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Johnson et al. link ARIA, a complication of anti-amyloid therapy, to clonal expansion of cytotoxic CD8 + T cells with glycolytic reprogramming and vascular trafficking potential, with implications for biomarker development and risk mitigation.

Dendritic cells (DCs) are required to establish thymic central tolerance. Here Srinivasan et al. use single-cell transcriptomics to define thymic conventional dendritic cell (cDC) subsets and find that CD8⁺ single-positive thymocytes modulate the thymus environment to regulate plasmacytoid DC and cDC2 homeostasis and interferon signatures in DCs, while CD4⁺ single-positive thymocytes regulate cDC1 activation via cognate and CD40L–CD40 interactions.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

This work presents a unified MS/MS spectral library of drugs and metabolites integrated with standardized pharmacologic metadata, enabling scalable, individualized profiling of drug exposure and metabolism directly from untargeted metabolomics data.

Data provided by Amazonian peoples are used to estimate the value of wild animals as a source of food, including its spatial distribution and nutritional value, providing information that will be key for improved management of forest ecosystems in the region.

Studies of the G-protein-coupled receptor NTSR1 show that the G protein selectivity of this receptor can be modified by small molecules, enabling the design of drugs that work by switching receptor subtype preference.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

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.

Meeting climate mitigation goals requires the early retirement or retrofitting of fossil fuel power plants, creating financial risks from stranded assets. A study now finds that state-owned companies dominate ownership of these risks, with the top 25 of these companies holding up to US$770 billion under a 1.5 °C scenario.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

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.

This prospective cohort study of patients with cancer incorporated antemortem follow-up visits and rapid autopsy analyses, and reports that spikes—rapidly increasing levels—of circulating tumor cell clusters, observed immediately before and at the time of death, along with tumor masses infiltrating large vessels, were cancer-related events associated with patient mortality.

The Sargasso Sea is a natural laboratory for understanding future conditions of warmer oceans and associated nutrient limitation. Here, the authors combined short- and long-read sequencing to survey Sargasso Sea viral communities.

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

A life cycle assessment study is used to examine the impacts of advanced cooling technologies on cloud infrastructure, from virtual machines to server architecture, data centre buildings and the grid.

The US COVID-19 Scenario Modeling Hub produced medium to long term projections based on different epidemic scenarios. In this study, the authors evaluate 14 rounds of projections by comparing them to the epidemic trajectories that occurred, and discuss lessons learned for future similar projects.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

Single-cell DNA sequencing identifies recurrent copy number changes in healthy breast tissue from women with wild-type or germline BRCA1 or BRCA2 mutations.

We find that justice considerations constrain the integrated Earth system boundaries more than safety considerations for climate and atmospheric aerosol loading, and our assessment provides a foundation for safeguarding the global commons for all people.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

Scaling up the recruitment of individuals who have recovered from infection deserves urgent consideration, argue Joshua M. Epstein, Lauren M. Sauer and colleagues.

Work by Klyshko and Kim et al. lays the foundation for simulating pump-probe experiments and demonstrates how the dynamic behaviour of proteins extends to the crystal environment, emphasizing the need for an ensemble view in understanding functional motions.

Genome-wide ancient DNA data from individuals from the Middle Bronze Age to Iron Age documents large-scale movement of people from the European continent between 1300 and 800 bc that was probably responsible for spreading early Celtic languages to Britain.

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.

The GREGoR consortium provides foundational resources and substrates for the future of rare disease genomics.

Prospective evaluation of a machine learning-based early warning system for sepsis, deployed at five hospitals, showed that healthcare providers interacted with the system at a high rate and that this interaction was associated with faster antibiotic ordering.

Prospective evaluation of a machine learning-based early warning system for sepsis, deployed at five hospitals, showed that interaction of health-care providers with the system was associated with better patient outcomes, including reduced in-hospital mortality.

Cas12a represents the next generation of gene editing. Here, the authors present the generation and validation of a Cas12a transgenic mouse model. Additionally, the authors create whole-genome Cas12a knockout libraries, and demonstrate their utility across multiple in vitro and in vivo screens.

A survey of sharks and rays on coral reefs within 66 marine protected areas across 36 countries showcases that the conservation benefits of full MPA protection to sharks almost double when accompanied by effective fisheries management.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

This multisite study detects a link between brain dynamic functional network connectivity and current and future post-traumatic stress symptom severity with a stronger effect in the female group.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

HIV envelope is a target for vaccine development, but induction of broadly neutralizing antibodies has been difficult. Here, the authors show that electroporation with a synthetic DNA vaccine construct allows in vivo production of HIV envelope native like trimers to induce autologous tier-2 neutralizing antibodies targeting a C3/V5 epitope in mice.

By modelling the radio, optical, UV and X-ray data of the unusually bright cosmological explosion AT 2022cmc, Pasham et al. argue for the presence of a highly collimated jet moving at ≳99.99% the speed of light.

Analyses of in vivo models, cell lines and patient-derived samples show that apolipoprotein B mRNA-editing catalytic subunit 3B (APOBEC3B) not only restrains lung tumor initiation but also that its upregulation is associated with resistance to targeted therapies. This study highlights the complex and context-dependent role of APOBEC3B in lung cancer.

In the observational ZERO Childhood Cancer Precision Medicine Program PRecISion Medicine for Children with Cancer (PRISM) trial, children with high-risk cancer were treated with molecular tumor board-recommended therapies, resulting in overall clinical response rates that translated into survival benefit after long-term follow-up.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

Industrial decarbonization poses both risks and benefits for communities. We show how community-based research can move pervasive yet nebulous calls for community engagement to processes that emphasize just and equitable governance.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.