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The structure of human prostaglandin E receptor EP4 in complex with antagonist ONO-AE3-208 and a functional antibody reveals a ligand-binding site at the interface of the lipid bilayer that is unique among GPCRs.

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.

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.

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.

Mitochondria with mutations in their DNA from cancer cells can be transferred to T cells in the tumour microenvironment, which leads to T cell dysfunction and impaired antitumour immunity.

The phase 2 trial, DESTINYCRC01, previously demonstrated durable activity of trastuzumab deruxtecan (T-DXd) in patients with HER2-positive metastatic colorectal cancer refractory to standard treatment. Here, the authors report the exploratory analysis of the DESTINY-CRC01 trial investigating markers of response or resistance to T-DXd.

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.

Seismological observations of the D′′ layer near the core–mantle boundary are difficult to interpret and the minerals present are unstable at ambient conditions. Yoneda et al.present experiments using analogues, suggesting the observations are due to preferred crystal orientations.

Exploratory analyses of the DESTINY-Gastric01 trial show that baseline HER2-associated biomarkers in circulating tumor DNA or tissue samples were associated with therapeutic response in patients with HER2-positive tumors, and these analyses identify potential drivers of resistance.

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.

The tumor suppressor p53 prevents malignant transformation and regulates stem cell function and differentiation. Here, the authors discover a p53-induced lncRNA, LOC644656, that regulates genotoxic stress-induced stem cell maldifferentiation and chemoresistance in cancer cells.

A close-up look at the action of space weathering on carbonaceous asteroids, provided by Ryugu’s returned samples, highlights its role on the dehydration of the first micrometre-thick layer of the surface, possibly hiding a water-rich interior. The depth of the 2.7 µm hydration band may be an indication of the level of space weathering withstood by a C-type asteroid.

A strong coupling between electric polarization and elastic deformation is important for creating electromechanical nanodevices, but such coupling typically requires inversion symmetry breaking and is elusive in metals. Here, a current-induced giant elastic deformation is reported in topological semimetals VTe₂ and MoTe₂, regardless of centrosymmetry, due to the Berry phase enhancement of the flexoelectric response.

Fusako Sakai-Takemura et al. report that self-renewal of human muscle progenitors is regulated by NOTCH/EP2 signaling. The findings deepen our understanding on self-renewal of muscle stem cells and contribute to the development of treatments for Duchenne muscular dystrophy.

Hirano et al. develop a heart failure diagnosis of triglyceride deposit cardiomyovasculopathy based on defective lipolysis and show long-term survival and patient recovery after tricaprin treatment.

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.

The saccus vasculosus is a circumventricular organ of the hypothalamus of many jawed fish whose function has remained a mystery for more than 300 years. Here the authors provide evidence that the saccus vasculosus functions as a sensor of seasonal changes in day length.

Peripheral CD4⁺ T cells can develop into Intestinal intraepithelial lymphocytes (IEL) in the lamina propria. Here the authors characterise how IEL generation from CD4⁺ T cells is regulated and show using scRNA sequencing that Ccr9 is involved in this process through limiting IEL precursor differentiation.

Cell lineage tracing is scaled up to hundreds of millions of simulated sequences with distributed computing.

GABAergic neuron progenitors in the cerebellum give rise to Purkinje cells and GABAergic interneurons. Here the authors show that the transcription factors Olig2 and Gsx1 regulate an identity transition from Purkinje cell progenitors to interneuron progenitors during mouse development.

The P681R mutation in the spike protein renders the Delta variant more pathogenic than prototypic SARS-CoV-2 in infected hamsters, and facilitates spike protein cleavage and enhances viral fusogenicity.

A key event during metastasis to the brain is the migration of cancer cells through the blood–brain barrier (BBB). Here the authors show that cancer-cell-derived extracellular vesicles promote metastasis by promoting BBB breaching.

MicroRNAs have a role in the acquisition of stem cell-like properties of cancer cells. Here the authors show that microRNA-27b mediates generation of a side-population of breast cancer stem cells, in part by regulating the protein ENPP1, which has been previously linked to the development of diabetes.

Existing neural network potentials are generally designed for narrow target materials. Here the authors develop a neural network potential which is able to handle any combination of 45 elements and show its applicability in multiple domains.

27 million Japanese are hypertensive disease and 89.6% of them are treated with any anti-hypertensive medications. This is the first study utilizing the National Database of Health Insurance Claims and Specific Health Checkups to determine the number and age-adjusted prevalence of hypertensive patients and treated hypertensive patients in Japan.

A method is proposed to predict drug-induced single-cell gene-expression profiles with tensor imputation, detect cell type-specific maker genes, and identify the trajectories of regulated pathways considering intercellular heterogeneity.

Cold atoms have recently become a versatile platform for the study of quantum transport phenomena. Here the authors realize an alternative experimental scheme for quantum transport with cold atoms, by using spin-dependent impurity scattering in a spinful Fermi gas instead of spatially separated particle distributions.