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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.

A fundamental limitation for the practical use of dynamic nuclear polarization using photo-excited triplet state - the need of strictly oriented single crystal - is overcome in this work through the development of fullerene-based polarizing agents.

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.

How has the genome duplication impacted the diversification of sexual characteristics in the teleost lineage? This study shows that androgen receptor ohnologs in medaka appear to have diverged in their roles for regulating morphological and behavioural sexual characteristics after loss from an ancestral role in spermatogenesis.

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.

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.

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.

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.

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.

In this study, the authors report primordial aqueous alteration signatures in water-soluble organic molecules from the carbonaceous asteroid Ryugu. This provides evidence o coevolutionary aqueous alteration between water and organics in this asteroid.

Type I collagen in the dermis is a major component of the skin, though how this collagen is formed and modified as remained unclear. Here they show that keratinocytes contribute to dermal collagen formation in axolotl skin in a conserved mechanism, offering new insights into collagen formation.

The population genome structure of Asian Toxoplasma remains incompletely understood. This study analyzes intercontinental genomic admixture in 17 isolates from Japan and China, providing insights into the evolution of parasites and their impact on public health.

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.

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.

The well-established self-assembly of surfactant micelles is used to produce a new mesoporous silica structure, a dodecagonal quasicrystal, which offers larger length scales than intermetallic quasicrystals and improved structural quality compared with soft-matter mesoscale quasicrystals.

Zeolites — microporous crystalline aluminosilicates — are widely used in industry as size- and shape-selective catalysts, but the micropores that enable this catalytic activity also cause diffusion limitations that adversely affect it. This can be overcome by reducing the thickness of the zeolite crystals and thus improving molecular diffusion. Here it is shown that bifunctional surfactants can direct the formation of zeolite structures that are only one unit cell thick.

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 asteroid Ryugu samples are by far the freshest extraterrestrial carbonaceous material. The authors report soluble ions and organic sulfur molecules linked with primordial brine and prebiotic organic evolution of the primitive asteroid.

Uracil was identified in the sample returned from the asteroid Ryugu. Having been provided to the early Earth as a component in such asteroidal materials, these molecules might have played a role for prebiotic chemical evolution on the early Earth

The selective growth of mesoporous gold thin films with control over the porosity is a challenging task. Here, the authors report a soft-templating method allowing the growth of tunable, mesoporous gold films and examine their optical properties

Ketogenesis is critical for survival during the neonatal and perinatal periods. Arima et al. determine that hepatic ketogenesis prevents hyperacetylation of mitochondrial proteins and disruption of mitochondrial energetics.

The molecular atlas of soluble organic compounds from Ryugu shows unprecedented molecular complexity and diversity resulting from alteration on a low temperature, water rich parent body.