@article{12106, abstract = {Regulation of chromatin states involves the dynamic interplay between different histone modifications to control gene expression. Recent advances have enabled mapping of histone marks in single cells, but most methods are constrained to profile only one histone mark per cell. Here, we present an integrated experimental and computational framework, scChIX-seq (single-cell chromatin immunocleavage and unmixing sequencing), to map several histone marks in single cells. scChIX-seq multiplexes two histone marks together in single cells, then computationally deconvolves the signal using training data from respective histone mark profiles. This framework learns the cell-type-specific correlation structure between histone marks, and therefore does not require a priori assumptions of their genomic distributions. Using scChIX-seq, we demonstrate multimodal analysis of histone marks in single cells across a range of mark combinations. Modeling dynamics of in vitro macrophage differentiation enables integrated analysis of chromatin velocity. Overall, scChIX-seq unlocks systematic interrogation of the interplay between histone modifications in single cells.}, author = {Yeung, Jake and Florescu, Maria and Zeller, Peter and De Barbanson, Buys Anton and Wellenstein, Max D. and Van Oudenaarden, Alexander}, issn = {1546-1696}, journal = {Nature Biotechnology}, pages = {813–823}, publisher = {Springer Nature}, title = {{scChIX-seq infers dynamic relationships between histone modifications in single cells}}, doi = {10.1038/s41587-022-01560-3}, volume = {41}, year = {2023}, } @article{12543, abstract = {Treating sick group members is a hallmark of collective disease defence in vertebrates and invertebrates alike. Despite substantial effects on pathogen fitness and epidemiology, it is still largely unknown how pathogens react to the selection pressure imposed by care intervention. Using social insects and pathogenic fungi, we here performed a serial passage experiment in the presence or absence of colony members, which provide social immunity by grooming off infectious spores from exposed individuals. We found specific effects on pathogen diversity, virulence and transmission. Under selection of social immunity, pathogens invested into higher spore production, but spores were less virulent. Notably, they also elicited a lower grooming response in colony members, compared with spores from the individual host selection lines. Chemical spore analysis suggested that the spores from social selection lines escaped the caregivers’ detection by containing lower levels of ergosterol, a key fungal membrane component. Experimental application of chemically pure ergosterol indeed induced sanitary grooming, supporting its role as a microbe-associated cue triggering host social immunity against fungal pathogens. By reducing this detection cue, pathogens were able to evade the otherwise very effective collective disease defences of their social hosts.}, author = {Stock, Miriam and Milutinovic, Barbara and Hönigsberger, Michaela and Grasse, Anna V and Wiesenhofer, Florian and Kampleitner, Niklas and Narasimhan, Madhumitha and Schmitt, Thomas and Cremer, Sylvia}, issn = {2397-334X}, journal = {Nature Ecology and Evolution}, pages = {450--460}, publisher = {Springer Nature}, title = {{Pathogen evasion of social immunity}}, doi = {10.1038/s41559-023-01981-6}, volume = {7}, year = {2023}, } @article{12863, abstract = {In the present study, essential and nonessential metal content and biomarker responses were investigated in the intestine of fish collected from the areas polluted by mining. Our objective was to determine metal and biomarker levels in tissue responsible for dietary intake, which is rarely studied in water pollution research. The study was conducted in the Bregalnica River, reference location, and in the Zletovska and Kriva Rivers (the Republic of North Macedonia), which are directly influenced by the active mines Zletovo and Toranica, respectively. Biological responses were analyzed in Vardar chub (Squalius vardarensis; Karaman, 1928), using for the first time intestinal cytosol as a potentially toxic cell fraction, since metal sensitivity is mostly associated with cytosol. Cytosolic metal levels were higher in fish under the influence of mining (Tl, Li, Cs, Mo, Sr, Cd, Rb, and Cu in the Zletovska River and Cr, Pb, and Se in the Kriva River compared to the Bregalnica River in both seasons). The same trend was evident for total proteins, biomarkers of general stress, and metallothioneins, biomarkers of metal exposure, indicating cellular disturbances in the intestine, the primary site of dietary metal uptake. The association of cytosolic Cu and Cd at all locations pointed to similar pathways and homeostasis of these metallothionein-binding metals. Comparison with other indicator tissues showed that metal concentrations were higher in the intestine of fish from mining-affected areas than in the liver and gills. In general, these results indicated the importance of dietary metal pathways, and cytosolic metal fraction in assessing pollution impacts in freshwater ecosystems.}, author = {Filipović Marijić, Vlatka and Krasnici, Nesrete and Valić, Damir and Kapetanović, Damir and Vardić Smrzlić, Irena and Jordanova, Maja and Rebok, Katerina and Ramani, Sheriban and Kostov, Vasil and Nastova, Rodne and Dragun, Zrinka}, issn = {1614-7499}, journal = {Environmental Science and Pollution Research}, pages = {63510--63521}, publisher = {Springer Nature}, title = {{Pollution impact on metal and biomarker responses in intestinal cytosol of freshwater fish}}, doi = {10.1007/s11356-023-26844-2}, volume = {30}, year = {2023}, } @article{14404, abstract = {A light-triggered fabrication method extends the functionality of printable nanomaterials}, author = {Balazs, Daniel and Ibáñez, Maria}, issn = {1095-9203}, journal = {Science}, number = {6665}, pages = {1413--1414}, publisher = {AAAS}, title = {{Widening the use of 3D printing}}, doi = {10.1126/science.adk3070}, volume = {381}, year = {2023}, } @inbook{13052, abstract = {Imaging of the immunological synapse (IS) between dendritic cells (DCs) and T cells in suspension is hampered by suboptimal alignment of cell-cell contacts along the vertical imaging plane. This requires optical sectioning that often results in unsatisfactory resolution in time and space. Here, we present a workflow where DCs and T cells are confined between a layer of glass and polydimethylsiloxane (PDMS) that orients the cells along one, horizontal imaging plane, allowing for fast en-face-imaging of the DC-T cell IS.}, author = {Leithner, Alexander F and Merrin, Jack and Sixt, Michael K}, booktitle = {The Immune Synapse}, editor = {Baldari, Cosima and Dustin, Michael}, isbn = {9781071631348}, issn = {1940-6029}, pages = {137--147}, publisher = {Springer Nature}, title = {{En-Face Imaging of T Cell-Dendritic Cell Immunological Synapses}}, doi = {10.1007/978-1-0716-3135-5_9}, volume = {2654}, 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}, } @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{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{14041, abstract = {Tissue morphogenesis and patterning during development involve the segregation of cell types. Segregation is driven by differential tissue surface tensions generated by cell types through controlling cell-cell contact formation by regulating adhesion and actomyosin contractility-based cellular cortical tensions. We use vertebrate tissue cell types and zebrafish germ layer progenitors as in vitro models of 3-dimensional heterotypic segregation and developed a quantitative analysis of their dynamics based on 3D time-lapse microscopy. We show that general inhibition of actomyosin contractility by the Rho kinase inhibitor Y27632 delays segregation. Cell type-specific inhibition of non-muscle myosin2 activity by overexpression of myosin assembly inhibitor S100A4 reduces tissue surface tension, manifested in decreased compaction during aggregation and inverted geometry observed during segregation. The same is observed when we express a constitutively active Rho kinase isoform to ubiquitously keep actomyosin contractility high at cell-cell and cell-medium interfaces and thus overriding the interface-specific regulation of cortical tensions. Tissue surface tension regulation can become an effective tool in tissue engineering.}, author = {Méhes, Elod and Mones, Enys and Varga, Máté and Zsigmond, Áron and Biri-Kovács, Beáta and Nyitray, László and Barone, Vanessa and Krens, Gabriel and Heisenberg, Carl-Philipp J and Vicsek, Tamás}, issn = {2399-3642}, journal = {Communications Biology}, publisher = {Springer Nature}, title = {{3D cell segregation geometry and dynamics are governed by tissue surface tension regulation}}, doi = {10.1038/s42003-023-05181-7}, volume = {6}, year = {2023}, } @article{14361, abstract = {Whether one considers swarming insects, flocking birds, or bacterial colonies, collective motion arises from the coordination of individuals and entails the adjustment of their respective velocities. In particular, in close confinements, such as those encountered by dense cell populations during development or regeneration, collective migration can only arise coordinately. Yet, how individuals unify their velocities is often not understood. Focusing on a finite number of cells in circular confinements, we identify waves of polymerizing actin that function as a pacemaker governing the speed of individual cells. We show that the onset of collective motion coincides with the synchronization of the wave nucleation frequencies across the population. Employing a simpler and more readily accessible mechanical model system of active spheres, we identify the synchronization of the individuals’ internal oscillators as one of the essential requirements to reach the corresponding collective state. The mechanical ‘toy’ experiment illustrates that the global synchronous state is achieved by nearest neighbor coupling. We suggest by analogy that local coupling and the synchronization of actin waves are essential for the emergent, self-organized motion of cell collectives.}, author = {Riedl, Michael and Mayer, Isabelle D and Merrin, Jack and Sixt, Michael K and Hof, Björn}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Synchronization in collectively moving inanimate and living active matter}}, doi = {10.1038/s41467-023-41432-1}, volume = {14}, year = {2023}, } @article{14449, abstract = {The rapid development of machine learning (ML) techniques has opened up the data-dense field of microbiome research for novel therapeutic, diagnostic, and prognostic applications targeting a wide range of disorders, which could substantially improve healthcare practices in the era of precision medicine. However, several challenges must be addressed to exploit the benefits of ML in this field fully. In particular, there is a need to establish “gold standard” protocols for conducting ML analysis experiments and improve interactions between microbiome researchers and ML experts. The Machine Learning Techniques in Human Microbiome Studies (ML4Microbiome) COST Action CA18131 is a European network established in 2019 to promote collaboration between discovery-oriented microbiome researchers and data-driven ML experts to optimize and standardize ML approaches for microbiome analysis. This perspective paper presents the key achievements of ML4Microbiome, which include identifying predictive and discriminatory ‘omics’ features, improving repeatability and comparability, developing automation procedures, and defining priority areas for the novel development of ML methods targeting the microbiome. The insights gained from ML4Microbiome will help to maximize the potential of ML in microbiome research and pave the way for new and improved healthcare practices.}, author = {D’Elia, Domenica and Truu, Jaak and Lahti, Leo and Berland, Magali and Papoutsoglou, Georgios and Ceci, Michelangelo and Zomer, Aldert and Lopes, Marta B. and Ibrahimi, Eliana and Gruca, Aleksandra and Nechyporenko, Alina and Frohme, Marcus and Klammsteiner, Thomas and Pau, Enrique Carrillo De Santa and Marcos-Zambrano, Laura Judith and Hron, Karel and Pio, Gianvito and Simeon, Andrea and Suharoschi, Ramona and Moreno-Indias, Isabel and Temko, Andriy and Nedyalkova, Miroslava and Apostol, Elena Simona and Truică, Ciprian Octavian and Shigdel, Rajesh and Telalović, Jasminka Hasić and Bongcam-Rudloff, Erik and Przymus, Piotr and Jordamović, Naida Babić and Falquet, Laurent and Tarazona, Sonia and Sampri, Alexia and Isola, Gaetano and Pérez-Serrano, David and Trajkovik, Vladimir and Klucar, Lubos and Loncar-Turukalo, Tatjana and Havulinna, Aki S. and Jansen, Christian and Bertelsen, Randi J. and Claesson, Marcus Joakim}, issn = {1664-302X}, journal = {Frontiers in Microbiology}, publisher = {Frontiers}, title = {{Advancing microbiome research with machine learning: Key findings from the ML4Microbiome COST action}}, doi = {10.3389/fmicb.2023.1257002}, volume = {14}, year = {2023}, } @article{14274, abstract = {Immune responses rely on the rapid and coordinated migration of leukocytes. Whereas it is well established that single-cell migration is often guided by gradients of chemokines and other chemoattractants, it remains poorly understood how these gradients are generated, maintained, and modulated. By combining experimental data with theory on leukocyte chemotaxis guided by the G protein–coupled receptor (GPCR) CCR7, we demonstrate that in addition to its role as the sensory receptor that steers migration, CCR7 also acts as a generator and a modulator of chemotactic gradients. Upon exposure to the CCR7 ligand CCL19, dendritic cells (DCs) effectively internalize the receptor and ligand as part of the canonical GPCR desensitization response. We show that CCR7 internalization also acts as an effective sink for the chemoattractant, dynamically shaping the spatiotemporal distribution of the chemokine. This mechanism drives complex collective migration patterns, enabling DCs to create or sharpen chemotactic gradients. We further show that these self-generated gradients can sustain the long-range guidance of DCs, adapt collective migration patterns to the size and geometry of the environment, and provide a guidance cue for other comigrating cells. Such a dual role of CCR7 as a GPCR that both senses and consumes its ligand can thus provide a novel mode of cellular self-organization.}, author = {Alanko, Jonna H and Ucar, Mehmet C and Canigova, Nikola and Stopp, Julian A and Schwarz, Jan and Merrin, Jack and Hannezo, Edouard B and Sixt, Michael K}, issn = {2470-9468}, journal = {Science Immunology}, keywords = {General Medicine, Immunology}, number = {87}, publisher = {American Association for the Advancement of Science}, title = {{CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration}}, doi = {10.1126/sciimmunol.adc9584}, volume = {8}, year = {2023}, } @article{13267, abstract = {Three-dimensional (3D) reconstruction of living brain tissue down to an individual synapse level would create opportunities for decoding the dynamics and structure–function relationships of the brain’s complex and dense information processing network; however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise ratio and prohibitive light burden in optical imaging, whereas electron microscopy is inherently static. Here we solved these challenges by developing an integrated optical/machine-learning technology, LIONESS (live information-optimized nanoscopy enabling saturated segmentation). This leverages optical modifications to stimulated emission depletion microscopy in comprehensively, extracellularly labeled tissue and previous information on sample structure via machine learning to simultaneously achieve isotropic super-resolution, high signal-to-noise ratio and compatibility with living tissue. This allows dense deep-learning-based instance segmentation and 3D reconstruction at a synapse level, incorporating molecular, activity and morphodynamic information. LIONESS opens up avenues for studying the dynamic functional (nano-)architecture of living brain tissue.}, author = {Velicky, Philipp and Miguel Villalba, Eder and Michalska, Julia M and Lyudchik, Julia and Wei, Donglai and Lin, Zudi and Watson, Jake and Troidl, Jakob and Beyer, Johanna and Ben Simon, Yoav and Sommer, Christoph M and Jahr, Wiebke and Cenameri, Alban and Broichhagen, Johannes and Grant, Seth G.N. and Jonas, Peter M and Novarino, Gaia and Pfister, Hanspeter and Bickel, Bernd and Danzl, Johann G}, issn = {1548-7105}, journal = {Nature Methods}, pages = {1256--1265}, publisher = {Springer Nature}, title = {{Dense 4D nanoscale reconstruction of living brain tissue}}, doi = {10.1038/s41592-023-01936-6}, volume = {20}, year = {2023}, } @article{14781, abstract = {Germ granules, condensates of phase-separated RNA and protein, are organelles that are essential for germline development in different organisms. The patterning of the granules and their relevance for germ cell fate are not fully understood. Combining three-dimensional in vivo structural and functional analyses, we study the dynamic spatial organization of molecules within zebrafish germ granules. We find that the localization of RNA molecules to the periphery of the granules, where ribosomes are localized, depends on translational activity at this location. In addition, we find that the vertebrate-specific Dead end (Dnd1) protein is essential for nanos3 RNA localization at the condensates’ periphery. Accordingly, in the absence of Dnd1, or when translation is inhibited, nanos3 RNA translocates into the granule interior, away from the ribosomes, a process that is correlated with the loss of germ cell fate. These findings highlight the relevance of sub-granule compartmentalization for post-transcriptional control and its importance for preserving germ cell totipotency.}, author = {Westerich, Kim Joana and Tarbashevich, Katsiaryna and Schick, Jan and Gupta, Antra and Zhu, Mingzhao and Hull, Kenneth and Romo, Daniel and Zeuschner, Dagmar and Goudarzi, Mohammad and Gross-Thebing, Theresa and Raz, Erez}, issn = {1534-5807}, journal = {Developmental Cell}, keywords = {Developmental Biology, Cell Biology, General Biochemistry, Genetics and Molecular Biology, Molecular Biology}, number = {17}, pages = {1578--1592.e5}, publisher = {Elsevier}, title = {{Spatial organization and function of RNA molecules within phase-separated condensates in zebrafish are controlled by Dnd1}}, doi = {10.1016/j.devcel.2023.06.009}, volume = {58}, year = {2023}, } @article{14786, abstract = {Acanthocephalans, intestinal parasites of vertebrates, are characterised by orders of magnitude higher metal accumulation than free-living organisms, but the mechanism of such effective metal accumulation is still unknown. The aim of our study was to gain new insights into the high-resolution localization of elements in the bodies of acanthocephalans, thus taking an initial step towards elucidating metal uptake and accumulation in organisms under real environmental conditions. For the first time, nanoscale secondary ion mass spectrometry (NanoSIMS) was used for high-resolution mapping of 12 elements (C, Ca, Cu, Fe, N, Na, O, P, Pb, S, Se, and Tl) in three selected body parts (trunk spines, inner part of the proboscis receptacle and inner surface of the tegument) of Dentitruncus truttae, a parasite of brown trout (Salmo trutta) from the Krka River in Croatia. In addition, the same body parts were examined using transmission electron microscopy (TEM) and correlated with NanoSIMS images. Metal concentrations determined using HR ICP-MS confirmed higher accumulation in D. truttae than in the fish intestine. The chemical composition of the acanthocephalan body showed the highest density of C, Ca, N, Na, O, S, as important and constitutive elements in living cells in all studied structures, while Fe was predominant among trace elements. In general, higher element density was found in trunk spines and tegument, as body structures responsible for substance absorption in parasites. The results obtained with NanoSIMS and TEM-NanoSIMS correlative imaging represent pilot data for mapping of elements at nanoscale resolution in the ultrastructure of various body parts of acanthocephalans and generally provide a contribution for further application of this technique in all parasite species.}, author = {Filipović Marijić, Vlatka and Subirana, Maria Angels and Schaumlöffel, Dirk and Barišić, Josip and Gontier, Etienne and Krasnici, Nesrete and Mijošek, Tatjana and Hernández-Orts, Jesús S. and Scholz, Tomáš and Erk, Marijana}, issn = {0048-9697}, journal = {Science of The Total Environment}, keywords = {Pollution, Waste Management and Disposal, Environmental Chemistry, Environmental Engineering}, publisher = {Elsevier}, title = {{First insight in element localisation in different body parts of the acanthocephalan Dentitruncus truttae using TEM and NanoSIMS}}, doi = {10.1016/j.scitotenv.2023.164010}, volume = {887}, year = {2023}, } @article{14799, abstract = {A round-robin study has been carried out to estimate the impact of the human element in small-angle scattering data analysis. Four corrected datasets were provided to participants ready for analysis. All datasets were measured on samples containing spherical scatterers, with two datasets in dilute dispersions and two from powders. Most of the 46 participants correctly identified the number of populations in the dilute dispersions, with half of the population mean entries within 1.5% and half of the population width entries within 40%. Due to the added complexity of the structure factor, far fewer people submitted answers on the powder datasets. For those that did, half of the entries for the means and widths were within 44 and 86%, respectively. This round-robin experiment highlights several causes for the discrepancies, for which solutions are proposed.}, author = {Pauw, Brian R. and Smales, Glen J. and Anker, Andy S. and Annadurai, Venkatasamy and Balazs, Daniel and Bienert, Ralf and Bouwman, Wim G. and Breßler, Ingo and Breternitz, Joachim and Brok, Erik S. and Bryant, Gary and Clulow, Andrew J. and Crater, Erin R. and De Geuser, Frédéric and Giudice, Alessandra Del and Deumer, Jérôme and Disch, Sabrina and Dutt, Shankar and Frank, Kilian and Fratini, Emiliano and Garcia, Paulo R.A.F. and Gilbert, Elliot P. and Hahn, Marc B. and Hallett, James and Hohenschutz, Max and Hollamby, Martin and Huband, Steven and Ilavsky, Jan and Jochum, Johanna K. and Juelsholt, Mikkel and Mansel, Bradley W. and Penttilä, Paavo and Pittkowski, Rebecca K. and Portale, Giuseppe and Pozzo, Lilo D. and Rochels, Leonhard and Rosalie, Julian M. and Saloga, Patrick E.J. and Seibt, Susanne and Smith, Andrew J. and Smith, Gregory N. and Spiering, Glenn A. and Stawski, Tomasz M. and Taché, Olivier and Thünemann, Andreas F. and Toth, Kristof and Whitten, Andrew E. and Wuttke, Joachim}, issn = {1600-5767}, journal = {Journal of Applied Crystallography}, number = {6}, pages = {1618--1629}, title = {{The human factor: Results of a small-angle scattering data analysis round robin}}, doi = {10.1107/S1600576723008324}, volume = {56}, year = {2023}, } @unpublished{13312, abstract = {Superconductor/semiconductor hybrid devices have attracted increasing interest in the past years. Superconducting electronics aims to complement semiconductor technology, while hybrid architectures are at the forefront of new ideas such as topological superconductivity and protected qubits. In this work, we engineer the induced superconductivity in two-dimensional germanium hole gas by varying the distance between the quantum well and the aluminum. We demonstrate a hard superconducting gap and realize an electrically and flux tunable superconducting diode using a superconducting quantum interference device (SQUID). This allows to tune the current phase relation (CPR), to a regime where single Cooper pair tunneling is suppressed, creating a $ \sin \left( 2 \varphi \right)$ CPR. Shapiro experiments complement this interpretation and the microwave drive allows to create a diode with $ \approx 100 \%$ efficiency. The reported results open up the path towards monolithic integration of spin qubit devices, microwave resonators and (protected) superconducting qubits on a silicon technology compatible platform.}, author = {Valentini, Marco and Sagi, Oliver and Baghumyan, Levon and Gijsel, Thijs de and Jung, Jason and Calcaterra, Stefano and Ballabio, Andrea and Servin, Juan Aguilera and Aggarwal, Kushagra and Janik, Marian and Adletzberger, Thomas and Souto, Rubén Seoane and Leijnse, Martin and Danon, Jeroen and Schrade, Constantin and Bakkers, Erik and Chrastina, Daniel and Isella, Giovanni and Katsaros, Georgios}, booktitle = {arXiv}, keywords = {Mesoscale and Nanoscale Physics}, title = {{Radio frequency driven superconducting diode and parity conserving Cooper pair transport in a two-dimensional germanium hole gas}}, doi = {10.48550/arXiv.2306.07109}, year = {2023}, } @misc{13126, abstract = {Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here, we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease.}, author = {Danzl, Johann G}, publisher = {Institute of Science and Technology Austria}, title = {{Research data for the publication "Imaging brain tissue architecture across millimeter to nanometer scales"}}, doi = {10.15479/AT:ISTA:13126}, year = {2023}, } @article{14257, abstract = {Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease.}, author = {Michalska, Julia M and Lyudchik, Julia and Velicky, Philipp and Korinkova, Hana and Watson, Jake and Cenameri, Alban and Sommer, Christoph M and Amberg, Nicole and Venturino, Alessandro and Roessler, Karl and Czech, Thomas and Höftberger, Romana and Siegert, Sandra and Novarino, Gaia and Jonas, Peter M and Danzl, Johann G}, issn = {1546-1696}, journal = {Nature Biotechnology}, publisher = {Springer Nature}, title = {{Imaging brain tissue architecture across millimeter to nanometer scales}}, doi = {10.1038/s41587-023-01911-8}, year = {2023}, } @article{13044, abstract = {Singlet oxygen (1O2) formation is now recognised as a key aspect of non-aqueous oxygen redox chemistry. For identifying 1O2, chemical trapping via 9,10-dimethylanthracene (DMA) to form the endoperoxide (DMA-O2) has become the mainstay method due to its sensitivity, selectivity, and ease of use. While DMA has been shown to be selective for 1O2, rather than forming DMA-O2 with a wide variety of potentially reactive O-containing species, false positives might hypothetically be obtained in the presence of previously overlooked species. Here, we first give unequivocal direct spectroscopic proof by the 1O2-specific near infrared (NIR) emission at 1270 nm for the previously proposed 1O2 formation pathways, which centre around superoxide disproportionation. We then show that peroxocarbonates, common intermediates in metal-O2 and metal carbonate electrochemistry, do not produce false-positive DMA-O2. Moreover, we identify a previously unreported 1O2-forming pathway through the reaction of CO2 with superoxide. Overall, we give unequivocal proof for 1O2 formation in non-aqueous oxygen redox and show that chemical trapping with DMA is a reliable method to assess 1O2 formation.}, author = {Mondal, Soumyadip and Jethwa, Rajesh B and Pant, Bhargavi and Hauschild, Robert and Freunberger, Stefan Alexander}, issn = {1364-5498}, journal = {Faraday Discussions}, keywords = {Physical and Theoretical Chemistry}, publisher = {Royal Society of Chemistry}, title = {{Singlet oxygen in non-aqueous oxygen redox: Direct spectroscopic evidence for formation pathways and reliability of chemical probes}}, doi = {10.1039/d3fd00088e}, year = {2023}, } @article{10758, abstract = {5-Carboxycytosine (5caC) is a rare epigenetic modification found in nucleic acids of all domains of life. Despite its sparse genomic abundance, 5caC is presumed to play essential regulatory roles in transcription, maintenance and base-excision processes in DNA. In this work, we utilize nuclear magnetic resonance (NMR) spectroscopy to address the effects of 5caC incorporation into canonical DNA strands at multiple pH and temperature conditions. Our results demonstrate that 5caC has a pH-dependent global destabilizing and a base-pair mobility enhancing local impact on dsDNA, albeit without any detectable influence on the ground-state B-DNA structure. Measurement of hybridization thermodynamics and kinetics of 5caC-bearing DNA duplexes highlighted how acidic environment (pH 5.8 and 4.7) destabilizes the double-stranded structure by ∼10–20 kJ mol–1 at 37 °C when compared to the same sample at neutral pH. Protonation of 5caC results in a lower activation energy for the dissociation process and a higher barrier for annealing. Studies on conformational exchange on the microsecond time scale regime revealed a sharply localized base-pair motion involving exclusively the modified site and its immediate surroundings. By direct comparison with canonical and 5-formylcytosine (5fC)-edited strands, we were able to address the impact of the two most oxidized naturally occurring cytosine derivatives in the genome. These insights on 5caC’s subtle sensitivity to acidic pH contribute to the long-standing questions of its capacity as a substrate in base excision repair processes and its purpose as an independent, stable epigenetic mark.}, author = {Dubini, Romeo C. A. and Korytiaková, Eva and Schinkel, Thea and Heinrichs, Pia and Carell, Thomas and Rovo, Petra}, issn = {2694-2445}, journal = {ACS Physical Chemistry Au}, number = {3}, pages = {237--246}, publisher = {American Chemical Society}, title = {{1H NMR chemical exchange techniques reveal local and global effects of oxidized cytosine derivatives}}, doi = {10.1021/acsphyschemau.1c00050}, volume = {2}, year = {2022}, } @article{11182, abstract = {Immune cells are constantly on the move through multicellular organisms to explore and respond to pathogens and other harmful insults. While moving, immune cells efficiently traverse microenvironments composed of tissue cells and extracellular fibers, which together form complex environments of various porosity, stiffness, topography, and chemical composition. In this protocol we describe experimental procedures to investigate immune cell migration through microenvironments of heterogeneous porosity. In particular, we describe micro-channels, micro-pillars, and collagen networks as cell migration paths with alternative pore size choices. Employing micro-channels or micro-pillars that divide at junctions into alternative paths with initially differentially sized pores allows us to precisely (1) measure the cellular translocation time through these porous path junctions, (2) quantify the cellular preference for individual pore sizes, and (3) image cellular components like the nucleus and the cytoskeleton. This reductionistic experimental setup thus can elucidate how immune cells perform decisions in complex microenvironments of various porosity like the interstitium. The setup further allows investigation of the underlying forces of cellular squeezing and the consequences of cellular deformation on the integrity of the cell and its organelles. As a complementary approach that does not require any micro-engineering expertise, we describe the usage of three-dimensional collagen networks with different pore sizes. Whereas we here focus on dendritic cells as a model for motile immune cells, the described protocols are versatile as they are also applicable for other immune cell types like neutrophils and non-immune cell types such as mesenchymal and cancer cells. In summary, we here describe protocols to identify the mechanisms and principles of cellular probing, decision making, and squeezing during cellular movement through microenvironments of heterogeneous porosity.}, author = {Kroll, Janina and Ruiz-Fernandez, Mauricio J.A. and Braun, Malte B. and Merrin, Jack and Renkawitz, Jörg}, issn = {2691-1299}, journal = {Current Protocols}, number = {4}, publisher = {Wiley}, title = {{Quantifying the probing and selection of microenvironmental pores by motile immune cells}}, doi = {10.1002/cpz1.407}, volume = {2}, year = {2022}, } @article{11444, abstract = {This article investigates library-related documents written by Gerard van Swieten (1700–72) during his tenure as Library Prefect in the Imperial Library of Vienna (1745–72). Van Swieten’s time as Library Prefect is considered through a textual analysis. Handwritten letters were deconstructed in terms of their appearance, layout, and tone in order to mine them for meaning. Furthermore, the contents were examined for library matters such as censorship, catalogues, and collection development. The Imperial Court Library held a prominent role as a repository for rare and valuable works, later becoming the National Library of Austria. Gerard van Swieten’s work as a librarian tends to be overlooked, perhaps because he is better known as the private physician of Maria Theresia, as well as a medical reformer. Nevertheless, he was a hard-working chief librarian deeply involved in all aspects of librarianship. Van Swieten endorsed modern scientific works, which were otherwise banned officially by the censorship commission, for the use of scholars in the library, expanded the collection by acquiring books through his network of scholars and publishers, and reissued library catalogues. He also provided for the comfort of users in the library reading room, at a time when such considerations were unusual. In conclusion, a proposal is made that van Swieten viewed his role as librarian with some importance and pride.}, author = {Chlebak, Clara A and Reid, Peter H.}, issn = {1758-3497}, journal = {Library and Information History}, number = {1}, pages = {23--41}, publisher = {Edinburgh University Press}, title = {{From the prefect’s desk: Gerard van Swieten’s library correspondence}}, doi = {10.3366/lih.2022.0097}, volume = {38}, year = {2022}, } @inproceedings{12894, author = {Schlögl, Alois and Hornoiu, Andrei and Elefante, Stefano and Stadlbauer, Stephan}, booktitle = {ASHPC22 - Austrian-Slovenian HPC Meeting 2022}, isbn = {978-3-200-08499-5}, location = {Grundlsee, Austria}, pages = {7}, publisher = {EuroCC Austria c/o Universität Wien}, title = {{Where is the sweet spot? A procurement story of general purpose compute nodes}}, doi = {10.25365/phaidra.337}, year = {2022}, } @article{9794, abstract = {Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular cells that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. Immunological challenge causes LNs to increase more than tenfold in size within a few days. Here, we characterized the biomechanics of LN swelling on the cellular and organ scale. We identified lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing fibroblastic reticular cells of the T-zone (TRCs) and their associated conduits to stretch. After an initial phase of relaxation, TRCs sensed the resulting strain through cell matrix adhesions, which coordinated local growth and remodeling of the stromal network. While the expanded TRC network readopted its typical configuration, a massive fibrotic reaction of the organ capsule set in and countered further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multitier fashion.}, author = {Assen, Frank P and Abe, Jun and Hons, Miroslav and Hauschild, Robert and Shamipour, Shayan and Kaufmann, Walter and Costanzo, Tommaso and Krens, Gabriel and Brown, Markus and Ludewig, Burkhard and Hippenmeyer, Simon and Heisenberg, Carl-Philipp J and Weninger, Wolfgang and Hannezo, Edouard B and Luther, Sanjiv A. and Stein, Jens V. and Sixt, Michael K}, issn = {1529-2916}, journal = {Nature Immunology}, pages = {1246--1255}, publisher = {Springer Nature}, title = {{Multitier mechanics control stromal adaptations in swelling lymph nodes}}, doi = {10.1038/s41590-022-01257-4}, volume = {23}, year = {2022}, } @article{10766, abstract = {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.}, author = {Slovakova, Jana and Sikora, Mateusz K and Arslan, Feyza N and Caballero Mancebo, Silvia and Krens, Gabriel and Kaufmann, Walter and Merrin, Jack and Heisenberg, Carl-Philipp J}, issn = {10916490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {8}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells}}, doi = {10.1073/pnas.2122030119}, volume = {119}, year = {2022}, } @article{10841, abstract = {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.}, author = {Dahhan, DA and Reynolds, GD and Cárdenas, JJ and Eeckhout, D and Johnson, Alexander J and Yperman, K and Kaufmann, Walter and Vang, N and Yan, X and Hwang, I and Heese, A and De Jaeger, G and Friml, Jiří and Van Damme, D and Pan, J and Bednarek, SY}, issn = {1532-298x}, journal = {Plant Cell}, number = {6}, pages = {2150--2173}, publisher = {Oxford Academic}, title = {{Proteomic characterization of isolated Arabidopsis clathrin-coated vesicles reveals evolutionarily conserved and plant-specific components}}, doi = {10.1093/plcell/koac071}, volume = {34}, year = {2022}, } @article{11705, abstract = {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.}, author = {Chang, Cheng and Liu, Yu and Lee, Seungho and Spadaro, Maria and Koskela, Kristopher M. and Kleinhanns, Tobias and Costanzo, Tommaso and Arbiol, Jordi and Brutchey, Richard L. and Ibáñez, Maria}, issn = {1521-3773}, journal = {Angewandte Chemie - International Edition}, number = {35}, publisher = {Wiley}, title = {{Surface functionalization of surfactant-free particles: A strategy to tailor the properties of nanocomposites for enhanced thermoelectric performance}}, doi = {10.1002/anie.202207002}, volume = {61}, year = {2022}, } @article{12065, abstract = {Capacity, rate performance, and cycle life of aprotic Li–O2 batteries critically depend on reversible electrodeposition of Li2O2. Current understanding states surface-adsorbed versus solvated LiO2 controls Li2O2 growth as surface film or as large particles. Herein, we show that Li2O2 forms across a wide range of electrolytes, carbons, and current densities as particles via solution-mediated LiO2 disproportionation, bringing into question the prevalence of any surface growth under practical conditions. We describe a unified O2 reduction mechanism, which can explain all found capacity relations and Li2O2 morphologies with exclusive solution discharge. Determining particle morphology and achievable capacities are species mobilities, true areal rate, and the degree of LiO2 association in solution. Capacity is conclusively limited by mass transport through the tortuous Li2O2 rather than electron transport through a passivating Li2O2 film. Provided that species mobilities and surface growth are high, high capacities are also achieved with weakly solvating electrolytes, which were previously considered prototypical for low capacity via surface growth.}, author = {Prehal, Christian and Mondal, Soumyadip and Lovicar, Ludek and Freunberger, Stefan Alexander}, issn = {2380-8195}, journal = {ACS Energy Letters}, number = {9}, pages = {3112--3119}, publisher = {American Chemical Society}, title = {{Exclusive solution discharge in Li-O₂ batteries?}}, doi = {10.1021/acsenergylett.2c01711}, volume = {7}, year = {2022}, } @article{12109, abstract = {Kelvin probe force microscopy (KPFM) is a powerful tool for studying contact electrification (CE) at the nanoscale, but converting KPFM voltage maps to charge density maps is nontrivial due to long-range forces and complex system geometry. Here we present a strategy using finite-element method (FEM) simulations to determine the Green's function of the KPFM probe/insulator/ground system, which allows us to quantitatively extract surface charge. Testing our approach with synthetic data, we find that accounting for the atomic force microscope (AFM) tip, cone, and cantilever is necessary to recover a known input and that existing methods lead to gross miscalculation or even the incorrect sign of the underlying charge. Applying it to experimental data, we demonstrate its capacity to extract realistic surface charge densities and fine details from contact-charged surfaces. Our method gives a straightforward recipe to convert qualitative KPFM voltage data into quantitative charge data over a range of experimental conditions, enabling quantitative CE at the nanoscale.}, author = {Pertl, Felix and Sobarzo Ponce, Juan Carlos A and Shafeek, Lubuna B and Cramer, Tobias and Waitukaitis, Scott R}, issn = {2475-9953}, journal = {Physical Review Materials}, number = {12}, publisher = {American Physical Society}, title = {{Quantifying nanoscale charge density features of contact-charged surfaces with an FEM/KPFM-hybrid approach}}, doi = {10.1103/PhysRevMaterials.6.125605}, volume = {6}, year = {2022}, } @article{12224, abstract = {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.}, author = {Muhia, Mary W and YuanXiang, PingAn and Sedlacik, Jan and Schwarz, Jürgen R. and Heisler, Frank F. and Gromova, Kira V. and Thies, Edda and Breiden, Petra and Pechmann, Yvonne and Kreutz, Michael R. and Kneussel, Matthias}, issn = {2399-3642}, journal = {Communications Biology}, keywords = {General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology, Medicine (miscellaneous)}, publisher = {Springer Nature}, title = {{Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes}}, doi = {10.1038/s42003-022-03446-1}, volume = {5}, year = {2022}, } @article{12228, abstract = {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.}, author = {Xu, Felix and Crisp, Antony and Schinkel, Thea and Dubini, Romeo C. A. and Hübner, Sarah and Becker, Sidney and Schelter, Florian and Rovo, Petra and Carell, Thomas}, issn = {1521-3773}, journal = {Angewandte Chemie International Edition}, keywords = {General Chemistry, Catalysis}, number = {45}, publisher = {Wiley}, title = {{Isoxazole nucleosides as building blocks for a plausible proto‐RNA}}, doi = {10.1002/anie.202211945}, volume = {61}, year = {2022}, } @article{12239, abstract = {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.}, author = {Johnson, Alexander J and Kaufmann, Walter and Sommer, Christoph M and Costanzo, Tommaso and Dahhan, Dana A. and Bednarek, Sebastian Y. and Friml, Jiří}, issn = {1674-2052}, journal = {Molecular Plant}, keywords = {Plant Science, Molecular Biology}, number = {10}, pages = {1533--1542}, publisher = {Elsevier}, title = {{Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution}}, doi = {10.1016/j.molp.2022.09.003}, volume = {15}, year = {2022}, } @article{12259, abstract = {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. }, author = {Choueiri, George H and Suri, Balachandra and Merrin, Jack and Serbyn, Maksym and Hof, Björn and Budanur, Nazmi B}, issn = {1089-7682}, journal = {Chaos: An Interdisciplinary Journal of Nonlinear Science}, keywords = {Applied Mathematics, General Physics and Astronomy, Mathematical Physics, Statistical and Nonlinear Physics}, number = {9}, publisher = {AIP Publishing}, title = {{Crises and chaotic scattering in hydrodynamic pilot-wave experiments}}, doi = {10.1063/5.0102904}, volume = {32}, year = {2022}, } @article{12262, abstract = {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.}, author = {Prattes, Michael and Grishkovskaya, Irina and Hodirnau, Victor-Valentin and Hetzmannseder, Christina and Zisser, Gertrude and Sailer, Carolin and Kargas, Vasileios and Loibl, Mathias and Gerhalter, Magdalena and Kofler, Lisa and Warren, Alan J. and Stengel, Florian and Haselbach, David and Bergler, Helmut}, issn = {1545-9985}, journal = {Nature Structural & Molecular Biology}, keywords = {Molecular Biology, Structural Biology}, number = {9}, pages = {942--953}, publisher = {Springer Nature}, title = {{Visualizing maturation factor extraction from the nascent ribosome by the AAA-ATPase Drg1}}, doi = {10.1038/s41594-022-00832-5}, volume = {29}, year = {2022}, } @article{12122, abstract = {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.}, author = {Weier, Ann-Kathrin and Homrich, Mirka and Ebbinghaus, Stephanie and Juda, Pavel and Miková, Eliška and Hauschild, Robert and Zhang, Lili and Quast, Thomas and Mass, Elvira and Schlitzer, Andreas and Kolanus, Waldemar and Burgdorf, Sven and Gruß, Oliver J. and Hons, Miroslav and Wieser, Stefan and Kiermaier, Eva}, issn = {1540-8140}, journal = {Journal of Cell Biology}, keywords = {Cell Biology}, number = {12}, publisher = {Rockefeller University Press}, title = {{Multiple centrosomes enhance migration and immune cell effector functions of mature dendritic cells}}, doi = {10.1083/jcb.202107134}, volume = {221}, year = {2022}, } @article{12291, abstract = {The phytohormone auxin triggers transcriptional reprogramming through a well-characterized perception machinery in the nucleus. By contrast, mechanisms that underlie fast effects of auxin, such as the regulation of ion fluxes, rapid phosphorylation of proteins or auxin feedback on its transport, remain unclear1,2,3. Whether auxin-binding protein 1 (ABP1) is an auxin receptor has been a source of debate for decades1,4. Here we show that a fraction of Arabidopsis thaliana ABP1 is secreted and binds auxin specifically at an acidic pH that is typical of the apoplast. ABP1 and its plasma-membrane-localized partner, transmembrane kinase 1 (TMK1), are required for the auxin-induced ultrafast global phospho-response and for downstream processes that include the activation of H+-ATPase and accelerated cytoplasmic streaming. abp1 and tmk mutants cannot establish auxin-transporting channels and show defective auxin-induced vasculature formation and regeneration. An ABP1(M2X) variant that lacks the capacity to bind auxin is unable to complement these defects in abp1 mutants. These data indicate that ABP1 is the auxin receptor for TMK1-based cell-surface signalling, which mediates the global phospho-response and auxin canalization.}, author = {Friml, Jiří and Gallei, Michelle C and Gelová, Zuzana and Johnson, Alexander J and Mazur, Ewa and Monzer, Aline and Rodriguez Solovey, Lesia and Roosjen, Mark and Verstraeten, Inge and Živanović, Branka D. and Zou, Minxia and Fiedler, Lukas and Giannini, Caterina and Grones, Peter and Hrtyan, Mónika and Kaufmann, Walter and Kuhn, Andre and Narasimhan, Madhumitha and Randuch, Marek and Rýdza, Nikola and Takahashi, Koji and Tan, Shutang and Teplova, Anastasiia and Kinoshita, Toshinori and Weijers, Dolf and Rakusová, Hana}, issn = {1476-4687}, journal = {Nature}, number = {7927}, pages = {575--581}, publisher = {Springer Nature}, title = {{ABP1–TMK auxin perception for global phosphorylation and auxin canalization}}, doi = {10.1038/s41586-022-05187-x}, volume = {609}, year = {2022}, } @article{10791, abstract = {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.}, author = {Hansen, Andi H and Pauler, Florian and Riedl, Michael and Streicher, Carmen and Heger, Anna-Magdalena and Laukoter, Susanne and Sommer, Christoph M and Nicolas, Armel and Hof, Björn and Tsai, Li Huei and Rülicke, Thomas and Hippenmeyer, Simon}, issn = {2753-149X}, journal = {Oxford Open Neuroscience}, number = {1}, publisher = {Oxford Academic}, title = {{Tissue-wide effects override cell-intrinsic gene function in radial neuron migration}}, doi = {10.1093/oons/kvac009}, volume = {1}, year = {2022}, } @article{10703, abstract = {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.}, author = {Gaertner, Florian and Reis-Rodrigues, Patricia and De Vries, Ingrid and Hons, Miroslav and Aguilera, Juan and Riedl, Michael and Leithner, Alexander F and Tasciyan, Saren and Kopf, Aglaja and Merrin, Jack and Zheden, Vanessa and Kaufmann, Walter and Hauschild, Robert and Sixt, Michael K}, issn = {1878-1551}, journal = {Developmental Cell}, number = {1}, pages = {47--62.e9}, publisher = {Cell Press ; Elsevier}, title = {{WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues}}, doi = {10.1016/j.devcel.2021.11.024}, volume = {57}, year = {2022}, } @inproceedings{12909, author = {Schlögl, Alois and Elefante, Stefano and Hornoiu, Andrei and Stadlbauer, Stephan}, booktitle = {ASHPC21 – Austrian-Slovenian HPC Meeting 2021}, isbn = {978-961-6980-77-7}, location = {Virtual}, pages = {5}, publisher = {University of Ljubljana}, title = {{Managing software on a heterogenous HPC cluster}}, doi = {10.3359/2021hpc}, year = {2021}, } @article{8582, abstract = {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.}, author = {Li, Hongjiang and von Wangenheim, Daniel and Zhang, Xixi and Tan, Shutang and Darwish-Miranda, Nasser and Naramoto, Satoshi and Wabnik, Krzysztof T and de Rycke, Riet and Kaufmann, Walter and Gütl, Daniel J and Tejos, Ricardo and Grones, Peter and Ke, Meiyu and Chen, Xu and Dettmer, Jan and Friml, Jiří}, issn = {14698137}, journal = {New Phytologist}, number = {1}, pages = {351--369}, publisher = {Wiley}, title = {{Cellular requirements for PIN polar cargo clustering in Arabidopsis thaliana}}, doi = {10.1111/nph.16887}, volume = {229}, year = {2021}, } @article{8927, abstract = {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.}, author = {Nardo, Alexander D. and Schneeweiss-Gleixner, Mathias and Bakail, May M and Dixon, Emmanuel D. and Lax, Sigurd F. and Trauner, Michael}, issn = {14783231}, journal = {Liver International}, number = {1}, pages = {20--32}, publisher = {Wiley}, title = {{Pathophysiological mechanisms of liver injury in COVID-19}}, doi = {10.1111/liv.14730}, volume = {41}, year = {2021}, } @article{9038, abstract = {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. }, author = {Aguilar-Merino, Patricia and Álvarez-Pérez, Gonzalo and Taboada-Gutiérrez, Javier and Duan, Jiahua and Prieto Gonzalez, Ivan and Álvarez-Prado, Luis Manuel and Nikitin, Alexey Y. and Martín-Sánchez, Javier and Alonso-González, Pablo}, issn = {20794991}, journal = {Nanomaterials}, number = {1}, publisher = {MDPI}, title = {{Extracting the infrared permittivity of SiO2 substrates locally by near-field imaging of phonon polaritons in a van der Waals crystal}}, doi = {10.3390/nano11010120}, volume = {11}, year = {2021}, } @article{9262, abstract = {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.}, author = {Mbianda, Johanne and Bakail, May M and André, Christophe and Moal, Gwenaëlle and Perrin, Marie E. and Pinna, Guillaume and Guerois, Raphaël and Becher, Francois and Legrand, Pierre and Traoré, Seydou and Douat, Céline and Guichard, Gilles and Ochsenbein, Françoise}, issn = {2375-2548}, journal = {Science Advances}, number = {12}, publisher = {American Association for the Advancement of Science}, title = {{Optimal anchoring of a foldamer inhibitor of ASF1 histone chaperone through backbone plasticity}}, doi = {10.1126/sciadv.abd9153}, volume = {7}, year = {2021}, } @article{9259, abstract = {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.}, author = {Vaahtomeri, Kari and Moussion, Christine and Hauschild, Robert and Sixt, Michael K}, issn = {1664-3224}, journal = {Frontiers in Immunology}, publisher = {Frontiers}, title = {{Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium}}, doi = {10.3389/fimmu.2021.630002}, volume = {12}, year = {2021}, } @article{9329, abstract = {Background: To understand information coding in single neurons, it is necessary to analyze subthreshold synaptic events, action potentials (APs), and their interrelation in different behavioral states. However, detecting excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) in behaving animals remains challenging, because of unfavorable signal-to-noise ratio, high frequency, fluctuating amplitude, and variable time course of synaptic events. New method: We developed a method for synaptic event detection, termed MOD (Machine-learning Optimal-filtering Detection-procedure), which combines concepts of supervised machine learning and optimal Wiener filtering. Experts were asked to manually score short epochs of data. The algorithm was trained to obtain the optimal filter coefficients of a Wiener filter and the optimal detection threshold. Scored and unscored data were then processed with the optimal filter, and events were detected as peaks above threshold. Results: We challenged MOD with EPSP traces in vivo in mice during spatial navigation and EPSC traces in vitro in slices under conditions of enhanced transmitter release. The area under the curve (AUC) of the receiver operating characteristics (ROC) curve was, on average, 0.894 for in vivo and 0.969 for in vitro data sets, indicating high detection accuracy and efficiency. Comparison with existing methods: When benchmarked using a (1 − AUC)−1 metric, MOD outperformed previous methods (template-fit, deconvolution, and Bayesian methods) by an average factor of 3.13 for in vivo data sets, but showed comparable (template-fit, deconvolution) or higher (Bayesian) computational efficacy. Conclusions: MOD may become an important new tool for large-scale, real-time analysis of synaptic activity.}, author = {Zhang, Xiaomin and Schlögl, Alois and Vandael, David H and Jonas, Peter M}, issn = {1872-678X}, journal = {Journal of Neuroscience Methods}, number = {6}, publisher = {Elsevier}, title = {{MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo}}, doi = {10.1016/j.jneumeth.2021.109125}, volume = {357}, year = {2021}, } @article{9330, abstract = {In nerve cells the genes encoding for α2δ subunits of voltage-gated calcium channels have been linked to synaptic functions and neurological disease. Here we show that α2δ subunits are essential for the formation and organization of glutamatergic synapses. Using a cellular α2δ subunit triple-knockout/knockdown model, we demonstrate a failure in presynaptic differentiation evidenced by defective presynaptic calcium channel clustering and calcium influx, smaller presynaptic active zones, and a strongly reduced accumulation of presynaptic vesicle-associated proteins (synapsin and vGLUT). The presynaptic defect is associated with the downscaling of postsynaptic AMPA receptors and the postsynaptic density. The role of α2δ isoforms as synaptic organizers is highly redundant, as each individual α2δ isoform can rescue presynaptic calcium channel trafficking and expression of synaptic proteins. Moreover, α2δ-2 and α2δ-3 with mutated metal ion-dependent adhesion sites can fully rescue presynaptic synapsin expression but only partially calcium channel trafficking, suggesting that the regulatory role of α2δ subunits is independent from its role as a calcium channel subunit. Our findings influence the current view on excitatory synapse formation. First, our study suggests that postsynaptic differentiation is secondary to presynaptic differentiation. Second, the dependence of presynaptic differentiation on α2δ implicates α2δ subunits as potential nucleation points for the organization of synapses. Finally, our results suggest that α2δ subunits act as transsynaptic organizers of glutamatergic synapses, thereby aligning the synaptic active zone with the postsynaptic density.}, author = {Schöpf, Clemens L. and Ablinger, Cornelia and Geisler, Stefanie M. and Stanika, Ruslan I. and Campiglio, Marta and Kaufmann, Walter and Nimmervoll, Benedikt and Schlick, Bettina and Brockhaus, Johannes and Missler, Markus and Shigemoto, Ryuichi and Obermair, Gerald J.}, issn = {1091-6490}, journal = {PNAS}, number = {14}, publisher = {National Academy of Sciences}, title = {{Presynaptic α2δ subunits are key organizers of glutamatergic synapses}}, doi = {10.1073/pnas.1920827118}, volume = {118}, year = {2021}, } @article{9334, abstract = {Polaritons with directional in-plane propagation and ultralow losses in van der Waals (vdW) crystals promise unprecedented manipulation of light at the nanoscale. However, these polaritons present a crucial limitation: their directional propagation is intrinsically determined by the crystal structure of the host material, imposing forbidden directions of propagation. Here, we demonstrate that directional polaritons (in-plane hyperbolic phonon polaritons) in a vdW crystal (α-phase molybdenum trioxide) can be directed along forbidden directions by inducing an optical topological transition, which emerges when the slab is placed on a substrate with a given negative permittivity (4H–silicon carbide). By visualizing the transition in real space, we observe exotic polaritonic states between mutually orthogonal hyperbolic regimes, which unveil the topological origin of the transition: a gap opening in the dispersion. This work provides insights into optical topological transitions in vdW crystals, which introduce a route to direct light at the nanoscale.}, author = {Duan, J. and Álvarez-Pérez, G. and Voronin, K. V. and Prieto Gonzalez, Ivan and Taboada-Gutiérrez, J. and Volkov, V. S. and Martín-Sánchez, J. and Nikitin, A. Y. and Alonso-González, P.}, issn = {23752548}, journal = {Science Advances}, number = {14}, publisher = {AAAS}, title = {{Enabling propagation of anisotropic polaritons along forbidden directions via a topological transition}}, doi = {10.1126/sciadv.abf2690}, volume = {7}, year = {2021}, } @article{9363, abstract = {Optogenetics has been harnessed to shed new mechanistic light on current and future therapeutic strategies. This has been to date achieved by the regulation of ion flow and electrical signals in neuronal cells and neural circuits that are known to be affected by disease. In contrast, the optogenetic delivery of trophic biochemical signals, which support cell survival and are implicated in degenerative disorders, has never been demonstrated in an animal model of disease. Here, we reengineered the human and Drosophila melanogaster REarranged during Transfection (hRET and dRET) receptors to be activated by light, creating one-component optogenetic tools termed Opto-hRET and Opto-dRET. Upon blue light stimulation, these receptors robustly induced the MAPK/ERK proliferative signaling pathway in cultured cells. In PINK1B9 flies that exhibit loss of PTEN-induced putative kinase 1 (PINK1), a kinase associated with familial Parkinson’s disease (PD), light activation of Opto-dRET suppressed mitochondrial defects, tissue degeneration and behavioral deficits. In human cells with PINK1 loss-of-function, mitochondrial fragmentation was rescued using Opto-dRET via the PI3K/NF-кB pathway. Our results demonstrate that a light-activated receptor can ameliorate disease hallmarks in a genetic model of PD. The optogenetic delivery of trophic signals is cell type-specific and reversible and thus has the potential to inspire novel strategies towards a spatio-temporal regulation of tissue repair.}, author = {Inglés Prieto, Álvaro and Furthmann, Nikolas and Crossman, Samuel H. and Tichy, Alexandra Madelaine and Hoyer, Nina and Petersen, Meike and Zheden, Vanessa and Bicher, Julia and Gschaider-Reichhart, Eva and György, Attila and Siekhaus, Daria E and Soba, Peter and Winklhofer, Konstanze F. and Janovjak, Harald L}, issn = {15537404}, journal = {PLoS genetics}, number = {4}, pages = {e1009479}, publisher = {Public Library of Science}, title = {{Optogenetic delivery of trophic signals in a genetic model of Parkinson's disease}}, doi = {10.1371/journal.pgen.1009479}, volume = {17}, year = {2021}, } @article{9361, abstract = {The multimeric matrix (M) protein of clinically relevant paramyxoviruses orchestrates assembly and budding activity of viral particles at the plasma membrane (PM). We identified within the canine distemper virus (CDV) M protein two microdomains, potentially assuming α-helix structures, which are essential for membrane budding activity. Remarkably, while two rationally designed microdomain M mutants (E89R, microdomain 1 and L239D, microdomain 2) preserved proper folding, dimerization, interaction with the nucleocapsid protein, localization at and deformation of the PM, the virus-like particle formation, as well as production of infectious virions (as monitored using a membrane budding-complementation system), were, in sharp contrast, strongly impaired. Of major importance, raster image correlation spectroscopy (RICS) revealed that both microdomains contributed to finely tune M protein mobility specifically at the PM. Collectively, our data highlighted the cornerstone membrane budding-priming activity of two spatially discrete M microdomains, potentially by coordinating the assembly of productive higher oligomers at the PM.}, author = {Gast, Matthieu and Kadzioch, Nicole P. and Milius, Doreen and Origgi, Francesco and Plattet, Philippe}, issn = {23795042}, journal = {mSphere}, number = {2}, publisher = {American Society for Microbiology}, title = {{Oligomerization and cell egress controlled by two microdomains of canine distemper virus matrix protein}}, doi = {10.1128/mSphere.01024-20}, volume = {6}, year = {2021}, } @article{9540, abstract = {The hexameric AAA-ATPase Drg1 is a key factor in eukaryotic ribosome biogenesis and initiates cytoplasmic maturation of the large ribosomal subunit by releasing the shuttling maturation factor Rlp24. Drg1 monomers contain two AAA-domains (D1 and D2) that act in a concerted manner. Rlp24 release is inhibited by the drug diazaborine which blocks ATP hydrolysis in D2. The mode of inhibition was unknown. Here we show the first cryo-EM structure of Drg1 revealing the inhibitory mechanism. Diazaborine forms a covalent bond to the 2′-OH of the nucleotide in D2, explaining its specificity for this site. As a consequence, the D2 domain is locked in a rigid, inactive state, stalling the whole Drg1 hexamer. Resistance mechanisms identified include abolished drug binding and altered positioning of the nucleotide. Our results suggest nucleotide-modifying compounds as potential novel inhibitors for AAA-ATPases.}, author = {Prattes, Michael and Grishkovskaya, Irina and Hodirnau, Victor-Valentin and Rössler, Ingrid and Klein, Isabella and Hetzmannseder, Christina and Zisser, Gertrude and Gruber, Christian C. and Gruber, Karl and Haselbach, David and Bergler, Helmut}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry}, number = {1}, publisher = {Springer Nature}, title = {{Structural basis for inhibition of the AAA-ATPase Drg1 by diazaborine}}, doi = {10.1038/s41467-021-23854-x}, volume = {12}, year = {2021}, } @article{9607, abstract = {While high risk of failure is an inherent part of developing innovative therapies, it can be reduced by adherence to evidence-based rigorous research practices. Numerous analyses conducted to date have clearly identified measures that need to be taken to improve research rigor. Supported through the European Union's Innovative Medicines Initiative, the EQIPD consortium has developed a novel preclinical research quality system that can be applied in both public and private sectors and is free for anyone to use. The EQIPD Quality System was designed to be suited to boost innovation by ensuring the generation of robust and reliable preclinical data while being lean, effective and not becoming a burden that could negatively impact the freedom to explore scientific questions. EQIPD defines research quality as the extent to which research data are fit for their intended use. Fitness, in this context, is defined by the stakeholders, who are the scientists directly involved in the research, but also their funders, sponsors, publishers, research tool manufacturers and collaboration partners such as peers in a multi-site research project. The essence of the EQIPD Quality System is the set of 18 core requirements that can be addressed flexibly, according to user-specific needs and following a user-defined trajectory. The EQIPD Quality System proposes guidance on expectations for quality-related measures, defines criteria for adequate processes (i.e., performance standards) and provides examples of how such measures can be developed and implemented. However, it does not prescribe any pre-determined solutions. EQIPD has also developed tools (for optional use) to support users in implementing the system and assessment services for those research units that successfully implement the quality system and seek formal accreditation. Building upon the feedback from users and continuous improvement, a sustainable EQIPD Quality System will ultimately serve the entire community of scientists conducting non-regulated preclinical research, by helping them generate reliable data that are fit for their intended use.}, author = {Bespalov, Anton and Bernard, René and Gilis, Anja and Gerlach, Björn and Guillén, Javier and Castagné, Vincent and Lefevre, Isabel A. and Ducrey, Fiona and Monk, Lee and Bongiovanni, Sandrine and Altevogt, Bruce and Arroyo-Araujo, María and Bikovski, Lior and De Bruin, Natasja and Castaños-Vélez, Esmeralda and Dityatev, Alexander and Emmerich, Christoph H. and Fares, Raafat and Ferland-Beckham, Chantelle and Froger-Colléaux, Christelle and Gailus-Durner, Valerie and Hölter, Sabine M. and Hofmann, Martine Cj and Kabitzke, Patricia and Kas, Martien Jh and Kurreck, Claudia and Moser, Paul and Pietraszek, Malgorzata and Popik, Piotr and Potschka, Heidrun and Prado Montes De Oca, Ernesto and Restivo, Leonardo and Riedel, Gernot and Ritskes-Hoitinga, Merel and Samardzic, Janko and Schunn, Michael and Stöger, Claudia and Voikar, Vootele and Vollert, Jan and Wever, Kimberley E. and Wuyts, Kathleen and Macleod, Malcolm R. and Dirnagl, Ulrich and Steckler, Thomas}, issn = {2050084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Introduction to the EQIPD quality system}}, doi = {10.7554/eLife.63294}, volume = {10}, year = {2021}, } @article{9603, abstract = {Mosaic analysis with double markers (MADM) offers one approach to visualize and concomitantly manipulate genetically defined cells in mice with single-cell resolution. MADM applications include the analysis of lineage, single-cell morphology and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous gene functions in vivo in health and disease. Yet, MADM can only be applied to <25% of all mouse genes on select chromosomes to date. To overcome this limitation, we generate transgenic mice with knocked-in MADM cassettes near the centromeres of all 19 autosomes and validate their use across organs. With this resource, >96% of the entire mouse genome can now be subjected to single-cell genetic mosaic analysis. Beyond a proof of principle, we apply our MADM library to systematically trace sister chromatid segregation in distinct mitotic cell lineages. We find striking chromosome-specific biases in segregation patterns, reflecting a putative mechanism for the asymmetric segregation of genetic determinants in somatic stem cell division.}, author = {Contreras, Ximena and Amberg, Nicole and Davaatseren, Amarbayasgalan and Hansen, Andi H and Sonntag, Johanna and Andersen, Lill and Bernthaler, Tina and Streicher, Carmen and Heger, Anna-Magdalena and Johnson, Randy L. and Schwarz, Lindsay A. and Luo, Liqun and Rülicke, Thomas and Hippenmeyer, Simon}, issn = {22111247}, journal = {Cell Reports}, number = {12}, publisher = {Cell Press}, title = {{A genome-wide library of MADM mice for single-cell genetic mosaic analysis}}, doi = {10.1016/j.celrep.2021.109274}, volume = {35}, year = {2021}, } @article{9822, abstract = {Attachment of adhesive molecules on cell culture surfaces to restrict cell adhesion to defined areas and shapes has been vital for the progress of in vitro research. In currently existing patterning methods, a combination of pattern properties such as stability, precision, specificity, high-throughput outcome, and spatiotemporal control is highly desirable but challenging to achieve. Here, we introduce a versatile and high-throughput covalent photoimmobilization technique, comprising a light-dose-dependent patterning step and a subsequent functionalization of the pattern via click chemistry. This two-step process is feasible on arbitrary surfaces and allows for generation of sustainable patterns and gradients. The method is validated in different biological systems by patterning adhesive ligands on cell-repellent surfaces, thereby constraining the growth and migration of cells to the designated areas. We then implement a sequential photopatterning approach by adding a second switchable patterning step, allowing for spatiotemporal control over two distinct surface patterns. As a proof of concept, we reconstruct the dynamics of the tip/stalk cell switch during angiogenesis. Our results show that the spatiotemporal control provided by our “sequential photopatterning” system is essential for mimicking dynamic biological processes and that our innovative approach has great potential for further applications in cell science.}, author = {Zisis, Themistoklis and Schwarz, Jan and Balles, Miriam and Kretschmer, Maibritt and Nemethova, Maria and Chait, Remy P and Hauschild, Robert and Lange, Janina and Guet, Calin C and Sixt, Michael K and Zahler, Stefan}, issn = {19448252}, journal = {ACS Applied Materials and Interfaces}, number = {30}, pages = {35545–35560}, publisher = {American Chemical Society}, title = {{Sequential and switchable patterning for studying cellular processes under spatiotemporal control}}, doi = {10.1021/acsami.1c09850}, volume = {13}, year = {2021}, } @article{9911, abstract = {A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated , quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted. This is clearly demonstrated by the well-documented and widespread difficulties that are routinely encountered in evaluating acquired data and reproducing scientific experiments. Indeed, studies have shown that more than 70% of researchers have tried and failed to repeat another scientist's experiments, while more than half have even failed to reproduce their own experiments. One factor behind the reproducibility crisis of experiments published in scientific journals is the frequent underreporting of imaging methods caused by a lack of awareness and/or a lack of knowledge of the applied technique. Whereas quality control procedures for some methods used in biomedical research, such as genomics (e.g. DNA sequencing, RNA-seq) or cytometry, have been introduced (e.g. ENCODE), this issue has not been tackled for optical microscopy instrumentation and images. Although many calibration standards and protocols have been published, there is a lack of awareness and agreement on common standards and guidelines for quality assessment and reproducibility. In April 2020, the QUality Assessment and REProducibility for instruments and images in Light Microscopy (QUAREP-LiMi) initiative was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi initiative is to establish a set of common QC standards, guidelines, metadata models and tools, including detailed protocols, with the ultimate aim of improving reproducible advances in scientific research. This White Paper (1) summarizes the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi initiative; (2) identifies the urgent need to address these obstacles in a grassroots manner, through a community of stakeholders including, researchers, imaging scientists, bioimage analysts, bioimage informatics developers, corporate partners, funding agencies, standards organizations, scientific publishers and observers of such; (3) outlines the current actions of the QUAREP-LiMi initiative and (4) proposes future steps that can be taken to improve the dissemination and acceptance of the proposed guidelines to manage QC. To summarize, the principal goal of the QUAREP-LiMi initiative is to improve the overall quality and reproducibility of light microscope image data by introducing broadly accepted standard practices and accurately captured image data metrics.}, author = {Nelson, Glyn and Boehm, Ulrike and Bagley, Steve and Bajcsy, Peter and Bischof, Johanna and Brown, Claire M. and Dauphin, Aurélien and Dobbie, Ian M. and Eriksson, John E. and Faklaris, Orestis and Fernandez-Rodriguez, Julia and Ferrand, Alexia and Gelman, Laurent and Gheisari, Ali and Hartmann, Hella and Kukat, Christian and Laude, Alex and Mitkovski, Miso and Munck, Sebastian and North, Alison J. and Rasse, Tobias M. and Resch-Genger, Ute and Schuetz, Lucas C. and Seitz, Arne and Strambio-De-Castillia, Caterina and Swedlow, Jason R. and Alexopoulos, Ioannis and Aumayr, Karin and Avilov, Sergiy and Bakker, Gert Jan and Bammann, Rodrigo R. and Bassi, Andrea and Beckert, Hannes and Beer, Sebastian and Belyaev, Yury and Bierwagen, Jakob and Birngruber, Konstantin A. and Bosch, Manel and Breitlow, Juergen and Cameron, Lisa A. and Chalfoun, Joe and Chambers, James J. and Chen, Chieh Li and Conde-Sousa, Eduardo and Corbett, Alexander D. and Cordelieres, Fabrice P. and Nery, Elaine Del and Dietzel, Ralf and Eismann, Frank and Fazeli, Elnaz and Felscher, Andreas and Fried, Hans and Gaudreault, Nathalie and Goh, Wah Ing and Guilbert, Thomas and Hadleigh, Roland and Hemmerich, Peter and Holst, Gerhard A. and Itano, Michelle S. and Jaffe, Claudia B. and Jambor, Helena K. and Jarvis, Stuart C. and Keppler, Antje and Kirchenbuechler, David and Kirchner, Marcel and Kobayashi, Norio and Krens, Gabriel and Kunis, Susanne and Lacoste, Judith and Marcello, Marco and Martins, Gabriel G. and Metcalf, Daniel J. and Mitchell, Claire A. and Moore, Joshua and Mueller, Tobias and Nelson, Michael S. and Ogg, Stephen and Onami, Shuichi and Palmer, Alexandra L. and Paul-Gilloteaux, Perrine and Pimentel, Jaime A. and Plantard, Laure and Podder, Santosh and Rexhepaj, Elton and Royon, Arnaud and Saari, Markku A. and Schapman, Damien and Schoonderwoert, Vincent and Schroth-Diez, Britta and Schwartz, Stanley and Shaw, Michael and Spitaler, Martin and Stoeckl, Martin T. and Sudar, Damir and Teillon, Jeremie and Terjung, Stefan and Thuenauer, Roland and Wilms, Christian D. and Wright, Graham D. and Nitschke, Roland}, issn = {1365-2818}, journal = {Journal of Microscopy}, number = {1}, pages = {56--73}, publisher = {Wiley}, title = {{QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy}}, doi = {10.1111/jmi.13041}, volume = {284}, year = {2021}, } @article{10123, abstract = {Solution synthesis of particles emerged as an alternative to prepare thermoelectric materials with less demanding processing conditions than conventional solid-state synthetic methods. However, solution synthesis generally involves the presence of additional molecules or ions belonging to the precursors or added to enable solubility and/or regulate nucleation and growth. These molecules or ions can end up in the particles as surface adsorbates and interfere in the material properties. This work demonstrates that ionic adsorbates, in particular Na⁺ ions, are electrostatically adsorbed in SnSe particles synthesized in water and play a crucial role not only in directing the material nano/microstructure but also in determining the transport properties of the consolidated material. In dense pellets prepared by sintering SnSe particles, Na remains within the crystal lattice as dopant, in dislocations, precipitates, and forming grain boundary complexions. These results highlight the importance of considering all the possible unintentional impurities to establish proper structure-property relationships and control material properties in solution-processed thermoelectric materials.}, author = {Liu, Yu and Calcabrini, Mariano and Yu, Yuan and Genç, Aziz and Chang, Cheng and Costanzo, Tommaso and Kleinhanns, Tobias and Lee, Seungho and Llorca, Jordi and Cojocaru‐Mirédin, Oana and Ibáñez, Maria}, issn = {1521-4095}, journal = {Advanced Materials}, keywords = {mechanical engineering, mechanics of materials, general materials science}, number = {52}, publisher = {Wiley}, title = {{The importance of surface adsorbates in solution‐processed thermoelectric materials: The case of SnSe}}, doi = {10.1002/adma.202106858}, volume = {33}, year = {2021}, } @article{10117, abstract = {Proximity labeling provides a powerful in vivo tool to characterize the proteome of subcellular structures and the interactome of specific proteins. The nematode Caenorhabditis elegans is one of the most intensely studied organisms in biology, offering many advantages for biochemistry. Using the highly active biotin ligase TurboID, we optimize here a proximity labeling protocol for C. elegans. An advantage of TurboID is that biotin's high affinity for streptavidin means biotin-labeled proteins can be affinity-purified under harsh denaturing conditions. By combining extensive sonication with aggressive denaturation using SDS and urea, we achieved near-complete solubilization of worm proteins. We then used this protocol to characterize the proteomes of the worm gut, muscle, skin, and nervous system. Neurons are among the smallest C. elegans cells. To probe the method's sensitivity, we expressed TurboID exclusively in the two AFD neurons and showed that the protocol could identify known and previously unknown proteins expressed selectively in AFD. The active zones of synapses are composed of a protein matrix that is difficult to solubilize and purify. To test if our protocol could solubilize active zone proteins, we knocked TurboID into the endogenous elks-1 gene, which encodes a presynaptic active zone protein. We identified many known ELKS-1-interacting active zone proteins, as well as previously uncharacterized synaptic proteins. Versatile vectors and the inherent advantages of using C. elegans, including fast growth and the ability to rapidly make and functionally test knock-ins, make proximity labeling a valuable addition to the armory of this model organism.}, author = {Artan, Murat and Barratt, Stephen and Flynn, Sean M. and Begum, Farida and Skehel, Mark and Nicolas, Armel and De Bono, Mario}, issn = {1083-351X}, journal = {Journal of Biological Chemistry}, number = {3}, publisher = {Elsevier}, title = {{Interactome analysis of Caenorhabditis elegans synapses by TurboID-based proximity labeling}}, doi = {10.1016/J.JBC.2021.101094}, volume = {297}, year = {2021}, } @article{10177, abstract = {Phonon polaritons (PhPs)—light coupled to lattice vibrations—with in-plane hyperbolic dispersion exhibit ray-like propagation with large wave vectors and enhanced density of optical states along certain directions on a surface. As such, they have raised a surge of interest, promising unprecedented manipulation of infrared light at the nanoscale in a planar circuitry. Here, we demonstrate focusing of in-plane hyperbolic PhPs propagating along thin slabs of α-MoO3. To that end, we developed metallic nanoantennas of convex geometries for both efficient launching and focusing of the polaritons. The foci obtained exhibit enhanced near-field confinement and absorption compared to foci produced by in-plane isotropic PhPs. Foci sizes as small as λp/4.5 = λ0/50 were achieved (λp is the polariton wavelength and λ0 is the photon wavelength). Focusing of in-plane hyperbolic polaritons introduces a first and most basic building block developing planar polariton optics using in-plane anisotropic van der Waals materials.}, author = {Martín-Sánchez, Javier and Duan, Jiahua and Taboada-Gutiérrez, Javier and Álvarez-Pérez, Gonzalo and Voronin, Kirill V. and Prieto Gonzalez, Ivan and Ma, Weiliang and Bao, Qiaoliang and Volkov, Valentyn S. and Hillenbrand, Rainer and Nikitin, Alexey Y. and Alonso-González, Pablo}, issn = {23752548}, journal = {Science Advances}, number = {41}, publisher = {American Association for the Advancement of Science}, title = {{Focusing of in-plane hyperbolic polaritons in van der Waals crystals with tailored infrared nanoantennas}}, doi = {10.1126/sciadv.abj0127}, volume = {7}, year = {2021}, } @article{10179, abstract = {Inhibitory GABAergic interneurons migrate over long distances from their extracortical origin into the developing cortex. In humans, this process is uniquely slow and prolonged, and it is unclear whether guidance cues unique to humans govern the various phases of this complex developmental process. Here, we use fused cerebral organoids to identify key roles of neurotransmitter signaling pathways in guiding the migratory behavior of human cortical interneurons. We use scRNAseq to reveal expression of GABA, glutamate, glycine, and serotonin receptors along distinct maturation trajectories across interneuron migration. We develop an image analysis software package, TrackPal, to simultaneously assess 48 parameters for entire migration tracks of individual cells. By chemical screening, we show that different modes of interneuron migration depend on distinct neurotransmitter signaling pathways, linking transcriptional maturation of interneurons with their migratory behavior. Altogether, our study provides a comprehensive quantitative analysis of human interneuron migration and its functional modulation by neurotransmitter signaling.}, author = {Bajaj, Sunanjay and Bagley, Joshua A. and Sommer, Christoph M and Vertesy, Abel and Nagumo Wong, Sakurako and Krenn, Veronica and Lévi-Strauss, Julie and Knoblich, Juergen A.}, issn = {1460-2075}, journal = {EMBO Journal}, number = {23}, publisher = {Embo Press}, title = {{Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration}}, doi = {10.15252/embj.2021108714}, volume = {40}, year = {2021}, } @article{10283, abstract = {During the past decade, the scientific community and outside observers have noted a concerning lack of rigor and transparency in preclinical research that led to talk of a “reproducibility crisis” in the life sciences (Baker, 2016; Bespalov & Steckler, 2018; Heddleston et al, 2021). Various measures have been proposed to address the problem: from better training of scientists to more oversight to expanded publishing practices such as preregistration of studies. The recently published EQIPD (Enhancing Quality in Preclinical Data) System is, to date, the largest initiative that aims to establish a systematic approach for increasing the robustness and reliability of biomedical research (Bespalov et al, 2021). However, promoting a cultural change in research practices warrants a broad adoption of the Quality System and its underlying philosophy. It is here that academic Core Facilities (CF), research service providers at universities and research institutions, can make a difference. It is fair to assume that a significant fraction of published data originated from experiments that were designed, run, or analyzed in CFs. These academic services play an important role in the research ecosystem by offering access to cutting-edge equipment and by developing and testing novel techniques and methods that impact research in the academic and private sectors alike (Bikovski et al, 2020). Equipment and infrastructure are not the only value: CFs employ competent personnel with profound knowledge and practical experience of the specific field of interest: animal behavior, imaging, crystallography, genomics, and so on. Thus, CFs are optimally positioned to address concerns about the quality and robustness of preclinical research.}, author = {Restivo, Leonardo and Gerlach, Björn and Tsoory, Michael and Bikovski, Lior and Badurek, Sylvia and Pitzer, Claudia and Kos-Braun, Isabelle C. and Mausset-Bonnefont, Anne Laure Mj and Ward, Jonathan and Schunn, Michael and Noldus, Lucas P.J.J. and Bespalov, Anton and Voikar, Vootele}, issn = {1469-3178}, journal = {EMBO Reports}, publisher = {EMBO Press}, title = {{Towards best practices in research: Role of academic core facilities}}, doi = {10.15252/embr.202153824}, volume = {22}, year = {2021}, } @article{10607, abstract = {The evidence linking innate immunity mechanisms and neurodegenerative diseases is growing, but the specific mechanisms are incompletely understood. Experimental data suggest that microglial TLR4 mediates the uptake and clearance of α-synuclein also termed synucleinophagy. The accumulation of misfolded α-synuclein throughout the brain is central to Parkinson's disease (PD). The distribution and progression of the pathology is often attributed to the propagation of α-synuclein. Here, we apply a classical α-synuclein propagation model of prodromal PD in wild type and TLR4 deficient mice to study the role of TLR4 in the progression of the disease. Our data suggest that TLR4 deficiency facilitates the α-synuclein seed spreading associated with reduced lysosomal activity of microglia. Three months after seed inoculation, more pronounced proteinase K-resistant α-synuclein inclusion pathology is observed in mice with TLR4 deficiency. The facilitated propagation of α-synuclein is associated with early loss of dopamine transporter (DAT) signal in the striatum and loss of dopaminergic neurons in substantia nigra pars compacta of TLR4 deficient mice. These new results support TLR4 signaling as a putative target for disease modification to slow the progression of PD and related disorders.}, author = {Venezia, Serena and Kaufmann, Walter and Wenning, Gregor K. and Stefanova, Nadia}, issn = {1873-5126}, journal = {Parkinsonism & Related Disorders}, pages = {59--65}, publisher = {Elsevier}, title = {{Toll-like receptor 4 deficiency facilitates α-synuclein propagation and neurodegeneration in a mouse model of prodromal Parkinson's disease}}, doi = {10.1016/j.parkreldis.2021.09.007}, volume = {91}, year = {2021}, } @article{9301, abstract = {Electrodepositing insulating lithium peroxide (Li2O2) is the key process during discharge of aprotic Li–O2 batteries and determines rate, capacity, and reversibility. Current understanding states that the partition between surface adsorbed and dissolved lithium superoxide governs whether Li2O2 grows as a conformal surface film or larger particles, leading to low or high capacities, respectively. However, better understanding governing factors for Li2O2 packing density and capacity requires structural sensitive in situ metrologies. Here, we establish in situ small- and wide-angle X-ray scattering (SAXS/WAXS) as a suitable method to record the Li2O2 phase evolution with atomic to submicrometer resolution during cycling a custom-built in situ Li–O2 cell. Combined with sophisticated data analysis, SAXS allows retrieving rich quantitative structural information from complex multiphase systems. Surprisingly, we find that features are absent that would point at a Li2O2 surface film formed via two consecutive electron transfers, even in poorly solvating electrolytes thought to be prototypical for surface growth. All scattering data can be modeled by stacks of thin Li2O2 platelets potentially forming large toroidal particles. Li2O2 solution growth is further justified by rotating ring-disk electrode measurements and electron microscopy. Higher discharge overpotentials lead to smaller Li2O2 particles, but there is no transition to an electronically passivating, conformal Li2O2 coating. Hence, mass transport of reactive species rather than electronic transport through a Li2O2 film limits the discharge capacity. Provided that species mobilities and carbon surface areas are high, this allows for high discharge capacities even in weakly solvating electrolytes. The currently accepted Li–O2 reaction mechanism ought to be reconsidered.}, author = {Prehal, Christian and Samojlov, Aleksej and Nachtnebel, Manfred and Lovicar, Ludek and Kriechbaum, Manfred and Amenitsch, Heinz and Freunberger, Stefan Alexander}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {small-angle X-ray scattering, oxygen reduction, disproportionation, Li-air battery}, number = {14}, publisher = {National Academy of Sciences}, title = {{In situ small-angle X-ray scattering reveals solution phase discharge of Li–O2 batteries with weakly solvating electrolytes}}, doi = {10.1073/pnas.2021893118}, volume = {118}, year = {2021}, } @article{10836, author = {Pranger, Christina L. and Fazekas-Singer, Judit and Köhler, Verena K. and Pali‐Schöll, Isabella and Fiocchi, Alessandro and Karagiannis, Sophia N. and Zenarruzabeitia, Olatz and Borrego, Francisco and Jensen‐Jarolim, Erika}, issn = {1398-9995}, journal = {Allergy}, keywords = {Immunology, Immunology and Allergy}, number = {5}, pages = {1553--1556}, publisher = {Wiley}, title = {{PIPE‐cloned human IgE and IgG4 antibodies: New tools for investigating cow's milk allergy and tolerance}}, doi = {10.1111/all.14604}, volume = {76}, year = {2021}, } @article{9928, abstract = {There are two elementary superconducting qubit types that derive directly from the quantum harmonic oscillator. In one, the inductor is replaced by a nonlinear Josephson junction to realize the widely used charge qubits with a compact phase variable and a discrete charge wave function. In the other, the junction is added in parallel, which gives rise to an extended phase variable, continuous wave functions, and a rich energy-level structure due to the loop topology. While the corresponding rf superconducting quantum interference device Hamiltonian was introduced as a quadratic quasi-one-dimensional potential approximation to describe the fluxonium qubit implemented with long Josephson-junction arrays, in this work we implement it directly using a linear superinductor formed by a single uninterrupted aluminum wire. We present a large variety of qubits, all stemming from the same circuit but with drastically different characteristic energy scales. This includes flux and fluxonium qubits but also the recently introduced quasicharge qubit with strongly enhanced zero-point phase fluctuations and a heavily suppressed flux dispersion. The use of a geometric inductor results in high reproducibility of the inductive energy as guaranteed by top-down lithography—a key ingredient for intrinsically protected superconducting qubits.}, author = {Peruzzo, Matilda and Hassani, Farid and Szep, Gregory and Trioni, Andrea and Redchenko, Elena and Zemlicka, Martin and Fink, Johannes M}, issn = {2691-3399}, journal = {PRX Quantum}, keywords = {quantum physics, mesoscale and nanoscale physics}, number = {4}, pages = {040341}, publisher = {American Physical Society}, title = {{Geometric superinductance qubits: Controlling phase delocalization across a single Josephson junction}}, doi = {10.1103/PRXQuantum.2.040341}, volume = {2}, year = {2021}, } @article{10223, abstract = {Growth regulation tailors development in plants to their environment. A prominent example of this is the response to gravity, in which shoots bend up and roots bend down1. This paradox is based on opposite effects of the phytohormone auxin, which promotes cell expansion in shoots while inhibiting it in roots via a yet unknown cellular mechanism2. Here, by combining microfluidics, live imaging, genetic engineering and phosphoproteomics in Arabidopsis thaliana, we advance understanding of how auxin inhibits root growth. We show that auxin activates two distinct, antagonistically acting signalling pathways that converge on rapid regulation of apoplastic pH, a causative determinant of growth. Cell surface-based TRANSMEMBRANE KINASE1 (TMK1) interacts with and mediates phosphorylation and activation of plasma membrane H+-ATPases for apoplast acidification, while intracellular canonical auxin signalling promotes net cellular H+ influx, causing apoplast alkalinization. Simultaneous activation of these two counteracting mechanisms poises roots for rapid, fine-tuned growth modulation in navigating complex soil environments.}, author = {Li, Lanxin and Verstraeten, Inge and Roosjen, Mark and Takahashi, Koji and Rodriguez Solovey, Lesia and Merrin, Jack and Chen, Jian and Shabala, Lana and Smet, Wouter and Ren, Hong and Vanneste, Steffen and Shabala, Sergey and De Rybel, Bert and Weijers, Dolf and Kinoshita, Toshinori and Gray, William M. and Friml, Jiří}, issn = {14764687}, journal = {Nature}, keywords = {Multidisciplinary}, number = {7884}, pages = {273--277}, publisher = {Springer Nature}, title = {{Cell surface and intracellular auxin signalling for H+ fluxes in root growth}}, doi = {10.1038/s41586-021-04037-6}, volume = {599}, year = {2021}, } @article{9887, abstract = {Clathrin-mediated endocytosis is the major route of entry of cargos into cells and thus underpins many physiological processes. During endocytosis, an area of flat membrane is remodeled by proteins to create a spherical vesicle against intracellular forces. The protein machinery which mediates this membrane bending in plants is unknown. However, it is known that plant endocytosis is actin independent, thus indicating that plants utilize a unique mechanism to mediate membrane bending against high-turgor pressure compared to other model systems. Here, we investigate the TPLATE complex, a plant-specific endocytosis protein complex. It has been thought to function as a classical adaptor functioning underneath the clathrin coat. However, by using biochemical and advanced live microscopy approaches, we found that TPLATE is peripherally associated with clathrin-coated vesicles and localizes at the rim of endocytosis events. As this localization is more fitting to the protein machinery involved in membrane bending during endocytosis, we examined cells in which the TPLATE complex was disrupted and found that the clathrin structures present as flat patches. This suggests a requirement of the TPLATE complex for membrane bending during plant clathrin–mediated endocytosis. Next, we used in vitro biophysical assays to confirm that the TPLATE complex possesses protein domains with intrinsic membrane remodeling activity. These results redefine the role of the TPLATE complex and implicate it as a key component of the evolutionarily distinct plant endocytosis mechanism, which mediates endocytic membrane bending against the high-turgor pressure in plant cells.}, author = {Johnson, Alexander J and Dahhan, Dana A and Gnyliukh, Nataliia and Kaufmann, Walter and Zheden, Vanessa and Costanzo, Tommaso and Mahou, Pierre and Hrtyan, Mónika and Wang, Jie and Aguilera Servin, Juan L and van Damme, Daniël and Beaurepaire, Emmanuel and Loose, Martin and Bednarek, Sebastian Y and Friml, Jiří}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {51}, publisher = {National Academy of Sciences}, title = {{The TPLATE complex mediates membrane bending during plant clathrin-mediated endocytosis}}, doi = {10.1073/pnas.2113046118}, volume = {118}, year = {2021}, } @article{8910, abstract = {A semiconducting nanowire fully wrapped by a superconducting shell has been proposed as a platform for obtaining Majorana modes at small magnetic fields. In this study, we demonstrate that the appearance of subgap states in such structures is actually governed by the junction region in tunneling spectroscopy measurements and not the full-shell nanowire itself. Short tunneling regions never show subgap states, whereas longer junctions always do. This can be understood in terms of quantum dots forming in the junction and hosting Andreev levels in the Yu-Shiba-Rusinov regime. The intricate magnetic field dependence of the Andreev levels, through both the Zeeman and Little-Parks effects, may result in robust zero-bias peaks—features that could be easily misinterpreted as originating from Majorana zero modes but are unrelated to topological superconductivity.}, author = {Valentini, Marco and Peñaranda, Fernando and Hofmann, Andrea C and Brauns, Matthias and Hauschild, Robert and Krogstrup, Peter and San-Jose, Pablo and Prada, Elsa and Aguado, Ramón and Katsaros, Georgios}, issn = {10959203}, journal = {Science}, number = {6550}, publisher = {American Association for the Advancement of Science}, title = {{Nontopological zero-bias peaks in full-shell nanowires induced by flux-tunable Andreev states}}, doi = {10.1126/science.abf1513}, volume = {373}, year = {2021}, } @misc{10110, abstract = {Pattern separation is a fundamental brain computation that converts small differences in input patterns into large differences in output patterns. Several synaptic mechanisms of pattern separation have been proposed, including code expansion, inhibition and plasticity; however, which of these mechanisms play a role in the entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation circuit, remains unclear. Here we show that a biologically realistic, full-scale EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator. Both external gamma-modulated inhibition and internal lateral inhibition mediated by PV+-INs substantially contributed to pattern separation. Both local connectivity and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness. Similarly, mossy fiber synapses with conditional detonator properties contributed to pattern separation. By contrast, perforant path synapses with Hebbian synaptic plasticity and direct EC–CA3 connection shifted the network towards pattern completion. Our results demonstrate that the specific properties of cells and synapses optimize higher-order computations in biological networks and might be useful to improve the deep learning capabilities of technical networks.}, author = {Guzmán, José and Schlögl, Alois and Espinoza Martinez, Claudia and Zhang, Xiaomin and Suter, Benjamin and Jonas, Peter M}, publisher = {IST Austria}, title = {{How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network}}, doi = {10.15479/AT:ISTA:10110}, year = {2021}, } @article{9429, abstract = {De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs.}, author = {Morandell, Jasmin and Schwarz, Lena A and Basilico, Bernadette and Tasciyan, Saren and Dimchev, Georgi A and Nicolas, Armel and Sommer, Christoph M and Kreuzinger, Caroline and Dotter, Christoph and Knaus, Lisa and Dobler, Zoe and Cacci, Emanuele and Schur, Florian KM and Danzl, Johann G and Novarino, Gaia}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {1}, publisher = {Springer Nature}, title = {{Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development}}, doi = {10.1038/s41467-021-23123-x}, volume = {12}, year = {2021}, } @article{8909, abstract = {Spin qubits are considered to be among the most promising candidates for building a quantum processor. Group IV hole spin qubits have moved into the focus of interest due to the ease of operation and compatibility with Si technology. In addition, Ge offers the option for monolithic superconductor-semiconductor integration. Here we demonstrate a hole spin qubit operating at fields below 10 mT, the critical field of Al, by exploiting the large out-of-plane hole g-factors in planar Ge and by encoding the qubit into the singlet-triplet states of a double quantum dot. We observe electrically controlled X and Z-rotations with tunable frequencies exceeding 100 MHz and dephasing times of 1μs which we extend beyond 15μs with echo techniques. These results show that Ge hole singlet triplet qubits outperform their electronic Si and GaAs based counterparts in speed and coherence, respectively. In addition, they are on par with Ge single spin qubits, but can be operated at much lower fields underlining their potential for on chip integration with superconducting technologies.}, author = {Jirovec, Daniel and Hofmann, Andrea C and Ballabio, Andrea and Mutter, Philipp M. and Tavani, Giulio and Botifoll, Marc and Crippa, Alessandro and Kukucka, Josip and Sagi, Oliver and Martins, Frederico and Saez Mollejo, Jaime and Prieto Gonzalez, Ivan and Borovkov, Maksim and Arbiol, Jordi and Chrastina, Daniel and Isella, Giovanni and Katsaros, Georgios}, issn = {1476-4660}, journal = {Nature Materials}, number = {8}, pages = {1106–1112}, publisher = {Springer Nature}, title = {{A singlet triplet hole spin qubit in planar Ge}}, doi = {10.1038/s41563-021-01022-2}, volume = {20}, year = {2021}, } @inbook{9756, abstract = {High-resolution visualization and quantification of membrane proteins contribute to the understanding of their functions and the roles they play in physiological and pathological conditions. Sodium dodecyl sulfate-digested freeze-fracture replica labeling (SDS-FRL) is a powerful electron microscopy method to study quantitatively the two-dimensional distribution of transmembrane proteins and their tightly associated proteins. During treatment with SDS, intracellular organelles and proteins not anchored to the replica are dissolved, whereas integral membrane proteins captured and stabilized by carbon/platinum deposition remain on the replica. Their intra- and extracellular domains become exposed on the surface of the replica, facilitating the accessibility of antibodies and, therefore, providing higher labeling efficiency than those obtained with other immunoelectron microscopy techniques. In this chapter, we describe the protocols of SDS-FRL adapted for mammalian brain samples, and optimization of the SDS treatment to increase the labeling efficiency for quantification of Cav2.1, the alpha subunit of P/Q-type voltage-dependent calcium channels utilizing deep learning algorithms.}, author = {Kaufmann, Walter and Kleindienst, David and Harada, Harumi and Shigemoto, Ryuichi}, booktitle = { Receptor and Ion Channel Detection in the Brain}, isbn = {9781071615218}, keywords = {Freeze-fracture replica: Deep learning, Immunogold labeling, Integral membrane protein, Electron microscopy}, pages = {267--283}, publisher = {Humana}, title = {{High-Resolution localization and quantitation of membrane proteins by SDS-digested freeze-fracture replica labeling (SDS-FRL)}}, doi = {10.1007/978-1-0716-1522-5_19}, volume = {169}, year = {2021}, } @article{8931, abstract = {Auxin is a major plant growth regulator, but current models on auxin perception and signaling cannot explain the whole plethora of auxin effects, in particular those associated with rapid responses. A possible candidate for a component of additional auxin perception mechanisms is the AUXIN BINDING PROTEIN 1 (ABP1), whose function in planta remains unclear. Here we combined expression analysis with gain- and loss-of-function approaches to analyze the role of ABP1 in plant development. ABP1 shows a broad expression largely overlapping with, but not regulated by, transcriptional auxin response activity. Furthermore, ABP1 activity is not essential for the transcriptional auxin signaling. Genetic in planta analysis revealed that abp1 loss-of-function mutants show largely normal development with minor defects in bolting. On the other hand, ABP1 gain-of-function alleles show a broad range of growth and developmental defects, including root and hypocotyl growth and bending, lateral root and leaf development, bolting, as well as response to heat stress. At the cellular level, ABP1 gain-of-function leads to impaired auxin effect on PIN polar distribution and affects BFA-sensitive PIN intracellular aggregation. The gain-of-function analysis suggests a broad, but still mechanistically unclear involvement of ABP1 in plant development, possibly masked in abp1 loss-of-function mutants by a functional redundancy.}, author = {Gelová, Zuzana and Gallei, Michelle C and Pernisová, Markéta and Brunoud, Géraldine and Zhang, Xixi and Glanc, Matous and Li, Lanxin and Michalko, Jaroslav and Pavlovicova, Zlata and Verstraeten, Inge and Han, Huibin and Hajny, Jakub and Hauschild, Robert and Čovanová, Milada and Zwiewka, Marta and Hörmayer, Lukas and Fendrych, Matyas and Xu, Tongda and Vernoux, Teva and Friml, Jiří}, issn = {0168-9452}, journal = {Plant Science}, keywords = {Agronomy and Crop Science, Plant Science, Genetics, General Medicine}, publisher = {Elsevier}, title = {{Developmental roles of auxin binding protein 1 in Arabidopsis thaliana}}, doi = {10.1016/j.plantsci.2020.110750}, volume = {303}, year = {2021}, } @unpublished{10095, abstract = {Growth regulation tailors plant development to its environment. A showcase is response to gravity, where shoots bend up and roots down1. This paradox is based on opposite effects of the phytohormone auxin, which promotes cell expansion in shoots, while inhibiting it in roots via a yet unknown cellular mechanism2. Here, by combining microfluidics, live imaging, genetic engineering and phospho-proteomics in Arabidopsis thaliana, we advance our understanding how auxin inhibits root growth. We show that auxin activates two distinct, antagonistically acting signalling pathways that converge on the rapid regulation of the apoplastic pH, a causative growth determinant. Cell surface-based TRANSMEMBRANE KINASE1 (TMK1) interacts with and mediates phosphorylation and activation of plasma membrane H+-ATPases for apoplast acidification, while intracellular canonical auxin signalling promotes net cellular H+-influx, causing apoplast alkalinisation. The simultaneous activation of these two counteracting mechanisms poises the root for a rapid, fine-tuned growth modulation while navigating complex soil environment.}, author = {Li, Lanxin and Verstraeten, Inge and Roosjen, Mark and Takahashi, Koji and Rodriguez Solovey, Lesia and Merrin, Jack and Chen, Jian and Shabala, Lana and Smet, Wouter and Ren, Hong and Vanneste, Steffen and Shabala, Sergey and De Rybel, Bert and Weijers, Dolf and Kinoshita, Toshinori and Gray, William M. and Friml, Jiří}, booktitle = {Research Square}, issn = {2693-5015}, title = {{Cell surface and intracellular auxin signalling for H+-fluxes in root growth}}, doi = {10.21203/rs.3.rs-266395/v3}, year = {2021}, } @misc{8181, author = {Hauschild, Robert}, publisher = {IST Austria}, title = {{Amplified centrosomes in dendritic cells promote immune cell effector functions}}, doi = {10.15479/AT:ISTA:8181}, year = {2020}, } @misc{8294, abstract = {Automated root growth analysis and tracking of root tips. }, author = {Hauschild, Robert}, publisher = {IST Austria}, title = {{RGtracker}}, doi = {10.15479/AT:ISTA:8294}, year = {2020}, } @techreport{8695, abstract = {A look at international activities on Open Science reveals a broad spectrum from individual institutional policies to national action plans. The present Recommendations for a National Open Science Strategy in Austria are based on these international initiatives and present practical considerations for their coordinated implementation with regard to strategic developments in research, technology and innovation (RTI) in Austria until 2030. They are addressed to all relevant actors in the RTI system, in particular to Research Performing Organisations, Research Funding Organisations, Research Policy, memory institutions such as Libraries and Researchers. The recommendation paper was developed from 2018 to 2020 by the OANA working group "Open Science Strategy" and published for the first time in spring 2020 for a public consultation. The now available final version of the recommendation document, which contains feedback and comments from the consultation, is intended to provide an impetus for further discussion and implementation of Open Science in Austria and serves as a contribution and basis for a potential national Open Science Strategy in Austria. The document builds on the diverse expertise of the authors (academia, administration, library and archive, information technology, science policy, funding system, etc.) and reflects their personal experiences and opinions.}, author = {Mayer, Katja and Rieck, Katharina and Reichmann, Stefan and Danowski, Patrick and Graschopf, Anton and König, Thomas and Kraker, Peter and Lehner, Patrick and Reckling, Falk and Ross-Hellauer, Tony and Spichtinger, Daniel and Tzatzanis, Michalis and Schürz, Stefanie}, pages = {36}, publisher = {OANA}, title = {{Empfehlungen für eine nationale Open Science Strategie in Österreich / Recommendations for a National Open Science Strategy in Austria}}, doi = {10.5281/ZENODO.4109242}, year = {2020}, } @article{8706, abstract = {As part of the Austrian Transition to Open Access (AT2OA) project, subproject TP1-B is working on designing a monitoring solution for the output of Open Access publications in Austria. This report on a potential Open Access monitoring approach in Austria is one of the results of these efforts and can serve as a basis for discussion on an international level.}, author = {Danowski, Patrick and Ferus, Andreas and Hikl, Anna-Laetitia and McNeill, Gerda and Miniberger, Clemens and Reding, Steve and Zarka, Tobias and Zojer, Michael}, issn = {10222588}, journal = {Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare}, number = {2}, pages = {278--284}, publisher = {Vereinigung Osterreichischer Bibliothekarinnen und Bibliothekare}, title = {{„Recommendation“ for the further procedure for open access monitoring. Deliverable of the AT2OA subproject TP1-B}}, doi = {10.31263/voebm.v73i2.3941}, volume = {73}, year = {2020}, } @book{7474, abstract = {This booklet is a collection of abstracts presented at the AHPC conference.}, editor = {Schlögl, Alois and Kiss, Janos and Elefante, Stefano}, isbn = {978-3-99078-004-6}, location = {Klosterneuburg, Austria}, pages = {72}, publisher = {IST Austria}, title = {{Austrian High-Performance-Computing meeting (AHPC2020)}}, doi = {10.15479/AT:ISTA:7474}, year = {2020}, } @article{7490, abstract = {In plants, clathrin mediated endocytosis (CME) represents the major route for cargo internalisation from the cell surface. It has been assumed to operate in an evolutionary conserved manner as in yeast and animals. Here we report characterisation of ultrastructure, dynamics and mechanisms of plant CME as allowed by our advancement in electron microscopy and quantitative live imaging techniques. Arabidopsis CME appears to follow the constant curvature model and the bona fide CME population generates vesicles of a predominantly hexagonal-basket type; larger and with faster kinetics than in other models. Contrary to the existing paradigm, actin is dispensable for CME events at the plasma membrane but plays a unique role in collecting endocytic vesicles, sorting of internalised cargos and directional endosome movement that itself actively promote CME events. Internalized vesicles display a strongly delayed and sequential uncoating. These unique features highlight the independent evolution of the plant CME mechanism during the autonomous rise of multicellularity in eukaryotes.}, author = {Narasimhan, Madhumitha and Johnson, Alexander J and Prizak, Roshan and Kaufmann, Walter and Tan, Shutang and Casillas Perez, Barbara E and Friml, Jiří}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants}}, doi = {10.7554/eLife.52067}, volume = {9}, year = {2020}, } @article{7792, abstract = {Phonon polaritons—light coupled to lattice vibrations—in polar van der Waals crystals are promising candidates for controlling the flow of energy on the nanoscale due to their strong field confinement, anisotropic propagation and ultra-long lifetime in the picosecond range1,2,3,4,5. However, the lack of tunability of their narrow and material-specific spectral range—the Reststrahlen band—severely limits their technological implementation. Here, we demonstrate that intercalation of Na atoms in the van der Waals semiconductor α-V2O5 enables a broad spectral shift of Reststrahlen bands, and that the phonon polaritons excited show ultra-low losses (lifetime of 4 ± 1 ps), similar to phonon polaritons in a non-intercalated crystal (lifetime of 6 ± 1 ps). We expect our intercalation method to be applicable to other van der Waals crystals, opening the door for the use of phonon polaritons in broad spectral bands in the mid-infrared domain.}, author = {Taboada-Gutiérrez, Javier and Álvarez-Pérez, Gonzalo and Duan, Jiahua and Ma, Weiliang and Crowley, Kyle and Prieto Gonzalez, Ivan and Bylinkin, Andrei and Autore, Marta and Volkova, Halyna and Kimura, Kenta and Kimura, Tsuyoshi and Berger, M. H. and Li, Shaojuan and Bao, Qiaoliang and Gao, Xuan P.A. and Errea, Ion and Nikitin, Alexey Y. and Hillenbrand, Rainer and Martín-Sánchez, Javier and Alonso-González, Pablo}, issn = {14764660}, journal = {Nature Materials}, pages = {964–968}, publisher = {Springer Nature}, title = {{Broad spectral tuning of ultra-low-loss polaritons in a van der Waals crystal by intercalation}}, doi = {10.1038/s41563-020-0665-0}, volume = {19}, year = {2020}, } @article{7875, abstract = {Cells navigating through complex tissues face a fundamental challenge: while multiple protrusions explore different paths, the cell needs to avoid entanglement. How a cell surveys and then corrects its own shape is poorly understood. Here, we demonstrate that spatially distinct microtubule dynamics regulate amoeboid cell migration by locally promoting the retraction of protrusions. In migrating dendritic cells, local microtubule depolymerization within protrusions remote from the microtubule organizing center triggers actomyosin contractility controlled by RhoA and its exchange factor Lfc. Depletion of Lfc leads to aberrant myosin localization, thereby causing two effects that rate-limit locomotion: (1) impaired cell edge coordination during path finding and (2) defective adhesion resolution. Compromised shape control is particularly hindering in geometrically complex microenvironments, where it leads to entanglement and ultimately fragmentation of the cell body. We thus demonstrate that microtubules can act as a proprioceptive device: they sense cell shape and control actomyosin retraction to sustain cellular coherence.}, author = {Kopf, Aglaja and Renkawitz, Jörg and Hauschild, Robert and Girkontaite, Irute and Tedford, Kerry and Merrin, Jack and Thorn-Seshold, Oliver and Trauner, Dirk and Häcker, Hans and Fischer, Klaus Dieter and Kiermaier, Eva and Sixt, Michael K}, issn = {1540-8140}, journal = {The Journal of Cell Biology}, number = {6}, publisher = {Rockefeller University Press}, title = {{Microtubules control cellular shape and coherence in amoeboid migrating cells}}, doi = {10.1083/jcb.201907154}, volume = {219}, year = {2020}, } @article{7888, abstract = {Embryonic stem cell cultures are thought to self-organize into embryoid bodies, able to undergo symmetry-breaking, germ layer specification and even morphogenesis. Yet, it is unclear how to reconcile this remarkable self-organization capacity with classical experiments demonstrating key roles for extrinsic biases by maternal factors and/or extraembryonic tissues in embryogenesis. Here, we show that zebrafish embryonic tissue explants, prepared prior to germ layer induction and lacking extraembryonic tissues, can specify all germ layers and form a seemingly complete mesendoderm anlage. Importantly, explant organization requires polarized inheritance of maternal factors from dorsal-marginal regions of the blastoderm. Moreover, induction of endoderm and head-mesoderm, which require peak Nodal-signaling levels, is highly variable in explants, reminiscent of embryos with reduced Nodal signals from the extraembryonic tissues. Together, these data suggest that zebrafish explants do not undergo bona fide self-organization, but rather display features of genetically encoded self-assembly, where intrinsic genetic programs control the emergence of order.}, author = {Schauer, Alexandra and Nunes Pinheiro, Diana C and Hauschild, Robert and Heisenberg, Carl-Philipp J}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Zebrafish embryonic explants undergo genetically encoded self-assembly}}, doi = {10.7554/elife.55190}, volume = {9}, year = {2020}, } @article{7864, abstract = {Purpose of review: Cancer is one of the leading causes of death and the incidence rates are constantly rising. The heterogeneity of tumors poses a big challenge for the treatment of the disease and natural antibodies additionally affect disease progression. The introduction of engineered mAbs for anticancer immunotherapies has substantially improved progression-free and overall survival of cancer patients, but little efforts have been made to exploit other antibody isotypes than IgG. Recent findings: In order to improve these therapies, ‘next-generation antibodies’ were engineered to enhance a specific feature of classical antibodies and form a group of highly effective and precise therapy compounds. Advanced antibody approaches include among others antibody-drug conjugates, glyco-engineered and Fc-engineered antibodies, antibody fragments, radioimmunotherapy compounds, bispecific antibodies and alternative (non-IgG) immunoglobulin classes, especially IgE. Summary: The current review describes solutions for the needs of next-generation antibody therapies through different approaches. Careful selection of the best-suited engineering methodology is a key factor in developing personalized, more specific and more efficient mAbs against cancer to improve the outcomes of cancer patients. We highlight here the large evidence of IgE exploiting a highly cytotoxic effector arm as potential next-generation anticancer immunotherapy.}, author = {Singer, Judit and Singer, Josef and Jensen-Jarolim, Erika}, issn = {14736322}, journal = {Current opinion in allergy and clinical immunology}, number = {3}, pages = {282--289}, publisher = {Wolters Kluwer}, title = {{Precision medicine in clinical oncology: the journey from IgG antibody to IgE}}, doi = {10.1097/ACI.0000000000000637}, volume = {20}, year = {2020}, } @article{8261, abstract = {Dentate gyrus granule cells (GCs) connect the entorhinal cortex to the hippocampal CA3 region, but how they process spatial information remains enigmatic. To examine the role of GCs in spatial coding, we measured excitatory postsynaptic potentials (EPSPs) and action potentials (APs) in head-fixed mice running on a linear belt. Intracellular recording from morphologically identified GCs revealed that most cells were active, but activity level varied over a wide range. Whereas only ∼5% of GCs showed spatially tuned spiking, ∼50% received spatially tuned input. Thus, the GC population broadly encodes spatial information, but only a subset relays this information to the CA3 network. Fourier analysis indicated that GCs received conjunctive place-grid-like synaptic input, suggesting code conversion in single neurons. GC firing was correlated with dendritic complexity and intrinsic excitability, but not extrinsic excitatory input or dendritic cable properties. Thus, functional maturation may control input-output transformation and spatial code conversion.}, author = {Zhang, Xiaomin and Schlögl, Alois and Jonas, Peter M}, issn = {0896-6273}, journal = {Neuron}, number = {6}, pages = {1212--1225}, publisher = {Elsevier}, title = {{Selective routing of spatial information flow from input to output in hippocampal granule cells}}, doi = {10.1016/j.neuron.2020.07.006}, volume = {107}, year = {2020}, } @article{8597, abstract = {Error analysis and data visualization of positive COVID-19 cases in 27 countries have been performed up to August 8, 2020. This survey generally observes a progression from early exponential growth transitioning to an intermediate power-law growth phase, as recently suggested by Ziff and Ziff. The occurrence of logistic growth after the power-law phase with lockdowns or social distancing may be described as an effect of avoidance. A visualization of the power-law growth exponent over short time windows is qualitatively similar to the Bhatia visualization for pandemic progression. Visualizations like these can indicate the onset of second waves and may influence social policy.}, author = {Merrin, Jack}, issn = {14783975}, journal = {Physical Biology}, number = {6}, publisher = {IOP Publishing}, title = {{Differences in power law growth over time and indicators of COVID-19 pandemic progression worldwide}}, doi = {10.1088/1478-3975/abb2db}, volume = {17}, year = {2020}, } @article{8744, abstract = {Understanding the conformational sampling of translation-arrested ribosome nascent chain complexes is key to understand co-translational folding. Up to now, coupling of cysteine oxidation, disulfide bond formation and structure formation in nascent chains has remained elusive. Here, we investigate the eye-lens protein γB-crystallin in the ribosomal exit tunnel. Using mass spectrometry, theoretical simulations, dynamic nuclear polarization-enhanced solid-state nuclear magnetic resonance and cryo-electron microscopy, we show that thiol groups of cysteine residues undergo S-glutathionylation and S-nitrosylation and form non-native disulfide bonds. Thus, covalent modification chemistry occurs already prior to nascent chain release as the ribosome exit tunnel provides sufficient space even for disulfide bond formation which can guide protein folding.}, author = {Schulte, Linda and Mao, Jiafei and Reitz, Julian and Sreeramulu, Sridhar and Kudlinzki, Denis and Hodirnau, Victor-Valentin and Meier-Credo, Jakob and Saxena, Krishna and Buhr, Florian and Langer, Julian D. and Blackledge, Martin and Frangakis, Achilleas S. and Glaubitz, Clemens and Schwalbe, Harald}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry}, publisher = {Springer Nature}, title = {{Cysteine oxidation and disulfide formation in the ribosomal exit tunnel}}, doi = {10.1038/s41467-020-19372-x}, volume = {11}, year = {2020}, } @article{8787, abstract = {Breakdown of vascular barriers is a major complication of inflammatory diseases. Anucleate platelets form blood-clots during thrombosis, but also play a crucial role in inflammation. While spatio-temporal dynamics of clot formation are well characterized, the cell-biological mechanisms of platelet recruitment to inflammatory micro-environments remain incompletely understood. Here we identify Arp2/3-dependent lamellipodia formation as a prominent morphological feature of immune-responsive platelets. Platelets use lamellipodia to scan for fibrin(ogen) deposited on the inflamed vasculature and to directionally spread, to polarize and to govern haptotactic migration along gradients of the adhesive ligand. Platelet-specific abrogation of Arp2/3 interferes with haptotactic repositioning of platelets to microlesions, thus impairing vascular sealing and provoking inflammatory microbleeding. During infection, haptotaxis promotes capture of bacteria and prevents hematogenic dissemination, rendering platelets gate-keepers of the inflamed microvasculature. Consequently, these findings identify haptotaxis as a key effector function of immune-responsive platelets.}, author = {Nicolai, Leo and Schiefelbein, Karin and Lipsky, Silvia and Leunig, Alexander and Hoffknecht, Marie and Pekayvaz, Kami and Raude, Ben and Marx, Charlotte and Ehrlich, Andreas and Pircher, Joachim and Zhang, Zhe and Saleh, Inas and Marel, Anna-Kristina and Löf, Achim and Petzold, Tobias and Lorenz, Michael and Stark, Konstantin and Pick, Robert and Rosenberger, Gerhild and Weckbach, Ludwig and Uhl, Bernd and Xia, Sheng and Reichel, Christoph Andreas and Walzog, Barbara and Schulz, Christian and Zheden, Vanessa and Bender, Markus and Li, Rong and Massberg, Steffen and Gärtner, Florian R}, issn = {20411723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Vascular surveillance by haptotactic blood platelets in inflammation and infection}}, doi = {10.1038/s41467-020-19515-0}, volume = {11}, year = {2020}, } @article{8971, abstract = {The actin-related protein (Arp)2/3 complex nucleates branched actin filament networks pivotal for cell migration, endocytosis and pathogen infection. Its activation is tightly regulated and involves complex structural rearrangements and actin filament binding, which are yet to be understood. Here, we report a 9.0 Å resolution structure of the actin filament Arp2/3 complex branch junction in cells using cryo-electron tomography and subtomogram averaging. This allows us to generate an accurate model of the active Arp2/3 complex in the branch junction and its interaction with actin filaments. Notably, our model reveals a previously undescribed set of interactions of the Arp2/3 complex with the mother filament, significantly different to the previous branch junction model. Our structure also indicates a central role for the ArpC3 subunit in stabilizing the active conformation.}, author = {Fäßler, Florian and Dimchev, Georgi A and Hodirnau, Victor-Valentin and Wan, William and Schur, Florian KM}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry}, publisher = {Springer Nature}, title = {{Cryo-electron tomography structure of Arp2/3 complex in cells reveals new insights into the branch junction}}, doi = {10.1038/s41467-020-20286-x}, volume = {11}, year = {2020}, } @article{10866, abstract = {Recent discoveries have shown that, when two layers of van der Waals (vdW) materials are superimposed with a relative twist angle between them, the electronic properties of the coupled system can be dramatically altered. Here, we demonstrate that a similar concept can be extended to the optics realm, particularly to propagating phonon polaritons–hybrid light-matter interactions. To do this, we fabricate stacks composed of two twisted slabs of a vdW crystal (α-MoO3) supporting anisotropic phonon polaritons (PhPs), and image the propagation of the latter when launched by localized sources. Our images reveal that, under a critical angle, the PhPs isofrequency curve undergoes a topological transition, in which the propagation of PhPs is strongly guided (canalization regime) along predetermined directions without geometric spreading. These results demonstrate a new degree of freedom (twist angle) for controlling the propagation of polaritons at the nanoscale with potential for nanoimaging, (bio)-sensing, or heat management.}, author = {Duan, Jiahua and Capote-Robayna, Nathaniel and Taboada-Gutiérrez, Javier and Álvarez-Pérez, Gonzalo and Prieto Gonzalez, Ivan and Martín-Sánchez, Javier and Nikitin, Alexey Y. and Alonso-González, Pablo}, issn = {1530-6992}, journal = {Nano Letters}, keywords = {Mechanical Engineering, Condensed Matter Physics, General Materials Science, General Chemistry, Bioengineering}, number = {7}, pages = {5323--5329}, publisher = {American Chemical Society}, title = {{Twisted nano-optics: Manipulating light at the nanoscale with twisted phonon polaritonic slabs}}, doi = {10.1021/acs.nanolett.0c01673}, volume = {20}, year = {2020}, } @article{7687, abstract = {A working group, which was established within the Network of Repository Managers (RepManNet), has dealt with common certifications for repositories. In addition, current requirements of the research funding agencies FWF and EU were also taken into account. The Core Trust Seal was examined in more detail. For this purpose, a questionnaire was sent to those organizations that are already certified with CTS in Austria. The answers were summarized and evaluated anonymously. It is recommended to go for a repository certification. Moreover, the development of a DINI certificate in Austria is strongly suggested.}, author = {Ernst, Doris and Novotny, Gertraud and Schönher, Eva Maria}, issn = {1022-2588}, journal = {Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare}, number = {1}, pages = {46--59}, publisher = {Vereinigung Osterreichischer Bibliothekarinnen und Bibliothekare}, title = {{(Core Trust) Seal your repository!}}, doi = {10.31263/voebm.v73i1.3491}, volume = {73}, year = {2020}, } @unpublished{7800, abstract = {De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). Here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 haploinsufficient mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3 mutant brain displays cortical lamination abnormalities due to defective neuronal migration and reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal columnar organization, Cul3 haploinsufficiency is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level, employing a quantitative proteomic approach, we show that Cul3 regulates cytoskeletal and adhesion protein abundance in mouse embryos. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neuronal cells results in atypical organization of the actin mesh at the cell leading edge, likely causing the observed migration deficits. In contrast to these important functions early in development, Cul3 deficiency appears less relevant at adult stages. In fact, induction of Cul3 haploinsufficiency in adult mice does not result in the behavioral defects observed in constitutive Cul3 haploinsufficient animals. Taken together, our data indicate that Cul3 has a critical role in the regulation of cytoskeletal proteins and neuronal migration and that ASD-associated defects and behavioral abnormalities are primarily due to Cul3 functions at early developmental stages.}, author = {Morandell, Jasmin and Schwarz, Lena A and Basilico, Bernadette and Tasciyan, Saren and Nicolas, Armel and Sommer, Christoph M and Kreuzinger, Caroline and Knaus, Lisa and Dobler, Zoe and Cacci, Emanuele and Danzl, Johann G and Novarino, Gaia}, booktitle = {bioRxiv}, publisher = {Cold Spring Harbor Laboratory}, title = {{Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development}}, doi = {10.1101/2020.01.10.902064 }, year = {2020}, } @unpublished{9750, abstract = {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 grow1,2. 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. Once 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.}, author = {Slovakova, Jana and Sikora, Mateusz K and Caballero Mancebo, Silvia and Krens, Gabriel and Kaufmann, Walter and Huljev, Karla and Heisenberg, Carl-Philipp J}, booktitle = {bioRxiv}, pages = {41}, publisher = {Cold Spring Harbor Laboratory}, title = {{Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion}}, doi = {10.1101/2020.11.20.391284}, year = {2020}, } @article{7885, abstract = {Eukaryotic cells migrate by coupling the intracellular force of the actin cytoskeleton to the environment. While force coupling is usually mediated by transmembrane adhesion receptors, especially those of the integrin family, amoeboid cells such as leukocytes can migrate extremely fast despite very low adhesive forces1. Here we show that leukocytes cannot only migrate under low adhesion but can also transmit forces in the complete absence of transmembrane force coupling. When confined within three-dimensional environments, they use the topographical features of the substrate to propel themselves. Here the retrograde flow of the actin cytoskeleton follows the texture of the substrate, creating retrograde shear forces that are sufficient to drive the cell body forwards. Notably, adhesion-dependent and adhesion-independent migration are not mutually exclusive, but rather are variants of the same principle of coupling retrograde actin flow to the environment and thus can potentially operate interchangeably and simultaneously. As adhesion-free migration is independent of the chemical composition of the environment, it renders cells completely autonomous in their locomotive behaviour.}, author = {Reversat, Anne and Gärtner, Florian R and Merrin, Jack and Stopp, Julian A and Tasciyan, Saren and Aguilera Servin, Juan L and De Vries, Ingrid and Hauschild, Robert and Hons, Miroslav and Piel, Matthieu and Callan-Jones, Andrew and Voituriez, Raphael and Sixt, Michael K}, issn = {14764687}, journal = {Nature}, pages = {582–585}, publisher = {Springer Nature}, title = {{Cellular locomotion using environmental topography}}, doi = {10.1038/s41586-020-2283-z}, volume = {582}, year = {2020}, } @article{8139, abstract = {Clathrin-mediated endocytosis (CME) is a crucial cellular process implicated in many aspects of plant growth, development, intra- and inter-cellular signaling, nutrient uptake and pathogen defense. Despite these significant roles, little is known about the precise molecular details of how it functions in planta. In order to facilitate the direct quantitative study of plant CME, here we review current routinely used methods and present refined, standardized quantitative imaging protocols which allow the detailed characterization of CME at multiple scales in plant tissues. These include: (i) an efficient electron microscopy protocol for the imaging of Arabidopsis CME vesicles in situ, thus providing a method for the detailed characterization of the ultra-structure of clathrin-coated vesicles; (ii) a detailed protocol and analysis for quantitative live-cell fluorescence microscopy to precisely examine the temporal interplay of endocytosis components during single CME events; (iii) a semi-automated analysis to allow the quantitative characterization of global internalization of cargos in whole plant tissues; and (iv) an overview and validation of useful genetic and pharmacological tools to interrogate the molecular mechanisms and function of CME in intact plant samples.}, author = {Johnson, Alexander J and Gnyliukh, Nataliia and Kaufmann, Walter and Narasimhan, Madhumitha and Vert, G and Bednarek, SY and Friml, Jiří}, issn = {1477-9137}, journal = {Journal of Cell Science}, number = {15}, publisher = {The Company of Biologists}, title = {{Experimental toolbox for quantitative evaluation of clathrin-mediated endocytosis in the plant model Arabidopsis}}, doi = {10.1242/jcs.248062}, volume = {133}, year = {2020}, } @article{6819, abstract = {Glyphosate (N-phosphonomethyl glycine) and its commercial herbicide formulations have been shown to exert toxicity via various mechanisms. It has been asserted that glyphosate substitutes for glycine in polypeptide chains leading to protein misfolding and toxicity. However, as no direct evidence exists for glycine to glyphosate substitution in proteins, including in mammalian organisms, we tested this claim by conducting a proteomics analysis of MDA-MB-231 human breast cancer cells grown in the presence of 100 mg/L glyphosate for 6 days. Protein extracts from three treated and three untreated cell cultures were analysed as one TMT-6plex labelled sample, to highlight a specific pattern (+/+/+/−/−/−) of reporter intensities for peptides bearing true glyphosate treatment induced-post translational modifications as well as allowing an investigation of the total proteome.}, author = {Antoniou, Michael N. and Nicolas, Armel and Mesnage, Robin and Biserni, Martina and Rao, Francesco V. and Martin, Cristina Vazquez}, issn = {1756-0500}, journal = {BMC Research Notes}, publisher = {BioMed Central}, title = {{Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells}}, doi = {10.1186/s13104-019-4534-3}, volume = {12}, year = {2019}, } @misc{9784, abstract = {Additional file 1: Table S1. Kinetics of MDA-MB-231 cell growth in either the presence or absence of 100Â mg/L glyphosate. Cell counts are given at day-1 of seeding flasks and following 6-days of continuous culture. Note: no differences in cell numbers were observed between negative control and glyphosate treated cultures.}, author = {Antoniou, Michael N. and Nicolas, Armel and Mesnage, Robin and Biserni, Martina and Rao, Francesco V. and Martin, Cristina Vazquez}, publisher = {Springer Nature}, title = {{MOESM1 of Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells}}, doi = {10.6084/m9.figshare.9411761.v1}, year = {2019}, } @inproceedings{12901, author = {Schlögl, Alois and Kiss, Janos and Elefante, Stefano}, booktitle = {AHPC19 - Austrian HPC Meeting 2019 }, location = {Grundlsee, Austria}, pages = {25}, publisher = {Institut für Mathematik und wissenschaftliches Rechnen der Universität Graz}, title = {{Is Debian suitable for running an HPC Cluster?}}, year = {2019}, } @article{6052, abstract = {Expansion microscopy is a relatively new approach to super-resolution imaging that uses expandable hydrogels to isotropically increase the physical distance between fluorophores in biological samples such as cell cultures or tissue slices. The classic gel recipe results in an expansion factor of ~4×, with a resolution of 60–80 nm. We have recently developed X10 microscopy, which uses a gel that achieves an expansion factor of ~10×, with a resolution of ~25 nm. Here, we provide a step-by-step protocol for X10 expansion microscopy. A typical experiment consists of seven sequential stages: (i) immunostaining, (ii) anchoring, (iii) polymerization, (iv) homogenization, (v) expansion, (vi) imaging, and (vii) validation. The protocol presented here includes recommendations for optimization, pitfalls and their solutions, and detailed guidelines that should increase reproducibility. Although our protocol focuses on X10 expansion microscopy, we detail which of these suggestions are also applicable to classic fourfold expansion microscopy. We exemplify our protocol using primary hippocampal neurons from rats, but our approach can be used with other primary cells or cultured cell lines of interest. This protocol will enable any researcher with basic experience in immunostainings and access to an epifluorescence microscope to perform super-resolution microscopy with X10. The procedure takes 3 d and requires ~5 h of actively handling the sample for labeling and expansion, and another ~3 h for imaging and analysis.}, author = {Truckenbrodt, Sven M and Sommer, Christoph M and Rizzoli, Silvio O and Danzl, Johann G}, journal = {Nature Protocols}, number = {3}, pages = {832–863}, publisher = {Nature Publishing Group}, title = {{A practical guide to optimization in X10 expansion microscopy}}, doi = {10.1038/s41596-018-0117-3}, volume = {14}, year = {2019}, } @article{6087, abstract = {Cell fate specification by lateral inhibition typically involves contact signaling through the Delta-Notch signaling pathway. However, whether this is the only signaling mode mediating lateral inhibition remains unclear. Here we show that in zebrafish oogenesis, a group of cells within the granulosa cell layer at the oocyte animal pole acquire elevated levels of the transcriptional coactivator TAZ in their nuclei. One of these cells, the future micropyle precursor cell (MPC), accumulates increasingly high levels of nuclear TAZ and grows faster than its surrounding cells, mechanically compressing those cells, which ultimately lose TAZ from their nuclei. Strikingly, relieving neighbor-cell compression by MPC ablation or aspiration restores nuclear TAZ accumulation in neighboring cells, eventually leading to MPC re-specification from these cells. Conversely, MPC specification is defective in taz−/− follicles. These findings uncover a novel mode of lateral inhibition in cell fate specification based on mechanical signals controlling TAZ activity.}, author = {Xia, Peng and Gütl, Daniel J and Zheden, Vanessa and Heisenberg, Carl-Philipp J}, journal = {Cell}, number = {6}, pages = {1379--1392.e14}, publisher = {Elsevier}, title = {{Lateral inhibition in cell specification mediated by mechanical signals modulating TAZ activity}}, doi = {10.1016/j.cell.2019.01.019}, volume = {176}, year = {2019}, } @article{6607, abstract = {Acute myeloid leukemia (AML) is a heterogeneous disease with respect to its genetic and molecular basis and to patients´ outcome. Clinical, cytogenetic, and mutational data are used to classify patients into risk groups with different survival, however, within-group heterogeneity is still an issue. Here, we used a robust likelihood-based survival modeling approach and publicly available gene expression data to identify a minimal number of genes whose combined expression values were prognostic of overall survival. The resulting gene expression signature (4-GES) consisted of 4 genes (SOCS2, IL2RA, NPDC1, PHGDH), predicted patient survival as an independent prognostic parameter in several cohorts of AML patients (total, 1272 patients), and further refined prognostication based on the European Leukemia Net classification. An oncogenic role of the top scoring gene in this signature, SOCS2, was investigated using MLL-AF9 and Flt3-ITD/NPM1c driven mouse models of AML. SOCS2 promoted leukemogenesis as well as the abundance, quiescence, and activity of AML stem cells. Overall, the 4-GES represents a highly discriminating prognostic parameter in AML, whose clinical applicability is greatly enhanced by its small number of genes. The newly established role of SOCS2 in leukemia aggressiveness and stemness raises the possibility that the signature might even be exploitable therapeutically.}, author = {Nguyen, Chi Huu and Glüxam, Tobias and Schlerka, Angela and Bauer, Katharina and Grandits, Alexander M. and Hackl, Hubert and Dovey, Oliver and Zöchbauer-Müller, Sabine and Cooper, Jonathan L. and Vassiliou, George S. and Stoiber, Dagmar and Wieser, Rotraud and Heller, Gerwin}, journal = {Scientific Reports}, number = {1}, publisher = {Nature Publishing Group}, title = {{SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness}}, doi = {10.1038/s41598-019-45579-0}, volume = {9}, year = {2019}, }