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Structure and Function of the Human Ribonucleosome

More than 50 years ago, a family of heterogenous nuclear ribonucleoproteins (hnRNPs) was detected and proposed to package and regulate transcript expression. Recently, scientists in the Allain, Blencowe, Mühlemann and […]

Mapping moral language on US presidential primary campaigns reveals rhetorical networks of political division and unity

During political campaigns, candidates use rhetoric to advance competing visions and assessments of their country. Research reveals that the moral language used in this rhetoric can significantly influence citizens’ political attitudes and behaviors; however, the moral language actually used in the rhetoric of elites during political campaigns remains understudied. Using a data set of every tweet (N = 139, 412) published by 39 US presidential candidates during the 2016 and 2020 primary elections, we extracted moral language and constructed network models illustrating how candidates’ rhetoric is semantically connected. These network models yielded two key discoveries. First, we find that party affiliation clusters can be reconstructed solely based on the moral words used in candidates’ rhetoric. Within each party, popular moral values are expressed in highly similar ways, with Democrats emphasizing careful and just treatment of individuals and Republicans emphasizing in-group loyalty and respect for social hierarchies. Second, we illustrate the ways in which outsider candidates like Donald Trump can separate themselves during primaries by using moral rhetoric that differs from their parties’ common language. Our findings demonstrate the functional use of strategic moral rhetoric in a campaign context and show that unique methods of text network analysis are broadly applicable to the study of campaigns and social movements. © The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Whole-mouse clearing and imaging at the cellular level with vDISCO

Homeostatic and pathological phenomena often affect multiple organs across the whole organism. Tissue clearing methods, together with recent advances in microscopy, have made holistic examinations of biological samples feasible. Here, we report the detailed protocol for nanobody(VHH)-boosted 3D imaging of solvent-cleared organs (vDISCO), a pressure-driven, nanobody-based whole-body immunolabeling and clearing method that renders whole mice transparent in 3 weeks, consistently enhancing the signal of fluorescent proteins, stabilizing them for years. This allows the reliable detection and quantification of fluorescent signal in intact rodents enabling the analysis of an entire body at cellular resolution. Here, we show the high versatility of vDISCO applied to boost the fluorescence signal of genetically expressed reporters and clear multiple dissected organs and tissues, as well as how to image processed samples using multiple fluorescence microscopy systems. The entire protocol is accessible to laboratories with limited expertise in tissue clearing. In addition to its applications in obtaining a whole-mouse neuronal projection map, detecting single-cell metastases in whole mice and identifying previously undescribed anatomical structures, we further show the visualization of the entire mouse lymphatic system, the application for virus tracing and the visualization of all pericytes in the brain. Taken together, our vDISCO pipeline allows systematic and comprehensive studies of cellular phenomena and connectivity in whole bodies. © 2023, Springer Nature Limited.

Fueling next-generation genome editing with DNA repair

Genome editing technologies generate targeted DNA lesions and rely on cellular DNA repair pathways for resolution. Understanding the DNA repair mechanisms responsible for resolving the specific damage caused by gene editing tools can significantly advance their optimization and facilitate their broader application in research and therapeutic contexts. Here we explore the cellular processes involved in repairing base and prime editor-generated DNA lesions and strategies to leverage and manipulate DNA repair pathways for desired genomic changes. © 2023 The Author(s)

Stochastic motion and transcriptional dynamics of pairs of distal DNA loci on a compacted chromosome

Chromosomes in the eukaryotic nucleus are highly compacted. However, for many functional processes, including transcription initiation, the pairwise motion of distal chromosomal elements such as enhancers and promoters is essential and necessitates dynamic fluidity. Here, we used a live-imaging assay to simultaneously measure the positions of pairs of enhancers and promoters and their transcriptional output while systematically varying the genomic separation between these two DNA loci. Our analysis reveals the coexistence of a compact globular organization and fast subdiffusive dynamics. These combined features cause an anomalous scaling of polymer relaxation times with genomic separation leading to long-ranged correlations. Thus, encounter times of DNA loci are much less dependent on genomic distance than predicted by existing polymer models, with potential consequences for eukaryotic gene expression. © 2023 American Association for the Advancement of Science. All rights reserved.