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Mendelian randomization (MR) and colocalization analyses are used to estimate causal effects of 1,002 plasma proteins on 225 phenotypes. Evidence from drug developmental programs shows that target-indication pairs with MR and colocalization support were more likely to be approved, highlighting the value of this approach for prioritizing therapeutic targets.

Two drugs, miconazole and clobetasol, have functions that modulate differentiation of oligodendrocyte progenitor cells directly, enhance remyelination, and significantly reduce disease severity in mouse models of multiple sclerosis.

A recurrent gain-of-function mutation in ARAF causes lymphatic anomaly in two unrelated patients, and treating one of the patients with an FDA-approved MEK inhibitor resulted in a remarkable recovery, exemplifying the power of precision medicine.

The marine nitrogen cycle was altered during the transition from glacial to interglacial conditions. An analysis of δ¹⁵N records throughout the world’s oceans suggests that rates of denitrification in the water column accelerated during the last deglaciation.

Anthony Bleyer, Eric Lander, Mark Daly and colleagues show that frameshift mutations in a large VNTR of MUC1 cause medullary cystic kidney disease type 1. Their discovery sheds light on the biology of this disease and highlights challenges in using massively parallel sequencing technologies to characterize certain types of sequence variants.

In the first-ever Undiagnosed Hackathon, nearly 100 experts from 28 countries combined advanced phenotyping and genomic techniques for 48 hours, ultimately providing diagnoses to 40% of the previously undiagnosed families. This inspiring model demonstrates the power of multidisciplinary collaboration and patient partnership in precision diagnostics.

TRACERx Lung: Intratumoral transcriptional heterogeneity, which often hinders the development of clinically useful RNA-expression-biased biomarkers for cancer, can now be overcome with an approach for the identification of clonal expression biomarkers.

Nutrient content analyses of marine finfish and current fisheries landings show that fish have the potential to substantially contribute to global food and nutrition security by alleviating micronutrient deficiencies in regions where they are prevalent.

A genome-wide association study of approximately 7,000 patients with neurodevelopmental disorders demonstrates that overall risk and clinical presentation in putative monogenic disorders is also influenced by common genetic variants present in the general population.

Implantation of a synthetic mid-urethral sling (SMUS) is the most widely used anti-incontinence surgery performed in women. Despite this widespread use, a dearth of knowledge of the safety, risks and potential complications of SMUS currently exists. Here, Jerry Blaivas and co-authors draw upon the available evidence to provide an in-depth review of the risks of SMUS-associated complications.

Pulmonary venous tumor cells disseminating before tumor resection are heterogeneous, predict relapse and seed future metastasis of lung cancer

Scalable and rapid target enrichment method for next-generation sequencing of clinical-grade, formalin-fixed paraffin-embedded cancer samples.

Although compound semiconductors like gallium arsenide (GaAs) offer advantages over silicon for photovoltaic and optoelectronic applications, these do not outweigh the costly process of growing large layers of these materials and transferring them to appropriate substrates. However, a new fabrication approach is now demonstrated: films of GaAs and AlGaAs are grown in thick, multilayered assemblies in a single sequence; the individual layers are then released and distributed over foreign substrates by printing.

Ozone depletion has altered conditions at the Earth’s surface and interacts with climate change. This Review assesses the effects on humans and ecosystems, including implications for food and water security, and the mitigating and ongoing influence of the Montreal Protocol.

Arul Chinnaiyan and colleagues report the curation of 7,256 RNA sequencing libraries from tumors, normal tissues and cell lines. They find 58,648 lncRNAs, of which 79% are previously unnannotated.

A 26-million-year record of equatorial sea surface temperatures reveals synchronous changes of tropical and polar temperatures during the Eocene epoch forced by variations in concentrations of atmospheric carbon dioxide, with a constant degree of polar amplification.

Proteomics, lipidomics and metabolomics of single gene deletion yeast strains sheds light on mitochondrial protein biology.

Multiregion spatial histology, exome and transcriptome data from patients with non-small cell lung cancer suggest that cancer subclones from immune cold regions diversify later than subclones from immune hot regions

MEK1 and MEK2 have key roles in tumorigenesis and, therefore, represent promising targets for cancer therapy. This Review discusses the mechanisms of action of different inhibitors of MEK1 and MEK2, the mechanisms of resistance to these inhibitors and their current clinical progress.

Jian Yang and colleagues propose a method that integrates summary data from GWAS and eQTL studies to identify genes whose expression levels are associated with complex traits because of pleiotropy. They apply the method to five human complex traits and prioritize 126 genes for future functional studies.

Community energy is a promising alternative to large-scale energy provision that could support decarbonization efforts. This study analyses business models, financing mechanisms and the financial performance of community energy projects in the UK to understand what is needed to better support the sector.

Prenatal immune suppression is regulated by fetal arginase-2-expressing dendritic cells which respond normally to toll-like receptor stimulation but, in contrast to adult dendritic cells, induce regulatory T cells and repress TNF-α secretion by effector T cells.

Five current human African trypanosomiasis drugs are used for genome-scale RNA interference target sequencing screens in Trypanosoma brucei, and reveal the transporters, organelles, enzymes and metabolic pathways that function to facilitate antitrypanosomal drug action.

Our ability to use conceptual knowledge to support various behaviours is termed semantic cognition. In this Review, Lambon Ralphet al. argue that this ability arises from two interacting neural systems, one for representation and one for control.

Advances in the treatment of childhood cancers have substantially improved cure rates, although the gains in survival are offset by an elevated burden of morbidities and an excess risk of early death owing predominantly to the adverse effects of therapy. In this Review, the authors summarize the evolution of paediatric cancer therapies over the past five decades as well as the associated landscape of treatment-related late and/or long-term health conditions experienced by childhood cancer survivors. In addition, they discuss strategies that are being explored to reduce the overall burden and consequences of these morbidities with the ultimate aim of improving not only the quantity but also the quality of life-years gained for this large, medically vulnerable population.