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  • In vivo, forces applied to molecular interactions between T cells and antigen-presenting cells are essential for specific foreign antigen recognition. A new technology, BATTLES, applies force to thousands of T cells interacting with tens of candidate antigens to identify antigens capable of efficient T cell activation. The method improves throughput over current methods that profile force-dependent interactions.

    Research Briefing
  • This paper explores the use of scanning transmission electron microscopy (STEM) to vitrified biological samples for biomolecular structure elucidation. Integrated differential phase contrast (iDPC)–STEM imaging of keyhole limpet hemocyanin and tobacco mosaic virus enabled cryo-EM structure determination at 6.5 and 3.5 Å resolution, respectively.

    • Ivan Lazić
    • Maarten Wirix
    • Carsten Sachse
    Article Open Access
  • Cell type-specific inference of differential expression (C-SIDE) is a statistical model that identifies which genes (within a determined cell type) are differentially expressed on the basis of spatial position, pathological changes or cell–cell interactions. C-SIDE facilitates differential expression analysis in spatial transcriptomics by jointly modeling cell type mixtures and spatially varying gene expression.

    Research Briefing
  • A systematic exploration of MINFLUX nanoscopy with DNA-PAINT labeling leads to improved nanoscopy in fixed cells and MINFLUX imaging with increased multiplexing, as exemplified by three-color imaging of mitochondria in mammalian cells.

    • Lynn M. Ostersehlt
    • Daniel C. Jans
    • Stefan Jakobs
    Brief Communication Open Access
  • As new technology enables researchers to find and characterize less-common post-translational modifications that drive gene expression and cellular metabolism, the movement to catalog the entire human proteome gains momentum

    • Caroline Seydel
    Technology Feature
  • Light microscopy enables researchers to observe cellular mechanisms with high spatial and temporal resolution. However, the increasing complexity of current imaging technologies, coupled with financial constraints of potential users, hampers the general accessibility and potential reach of cutting-edge microscopy. Open microscopy can address this issue by making well-designed and well-documented hardware and software solutions openly available to a broad audience. In this Comment, we provide a definition of open microscopy and present recent projects in the field. We discuss current and future challenges of open microscopy and their implications for funders, policymakers, researchers and scientists. We believe that open microscopy requires a holistic approach. Sample preparation, designing and building of hardware components, writing software, data acquisition and data interpretation must go hand in hand to enable interdisciplinary and reproducible science to the benefit of society.

    • Johannes Hohlbein
    • Benedict Diederich
    • Kirti Prakash
  • The DAQ score assesses the consistency of amino acid assignment in protein structure models with local density from cryo-EM maps. The method complements existing quality metrics and is a versatile tool for highlighting problematic regions of model structures.

    • Genki Terashi
    • Xiao Wang
    • Daisuke Kihara
  • PROBER is a fast and sensitive episome-based method to identify sequence-specific DNA-binding proteins from living cells using proximity proteomics. This method quantifies steady-state and inducible association of transcription factors and corresponding chromatin regulators to specific DNA sequences as well as binding quantitative trait loci present as a result of single nucleotide variants.

    Research Briefing