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Tan and colleagues present “cycling molecular assemblies” that borrow cellular lipidation machinery to build nanostructures inside the Golgi apparatus. These tools enable rapid organelle imaging and selective destruction of cancer cells.

Plasmodium vivax is responsible for most malaria cases outside Africa and drug resistance is a concern. The authors use genomic approaches to identify a deletion near the MDR1 gene that affects its expression and is associated with lower mefloquine susceptibility.

Using inbred medaka strains, the authors mapped 59 genetic loci linked to heart rate. Gene editing validated conserved genes affecting heart rate and morphology, highlighting the power of isogenic strains in uncovering mechanisms of cardiac traits and disease.

Neural crest cells have been implicated in heart development, yet the mechanisms by which they act have remained elusive. Here, the authors show neural crest cells modulate Wnt signalling in cardiac progenitors, providing new insight into the mechanisms underpinning congenital heart defects.

Targeting neurons that regulate energy balance may offer new approaches for obesity treatment. Here, authors show that chemogenetic and pharmacological manipulation of GABAergic neurons in the DRN/vlPAG increases adaptive thermogenesis and reduces weight gain in mice fed a highfat diet.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

APOBEC deaminases restrict retroviruses but can also mutate human DNA. Here, the authors show that cancerassociated APOBEC3s with low RNA binding, known to enter the nucleus, are selectively recognized by E3 ligases and degraded, eliminating harmful nuclear enzymes, and limiting genome mutation.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

As Nature Aging celebrates its fifth anniversary, the journal asks some of the researchers who contributed to the journal early on to reflect on the past and the future of aging and age-related disease research, the impact of the field on human health now and in the future, and what challenges need to be addressed to ensure sustained progress.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

New hominin fossils from the Grotte à Hominidés at Thomas Quarry I (ThI-GH) in Casablanca, Morocco, dated to around 773 thousand years ago are similar in age to Homo antecessor, yet are morphologically distinct.

Quantifying ecosystem dynamics is critical in the face of rapid environmental change. This study uses airborne eDNA to quantify changes in organism abundances across the tree of life and reveal a regional decline in biodiversity over three decades.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Genome-wide association studies incorporating data for populations of African ancestry provide an expanded view of the genetic basis of schizophrenia, which has previously been studied mainly in European and East Asian cohorts.

In an arm of an ongoing multicenter phase 2 trial testing different therapies in patients with genetically profiled grade 2 or 3 meningiomas, treatment with an oral CDK4/6 inhibitor met the primary endpoint for progression-free survival at 6 months in patients with CDK or NF2 alterations.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Climate change can alter when and how animals grow, breed, and migrate, but it is unclear whether this allows populations to persist. This global study shows that shifts in seasonal timing are key to helping vertebrate species maintain population growth under global warming.

A prospective nationwide genomic screening pilot for ten genes in young adults in Australia detected pathogenic variants in 2% of the population, most of whom were ineligible for government-funded genomic testing.

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).

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

A van der Waals heterostructure made from atomic layers of ferroelectric CuCrP₂S₆ and ferromagnetic Fe₃GeTe₂ can offer reversible, non-volatile ferroelectric control of two-dimensional magnetism.

Using single broadband X-ray pulses from a free-electron laser on a gaseous neon target, coherent, nonlinear four-photon interactions with core–shell electrons is demonstrated, representing a strategy for multidimensional correlation spectroscopy at the atomic scale.

De novo and inherited dominant variants in genes encoding U4 and U6 small nuclear RNAs are identified in individuals with retinitis pigmentosa. The variants cluster at nucleotide positions distinct from those implicated in neurodevelopmental disorders.

A cavity-array microscope is realized using intra-cavity lenses to create a two-dimensional array of over 40 modes, each coupled to a single atom in free-space.

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.

The reconstitution of complex biological processes in cell-free systems can support the detailed characterisation of biochemical mechanisms which are difficult to probe in vivo. Here authors present an all-cell-free T7 phage cycle, consisting of cell-sized liposomes encapsulating a cell-free gene expression reaction and a phage receptor at the membrane.

Early results from the phase 2b VIBRANT-HD trial of the oral splicing modulator branaplam in Huntington’s disease suggested reduced cerebrospinal fluid huntingtin levels, but safety monitoring revealed signs of peripheral neurotoxicity, prompting early termination of the study.

The identification of cellular targets for natural products that potently inhibit the growth of cancer cell lines implicates oxysterol-binding proteins in the growth of cancer cells. These natural products, termed ORPphilins, also affect sphingomyelin biosynthesis.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

During the Last Glacial Maximum, the deep Northwest Atlantic was only about 2 °C colder than today, suggesting sustained production of relatively warm North Atlantic Deep Water during the Last Glacial Maximum.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Wastewater-based surveillance tends to focus on specific pathogens. Here, the authors mapped the wastewater virome from 62 cities worldwide to identify over 2,500 viruses, revealing city-specific virome fingerprints and showing that wastewater metagenomics enables early detection of emerging viruses.

Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Polymer thin films that emit and absorb circularly polarised light are promising in achieving important technological advances, but the origin of the large chiroptical effects in such films has remained elusive. Here the authors demonstrate that in non-aligned polymer thin films, large chiroptical effects are caused by magneto-electric coupling, not structural chirality as previously assumed.

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.

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.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.