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Tracking local material structure at picosecond timescales is realized using XFEL facilities. This pair distribution function measurement tracks the redevelopment of structural order through a non-equilibrium transition.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

Tuberculosis is a major cause of mortality, and the rise of drug-resistant strains of Mycobacterium tuberculosis requires the urgent development of safe and effective treatments. In this work, the authors develop a compound against lysyl-tRNA synthetase, demonstrating on-target mechanism of action and efficacy in vivo.

Senescent cells accumulate with age and contribute to the functional decline of many tissues; however, their role in skeletal muscle is not well understood. Here the authors comprehensively assess cellular senescence in skeletal muscle of young and old mice and detail senescence features in subpopulations of p16⁺ fibroadipogenic progenitors and p21⁺ myofibers.

A study finds that a protease called granzyme K can activate the entire complement cascade, explaining how it can drive destructive inflammation in inflammatory diseases such as rheumatoid arthritis.

Ventricular arrhythmias after heart attack are a leading cause of death. Here the authors show, in a porcine model, that KCNE3 and KCNE4 upregulation and a unique pattern of repolarization heterogeneity in the scar facilitate reentrant ventricular tachycardia.

The differential effects of targeting individual domains of multidomain enzymatic proteins are generally poorly understood. Here, the authors demonstrate lineage-specific sensitivities to domain-specific inhibition of EP300/CBP proteins across cancer and link these effects in group 3 medulloblastoma to control of a transcriptional dependency network.

Layered Ni-rich oxide cathodes are susceptible to challenges with surface reconstruction and strain propagation, limiting their cyclability. The authors propose a solution involving oriented attachment-driven reactions, utilizing Wadsley–Roth nanocrystals and layered oxide to induce an epitaxial entropy-assisted coating, effectively addressing these issues.

Chronic inflammation, marked by C-reactive protein, has been associated with changes in methylation, but the causal relationship is unclear. Here, the authors perform a Epigenome-wide association meta-analysis for C-reactive protein levels and find that these methylation changes are likely the consequence of inflammation and could contribute to disease.

Mitochondrial metabolism has been associated with tumourigenesis in acute myeloid leukaemia (AML) and currently considered as a potential therapeutic target. Here, the authors show, in patients with AML, that germline mutations in mitochondrial complex I are mutually exclusive with somatic mutations in the metabolic enzyme IDH1, and find IDH1 mutant cells have increased sensitivity to complex I inhibitors.

Monoclonal antibodies show great promise in treating Covid-19 patients. Here, Maisonnasse, Aldon and colleagues report pre-clinical results for COVA1-18 and demonstrate that it reduces viral infectivity in three animal models with over 95% efficacy in macaques upper respiratory tract.

Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.

Previous work has identified several genes where mutations lead to breast cancer, but other genetic and environmental factors must still be accounted for. A large study of genetic association with breast cancer points to four novel genes and many more genetic markers that should be pursued for their link to cancer susceptibility.

Primary biliary cirrhosis is an autoimmune liver disease with poor therapeutic options. Here Cordell et al. a perform meta-analysis of European genome-wide association studies identifying six novel risk loci and a number of potential therapeutic pathways.

A meta-analysis of genome-wide association studies in more than 66,000 individuals identifies 68 new genomic loci that reliably associate with platelet count and volume, and reveals new gene functions.

Cardelino leverages variant information from single-cell RNA-seq data for inferring clonal tree configuration and mapping cells to their clone of origin.

Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

Single-cell transcriptomic and proteomic data from synovial tissue from individuals with rheumatoid arthritis classify patients into groups based on abundance of cell states that can provide insights into pathology and predict individual treatment responses.

Activating mutations in the receptor tyrosine kinase Met can promote tumorigenesis. These Met mutants are now shown to undergo altered endocytic trafficking, and the retention of active Met at endosomes correlates with increased tumour formation and metastasis.

Fibroblasts play critical roles in tissue homeostasis, but in pathologic states they can drive fibrosis, inflammation, and tissue destruction. Here, Faust et al. find that healthy human synovial fibroblasts under the influence of adjacent adipocytes have altered lipid metabolism driven by cortisol signaling. Both adipocytes and these characteristics are lost in inflammatory arthritis.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

X-ray imaging in three dimensions is now possible from a set of 2D coherent Bragg diffraction patterns. This approach overcomes the necessity of having to rotate the sample for a 3D reconstruction.

Previous studies identified an association between the 2q35 locus and breast cancer. Here, the authors show that a SNP at 2q35, rs4442975, is associated with oestrogen receptor positive disease and suggest that this effect is mediated through the downregulation of a known breast cancer gene, IGFBP5.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Focal adhesion kinase (FAK) regulates angiogenesis and FAK inhibitors are currently developed as anticancer drugs. Here Kostourou and colleagues show that genetic FAK heterozygosity or low doses of a pharmacological FAK inhibitor unexpectedly increase angiogenesis and tumour growth in vitro and in vivo.

It is important to understand the mechanisms of thermally induced battery degradation and any safety hazards. Here, the authors use high-speed synchrotron radiation X-ray computed tomography to shed light on the structural and thermal dynamics associated with thermal runaway and failure of commercial Li-ion batteries.

Robust coherent diffractive imaging generally requires many exposures that may damage samples. Here, the authors develop a single-shot X-ray imaging method applicable to general samples for materials and biological sciences, also enabling imaging of dynamic processes, using a pulsed X-ray laser.

Medulloblastoma is the most common malignant brain tumour in children; having assembled over 1,000 samples the authors report that somatic copy number aberrations are common in medulloblastoma, in particular a tandem duplication of SNCAIP, a gene associated with Parkinson’s disease, which is restricted to subgroup 4α, and translocations of PVT1, which are restricted to Group 3.

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

Pamela Sklar and colleagues report a genome-wide association study of bipolar disorder and identify variants in the genes encoding ankyrin-3 and the alpha-1C subunit of the L-type voltage-gated calcium channel as increasing risk.

Coherent X-ray diffraction spectroscopy has recently emerged as a powerful tool for imaging strain at the nanoscale. Developments in both fabrication and experimental techniques have now enabled all nine components of the strain tensor in a nanorod to be determined, demonstrating the ability of coherent X-ray diffraction spectroscopy to yield measurements of strain in three dimensions with a resolution of a few tens of nanometres.

Intact single crystals of the enzyme lysozyme can be used to study the time-dependent, protein-directed growth of gold nanoparticles.

It is demonstrated that Bragg coherent diffraction imaging can be used to visualize dislocation propagation in three dimensions during the repeated growth and dissolution of calcite crystals.

Self-assembled monolayers of thiols have applications ranging from surface coatings to nanomechanical sensors, where they transmit analyte-induced stress to a cantilever detector. For gold nanocrystals it is now shown that the adsorption of propanethiol alone can induce large chemical stress, with different directionality on curved and flat surfaces.

Diffractive imaging of an important class of battery electrodes during cycling shows that lattice strain is a crucial yet overlooked factor that contributes to voltage fade over time.

Derailed differentiation of human-specific progenitors of the developing cerebellar rhombic lip is the cause of group 4 medulloblastoma, the most common childhood brain tumour. 

Land management and ownership by Indigenous Peoples are critical components of conservation strategies, but information on these has previously never been aggregated. Here, global data is compiled to show that Indigenous Peoples have tenure rights or manage a quarter of the world’s land area and 40% of all protected areas and intact ecosystems.

Multi-omic mapping shows that group 3 and group 4 medulloblastomas have a common, human-specific developmental origin in the cerebellar rhombic lip, providing a basis for their ambiguous molecular features and overlapping anatomical location, and for the difficulty of modelling these tumours in mice.

The Sc2.0 consortia is reengineering the yeast genome. To expand the Sc2.0 genetic repertoire, the authors build a neo-chromosome comprising variable loci from diverse yeast isolates, providing phenotypic plasticity for use in synthetic backgrounds.

Activated B cells and T cells accumulate within joints of patients with rheumatoid arthritis. Here, the authors use single-cell transcriptome and repertoire profiling to identify clonally expanded synovial B cells and T cells and define their phenotypes and predicted cell-cell interactions.

Insufficient AHR activation has been suggested in SLE, and augmenting AHR activation therapeutically may prevent CXCL13⁺ T_PH/T_FH differentiation and the subsequent recruitment of B cells and formation of lymphoid aggregates in inflamed tissues.

Iceberg-trajectory models along with multi-proxy evidence from sediment cores from the Indian Ocean show that northward shifts in Antarctic iceberg melt redistributed freshwater in the Southern Ocean during the Pleistocene.

As demand for organ transplants exceeds availability there has been an unmet need to extend preservation of deceased donor kidneys. Here, the authors show that a cell-free nutrient-supplemented perfusate allows 4-day preservation of human kidneys using spatially resolved lipidomics and metabolomics.

The most advanced P. falciparum circumsporozoite protein (PfCSP)-based malaria vaccine confers partial protection. Here, Pholcharee et al. present crystal structures, binding affinities/kinetics, and in vivo protection of 8 anti-NANP antibodies to understand in vivo protection of PfCSP-targeting antibodies.