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Drivers of viral evolution in SARS-CoV-2 are insufficiently understood. In this study, the authors show how a key SARS-CoV-2 mutation, NSP4 T492I, is potentially responsible for accelerating genome evolution to develop adaptive variants (e.g. Omicron).

The understudied lipid kinase PIP4K2C binds SARS-CoV-2 nonstructural protein 6 and regulates virus-induced autophagic flux impairment, suppressing viral protein degradation. PIP4K2C inhibition is a candidate strategy to combat emerging viruses.

Mice have lineage-negative IL-7Rα⁺ (innate lymphoid) cells that contribute to type 2 immunity. Spits and colleagues identify a similar CRTH2⁺CD161⁺ population in human lungs and gut that produces IL-13 after stimulation.

Mouse lymphoid tissue–inducer (LTi) cells require the transcription factor RORγt. Cupedo's group identifies RORγt⁺ human LTi cell equivalents as committed natural killer cell precursors, and teams led by Vivier and Diefenbach describe RORγt-expressing interleukin 22–producing natural killer cells in mouse gut.

The tumour suppressor PTEN is required for maintenance of haematopoietic stem cells, but not leukaemia-initiating cells — this specific effect is mediated by the mTOR pathway and mitigated by rapamycin.

Immune cells contribute to the aortic wall destruction during abdominal aortic aneurysm (AAA) development. Here, Peshkova et al. show that cytokine signaling through interleukin-27 receptor is required for Angiotensin II-induced myelopoiesis and mature myeloid cells production, thus contributing to their aortic accumulation and aneurysm progression

Endothelial cells form a vascular niche that supports haematopoietic stem cell function. Akt activation in endothelial cells upregulates angiocrine factors to promote long-term haematopoietic stem cell repopulation capacity while co-activation of Akt and MAPK shift the balance towards maintenance and differentiation of their progenitors.

Observations of SN 2021yfj reveal that its progenitor is a massive star stripped down to its O/Si/S core, which remarkably continued to expel vast quantities of silicon-, sulfur-, and argon-rich material before the explosion, informing us that current theories for how stars evolve are too narrow.

Basu et al. find that the transcription factor ThPOK is not restricted to T cells, as it also is expressed in myeloid cell progenitors and contributes to the lineage choice of monocyte-dendritic cells as opposed to neutrophils.

JMML is an aggressive hematologic malignancy with myeloproliferative characteristics affecting young children. Here the authors report that C-type lectin-like molecule-1 (CLL-1) is upregulated in JMML and they develop CLL-1 CAR T cells showing in vitro and in vivo anti-JMML activity.

Cytokine-producing innate lymphoid cells are found at mucosal surfaces. Artis and Wherry and their colleagues show that innate 'nuocyte-like' cells accumulate in virus-infected lungs and contribute to the repair of tissues.

Body size and composition are complex traits that are challenging to characterize due to environmental and genetic influences. Here, Arehart et al. disentangle shared and distinct genetic signals underlying body size and composition.

Pressure overload in the heart, such as from aortic stenosis, triggers early molecular changes before visible damage occurs. Here, the authors show that combining proteomics, transcriptomics, and genetic data reveals key drivers of heart failure, highlighting potential targets for treatment.

An NNMT inhibitor reduces tumour burden and metastasis in multiple mouse cancer models and restores immune checkpoint blockade efficacy by decreasing cancer-associated-fibroblast-mediated recruitment of myeloid-derived suppressor cells and reinvigorating CD8⁺ T cell activation.

The induction of immunogenic cell death (ICD) can potentiate antitumour immunity. Here the authors show that USP18, a negative regulator of IFN signaling protects cancer cells from ICD by suppressing the expression of canonical and non-canonical IFN-stimulated genes.

To better understand the etiology of frailty, the authors perform a large genetic study. They identified 45 additional variants and implicated MET, CHST9, ILRUN, APOE, CGREF1 and PPP6C as potential causal genes, linking frailty to immune regulation, metabolism and cellular signaling.

Efficient oxygen activation limits oxidative catalysis. Here, incorporating single-atom Zr into CeO₂-supported Pt catalysts creates Zr₁–O–Pt₁ structures, significantly enhancing catalytic performance via boosted surface and chemisorbed oxygen activation.

Mirchandani and colleagues show that tissue hypoxia alters the number and phenotype of circulating monocytes and their differentiation into lung macrophages, with important implications for the resolution of inflammation in the lung.

It is difficult to image haematopoietic stem cells (HSC) in their niche. Here, the authors present a new high-throughput computational approach to visualise HSCs in vivoat a high spatial and temporal resolution and also use a Msi2-reporter to label endogenous HSCs and progenitors, enabling cell tracking

A survey across 90 societies reveals that variation and change in everyday norms are explained by a single value dimension: the priority societies place on individualizing versus binding moral concerns.

It is unclear whether the transfer of plasmids carrying antibiotic resistance genes can explain their persistence when antibiotics are not present. Here, Lopatkin et al. show that conjugal plasmids, even when costly, are indeed transferred at sufficiently high rates to be maintained in the absence of antibiotics.

Amino acids are required for cell survival and growth. However, the different requirements of amino acid metabolic pathways in normal haematopoiesis and leukaemogenesis have not been explored. Here the authors focus on the transporter of neutral amino acids and show that malignant blood cells rely more on ASCT2-mediated amino acid metabolism than normal cells.

Anxiety-like behaviour in mice, as a result of psychological stress, is shown to be mediated by GDF15 release in response to adipose tissue lipolysis.

'Lymphoid priming' in human bone marrow is traditionally thought to begin with the expression of CD10 on CD34⁺ progenitors. Crooks and colleagues now demonstrate lymphoid priming in a subset of CD10^–CD34⁺ progenitors that are CD62L^hi.

The transcription factor CREM is a pivotal regulator of NK cell function, making CREM a valuable target to increase the efficacy of anticancer immunotherapies based on this cell population and chimeric antigen receptors.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Here, the authors leverage whole-genome sequencing from >88,000 diverse individuals to uncover 18 BMI-related genetic signals, including novel variants in participants of African genetic ancestry, highlighting the value of diversity in genetic discovery.

Description of the cryo-EM structures of the parathyroid hormone type 1 receptor associated with G_q reveals two distinct extracellular conformations with N-glycans stabilizing a ligand-tilted conformation.

The nuclear lamina bridges mechanical forces from the cytoskeleton to the nucleus, and while Lamin A/C is known to be crucial for this process, its regulation remains unclear. Here the authors show that levels of Lamin A/C scale with apico-basal compression of cells independently of tissue stiffness using Drosophila epithelial tissues and mammalian cells.

A comprehensive analysis of the cell-specific molecular regulatory mechanisms underlying post-traumatic stress disorder in the human prefrontal cortex.

Hydrogel materials have emerged as versatile platforms for biomedical applications. Here this group reports an mRNA lipid nanoparticle-incorporated microgel matrix for immune cell recruitment/antigen expression and presentation/cellular interaction thereby eliciting antitumor efficacy with a single dose.

The morphogenetic events that occur during gastrulation involve dramatic cell- and tissue-level changes. Here they show that propagation of nematic order, leading to long-range spatial correlation, is universally conserved during metazoan embryogenesis.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

The estimation of low energies of many-body systems is a cornerstone of the computational quantum sciences. This paper demonstrates on a superconducting quantum processor that the Krylov quantum diagonalization algorithm is poised to complement its classical counterparts at the foundation of computational methods for quantum systems.

IL-33 induces tertiary lymphoid structures.

Metabolic and alcohol-related liver disease presents challenges in clinical trials due to complex pathophysiology. This Review discusses noninvasive imaging, serum biomarkers and adaptive designs as modalities to enhance patient-centric end points, aiming to refine diagnostics and improve drug development.

Bulk ex vivo and single-cell in vivo CRISPR knockout screens are used to characterize 680 chromatin factors during mouse hematopoiesis, highlighting lineage-specific and normal and leukemia-specific functions.

Joyce, Pascual et al. identify luminal progenitors as likely cells-of-origin in BRCA2-mutant breast cancer, exhibiting dysregulated proteostasis and translation, which may be therapeutically targeted via mTORC1 inhibition.

An analysis of bowel samples from bowhead whales collected yearly from 2004–2022 indicates increasing algal toxin concentrations in Arctic food webs due to warming ocean conditions.

Brainstem gliomas are an aggressive form of paediatric cancer. Here, the authors use metabolomics to assess differences in metabolites during radiotherapy.