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The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

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.

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

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.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

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).

Little sulfur from the 2022 Hunga submarine eruption reached the atmosphere due to seawater–magma interactions, indicating that the climate impact of this type of eruption may be underestimated, according to analysis of ash collected throughout the event.

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.

Scientists disagree about area-based conservation’s role in addressing biodiversity loss. This Perspective examines how conservation scientists, land systems scientists and political ecologists approach these debates differently and argues that environmental data justice frameworks can bridge epistemic divides, helping researchers to develop more effective and equitable conservation interventions.

Hebart et al. developed a computational model of similarity judgements for 1,854 natural objects. The model accurately predicted similarity and revealed 49 interpretable dimensions that reflect both perceptual and conceptual object properties.

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.

Here the authors identify hotspots for wetland carbon uptake and regions where wetland carbon sinks are most susceptible to hydrological shifts. They show that two decades of improved carbon sinks in northern mid- to high-latitude wetlands are offset by declining efficiencies elsewhere.

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.

Observations from the Lucy spacecraft of the small main-belt asteroid (152830) Dinkinesh reveals unexpected complexity, with a longitudinal trough and equatorial ridge, as well as the discovery of the first contact binary satellite.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Ice streams are fundamental to ice sheet dynamics, but the mechanisms controlling their flow remain elusive. Here, the authors perform macro- and microscale analyses of mega-scale glacial lineations, which indicate a continuously accreting, shallow-deforming bed during ice stream flow.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

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.

Aarrestad et al. show that, in contrast to psychedelics, the nonhallucinogenic psychoplastogen tabernanthalog promotes neuroplasticity through 5-HT_2AR activation without immediately increasing extracellular glutamate levels or immediate early gene expression.

The RNA editing enzyme ADAR1 blocks interferon responses triggered by cytosolic RNA sensors, and has been proposed as a potential target in immuno-oncology. Here, the authors report that BRCA1/2 and ADAR1 are synthetic lethal, showing that ADAR1 depletion in BRCA1-mutant cells causes autocrine interferon poisoning

Public companies continued to ride the crest of the wave of financing, licensing deals and regulatory approvals, but clouds may be looming on the horizon for the biggest biotech players. Chris Morrison and Riku Lähteenmäki report.

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.

DNA from ancient wolves spanning 100,000 years sheds light on wolves’ evolutionary history and the genomic origin of dogs.

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.

In the second case in which a genetically modified pig heart was transplanted into a living person, the xenografted heart functioned well initially, but antibody-mediated rejection occurred thereafter, pointing to the need for improved strategies to avoid this complication.

Solar photovoltaics is entering a multi-terawatt era, driven by decades of cost, performance and reliability gains. In this Perspective Alberi et al. discuss the role of historical and future learning, highlighting the increasing importance of sustainability considerations.

Neural Decomposition (NEURD) is a software package that decomposes neuronal data from high-resolution electron microscopy volumes into feature-rich graph representations to facilitate analysis for neuroscience research.

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.

A phase 2 randomized controlled trial of ustekinumab in 72 adolescents with recent-onset type 1 diabetes showed that treatment was well tolerated and β-cell function was 49% higher in the intervention group compared to the placebo arm after 12 months.

The PSA (KLK3) genetic variant rs17632542 is associated with reduced prostate cancer risk and lower serum PSA levels, although the underlying reasons are unclear. Here, the authors show that this PSA variant reduced proteolytic activity and leads to smaller tumours, but also increases invasion and bone metastasis, indicating its dual risk association depending on tumour context; the variant is associated with both lower risk and poor clinical outcomes.

Contier et al. show that dimensions are superior to categories at predicting brain responses to visual objects.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

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

Dense calcium imaging combined with co-registered high-resolution electron microscopy reconstruction of the brain of the same mouse provide a functional connectomics map of tens of thousands of neurons of a region of the primary cortex and higher visual areas.

It may have taken only a decade to repeatedly destabilize the Antarctic Ice Sheet after the last Ice Age as shown by a new data-model study. The ice sheet lost ice for centuries each time before it abruptly re-stabilized again.

Empirically based models of disease progression in familial frontotemporal dementia reveal the relative ordering of clinical, neuroimaging, and fluid biomarker changes and facilitate novel clinical trial designs

A chemical screen identified BET bromodomain inhibitors as promoters of keratinocyte regenerative function and skin wound healing. Specifically, low-dose transient treatment with BET inhibitors imposes an activated, migratory state in keratinocytes.