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Humanized glucagon-like peptide 1 receptor (GLP1R) mouse models are used to investigate the neural circuitry through which small-molecule GLP1R agonists modulate feeding, with implications for how these orally delivered weight-loss drugs engage brain reward circuits.

Lithium-ion battery cathode lifetime is limited by large expansion and contraction during cycling. This study uses electrochemical activation to suppress collapse in LiNi_0.9Mn_0.1O₂ cathodes, achieving improved capacity and cycle life.

Using RNAi and CRISPR knockouts, the authors measured sex-specific fitness effects of recent and older genes in somatic and germline tissues of Drosophila melanogaster, revealing antagonistic selection between sexes and tissues.

When senescent cells accumulate during adulthood they negatively influence lifespan and promote age-dependent changes in several organs; clearance of these cells delayed tumorigenesis in mice and attenuated age-related deterioration of several organs without overt side effects, suggesting that the therapeutic removal of senescent cells may be able to extend healthy lifespan.

Intensive control using village malaria posts and mass drug administration reduces parasite effective population size and increases genetic drift, driving founder effects and rapid shifts in resistance allele frequency.

Macrophages can sample antigens from living cells through a trogocytosis-like mechanism that routes ingested material away from degradation, a finding that delineates a previously unknown pathway for antigen presentation to CD8 T cells.

An Fe^III/V redox mechanism in Li₄FeSbO₆ on delithiation without Fe^IV or oxygen formation with resistance to aging, high operating potential and low voltage hysteresis is demonstrated, with implications for Fe-based high-voltage applications.

Here authors define a detailed ontology of point defects in Ti3C2 MXenes through STEM imaging, computer vision and statistical analysis, and MC-MD simulations, providing a framework to understand the 3D structure of MXenes that is applicable to a wide class of 2D materials.

The authors study epitaxial thin films of the pyrochlore-sublattice compound LiTi2O4 by RIXS and ARPES. They observe cooperation between strong electron correlations and strong electron-phonon coupling, giving rise to a mobile polaronic ground state in which charge motion and lattice distortions are coupled.

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.

Longitudinal metatranscriptomics in a prospective cohort of 1,164 adults hospitalized for COVID-19 reveals that azithromycin offered no apparent anti-inflammatory benefit but enriched the respiratory microbiome with potential pathogens and antimicrobial resistance genes.

Obi, Yan and colleagues identified an HIV-1-encoded circular RNA (circHIV) in plasma from people living with HIV and in infected primary cells and T-cell lines. CircHIV binds to the viral Tat protein and enhances transcription from the viral promoter.

Li-rich oxides were found to slowly release considerable quantities of oxygen at varying states of charge. These observations point to the intrinsic instability of oxygen in partially charged oxides and highlight the need for degradation 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.

The RNA methyltransferase activity of SPOUT1/CENP-32 is crucial for accurate mitotic spindle organization. Here, the authors describe a neurodevelopmental disorder caused by bi-allelic pathogenic SPOUT1 variants with reduced activity and compromised function in spindle organization.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

This study defines the consequences of ARID1A and ARID1B loss in dedifferentiated or undifferentiated endometrial carcinoma, finding that altered SWI/SNF chromatin remodeler complex subtypes support oncogenesis, informing potential therapeutic opportunities.

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

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.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

Conducting a simulated turtlegrass herbivory experiment across 650 experimental plots and 13 seagrass meadows, the authors show that the negative effects of herbivory increase with latitude, driven by low levels of light insolation at high latitudes.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Mitochondria play roles in sensing environmental and physiological stress, but their response can become maladaptive during chronic stress. Here they identify a protective miRNA response in C. elegans that maintains tissue health by attenuating mitochondrial stress signaling.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

PCSK9 regulates low density lipoprotein-cholesterol import and determines organ preference of metastatic pancreatic ductal adenocarcinoma, with PCSK9-low cells metastasizing to the liver and PCSK9-high cells preferring the lung.

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.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Inorganic lithium superionic conductors are central to the development of solid-state batteries, but the availability of practical superionic conductors is still limited. This Review highlights structural and chemical strategies to enhance ionic conductivity and maps a strategic approach to discover, design and optimize fast lithium-ion conductors for safe and high-energy-density all-solid-state batteries.

A common mechanism of inhibition of the essential lipid II flippase MurJ by three distinct phage-encoded single-gene lysis proteins provides insights into potential new targets for antimicrobial development.

Engineering polymerases to synthesize alternative genetic polymers remains a challenging problem in synthetic biology. Using DNA shuffling and droplet microfluidics, the current study provides a short evolutionary path from a DNA polymerase to one with robust RNA-synthesizing activity.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

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.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

Mutations in the PBAF chromatin-remodeling complex cause various neurodevelopmental disorders. This study shows that PBAF shapes distinct motor neuron identities, revealing how its disruption impairs movement and offering insight into neurodevelopmental disorders caused by PBAF mutations.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Stomata enable gas exchange for photosynthesis but close to promote survival during drought. Here, Henry et al. provide evidence for a safety-efficiency trade-off whereby plants with greater stomatal conductance under well-watered conditions are more sensitive to stomatal closure during dehydration.

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.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Magneto-optical traps (MOTs) are a workhorse for laser cooling of atoms and were recently extended to molecules. Yet, new mechanisms for molecular trapping and cooling are still an open area of exploration. Here, the authors show a blue-detuned MOT based on a conveyor-belt effect for CaF molecules, yielding higher number densities, comparable with some atomic MOTs.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

High-quality chemical safety information is essential, but information is often fragmented, inconsistent and incomplete. As a result, users face unrealistic expectations in applying risk-based principles. This article highlights persistent challenges and urges stakeholders to improve access, accuracy and application of chemical safety data.