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Modeling analysis from the Global Dietary Database estimated that 70% of new global cases of type 2 diabetes are attributable to suboptimal intake of 11 dietary factors, with substantial differences in dietary risks across world regions and nations.

Cryo-EM has facilitated structural studies of membrane proteins, but inactive GPCRs have remained inaccessible due to their small size. Robertson et al. demonstrate a common nanobody-based approach to streamline the determination of such structures.

The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.

This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

Cassava is a major source of food in tropical and subtropical regions. Here the authors sequence the genomes of wild and domesticated cassava varieties and identify genes that have been selected for and against during the evolution and domestication of this economically important crop.

The One Thousand Plant Transcriptomes Initiative provides a robust phylogenomic framework for examining green plant evolution that comprises the transcriptomes and genomes of diverse species of green plants.

Structural changes mediated by advanced glycation end-products enhance extracellular matrix viscoelasticity, and that viscoelasticity can promote cancer progression in vivo, independent of stiffness.

Interpreting untargeted mass spectrometry (MS) data is challenging due to incomplete reference libraries. Here, the authors created the nearest neighbor suspect spectral library from largescale public MS data, significantly enhancing the ability to hypothesize structures for unknown mass spectra.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

Bitopic functionalized ligands based on fentanyl can target the sodium ion-binding site of the mu-opioid receptor and selectively modulate downstream signalling pathways, potentially leading to safer analgesics.

The role of gastrin related peptide (GRP+) neurons in itch is debated. Here, the authors generate a conditional knock-in mouse to label and manipulate GRP expressing DRG neurons and investigate their role in itch and nociception.

Lead halide perovskites have recently emerged as a promising platform for the study of polariton superfluidity at room temperature. Here the authors report a complete set of quantum fluid phase transitions in both 1D and 2D homogeneous single crystals of CsPbBr₃.

This Perspective lays out the impetus and goals of the Cellular Senescence Network established to comprehensively identify and characterize senescent cells (SnCs) across tissues and lifespan, providing a publicly available SnC atlas.

Promyelocytic leukemia protein (PML) is a scaffolding protein that organizes PML nuclear bodies. Here the authors present the tetrameric crystal structure of the PML RING domain and show that RING tetramerization is functionally important for nuclear body formation and PML sumoylation.

Rheumatoid arthritis patients respond differently to anti-TNF treatment. Using community-based challenge, the authors show that currently available data does not reveal meaningful genetic predictors of response to anti-TNF therapy, thus confirming clinical observations.

This study demonstrated that a PIN2-based transient polar auxin transport, through a file of elongated marginal cells (MCs), in the borders of cotyledons, underpins the formation of an auxin maximum at the tip of cotyledons. This auxin maximum contributes to the coordinated morphogenesis of the interdigitated puzzle-shaped pavement cells at the very early stage of cotyledon expansion.

BK channels are regulated by membrane voltage and intracellular Ca2+ but the structural features that block the ion flow in the closed state remain unknown. Here authors use molecular dynamics simulation and show that a physical gate is not required; instead ion flow is regulated by hydrophobic dewetting due to changes in pore shape and surface hydrophobicity.

MYCN is frequently amplified in neuroblastomas. Here, the authors show that MYCN disrupts the molecular clock by downregulating clock activator RORα and that the reactivation of RORα restores BMAL1 activity, and inhibits lipid metabolism and neuroblastoma growth

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

Cryo-EM structures of µ-opioid receptor complexes with two agonists coupled to molecular dynamics simulations and functional assays highlight distinct efficacy for G protein subtype activation and β-arrestin recruitment.

The prodrug gliocidin effectively kills glioblastoma cells by targeting de novo purine synthesis, improving survival in mouse models.

Genomic, transcriptomic and DNA methylation data from tissue samples from 208 Chinese patients with prostate cancer define the landscape of alterations in this population, and comparison with data from Western cohorts suggests that the disease may stratify into different molecular subtypes.

When a viscous fluid is displaced by a less viscous phase between two plates, a finger-like instability occurs. Here the authors demonstrate how applying an external electric field can suppress the fingering instability without the need to alter the fluid flow rate or the gap geometry.

Non-addictive treatments for pain are much needed. Here, the authors identify in vivo active leads for inflammatory pain using large library docking against the EP4 prostaglandin receptor.

Intermediate-depth waters in the Atlantic and Pacific Oceans were well equilibrated with the atmosphere through the last deglaciation, according to radiocarbon data from deep-sea corals.

Multi-ancestry genome-wide association analyses identify new risk loci for Parkinson’s disease, and fine-mapping and co-localization analyses implicate candidate genes whose expression is associated with disease susceptibility.

Biased signaling in κ-opiod receptors (KOR) offer an attractive strategy for pain management. Here the authors identify determinants of KOR signaling bias using structural methods in combination with molecular dynamics simulations.

A second harmonic with a conversion efficiency of 0.049% W⁻¹, originating from surface nonlinearity and bulk multipole response in a silica whispering-gallery microcavity, is observed with a continuous-wave pump power below 1 mW.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Massively parallel DNA sequencing allows entire genomes to be screened for genetic changes associated with tumour progression. Here, the genomes of four DNA samples from a 44-year-old African-American patient with basal-like breast cancer were analysed. The samples came from peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The findings indicate that cells with a distinct subset of the primary tumour mutation might be selected during metastasis and xenografting.

Studies on the µ-opioid receptor using fluorescent labelling of intracellular residues and energy transfer experiments in the presence of different ligands with or without G-protein binding reveals conformational changes that correlate to ligand efficacy.

The gut virome is a complex ecosystem and has a critical role in human health. This Review outlines gut virome composition and functional relevance, and its role in human health and disease. Methodological challenges in advancing our knowledge of the gut virome are also discussed.

How accurate are social scientists in predicting societal change, and what processes underlie their predictions? Grossmann et al. report the findings of two forecasting tournaments. Social scientists’ forecasts were on average no more accurate than those of simple statistical models.

The detection of microorganism-associated ligands by plant cells activates a signalling cascade in which the kinase BIK1 is monoubiquinated, released from the FLS2–BAK1 complex, and internalized by endocytosis.

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.

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.

Treatment of KRAS^G12C-mutant cancer cells with the KRAS(G12C) inhibitor AMG 510 leads to durable response in mice, and anti-tumour activity in patients suggests that AMG 510 could be effective in patients for whom treatments are currently lacking.

Baobab is a long-lived tree that holds great economic, ecological, and cultural value. Here, the authors report haploid chromosome-level reference genome of Adansonia digitata and draft assemblies for a sibling tree, two trees from distinct locations in Africa, and a related species from Madagascar.

Clinical and genetic evaluation of individuals with childhood-onset amyotrophic lateral sclerosis identifies a new monogenic cause for early-onset ALS and proposes a specific metabolic mechanism leading to motor neuron disease via sphingolipid excess.

To help determine how life history traits of individuals result in emergent properties of a population, laboratory studies of Caenorhabditis elegans were combined with an individual-based simulation, pointing out to potential factors that influence old age as a cause of death.

This study uses gene expression predictors for the dorsolateral prefrontal cortex and other brain regions to perform a transcriptomic imputation analysis of schizophrenia, identifying 413 genic associations across 13 brain regions and 36 significantly enriched pathways.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

New agonists of the serotonin 5-HT_2A receptor (5-HT_2AR) confer high brain permeability and antidepressant activity and—in contrast to classic 5-HT_2AR agonists—lack psychedelic activity.

In an extended follow-up of a phase 1 trial evaluating a first-generation GD2-directed CAR-T cell therapy in patients with neuroblastoma, one patient has had a sustained clinical response for over 18 years without requiring any additional therapy, with translational data from long-term survivors providing broader insights into potential determinants of CAR-T cell response.

Pachytene Piwi-interacting RNAs (piRNAs) expressed in mammalian germ lines are abundant, but their evolution and function are not fully understood. Here, the authors find that pachytene piRNA loci are hotspots of structural variation, which underlies rapid piRNA birth, divergence, and loss.