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ATP synthase powers cells by converting proton translocation into energy. Here, authors reveal distinct structural features of the P. aeruginosa ATP synthase that regulate activity and may serve as targets for new antimicrobial therapies.

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.

Genomic analyses of DNA from modern individuals show that, about 800 years ago, pre-European contact occurred between Polynesian individuals and Native American individuals from near present-day Colombia, while remote Pacific islands were still being settled.

Pulmonary type 2 inflammation is associated with type 2 innate lymphoid cells. Here the authors use the Collaborative Cross mouse panel to show that ILC2 abundance during type 2 lung inflammation is different across the panel and identify free-fatty acid receptor 3 (Ffar3) as a gene responsible and show cytokine and ILC2 functional changes.

Multidrug efflux pumps help bacteria survive stress and promote antibiotic resistance. Here, authors define the molecular detail of an anaerobic-connected pump MdtF uncovering acid-responsive activity which may enable toxin control in certain niches.

The authors report on imaging developments of solid-density plasmas and the current filamentation instability by means of the LCLS-XFEL at SLAC. This offers insights on the instability in the solid density region, stimulating new modelling of laser-solid interactions.

Understanding tumor heterogeneity and its impact on prostate cancer progression remains elusive. Here, single nucleus snATAC and snRNA sequencing of a multi-loci sampled cohort of advanced prostate cancer patients identifies an inflammatory-like state underlying metastatic dissemination to the lymph nodes.

Targeting individual DNA secondary structures in the genome with small molecules is challenging. Here, the authors develop ATENA, a CRISPR-based platform for targeting specific DNA structures in cells with high precision, helping to elucidate their biological roles and guide therapeutic design.

This study provides new insights into the role of endoglin (ENG) as a co-receptor in endothelial cells and addresses a gap-in-knowledge on how ENG could be involved in both TGF-β and BMP9 signalling. Such knowledge greatly facilitates therapeutic targeting of ENG-related pathways.

Small proteins (<50 kDa) are difficult to resolve by cryo-EM due to low signal-to-noise ratios and alignment challenges. Here, authors engineered conformationally rigid antibody fragments (Rigid Fabs) enabling high-resolution cryo-EM structures of small (~20 kDa) proteins like KRAS.

Single-molecule chromatin fiber sequencing exposes single-cell-level heterogeneity in the chromatin architecture of individual regulatory elements.

This study shows that spatial contexts with more reliable brain representations better support memory for future experiences within them, revealing how stable neural maps help the brain organize and recall life events.

STING–type-I interferon pathway regulates the immunogenicity of several cancer types, including head and neck squamous cell carcinoma. Here the authors describe that glutamine metabolism in the tumour microenvironment dampens the STING–type-I interferon pathway by epigenetically silencing the expression of BATF2, which functions as a tumour suppressor.

Gravitational lens modelling of a million-solar-mass dark object reveals that it cannot be a free-floating black hole or dark-matter halo as predicted by cold dark matter, instead indicating a peculiar and highly concentrated mass distribution.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

Most human genes undergo alternative splicing, but population-level variation is poorly understood. Here, the authors map over 57,000 naturally variable exons across 838 individuals, revealing widespread splicing diversity and its impact on gene expression and genetic interpretation.

Laboratory automation, machine learning, and metabolic engineering may be combined to quickly and efficiently build productive microbial strains. Here the authors used these techniques in P. putida to boost isoprenol titers 5-fold over six DBTL cycles while sampling a reduced design space.

Colorectal cancer is often diagnosed at later stages, leading to poor prognosis. Here, the authors utilise analysis of rectal mucus specimens using host and microbial analysis to detect cancer lesions.

The endoplasmic-reticulum (ER) transmembrane protein IRE1 mitigates ER stress through kinase-ribonuclease and scaffolding activities. However, a significant nonenzymatic IRE1 dependency has been shown in cancer. Here, the authors design a proteolysis-targeting chimera (PROTAC) to fully disrupt cellular IRE1 protein, selectively blocking growth of IRE1-dependent cancer cells.

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.

The clinical adaptation of CRISPR assays is constrained by complexity and the absence of quality control. Here, authors report a thermally regulated asynchronous CRISPR-enhanced assay enabling direct, highly sensitive one-step detection of monkeypox virus and a human gene in clinical samples.

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

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.

Germano-silicate used as a building material for integrated photonics circuits substantially reduces optical losses, approaching levels comparable to those in optical fibres.

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.

Microplastics (MPs) represent an environmental hazard which must be resolved by efficient, cheap, and sustainable remediation technology. Here the authors use an engineered algae to capture MPs and treat wastewater, the captured algae-plastic mix is upcycled into a tougher bioplastic composite.

Visual experience synchronizes V1–LM theta oscillations, strengthens V1 → LM connectivity, and drives dendritic spine remodeling in WT mice, the processes disrupted in Fmr1 KO mice, revealing impaired inter-areal binding in Fragile X syndrome.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

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.

Heterogeneity within clonal cell populations affects bioprocess engineering. Here, the authors report a biosensor-based toolkit to investigate phenotypic heterogeneity in engineered yeast, reveal pH-based subpopulations and metabolite production states, and modulate/shift subpopulation dynamics to increase lycopene production.

Coordinated X-ray and radio observations reveal that disk winds and jets occur mutually exclusively in 4U 1630–472, providing new observational constraints on the interplay between different modes of outflow in X-ray binaries.

Regrowth of lost enamel in tooth decay and sensitivity is a major obstacle to overcome. Here, the authors report on a protein-based material that mimics features of natural enamel formation, allowing for epitaxial growth of apatite nanocrystals to restore enamel structure and function.

The authors report superconducting topological surface states (TSS) on MBE-grown Fe(Te,Se) films by high-resolution laser-ARPES. Near the FeTe limit, the surface state disappears due to an electron-correlation-driven topological transition associated with decoherence of the d_xy-orbital-derived bands.

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.

Turley and colleagues find that Gremlin1-expressing lymph node fibroblastic reticular cells support dendritic cell homeostasis via provision of FLT3L.

Here, the authors integrate genomic and transcriptomic data obtained from African-ancestry female participants and identify six genes associated with breast cancer risk which provides biological insights into this common cancer in an underrepresented population.

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.

This study explores the genetic structure of hepatitis C virus outbreaks in rural U.S communities affected by the opioid crisis. Analysis of intra-host viral populations from 692 participants reveals hidden transmission networks.

How to effectively communicate climate change to the public has long been studied and debated. Through a registered report megastudy, researchers tested the ten most-cited climate change messaging strategies published, finding that many had significant, but small, effects on climate change attitudes.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

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.

Scaling Si spin qubits relies on the uniform control of qubit-host interactions. This work finds correlations in qubit energy levels across a manufactured device arising from placement of Ge in the quantum well, consistent with atomistic modeling.

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.

CaBLAM is a bioluminescent genetically encoded calcium indicator that delivers high-contrast signals as shown in cell culture, in the in vivo mouse brain and in zebrafish larvae.

Human challenge studies with SARS-CoV-2 have shown changes in the innate and adaptive immune response. Here the authors are examining potential correlates of infection in virus challenged recipients by assessing baseline immune parameters and how this predicts virus control.

The tolerogenic activity of type 1 conventional dendritic cells (cDC1s) is determined by EPOR, which is preferentially expressed in cDC1s and induces antigen-specific FOXP3-expressing regulatory T cells.

The host microbiome may influence asthma susceptibility differently across diverse geographic or ethnic populations. Here the authors perform a microbiome study of asthma in US Hispanic/Latino adults and evaluate the influence of obesity and genetic factors on the relationship between microbiome characteristics and asthma.