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Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.

An integrated transcriptome, genome, methylome and proteome analysis of over 200 lung adenocarcinomas reveals high rates of somatic mutations, 18 statistically significantly mutated genes including RIT1 and MGA, splicing changes, and alterations in MAPK and PI(3)K pathway activity.

Matthew Meyerson, Ramaswamy Govindan and colleagues examine the exome sequences and copy number profiles of 660 lung adenocarcinoma and 484 lung squamous cell carcinoma tumors. They identify novel significantly mutated genes and amplification peaks and find that around half of the tumors have at least five predicted neoepitopes.

The widespread occurrence of young grabens associated with larger compressional structures on Mercury’s surface suggests contractional tectonism has continued on the planet into geologically recent times.

Here, the authors show through recordings of magnetic and haemodynamic brain activity, that prediction error computations—representing the difference between heard and predicted speech sounds—are fundamental to the recognition of spoken words in human listeners.

New antimalarials are urgently needed. Here, the authors identify Open Source Malaria compound, OSMS-106, as a reaction hijacking inhibitor of the malaria parasite protein synthesis machinery, with potential use for treatment and prophylaxis.

The helicity barrier mechanism causes transfer of Alfvénic turbulent energy into ion-cyclotron waves in the solar atmosphere, playing a key role in solar-wind heating and in generating the observed differences between slow and fast solar wind.

Genome-wide analyses of ancient DNA from individuals from California and Mexico shed light on the spread of Mexican ancestry to California and how it correlates with linguistic flow.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

Bayesian Flow Networks generate diverse, novel, and coherent protein sequences, surpassing prior unconditional generation methods. They also permit flexible conditional generation during inference, which is demonstrated on antibody inpainting tasks.

The sustainable and scalable synthesis of chiral amines remains a significant challenge in industrial chemistry, particularly due to the limitations of current biocatalytic processes in achieving high productivity and selectivity at scale. This study reports a dynamic kinetic resolution strategy that integrates flash thermal racemization with enzymatic resolution in a continuous flow system, achieving unprecedented productivity, excellent enantioselectivity, and industry-relevant green chemistry metrics at scales up to 100 grams.

Mouldable hydrogels find a variety of applications in the biomedical industry. Here, Appel et al. show a method to fabricate hydrogels through a self-assembly process based on the interaction between biopolymers and functional nanoparticles for multistage drug delivery in vivo.

Binding of the Tudor domain of the PHD finger protein PHF1 to H3K36me3 inhibits Polycomb PRC2 complex methyltransferase activity. Here, Musselman et al.characterize this interaction in the context of the full nucleosome and show dual binding of the PHF1 Tudor domain to H3K36me3 and double-stranded DNA.

Sexual interactions with males shorten the lifespan of the opposite sex in several species, including Caenorhabditis elegans, but the mechanisms are not fully understood. Here the authors use transcriptomic profiling in C. elegans to systematically identify the genetic pathways involved in male-induced demise, which include upregulation of a conserved ion channel that regulates fat metabolism.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

Seder and colleagues use a self-assembling nanoparticle vaccine and adjuvant to expand stem-like CD8⁺ T cells and trigger potent antitumor responses.

Prospective assessment of a T-cell-inflamed gene signature and tumor mutational burden is feasible in patients with non-small cell lung cancer randomized to receive various anti-PD-1-based treatment combinations, with an encouraging objective response rate for first-line pembrolizumab + lenvatinib in one biomarker-defined group.

Leaf rust and stripe rust of wheat are two important fungal diseases of cultivated wheat and they are caused by infection of different pathogens. Here, the authors report the nucleotide-binding leucine-rich repeat (NLR) protein encoding gene Yr87/Lr85 confers resistance to both diseases.

Multi-ancestry genome-wide analyses identify new risk loci for age-related macular degeneration. Ancestry-specific analyses identify distinct effects at major risk loci, including smaller effect sizes for CFH risk alleles in haplotypes of African ancestry.

A multiancestry genome-wide association study of chronic alanine aminotransferase elevation identifies candidate risk loci for nonalcoholic fatty liver disease, with replication in external cohorts defined by histology or imaging.

Maize production is dependent on Nitrogen fertilizer input. Here, the authors use long-term and short-term experiments to demonstrate that economic and environmental optimum nitrogen fertilization rates have increased between 1991 and 2021.

The role of nicotinic acetylcholine receptors in human cortical development remains largely unexplored. Here authors investigate CHRNA7 and CHRFAM7A, uncovering their involvement in radial glial cell proliferation and neuronal differentiation, and identify YAP1 as a downstream effector of cholinergic signaling.

The BioDIGS project is a nationwide initiative involving students, researchers and educators across more than 40 research and teaching institutions. Participants lead sample collection, computational analysis and results interpretation to understand the relationships between the soil microbiome, environment and health.

Understanding the effect of vaccination on emerging SARS-CoV-2 variants of concern is of increasing importance. Here, James et al. report that two doses of vaccination with the Pfizer-BioNTech vaccine induce more robust immune responses to the B.1.1.7 and B.1.351 SARS-CoV-2 lineages than does natural infection.

In Vibrio cholerae, a type IVa pilus (T4aP) binds to exogenous DNA, and threads this DNA through the outer membrane secretin, PilQ. Here authors present the cryoEM structure of PilQ from native V. cholerae cells and design a series of mutants to reversibly regulate VcPilQ gate dynamics.

HIV reservoir dynamics are still incompletely understood. Here, the authors use barcoded HIV in a humanized mouse model to show that cell clones linked to viremia are likely eliminated, while proliferated cell clones contribute to viremia, are likely more resistant to elimination and might fuel viral persistence.

A study of retrotransposon activity repurposes a retroelement called R2Tocc to create a programmable system called STITCHR that enables diverse genome edits including efficient, scarless large payload insertions.

Here, the authors perform transcriptional profiling on tracheal aspirates of adults requiring mechanical ventilation for SARS-CoV2-induced acute respiratory distress syndrome (ARDS) and identify a dysregulated host response predicted to predicted to be potentially modulated by dexamethasone.

A selection-based screen has now revealed preferences in small-molecule chemotypes that bind RNA as well as preferences in the RNA motifs that bind small molecules. Analysis of these data enabled the design of a small molecule that selectively binds a non-coding microRNA and upregulates expression of vascular endothelial growth factor A.

As proof of principle, an analysis using a suite of human-aligned immunocompetent mouse models of hepatocellular carcinoma identifies a promising therapeutic candidate, cladribine, which acts in a highly effective subtype-specific manner in combination with standard-of-care therapy.

Phosphatase of regenerating liver 3 (PRL3) is usually found intracellularly, and is over-expressed in cancer cells. Here the authors show that PRL-3 is also detectable on cell surface, and can be recognized by PRL3-zumab to recruit immune cells into tumor to promote anti-tumor immunity, thereby implicating PRL-3 as a potential tumor antigen.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

While greater yam provides food and income security for millions of people around the world, there are limited genomic resources available. Here, the authors report a chromosome-scale assembly of the greater yam genome as well as quantitative trait loci associated with anthracnose resistance and tuber traits.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease. Here, Wray and colleagues identify association of the GPX3-TNIP1 locus with ALS using cross-ethnic meta-analyses.

Cooperative interactions among tumor cells may have important implications for metastasis. Here, the authors examined the spatio-temporal nature of interactions among clonal populations of ovarian carcinoma cells and found that transient interactions cells can promote metastases via commensal interactions.

A genomic and transcriptomic analysis of 2,754 childhood acute lymphoblastic leukemias identifies 376 putative driver genes, and associations between disease subtypes and prognosis.

Fractal topologies are ubiquitous, and synthetic fractal objects provide unique functional advantages by virtue of their high surface area:volume ratios. Now, a computationally guided bottom-up design approach for constructing protein-based fractal assemblies in response to phosphorylation has been developed. Designed assemblies are shown to perform reversible and efficient molecular capture.

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.

During female gametogenesis in plants, the Megaspore Mother Cell (MMC) accumulates β−1,3-glucan. Here Pinto et al. show that increased β−1,3-glucanase in the MMC delays β−1,3-glucan deposition, disrupts cell identity, and halts gametogenesis.

Iris Heid, Gonçalo Abecasis, Sudha Iyengar and colleagues report the results of a large genome-wide association meta-analysis of macular degeneration based on over 43,000 subjects. They identify 16 new risk loci, including some very rare coding variants.

Existing datasets of nitrogen (N) balance in agriculture are often discrepant. Comparing 13 of them regarding five metrics (fertilizer application, manure application, biological N fixation, atmospheric deposition, and N harvested as crop products) over 1961–2015 reveals why. Recommendations for improving N quantification and an N budget benchmark dataset are also proposed.

An analysis of the impact of logging intensity on biodiversity in tropical forests in Sabah, Malaysia, identifies a threshold of tree biomass removal below which logged forests still have conservation value.

This paper describes molecular subtypes of cervical cancers, including squamous cell carcinoma and adenocarcinoma clusters defined by HPV status and molecular features, and distinct molecular pathways that are activated in cervical carcinomas caused by different somatic alterations and HPV types.

GABA-releasing neurons from the ventral tegmental area that project to the nucleus accumbens are shown to block the firing of cholinergic accumbal interneurons, affecting learning in mice.

Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.

The integration of α-tantalum in superconducting circuits has significantly enhanced transmon qubit coherence times, yet conventional high-temperature deposition methods pose compatibility challenges with thermally sensitive components. Here, the authors demonstrate a room-temperature growth process using a niobium seed layer, resulting in resonators with state-of-the-art quality factors, thereby expanding the practical applications of α-tantalum in superconducting circuits.

Parvalbumin-positive interneurons in the hippocampal CA3 substantially reduce firing on approach to and at goal locations while food-deprived mice learn to find food.