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Humanized mice bearing full-length human genes recapitulate human biology but are challenging to generate. Here, the authors develop TECHNO, a twostep CRISPR–ES cell method that efficiently replaces mouse loci with >200-kbp human orthologs, enabling versatile in vivo disease modeling.

PTBP1 in Sertoli cells promotes spermatogenesis by sustaining RICTOR-dependent mTORC2-PKCα signaling and F-actin organization, thereby preserving male fertility.

In a new study, Yasuhiro Kobayashi and his colleagues show that noncanonical Wnt signaling regulates balanced osteoblast-induced osteoclastogenesis during normal physiology and that this pathway is perturbed in pathophysiological states, such as rheumatoid arthritis. These results explain further how osteoblasts cross-talk with preosteoclasts to ensure matched bone resorption with bone formation during skeletal homeostasis in the adult and also suggest a new target to treat arthritis.

Sawada et al. show simultaneous activation of the STING and lymphotoxin beta receptor signaling induces B cell-activating germinal center responses within tumor environment and enhances antitumor responses.

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.

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.

In view of previous work suggesting that low-voltage areas may promote atrial fibrillation, a multicenter, randomized controlled trial tested the hypothesis that ablation of low-voltage areas in addition to pulmonary vein isolation might reduce the recurrence of atrial arrhythmic events, but found no significant benefit to the combined procedure.

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.

Understanding the impact of the athermal effect on microstructures is crucial for designing and manufacturing semiconductor and metal materials. Here, the authors propose a method using pre-micromachined structures to decouple thermal and athermal effects and experimentally validate its feasibility.

Transcriptomic and behavioural analyses of medaka fish demonstrate how photoperiodic activation of the long noncoding RNA LDAIR regulates behaviour in response to seasonal change.

Previous genome-wide association studies have identified risk loci for pancreatic cancer but were centered on individuals of European ancestry. Here the authors identify GP2 gene variants associated with pancreatic cancer susceptibility in populations of East Asian ancestry.

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.

Hirano et al. show that expression of the MYC family member Mycl in adult pancreatic islets can increase proliferation and expand the functional β-cell population, thereby improving glucose control.

The mechanisms by which in vivo expression of the Yamanaka transcription factors (OSKM) renders somatic cells permissive for differentiation remain unclear. Here, the authors show that in vivo reprogramming using OSKM generates germ cell tumors and drives acquisition of totipotency-like features in somatic cells through DMRT1.

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.

The sample taken from carbonaceous asteroid Ryugu and brought back to Earth by the Hayabusa2 spacecraft contains outer Solar System-derived materials uncontaminated by terrestrial processes. Even CI carbonaceous chondrites, despite their closeness to solar abundances, are not pristine.

Thermal imaging data obtained from the spacecraft Hayabusa2 reveal that the carbonaceous asteroid 162173 Ryugu is an object of unusually high porosity.

The Hayabusa2 spacecraft returned 5.4 g of material from the asteroid Ryugu. A first analysis of the samples found an estimated density of 1,282 ± 231 kg m⁻³, considerably lower than even the most porous meteorites. Together with preliminary spectral analysis, these results indicate that Ryugu is similar to CI chondrites, but darker, more porous and more brittle.

CagA is the main virulence factor of Helicobacter pylori and is delivered directly by the bacterium into epithelial cells where it interferes with cell signalling. Here Hatekeyama and colleagues show that CagA binds to the polarity protein, PAR1, inhibiting its phosphorylation and disrupting epithelial cell polarity: this study provides the first molecular link between a human pathogen and the PAR cell polarity machinery.

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.

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.

A chemical profiling methodology is described for seaweed biomass based on comprehensive characterization of the water-soluble, water-insoluble and solid-state components. For nuclear magnetic resonance (NMR) measurements of seaweed water-insoluble components, an extraction method was developed by modification and optimization of physical pretreatments and extraction processes. Compositional variations were evaluated by NMR and attenuated total reflectance Fourier transform infrared spectroscopy, and subsequently indicated red, brown and green algae-specific profiles derived from multivariate statistical analysis.