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Rathmell and colleagues show that metabolic reprograming of regulatory T cells is associated with severity of critical illness in patients with and without sepsis.

Bohlen and colleagues report that the E3 ubiquitin ligase CBL is necessary for the development, tolerance and activation of B cells in humans, unlike in mice where CBL deficiency results in loss of T cells.

Non-pharmaceutical interventions for COVID-19 also reduced circulation of endemic viruses which may have led to immune waning. Here, the authors use multiplex serology data from King County, Washington, US to characterise age-specific changes in antibody levels to a range of endemic viruses during the COVID-19 pandemic.

Living biophotovoltaics generate bioelectricity by harnessing photosynthetic microorganisms, but barriers to electron transfer across the abiotic/biotic interface hinder solar-to-electricity conversion. Here, the authors report a method for boosting photocurrent by integrating the photosynthetic cyanobacteria with a conductive conjugated polyelectrolyte to form 3D living biocomposites.

Deep-sea hydrothermal plumes support an array of microbial metabolisms, but the fate of organic carbon in these systems is unknown. Here, the authors used metabolic rate assays and metagenomic data to show that heterotrophic bacteria contribute significantly to carbon cycling in the deep sea.

This study shows that many plants form a second, deeper root layer underground, enabling access to nutrient-rich deep soil. This previously unnoticed rooting pattern adds to the growing recognition that deep soil dynamics are overlooked.

Bendelac, McDonald and colleagues show that the NK cell-committed precursor in the mouse bone marrow expresses the transcription factor Eomes.

Mesocosm experiments revealed that both phytoplankton community composition and cellular acclimation influence marine particulate C:N:P ratios, with community shifts more sensitive to nitrogen supply and acclimation to the nutrient N:P supply ratio

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

Sequence depth and read length determine the quality of genome assembly. Here, the authors leverage a set of PacBio reads to develop guidelines for sequencing and assembly of complex plant genomes in order to allocate finite resources using maize as an example.

A possible kilonova associated with a nearby, long-duration gamma-ray burst suggests that gamma-ray bursts with long and complex light curves can be spawned from the merger of two compact objects, contrary to the established gamma-ray burst paradigm.

Citrobacter rodentiumis an intestinal pathogen of mice widely used to model enteropathogenicE. coli infection in humans. Using a forward genetic approach, Papapietro and colleagues identify R-Spondin 2 expression and resulting Wnt signalling activation as a major regulator of C. rodentium-induced colitis.

Spatiotemporal characterization of microbial diversity and antibiotic resistance in a tertiary-care hospital reveals broad distribution and persistence of antibiotic-resistant organisms that could cause opportunistic infections in a healthcare setting.

The structure of ties in social networks determines who receives information first, and those early opportunities often confer a competitive advantage. The authors develop the H3 hypergraph model, which reveals how hyperedge homophily drives inequality in information access and suggests that targeted interventions informed by higher-order dynamics can help close those gaps.

In a randomized phase 2 trial, sotigalimab, a CD40 agonist, did not significantly improve overall survival in patients with previously untreated metastatic pancreatic cancer when combined with chemotherapy or with nivolumab and chemotherapy. Multi-omic exploratory analyses provide insights into immunologic features associated with clinical benefit.

Combining a large-scale dataset of 23 ungulate species (in which newborns follow contrasting tactics of predator avoidance) with continuous-time stochastic movement models, the authors reveal that there are multiple dimensions of maternal movement behaviour and space use.

The Vertebrate Genome Project has used an optimized pipeline to generate high-quality genome assemblies for sixteen species (representing all major vertebrate classes), which have led to new biological insights.

ACE2 binding is an ancestral, widespread trait of sarbecovirus receptor-binding domains, and many single mutations enable binding to different ACE2 receptors.

SF3B1 mutations confer sensitivity to poly (ADP-ribose) polymerase inhibitors (PARPi). Mechanistically, this is independent of homologous recombination repair and instead relies on a defective replication stress response due to a reduction of the cyclin-dependent kinase 2 interacting protein (CINP). PARPi treatment of SF3B1 mutant (SF3B1^MUT) tumors leads to replication stress induced by increased fork origin firing and culminates in cell cycle stalling.

Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.

Fluorescent protein reporters based on GFP exist, but have intrinsic disadvantages. Here the authors incorporate pH, Ca²⁺ and protein–protein interaction sensing modalities into de novo designed mini-fluorescence-activating proteins (mFAPs), with increased photostability and smaller size, which bind a range of DFHBI chromophore variants.

SARS-CoV-2 variants of concern are less susceptible to therapeutic neutralizing antibodies, given mutations in the surface glycoprotein S. Here, Case et al. show that therapeutic antibodies S309 and AZD7442 reduce lung infection with SARSCoV-2 Omicron lineages in humanized mouse model despite the loss of neutralizing potency in vitro.

A machine-learning-based strategy called CellOracle combines computational perturbation with modelling of gene-regulatory networks to analyse how cell identity is regulated by transcription factors, and correctly predicts phenotypic changes after transcription factor perturbation in the developing zebrafish.

Among additive manufacturing methods vat photopolymerization (VP) is desired owing to improved efficiency, excellent surface finish, and printing resolution at the micron-scale but the major portion of resins available for VP are based on systems with limited or negligible recyclability. Here, the authors describe an approach that enables the printing of a resin that is amenable to re-printing with retained properties and appearance.

Early-career investigators face growing challenges: dwindling public funding, limited trial leadership opportunities, systemic mentorship barriers, and widening global disparities. At the 20th Breast International Group (BIG) – NCI National Clinical Trials Network (NCTN) annual meeting, four key themes emerged: funding, mentorship, clinical trials, and translational research. This report outlines recommendations for funding and mentorship. Investment in this area is strategic to ensure continued advances for patients globally.

Evidence is presented for a Pines’ demon as a three-dimensional acoustic plasmon in the multiband metal Sr₂RuO₄ from momentum-resolved electron energy-loss spectroscopy using a collimated, defocused beam with high momentum resolution.

Acquired resistance to immune checkpoint inhibitors represents an important clinical challenge. Here, in a pancreatic ductal adenocarcinoma model of acquired resistance to immunotherapy, the authors show that plasticity-induced repression of Irf6 is associated with tumor cell-intrinsic resistance to cytotoxic T-cell activity.

IFNγ-inducible guanylate binding proteins (GBPs) recognize the Toxoplasma gondii vacuole during infection. Here, the authors report that inducible nitric oxide synthase (iNOS) is necessary for efficient parasite clearance by GBPs and that reactive nitrogen species produced by iNOS lead to nitration of the parasite vacuole and collapse of the intravacuolar network space, preventing parasite escape from GBP targeting.

Solanum pimpinellifolium (SP) is the progenitor of cultivated tomato and an important germplasm. Here, the authors assemble SP genome, identify structural variants (SVs) by comparing with modern cultivar, reveal SVs associated with important breeding traits, and detect SVs harboring master regulators of fruit quality traits.

An HIV vaccine that elicits both antibodies and cellular immune responses confers long-lasting protection against viral challenge in nonhuman primates.

Protein lysine methyltransferases modulate the activities of chromatin and non-chromatin proteins by specific methylation of lysine side chains. A large-scale structure-based design approach has yielded a new chemical probe that potently and selectively inhibits G9a and GLP methyltransferases in cells.

Metal-organic frameworks have shown promise as nanoreactors, facilitating the synthesis of molecules that are otherwise difficult to isolate. Here, the authors design a framework featuring unobstructed adenine linkers to which thymine molecules can base-pair, allowing for thymine dimerization in the pores upon UV irradiation.

Single-cell whole-genome sequencing shows that 'foreground' cell-to-cell structural variation and alterations in copy number are associated with genomic diversity and evolution in triple-negative breast and high-grade serous ovarian cancers.

Perivascular and leptomeningeal macrophages, collectively termed here parenchymal border macrophages, are shown to regulate flow dynamics of cerebrospinal fluid, implicating this cell population as new therapeutic targets in neurological diseases such as Alzheimer’s.

Chemotherapy priming sensitizes triple-negative breast cancers to immune checkpoint blockade. However, immune suppressive myeloid cells may impede its optimal effect. Here authors characterise the immune suppressive myeloid cells via single-cell analyses of immune cells from low dose chemotherapy treated breast tumours and identify STAT1 signalling as a regulator for immune suppressive state.

An approach that combines a pH-sensitive synaptic biomarker expressed in vivo with the ex vivo staining of oligodendrocyte precursor cells enables quantification of synapse engulfment by oligodendrocyte precursor cells at single-cell and population-level resolution.

Designing a scalable platform to generate electricity from the energy exchange mechanism between two surfaces separated by nanometer distances remains a challenge. Here, the authors demonstrate reconfigurable, scalable and fully integrated near-field thermo-photovoltaics for on-demand heat recycling.

Patient drug regime compliance is a major issue; sustained release implants could address this. Here, the authors report on a phase inverted in situ forming implant of PLGA for the sustained release of antiretroviral drugs and optimize and demonstrate the release of 6 different drugs over a period of up to a year.

Using single-cell RNA sequencing, CyTOF and multiplex immunohistochemistry, Steele et al. survey the immune landscape in pancreatic cancers, adjacent tissue and blood, observing heterogeneous immune checkpoint receptor expression within patients.

The benefit of combined CDK4/6 and anti-HER2 therapy in breast cancer is limited due to acquired resistance. Here, the authors perform single-cell analysis and show an immature myeloid cell population to infiltrate resistant tumors, and that combined cabozantinib and checkpoint therapy overcome this resistance with a sustained efficacy.

The DNA-binding factor SATB1 is known as a chromatin organizer. Schultze and colleagues show regulation of SATB1 expression by the transcription factor Foxp3 is necessary to confer suppression of effector cell activity.

This protocol for concomitant high-throughput mitochondrial DNA genotyping and accessible chromatin profiling of single cells allows paired analysis of clonal relationships and cell states.

The authors present a multiplex, high-throughput method based on a commercially available multipipettor device to study mechanotransduction in cancer cells and immune cells in response to physiological fluid shear stress.

This protocol describes how to construct and use an open-source robot for automatically performing cranial microsurgeries such as skull thinning and various-sized craniotomies in mice.

This protocol describes a lentiviral tagging approach that permits sequential rounds of cell labeling and lineage reconstruction in cells amenable to viral transduction. Transcriptomes and CellTags are captured simultaneously on a droplet-based scRNA-seq platform.