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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.

Cytotoxic T lymphocytes (CTL) have been implicated in anti-PIT-1 hypophysitis, an autoimmune disease, but direct evidence is lacking. Here the authors use induced pluripotent stem cells to generate pituitary organoid and find that CTL-mediating killing is only evident in autologous organoid/CTL co-culture, thereby supporting CTL functions in this disease.

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.

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.

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.

Despite impressive performances of current large AI models, symbolic and abstract reasoning tasks often elicit failure modes in these systems. In this Perspective, Ito et al. propose to make use of computational complexity theory, formulating algebraic problems as computable circuits to address the challenge of mathematical and symbolic reasoning in AI systems.

The authors identified a transcriptional module, FAMA–WASABI MAKER (WSB), for the development of stomata and idioblast myrosin cells. They propose that the conserved and reduced FAMA–WSB module was co-opted before evolving to induce idioblast development.

A total of 1074 patients with a history of ischemic stroke enrolled in The Recurrent Stroke Prevention Clinical Outcome (RESPECT) Study were assigned to intensive blood pressure (BP) control group (blood pressure < 120/80 mmHg) or standard blood pressure control group (blood pressure < 140/90 mmHg) and were followed up for a mean of 3.9 years. Seventy-eight first recurrent strokes occurred, including 70 ischemic stroke and 8 intracerebral hemorrhage. Intensive treatment did not change annual risk of ischemic stroke (1.74% vs. 1.75%, P = 0.999), but markedly reduced risk of hemorrhagic stroke (0.00% vs. 0.39%, P = 0.005). Beneficial effect of intensive BP control were observed for risk of hemorrhagic stroke in the patients with a history of ischemic stroke.

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.

Synthetic methods for the preparation of perfluorinated aromatic compounds are desirable in materials science. Here, the authors synthesize perfluorocycloparaphenylenes, fully fluorinated carbon nanorings, through a nickel-mediated one-pot method.

JN.1 lineage is a globally dominant variant of SARS-CoV-2. Here, the authors examine structural insights into the BA.2.86 and JN.1 spike dynamics to help understand the mechanisms underlying SARS-CoV-2 infection and its neutralizing-antibody evasion.

In Arabidopsis cells undergoing mitosis, centromere distribution is shown to be regulated by two steps: scattering in M-phase and stabilization in interphase. This may affect the maintenance of genome integrity rather than gene regulation.

The authors show IRON MAN peptides have an essential role in symbiotic nitrogen fixation during legume-rhizobium symbiosis. The peptides additionally function to regulate nitrogen homeostasis by controlling nitrogen-iron balance.

Using more than 100 independent iPSC lines derived from patients with Alzheimer’s disease, the authors discovered loci associated with the neuronal production of amyloid β and confirmed their influence using RNA interference.

Both strigolactone and DELLA plant signalling pathways have a role in shoot branching. In this study, Nakamura et al.show that DWARF14 cleaves strigolactones creating a binding surface for the DELLA protein SLR1, thereby providing a mechanism for pathway crosstalk.

Targeting gluten antigens presents a plausible therapy option for celiac disease. Here the authors generate and characterize a broadly neutralizing antibody recognizing more than 25 gluten peptide:HLA-DQ2.5 complexes, with structural analyses implicating its mode of interaction, and with mouse in vivo studies supporting its therapeutic feasibility.

The brain dynamically transforms cognitive information. Here the authors build task-performing, functioning neural network models of sensorimotor transformations constrained by human brain data without the use of typical deep learning techniques.

Short-wavelength lasers based on wide-bandgap GaN photonic crystals are promising for high-brightness illumination and materials processing. Here, the authors develop a nano-fabrication method for GaN/air photonic crystals, achieving high lasing operation performance in terms of output power, beam quality, and low threshold current.

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.

Previous studies of the skin have suggested a neutral-to-acidic pH gradient in the outermost layer. Here, the authors perform quantitative intravital pH imaging of the stratum corneum, the outermost epidermal layer, and demonstrate three distinct pH zones - rather than a gradient - with different biological functions.

Resting-state functional connections have been associated with cognitive abilities but it is unclear how these connections contribute to cognition. Here Ito et al present a new approach, information transfer mapping, showing that task-relevant information can be predicted by estimated activity flow through resting-state networks.

The two homoeologous subgenomes in the allotetraploid frog Xenopus laevis evolved asymmetrically; one often retained the ancestral state, whereas the other experienced gene loss, deletion, rearrangement and reduced gene expression.

Leguminous plants host nitrogen-fixing bacteria in root nodules, but cease symbiosis when sufficient nitrogen is available. Here, the authors show that the Lotus japonicus transcription factor NRSYM1 activates the production of CLE-RS2 in nitrogen-sufficient conditions to prevent nodulation

This study uncovers the role of aromatic clusters in the receptor extracellular loop of sialic-acid-binding immunoglobulin-like lectins that recognize carbon nanotubes and suggests inhibiting Syk signalling as a therapeutic intervention against inflammation.

Predicting RNA degradation is a fundamental task in designing RNA-based therapeutics. Two crowdsourcing platforms, Kaggle and Eterna, united to develop accurate deep learning models for RNA degradation on a timescale of 6 months.

An understanding of charge dynamics and direct observations of charge generation, transfer and recombination is important to help develop and apply various materials for electronic devices. The authors develop a time-resolved electrostatic force microscopy technique to visually observe charge migration on the nanoscale at a sub-microsecond timeframe.

Here, Kodama et al. describe the discovery, isolation and characterization of a novel tick-borne orthonairovirus, designated Yezo virus (YEZV), from patients with an acute febrile illness in Japan. Serological testing of wildlife and molecular screening of ticks suggest an endemic circulation of YEZV in Japan.

The EWS-ATF1 fusion gene causes clear cell sarcoma (CCS). Here, the authors show that the downstream effects of EWS-ATF1 expression are strictly context dependent, and reveal the cell of origin for CCS to be Tppp3-expressing cells in peripheral nerves.

Deracemization is a powerful method which allows transformation of racemic mixtures into excess enantiomer, but was applied only to small chiral molecular systems so far. Here the authors report deracemization of a kinetically stable bisporphyrin helicate upon encapsulation of chiral aromatic guests.

Chalcone synthase is the first committed enzyme in the plant flavonoid biosynthesis pathway, yet shows low product specificity in vitro. Here Waki et al. show that chalcone isomerase-like proteins bind to and reduce the catalytic promiscuity of chalcone synthase, ensuring efficient flavonoid production in planta.