelectric performance. In particular, we use bismuth thiolates to functionalize surfactant-free SnTe particles’ surfaces. Upon thermal processing, bismuth thiolates decomposition renders SnTe-Bi2S3 nanocomposites with synergistic functions: 1) carrier concentration optimization by Bi doping; 2) Seebeck coefficient enhancement and bipolar effect suppression by energy filtering; and 3) lattice thermal conductivity reduction by small grain domains, grain boundaries and nanostructuration. Overall, the SnTe-Bi2S3 nanocomposites exhibit peak z T up to 1.3 at 873 K and an average z T of ≈0.6 at 300–873 K, which is among the highest reported for solution-processed SnTe. AU - Chang, Cheng AU - Liu, Yu AU - Lee, Seungho AU - Spadaro, Maria AU - Koskela, Kristopher M. AU - Kleinhanns, Tobias AU - Costanzo, Tommaso AU - Arbiol, Jordi AU - Brutchey, Richard L. AU - Ibáñez, Maria ID - 11705 IS - 35 JF - Angewandte Chemie - International Edition SN - 1433-7851 TI - Surface functionalization of surfactant-free particles: A strategy to tailor the properties of nanocomposites for enhanced thermoelectric performance VL - 61 ER - TY - JOUR AB - Capacity, rate performance, and cycle life of aprotic Li–O2 batteries critically depend on reversible electrodeposition of Li2O2. Current understanding states surface-adsorbed versus solvated LiO2 controls Li2O2 growth as surface film or as large particles. Herein, we show that Li2O2 forms across a wide range of electrolytes, carbons, and current densities as particles via solution-mediated LiO2 disproportionation, bringing into question the prevalence of any surface growth under practical conditions. We describe a unified O2 reduction mechanism, which can explain all found capacity relations and Li2O2 morphologies with exclusive solution discharge. Determining particle morphology and achievable capacities are species mobilities, true areal rate, and the degree of LiO2 association in solution. Capacity is conclusively limited by mass transport through the tortuous Li2O2 rather than electron transport through a passivating Li2O2 film. Provided that species mobilities and surface growth are high, high capacities are also achieved with weakly solvating electrolytes, which were previously considered prototypical for low capacity via surface growth. AU - Prehal, Christian AU - Mondal, Soumyadip AU - Lovicar, Ludek AU - Freunberger, Stefan Alexander ID - 12065 IS - 9 JF - ACS Energy Letters TI - Exclusive solution discharge in Li-O₂ batteries? VL - 7 ER - TY - JOUR AB - Kelvin probe force microscopy (KPFM) is a powerful tool for studying contact electrification (CE) at the nanoscale, but converting KPFM voltage maps to charge density maps is nontrivial due to long-range forces and complex system geometry. Here we present a strategy using finite-element method (FEM) simulations to determine the Green's function of the KPFM probe/insulator/ground system, which allows us to quantitatively extract surface charge. Testing our approach with synthetic data, we find that accounting for the atomic force microscope (AFM) tip, cone, and cantilever is necessary to recover a known input and that existing methods lead to gross miscalculation or even the incorrect sign of the underlying charge. Applying it to experimental data, we demonstrate its capacity to extract realistic surface charge densities and fine details from contact-charged surfaces. Our method gives a straightforward recipe to convert qualitative KPFM voltage data into quantitative charge data over a range of experimental conditions, enabling quantitative CE at the nanoscale. AU - Pertl, Felix AU - Sobarzo Ponce, Juan Carlos A AU - Shafeek, Lubuna B AU - Cramer, Tobias AU - Waitukaitis, Scott R ID - 12109 IS - 12 JF - Physical Review Materials TI - Quantifying nanoscale charge density features of contact-charged surfaces with an FEM/KPFM-hybrid approach VL - 6 ER - TY - JOUR AB - Muskelin (Mkln1) is implicated in neuronal function, regulating plasma membrane receptor trafficking. However, its influence on intrinsic brain activity and corresponding behavioral processes remains unclear. Here we show that murine Mkln1 knockout causes non-habituating locomotor activity, increased exploratory drive, and decreased locomotor response to amphetamine. Muskelin deficiency impairs social novelty detection while promoting the retention of spatial reference memory and fear extinction recall. This is strongly mirrored in either weaker or stronger resting-state functional connectivity between critical circuits mediating locomotor exploration and cognition. We show that Mkln1 deletion alters dendrite branching and spine structure, coinciding with enhanced AMPAR-mediated synaptic transmission but selective impairment in synaptic potentiation maintenance. We identify muskelin at excitatory synapses and highlight its role in regulating dendritic spine actin stability. Our findings point to aberrant spine actin modulation and changes in glutamatergic synaptic function as critical mechanisms that contribute to the neurobehavioral phenotype arising from Mkln1 ablation. AU - Muhia, Mary W AU - YuanXiang, PingAn AU - Sedlacik, Jan AU - Schwarz, Jürgen R. AU - Heisler, Frank F. AU - Gromova, Kira V. AU - Thies, Edda AU - Breiden, Petra AU - Pechmann, Yvonne AU - Kreutz, Michael R. AU - Kneussel, Matthias ID - 12224 JF - Communications Biology KW - General Agricultural and Biological Sciences KW - General Biochemistry KW - Genetics and Molecular Biology KW - Medicine (miscellaneous) SN - 2399-3642 TI - Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes VL - 5 ER - TY - JOUR AB - The question of how RNA, as the principal carrier of genetic information evolved is fundamentally important for our understanding of the origin of life. The RNA molecule is far too complex to have formed in one evolutionary step, suggesting that ancestral proto-RNAs (first ancestor of RNA) may have existed, which evolved over time into the RNA of today. Here we show that isoxazole nucleosides, which are quickly formed from hydroxylamine, cyanoacetylene, urea and ribose, are plausible precursors for RNA. The isoxazole nucleoside can rearrange within an RNA-strand to give cytidine, which leads to an increase of pairing stability. If the proto-RNA contains a canonical seed-nucleoside with defined stereochemistry, the seed-nucleoside can control the configuration of the anomeric center that forms during the in-RNA transformation. The results demonstrate that RNA could have emerged from evolutionarily primitive precursor isoxazole ribosides after strand formation. AU - Xu, Felix AU - Crisp, Antony AU - Schinkel, Thea AU - Dubini, Romeo C. A. AU - Hübner, Sarah AU - Becker, Sidney AU - Schelter, Florian AU - Rovo, Petra AU - Carell, Thomas ID - 12228 IS - 45 JF - Angewandte Chemie International Edition KW - General Chemistry KW - Catalysis SN - 1433-7851 TI - Isoxazole nucleosides as building blocks for a plausible proto‐RNA VL - 61 ER - TY - JOUR AB - Biological systems are the sum of their dynamic three-dimensional (3D) parts. Therefore, it is critical to study biological structures in 3D and at high resolution to gain insights into their physiological functions. Electron microscopy of metal replicas of unroofed cells and isolated organelles has been a key technique to visualize intracellular structures at nanometer resolution. However, many of these methods require specialized equipment and personnel to complete them. Here, we present novel accessible methods to analyze biological structures in unroofed cells and biochemically isolated organelles in 3D and at nanometer resolution, focusing on Arabidopsis clathrin-coated vesicles (CCVs). While CCVs are essential trafficking organelles, their detailed structural information is lacking due to their poor preservation when observed via classical electron microscopy protocols experiments. First, we establish a method to visualize CCVs in unroofed cells using scanning transmission electron microscopy tomography, providing sufficient resolution to define the clathrin coat arrangements. Critically, the samples are prepared directly on electron microscopy grids, removing the requirement to use extremely corrosive acids, thereby enabling the use of this method in any electron microscopy lab. Secondly, we demonstrate that this standardized sample preparation allows the direct comparison of isolated CCV samples with those visualized in cells. Finally, to facilitate the high-throughput and robust screening of metal replicated samples, we provide a deep learning analysis method to screen the “pseudo 3D” morphologies of CCVs imaged with 2D modalities. Collectively, our work establishes accessible ways to examine the 3D structure of biological samples and provide novel insights into the structure of plant CCVs. AU - Johnson, Alexander J AU - Kaufmann, Walter AU - Sommer, Christoph M AU - Costanzo, Tommaso AU - Dahhan, Dana A. AU - Bednarek, Sebastian Y. AU - Friml, Jiří ID - 12239 IS - 10 JF - Molecular Plant KW - Plant Science KW - Molecular Biology SN - 1674-2052 TI - Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution VL - 15 ER - TY - JOUR AB - Theoretical foundations of chaos have been predominantly laid out for finite-dimensional dynamical systems, such as the three-body problem in classical mechanics and the Lorenz model in dissipative systems. In contrast, many real-world chaotic phenomena, e.g., weather, arise in systems with many (formally infinite) degrees of freedom, which limits direct quantitative analysis of such systems using chaos theory. In the present work, we demonstrate that the hydrodynamic pilot-wave systems offer a bridge between low- and high-dimensional chaotic phenomena by allowing for a systematic study of how the former connects to the latter. Specifically, we present experimental results, which show the formation of low-dimensional chaotic attractors upon destabilization of regular dynamics and a final transition to high-dimensional chaos via the merging of distinct chaotic regions through a crisis bifurcation. Moreover, we show that the post-crisis dynamics of the system can be rationalized as consecutive scatterings from the nonattracting chaotic sets with lifetimes following exponential distributions. AU - Choueiri, George H AU - Suri, Balachandra AU - Merrin, Jack AU - Serbyn, Maksym AU - Hof, Björn AU - Budanur, Nazmi B ID - 12259 IS - 9 JF - Chaos: An Interdisciplinary Journal of Nonlinear Science KW - Applied Mathematics KW - General Physics and Astronomy KW - Mathematical Physics KW - Statistical and Nonlinear Physics SN - 1054-1500 TI - Crises and chaotic scattering in hydrodynamic pilot-wave experiments VL - 32 ER - TY - JOUR AB - The AAA-ATPase Drg1 is a key factor in eukaryotic ribosome biogenesis that initiates cytoplasmic maturation of the large ribosomal subunit. Drg1 releases the shuttling maturation factor Rlp24 from pre-60S particles shortly after nuclear export, a strict requirement for downstream maturation. The molecular mechanism of release remained elusive. Here, we report a series of cryo-EM structures that captured the extraction of Rlp24 from pre-60S particles by Saccharomyces cerevisiae Drg1. These structures reveal that Arx1 and the eukaryote-specific rRNA expansion segment ES27 form a joint docking platform that positions Drg1 for efficient extraction of Rlp24 from the pre-ribosome. The tips of the Drg1 N domains thereby guide the Rlp24 C terminus into the central pore of the Drg1 hexamer, enabling extraction by a hand-over-hand translocation mechanism. Our results uncover substrate recognition and processing by Drg1 step by step and provide a comprehensive mechanistic picture of the conserved modus operandi of AAA-ATPases. AU - Prattes, Michael AU - Grishkovskaya, Irina AU - Hodirnau, Victor-Valentin AU - Hetzmannseder, Christina AU - Zisser, Gertrude AU - Sailer, Carolin AU - Kargas, Vasileios AU - Loibl, Mathias AU - Gerhalter, Magdalena AU - Kofler, Lisa AU - Warren, Alan J. AU - Stengel, Florian AU - Haselbach, David AU - Bergler, Helmut ID - 12262 IS - 9 JF - Nature Structural & Molecular Biology KW - Molecular Biology KW - Structural Biology SN - 1545-9993 TI - Visualizing maturation factor extraction from the nascent ribosome by the AAA-ATPase Drg1 VL - 29 ER - TY - JOUR AB - Centrosomes play a crucial role during immune cell interactions and initiation of the immune response. In proliferating cells, centrosome numbers are tightly controlled and generally limited to one in G1 and two prior to mitosis. Defects in regulating centrosome numbers have been associated with cell transformation and tumorigenesis. Here, we report the emergence of extra centrosomes in leukocytes during immune activation. Upon antigen encounter, dendritic cells pass through incomplete mitosis and arrest in the subsequent G1 phase leading to tetraploid cells with accumulated centrosomes. In addition, cell stimulation increases expression of polo-like kinase 2, resulting in diploid cells with two centrosomes in G1-arrested cells. During cell migration, centrosomes tightly cluster and act as functional microtubule-organizing centers allowing for increased persistent locomotion along gradients of chemotactic cues. Moreover, dendritic cells with extra centrosomes display enhanced secretion of inflammatory cytokines and optimized T cell responses. Together, these results demonstrate a previously unappreciated role of extra centrosomes for regular cell and tissue homeostasis. AU - Weier, Ann-Kathrin AU - Homrich, Mirka AU - Ebbinghaus, Stephanie AU - Juda, Pavel AU - Miková, Eliška AU - Hauschild, Robert AU - Zhang, Lili AU - Quast, Thomas AU - Mass, Elvira AU - Schlitzer, Andreas AU - Kolanus, Waldemar AU - Burgdorf, Sven AU - Gruß, Oliver J. AU - Hons, Miroslav AU - Wieser, Stefan AU - Kiermaier, Eva ID - 12122 IS - 12 JF - Journal of Cell Biology KW - Cell Biology SN - 0021-9525 TI - Multiple centrosomes enhance migration and immune cell effector functions of mature dendritic cells VL - 221 ER - TY - JOUR AB - The phytohormone auxin triggers transcriptional reprogramming through a well-characterized perception machinery in the nucleus. By contrast, mechanisms that underlie fast effects of auxin, such as the regulation of ion fluxes, rapid phosphorylation of proteins or auxin feedback on its transport, remain unclear1,2,3. Whether auxin-binding protein 1 (ABP1) is an auxin receptor has been a source of debate for decades1,4. Here we show that a fraction of Arabidopsis thaliana ABP1 is secreted and binds auxin specifically at an acidic pH that is typical of the apoplast. ABP1 and its plasma-membrane-localized partner, transmembrane kinase 1 (TMK1), are required for the auxin-induced ultrafast global phospho-response and for downstream processes that include the activation of H+-ATPase and accelerated cytoplasmic streaming. abp1 and tmk mutants cannot establish auxin-transporting channels and show defective auxin-induced vasculature formation and regeneration. An ABP1(M2X) variant that lacks the capacity to bind auxin is unable to complement these defects in abp1 mutants. These data indicate that ABP1 is the auxin receptor for TMK1-based cell-surface signalling, which mediates the global phospho-response and auxin canalization. AU - Friml, Jiří AU - Gallei, Michelle C AU - Gelová, Zuzana AU - Johnson, Alexander J AU - Mazur, Ewa AU - Monzer, Aline AU - Rodriguez Solovey, Lesia AU - Roosjen, Mark AU - Verstraeten, Inge AU - Živanović, Branka D. AU - Zou, Minxia AU - Fiedler, Lukas AU - Giannini, Caterina AU - Grones, Peter AU - Hrtyan, Mónika AU - Kaufmann, Walter AU - Kuhn, Andre AU - Narasimhan, Madhumitha AU - Randuch, Marek AU - Rýdza, Nikola AU - Takahashi, Koji AU - Tan, Shutang AU - Teplova, Anastasiia AU - Kinoshita, Toshinori AU - Weijers, Dolf AU - Rakusová, Hana ID - 12291 IS - 7927 JF - Nature SN - 0028-0836 TI - ABP1–TMK auxin perception for global phosphorylation and auxin canalization VL - 609 ER - TY - JOUR AB - The mammalian neocortex is composed of diverse neuronal and glial cell classes that broadly arrange in six distinct laminae. Cortical layers emerge during development and defects in the developmental programs that orchestrate cortical lamination are associated with neurodevelopmental diseases. The developmental principle of cortical layer formation depends on concerted radial projection neuron migration, from their birthplace to their final target position. Radial migration occurs in defined sequential steps, regulated by a large array of signaling pathways. However, based on genetic loss-of-function experiments, most studies have thus far focused on the role of cell-autonomous gene function. Yet, cortical neuron migration in situ is a complex process and migrating neurons traverse along diverse cellular compartments and environments. The role of tissue-wide properties and genetic state in radial neuron migration is however not clear. Here we utilized mosaic analysis with double markers (MADM) technology to either sparsely or globally delete gene function, followed by quantitative single-cell phenotyping. The MADM-based gene ablation paradigms in combination with computational modeling demonstrated that global tissue-wide effects predominate cell-autonomous gene function albeit in a gene-specific manner. Our results thus suggest that the genetic landscape in a tissue critically affects the overall migration phenotype of individual cortical projection neurons. In a broader context, our findings imply that global tissue-wide effects represent an essential component of the underlying etiology associated with focal malformations of cortical development in particular, and neurological diseases in general. AU - Hansen, Andi H AU - Pauler, Florian AU - Riedl, Michael AU - Streicher, Carmen AU - Heger, Anna-Magdalena AU - Laukoter, Susanne AU - Sommer, Christoph M AU - Nicolas, Armel AU - Hof, Björn AU - Tsai, Li Huei AU - Rülicke, Thomas AU - Hippenmeyer, Simon ID - 10791 IS - 1 JF - Oxford Open Neuroscience TI - Tissue-wide effects override cell-intrinsic gene function in radial neuron migration VL - 1 ER - TY - JOUR AB - When crawling through the body, leukocytes often traverse tissues that are densely packed with extracellular matrix and other cells, and this raises the question: How do leukocytes overcome compressive mechanical loads? Here, we show that the actin cortex of leukocytes is mechanoresponsive and that this responsiveness requires neither force sensing via the nucleus nor adhesive interactions with a substrate. Upon global compression of the cell body as well as local indentation of the plasma membrane, Wiskott-Aldrich syndrome protein (WASp) assembles into dot-like structures, providing activation platforms for Arp2/3 nucleated actin patches. These patches locally push against the external load, which can be obstructing collagen fibers or other cells, and thereby create space to facilitate forward locomotion. We show in vitro and in vivo that this WASp function is rate limiting for ameboid leukocyte migration in dense but not in loose environments and is required for trafficking through diverse tissues such as skin and lymph nodes. AU - Gaertner, Florian AU - Reis-Rodrigues, Patricia AU - De Vries, Ingrid AU - Hons, Miroslav AU - Aguilera, Juan AU - Riedl, Michael AU - Leithner, Alexander F AU - Tasciyan, Saren AU - Kopf, Aglaja AU - Merrin, Jack AU - Zheden, Vanessa AU - Kaufmann, Walter AU - Hauschild, Robert AU - Sixt, Michael K ID - 10703 IS - 1 JF - Developmental Cell SN - 1534-5807 TI - WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues VL - 57 ER - TY - GEN AU - Schlögl, Alois AU - Elefante, Stefano AU - Hornoiu, Andrei AU - Stadlbauer, Stephan ID - 12909 SN - 978-961-6980-77-7 T2 - ASHPC21 – Austrian-Slovenian HPC Meeting 2021 TI - Managing software on a heterogenous HPC cluster ER - TY - JOUR AB - Cell and tissue polarization is fundamental for plant growth and morphogenesis. The polar, cellular localization of Arabidopsis PIN‐FORMED (PIN) proteins is crucial for their function in directional auxin transport. The clustering of PIN polar cargoes within the plasma membrane has been proposed to be important for the maintenance of their polar distribution. However, the more detailed features of PIN clusters and the cellular requirements of cargo clustering remain unclear. Here, we characterized PIN clusters in detail by means of multiple advanced microscopy and quantification methods, such as 3D quantitative imaging or freeze‐fracture replica labeling. The size and aggregation types of PIN clusters were determined by electron microscopy at the nanometer level at different polar domains and at different developmental stages, revealing a strong preference for clustering at the polar domains. Pharmacological and genetic studies revealed that PIN clusters depend on phosphoinositol pathways, cytoskeletal structures and specific cell‐wall components as well as connections between the cell wall and the plasma membrane. This study identifies the role of different cellular processes and structures in polar cargo clustering and provides initial mechanistic insight into the maintenance of polarity in plants and other systems. AU - Li, Hongjiang AU - von Wangenheim, Daniel AU - Zhang, Xixi AU - Tan, Shutang AU - Darwish-Miranda, Nasser AU - Naramoto, Satoshi AU - Wabnik, Krzysztof T AU - de Rycke, Riet AU - Kaufmann, Walter AU - Gütl, Daniel J AU - Tejos, Ricardo AU - Grones, Peter AU - Ke, Meiyu AU - Chen, Xu AU - Dettmer, Jan AU - Friml, Jiří ID - 8582 IS - 1 JF - New Phytologist SN - 0028646X TI - Cellular requirements for PIN polar cargo clustering in Arabidopsis thaliana VL - 229 ER - TY - JOUR AB - The recent outbreak of coronavirus disease 2019 (COVID‐19), caused by the Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) has resulted in a world‐wide pandemic. Disseminated lung injury with the development of acute respiratory distress syndrome (ARDS) is the main cause of mortality in COVID‐19. Although liver failure does not seem to occur in the absence of pre‐existing liver disease, hepatic involvement in COVID‐19 may correlate with overall disease severity and serve as a prognostic factor for the development of ARDS. The spectrum of liver injury in COVID‐19 may range from direct infection by SARS‐CoV‐2, indirect involvement by systemic inflammation, hypoxic changes, iatrogenic causes such as drugs and ventilation to exacerbation of underlying liver disease. This concise review discusses the potential pathophysiological mechanisms for SARS‐CoV‐2 hepatic tropism as well as acute and possibly long‐term liver injury in COVID‐19. AU - Nardo, Alexander D. AU - Schneeweiss-Gleixner, Mathias AU - Bakail, May M AU - Dixon, Emmanuel D. AU - Lax, Sigurd F. AU - Trauner, Michael ID - 8927 IS - 1 JF - Liver International SN - 14783223 TI - Pathophysiological mechanisms of liver injury in COVID-19 VL - 41 ER - TY - JOUR AB - Layered materials in which individual atomic layers are bonded by weak van der Waals forces (vdW materials) constitute one of the most prominent platforms for materials research. Particularly, polar vdW crystals, such as hexagonal boron nitride (h-BN), alpha-molybdenum trioxide (α-MoO3) or alpha-vanadium pentoxide (α-V2O5), have received significant attention in nano-optics, since they support phonon polaritons (PhPs)―light coupled to lattice vibrations― with strong electromagnetic confinement and low optical losses. Recently, correlative far- and near-field studies of α-MoO3 have been demonstrated as an effective strategy to accurately extract the permittivity of this material. Here, we use this accurately characterized and low-loss polaritonic material to sense its local dielectric environment, namely silica (SiO2), one of the most widespread substrates in nanotechnology. By studying the propagation of PhPs on α-MoO3 flakes with different thicknesses laying on SiO2 substrates via near-field microscopy (s-SNOM), we extract locally the infrared permittivity of SiO2. Our work reveals PhPs nanoimaging as a versatile method for the quantitative characterization of the local optical properties of dielectric substrates, crucial for understanding and predicting the response of nanomaterials and for the future scalability of integrated nanophotonic devices. AU - Aguilar-Merino, Patricia AU - Álvarez-Pérez, Gonzalo AU - Taboada-Gutiérrez, Javier AU - Duan, Jiahua AU - Prieto Gonzalez, Ivan AU - Álvarez-Prado, Luis Manuel AU - Nikitin, Alexey Y. AU - Martín-Sánchez, Javier AU - Alonso-González, Pablo ID - 9038 IS - 1 JF - Nanomaterials TI - Extracting the infrared permittivity of SiO2 substrates locally by near-field imaging of phonon polaritons in a van der Waals crystal VL - 11 ER - TY - JOUR AB - Sequence-specific oligomers with predictable folding patterns, i.e., foldamers, provide new opportunities to mimic α-helical peptides and design inhibitors of protein-protein interactions. One major hurdle of this strategy is to retain the correct orientation of key side chains involved in protein surface recognition. Here, we show that the structural plasticity of a foldamer backbone may notably contribute to the required spatial adjustment for optimal interaction with the protein surface. By using oligoureas as α helix mimics, we designed a foldamer/peptide hybrid inhibitor of histone chaperone ASF1, a key regulator of chromatin dynamics. The crystal structure of its complex with ASF1 reveals a notable plasticity of the urea backbone, which adapts to the ASF1 surface to maintain the same binding interface. One additional benefit of generating ASF1 ligands with nonpeptide oligourea segments is the resistance to proteolysis in human plasma, which was highly improved compared to the cognate α-helical peptide. AU - Mbianda, Johanne AU - Bakail, May M AU - André, Christophe AU - Moal, Gwenaëlle AU - Perrin, Marie E. AU - Pinna, Guillaume AU - Guerois, Raphaël AU - Becher, Francois AU - Legrand, Pierre AU - Traoré, Seydou AU - Douat, Céline AU - Guichard, Gilles AU - Ochsenbein, Françoise ID - 9262 IS - 12 JF - Science Advances SN - 2375-2548 TI - Optimal anchoring of a foldamer inhibitor of ASF1 histone chaperone through backbone plasticity VL - 7 ER - TY - JOUR AB - Gradients of chemokines and growth factors guide migrating cells and morphogenetic processes. Migration of antigen-presenting dendritic cells from the interstitium into the lymphatic system is dependent on chemokine CCL21, which is secreted by endothelial cells of the lymphatic capillary, binds heparan sulfates and forms gradients decaying into the interstitium. Despite the importance of CCL21 gradients, and chemokine gradients in general, the mechanisms of gradient formation are unclear. Studies on fibroblast growth factors have shown that limited diffusion is crucial for gradient formation. Here, we used the mouse dermis as a model tissue to address the necessity of CCL21 anchoring to lymphatic capillary heparan sulfates in the formation of interstitial CCL21 gradients. Surprisingly, the absence of lymphatic endothelial heparan sulfates resulted only in a modest decrease of CCL21 levels at the lymphatic capillaries and did neither affect interstitial CCL21 gradient shape nor dendritic cell migration toward lymphatic capillaries. Thus, heparan sulfates at the level of the lymphatic endothelium are dispensable for the formation of a functional CCL21 gradient. AU - Vaahtomeri, Kari AU - Moussion, Christine AU - Hauschild, Robert AU - Sixt, Michael K ID - 9259 JF - Frontiers in Immunology TI - Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium VL - 12 ER -