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A single-cell multiomic immune cell atlas from 235 Japanese, including patients with COVID-19 and healthy individuals, linked with host genetics including germline and somatic mutation, plasma proteomics and metagenomics data reveals that immune cells are dynamically regulated in a cell state-dependent manner.

The role of polyclonal competition in immunotherapy response is poorly understood. Here, the authors perform multiregional sequencing of a metastatic urothelial carcinoma patient that exhibited different treatment responses to anti-PD-1 therapy at each tumour site and identify distinct cancer-related properties.

A genome-wide association study highlights a variant in DOCK2, which is common in East Asian populations but rare in Europeans, as a host genetic risk factor for severe COVID-19.

The synthetic production of model protocells, which represent potential intermediates between nonliving material and living cells, may help to explain the origin of cellular life. Here, Kuriharaet al. develop a giant vesicle-based model protocell that is able to self-proliferate recursively in response to external stimuli.

Analysis of the blood DNA virome in patients with COVID-19 and autoimmune disease associates endogenous HHV-6 (eHHV-6) and high anellovirus load with increased disease risk, most notably for systemic lupus erythematosus. eHHV-6 carriers show a distinct immune response.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

Laser-matter interaction has been intensively studied in equilibrium states, but irreversible processes in a highly nonequilibrium state at nanoscales remains elusive due to experimental challenges. Here, Ihm et al. image heterogeneous melting of gold nanoparticles with nanometer and picosecond resolution.

DNA repair-deficient tumours are eligible for effective targeted therapies, but reliable diagnostic strategies based on functional assays are needed. Here the authors develop methods for the rapid assessment of homologous recombination and mismatch repair status in tumor tissues, allowing drug efficacy to be predicted.

E. coli and human tRNAs contain 3-(3-amino-3-carboxypropyl)uridine (acp³U) modification. Here the authors identify E. coli TapT and human DTWD1/2 as tRNA aminocarboxypropyltransferases responsible for acp³U formation. Inhibition of acp³U modification results in genome instability in heat-stressed E. coli and growth defects in human cells.

This paper unveils the complexity of human immune cell splicing, highlighting cell-specific isoforms and establishing connections between alternative splicing and complex traits. These findings have implications for understanding diseases and the evolution of the genome.

In quantum chromodynamics, the condensation of quark–antiquark pairs breaks the chiral symmetry of vacuum. Experiments with pionic tin atoms demonstrate that the symmetry is partially restored at high densities.

Precise protein synthesis is achieved by tRNA modifications. Here the authors revealed that modified cytidines in tRNA^Ile use their long side chains to make additional interactions with mRNA for stable tRNA binding on the ribosome.

A tRNA modification, named 2-aminovaleramididine (ava²C), has been discovered in plant organelles and bacteria. Structural analysis shows specific codon recognition by this modification, highlighting the evolutionary diversity of the essential tRNA modifications.

The first main-chain type triphenylarsine (AsPh₃) polymers were synthesized by Suzuki-Miyaura polycondensation. The electronic and photophysical properties of the AsPh₃ polymers were comparison with model compounds by experimental and computational methods. As a result, it was found that the conjugated systems were expanded through the arsenic atoms. The present AsPh₃ polymers are promising as luminescent materials.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Here the authors demonstrate the use of time-resolved serial femtosecond crystallography to capture intermediates in a chemical reaction in synthetic CO-releasing Mn-carbonyl complex fixed in lysozyme protein crystals, providing useful insights for the design of artificial metalloenzyme reactions.

Poor access to suitable light-sheet microscopes remains a big obstacle for many end-users in biomedical research. Here, the authors present descSPIM, a low-cost, low-expertise light-sheet microscope for routine 3D imaging of cleared samples.

In this study, authors examine Staphylococcus aureus adaptability in hospitals, highlighting how a lineage evolved to reversibly suppress Agr, enhancing antibiotic resistance and colonization.

Serial femtosecond crystallography experiments with diverse protein microcrystal suspensions are facilitated using a grease matrix as a carrier medium for sample injection.

Peripheral blood mononuclear cells from 73 Japanese patients with coronavirus disease 2019 (COVID-19) and 75 healthy controls were analyzed using single-cell transcriptomics. Combining these data with genotyping data highlights the interplay between host genetics and the immune response in modulating disease severity.

Researchers report sub-ångström fundamental-wavelength lasing at the SPring-8 Angstrom Compact Free-Electron Laser in Japan. The output has a maximum power of more than 10 GW, a pulse duration of 10⁻¹⁴ s and a lasing wavelength of 0.634 Å.

Serial femtosecond crystallography reveals the structural dynamics of photosystem II during the S-state transitions that produce dioxygen, providing insight into electron transfer, water insertion, proton release and O–O bond formation on sub-microsecond timescales.

Splicing QTL (sQTL), genetic variants regulating alternative splicing, can be biologically important, but complex to detect and interpret. Here, the authors identify sQTL by focusing on protein coding sequences, as an alternative to junction-based approaches.

Small molecules that target RNA Polymerase I inhibit ribosome biogenesis to activate p53 through the nucleolar surveillance response pathway. Here, the authors show that p53 induction by ribosome stress is dependent on extracellular glutamine availability.

Classical monocytes can differentiate into pro-inflammatory or pro-resolving macrophages. Here the authors characterise mouse macrophage differentiation and show that Ly6C^hi classical monocytes can differentiate into Ly6C^lo pro-resolving macrophages which are involved in the resolution of skin allergic inflammation.

Advanced colorectal cancers are characterised by intra-tumour heterogeneity dictated by neutral evolution. Here the authors analyse early colorectal tumours by whole-exome sequencing and find that Darwinian evolution determines the fate of early lesions in colorectal adenoma and carcinoma in situ.

Autophagic activity decreases with age via unknown mechanisms. Here the authors show that expression of the negative autophagy regulator Rubicon increases with age, that its genetic ablation improves lifespan and ameliorates a number of age-associated phenotypes in invertebrates and in mouse models.

Mutant forms of the transmembrane receptor activin receptor-like kinase 2 are associated with different genetic diseases. Here, the authors report that disease-associated forms of this receptor cause intracellular domains to dimerize in response to ligand binding of extracellular domains.

Kuchitsu et al. show that STING-positive vesicles of a recycling endosome origin are encapsulated into lysosomes after STING ubiquitination and this process requires ESCRT proteins Tsg101 and Vps4.

Multi-ancestry genome-wide association analyses identify 124 risk loci for rheumatoid arthritis, of which 34 are novel. A polygenic risk score based on multi-ancestry data showed comparable performance between populations of European and East Asian ancestries.

Homeobox protein Mohwak (Mkx) is involved in tendon and ligament development. Here the authors show that Mkx in the outer annulus fibrosus of the intervertebral disc plays a role in maintenance of the IVD, showing that stem cells overexpressing Mkx enhance therapeutic IVD regeneration in mice.

Three-dimensional imaging is typically complex and time consuming. Here, the authors report the use of X-ray free-electron laser pulses for single-shot three-dimensional imaging of nanocrystals at ~5.5 nm resolution, using the symmetry in the nanocrystal and the curvature of the Ewald sphere.

Here, the authors realize an ultra-high fluence X-ray laser by high-gain multilayer focusing optics. This enables in-solution imaging with 2-nm resolution in a single-pulse exposure, making strides toward biomolecular imaging under physiological conditions.

The self-replication process of a giant vesicle encapsulating double-stranded DNA has been observed, which represents a supramolecular approach to the construction of a protocell. Growth and division of the vesicle occurred rapidly on addition of a membrane precursor, and amplified DNA was distributed amongst the resulting daughter giant vesicles.

In the Nankai subduction zone a low-velocity zone (LVZ) has been detected. Here, the authors present shear wave velocity profiles to show that low frequency earthquakes correlate with the distribution of the LVZ in the Nankai subduction zone.

In the thymus, low-affinity T cell antigen receptor (TCR) engagement facilitates positive selection of the T cell repertoire. Takahama and colleagues now show TCR responsiveness of mature CD8⁺ T cells is fine-tuned by their affinity for positively selecting peptides in the thymus.