Multimodal, broadly neutralizing antibodies against SARS-CoV-2 identified by high-throughput native pairing of BCRs from bulk B cells.

TruAB Discovery is an approach that integrates cellular immunology, high-throughput immunosequencing, bioinformatics, and computational biology in order to discover naturally occurring human antibodies for prophylactic or therapeutic use. We adapted our previously described pairSEQ technology to pair B cell receptor heavy and light chains of SARS-CoV-2 spike protein-binding antibodies derived from enriched antigen-specific memory B cells and bulk antibody-secreting cells. We identified approximately 60,000 productive, in-frame, paired antibody sequences, from which 2,093 antibodies were selected for functional evaluation based on abundance, isotype and patterns of somatic hypermutation. The exceptionally diverse antibodies included RBD-binders with broad neutralizing activity against SARS-CoV-2 variants, and S2-binders with broad specificity against betacoronaviruses and the ability to block membrane fusion. A subset of these RBD- and S2-binding antibodies demonstrated robust protection against challenge in hamster and mouse models. This high-throughput approach can accelerate discovery of diverse, multifunctional antibodies against any target of interest.

An interactive web application for the dissemination of human systems immunology data.

BACKGROUND: Systems immunology approaches have proven invaluable in translational research settings. The current rate at which large-scale datasets are generated presents unique challenges and opportunities. Mining aggregates of these datasets could accelerate the pace of discovery, but new solutions are needed to integrate the heterogeneous data types with the contextual information that is necessary for interpretation. In addition, enabling tools and technologies facilitating investigators' interaction with large-scale datasets must be developed in order to promote insight and foster knowledge discovery. METHODS: State of the art application programming was employed to develop an interactive web application for browsing and visualizing large and complex datasets. A collection of human immune transcriptome datasets were loaded alongside contextual information about the samples. RESULTS: We provide a resource enabling interactive query and navigation of transcriptome datasets relevant to human immunology research. Detailed information about studies and samples are displayed dynamically; if desired the associated data can be downloaded. Custom interactive visualizations of the data can be shared via email or social media. This application can be used to browse context-rich systems-scale data within and across systems immunology studies. This resource is publicly available online at [Gene Expression Browser Landing Page ( https://gxb.benaroyaresearch.org/dm3/landing.gsp )]. The source code is also available openly [Gene Expression Browser Source Code ( https://github.com/BenaroyaResearch/gxbrowser )]. CONCLUSIONS: We have developed a data browsing and visualization application capable of navigating increasingly large and complex datasets generated in the context of immunological studies. This intuitive tool ensures that, whether taken individually or as a whole, such datasets generated at great effort and expense remain interpretable and a ready source of insight for years to come.

Novel high-pressure monoclinic metallic phase of V2O3.

Vanadium sesquioxide, V2O3, is a prototypical metal-to-insulator system where, in temperature-dependent studies, the transition always coincides with a corundum-to-monoclinic structural transition. As a function of pressure, V2O3 follows the expected behavior of increased metallicity due to a larger bandwidth for pressures up to 12.5 GPa. Surprisingly, for higher pressures when the structure becomes unstable, the resistance starts to increase. Around 32.5 GPa at 300 K, we observe a novel pressure-induced corundum-to-monoclinic transition between two metallic phases, showing that the structural phase transition can be decoupled from the metal-insulator transition. Using x-ray Raman scattering, we find that screening effects, which are strong in the corundum phase, become weakened at high pressures. Theoretical calculations indicate that this can be related to a decrease in coherent quasiparticle strength, suggesting that the high-pressure phase is likely a critical correlated metal, on the verge of Mott-insulating behavior.

A microdiffraction set-up for nanoporous metal-organic-framework-type solids.

For the past decade, the emerging class of porous metal-organic frameworks has been becoming one of the most promising materials for the construction of extralarge pore networks in view of potential applications in catalysis, separation and gas storage. The knowledge of the atomic arrangements in these crystalline compounds is a key point for the understanding of the chemical and physical properties. Their crystal size limits the use of single-crystal diffraction analysis, and synchrotron radiation facilities may allow for the analysis of tiny crystals. We present here a microdiffraction set-up for the collection of Bragg intensities, which pushes down the limit to the micrometre scale by using a microfocused X-ray beam of 1 mum. We report the structure determination of a new porous metal-organic-framework-type aluminium trimesate (MIL-110) from a single crystal of a few micrometres length, showing very weak scattering factors owing to the composition of the framework (light elements) and very low density. Its structure is built up from a honeycomb-like network with hexagonal 16 A channels, involving the connection of octahedrally coordinated aluminium octameric motifs with the trimesate ligands. Solid-state NMR (27Al,13C,1H) and molecular modelling are finally considered for the structural characterization.