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Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

Mycobacterium tuberculosis owes its success partly to its ability to enter a ‘dormant’, non-replicative state, reactivating years or even decades after initial infection. In this work, authors find that a key alteration in a gene involved in this dormancy response has evolved, or is evolving, in parallel in human-adapted lineages across the globe.

High-latitude soils are future soil organic carbon loss hotspots, with losses dominated by particulate organic carbon (POC). The fraction of POC in total SOC (f_POC) is a key indicator, emphasizing the climate importance of preserving POC.

Antibody mediated prevention (AMP) trials with the broadly neutralizing antibody VRC01 showed protection against VRC01-sensitive viruses. Here, by deep sequencing plasma samples from 172 participants of the AMP trials, the authors show a high frequency of multilineage HIV infections (38%), including coinfection with both sensitive and resistant viruses, and demonstrate that VRC01 doesn’t alter the transmission bottleneck.

When 100 social and behavioural science claims were examined, 34% of reanalyses closely matched the original results, with 74% reaching the same conclusion, revealing limited robustness of single-path analyses and the need to address analytical uncertainty.

Using an evolutionary optimization approach, the authors report a culture medium that matures stem cell-derived heart cells, improving their structure, metabolism and electrical activity to advance highly functional models for in vitro testing.

Exhaustion is a functional state that hampers anti-cancer and antiviral CD8 T cell activity, and is preceded by a stem-like state, maintained by the transcription factor TCF1. Here authors develop mouse models that allow a precise understanding of the developmental trajectory between the stem-cell-like and exhausted states of CD8 T cells and find that while constitutive overexpression of TCF1 expands the stem-like T cell pool, TCF1 expression specifically in already exhausted cells is unable to promote dedifferentiation.

Phages install chemically complex DNA hypermodifications as anti-defense strategies. Here, the authors uncover transfer and rearrangement of glycine on dA driven by Mom, a tRNA-dependent DNA aminoacyltransferase encoded by phage Mu.

The impact of cooling through the Eocene-Oligocene transition on the marine biosphere is not well constrained. Here the authors construct a high-resolution record of foraminiferal species richness history spanning this transition that reveals differential diversity trends depending on foraminiferal habitat and life mode.

This study identifies extensive lateral interdigitations in the kidney’s ascending thin limb and demonstrates that Claudin-10b regulates both epithelial architecture and urine-concentrating function in this distinct nephron segment.

KRAS G12C inhibitors have improved outcomes but mainly in non-small cell lung cancer and colorectal cancer, despite it being a well-established oncogene in a range of cancer types. Here, the authors present a first-in-human phase I/II clinical trial investigating the next-generation KRAS G12C inhibitor, olomorasib, in KRAS G12C-mutant advanced solid tumors.

It remains unclear why some BRCA-deficient high-grade serous carcinomas (HGSC) do not respond to platinum-based therapy. Here, multi-omic analysis of BRCA1- and BRCA2-deficient HGSC attributes co-occurring mutations, DNA repair deficiency and tumor microenvironment features to short survival in these patients.

Leveraging multi-element symbiosis, protective interfacial nanolayers are engineered in an intermetallic alloy. This results in a high fatigue limit of ~1,100 MPa, far exceeding that of conventional intermetallic alloys.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

A chromosome-level brachiopod genome reveals deep conservation of BMP-mediated dorsal–ventral patterning and neural inhibition, suggesting the spiralian ancestor retained the ancestral mechanism in bilaterians.

Crop losses from pests threaten global food security. Here, the authors survey the biosynthetic repertoire of hypocrealean fungi, identifying over 5,200 biosynthetic gene clusters, most encoding unknown products, and linking several to bioactive molecules for sustainable pest control.

Decreased brain volumes and increased NfL levels can be observed earlier than disease diagnosis in short-tandem-repeat-associated neurological diseases.

Biallelic variants in RNU4-2 cause a recessive neurodevelopmental disorder that is phenotypically and molecularly distinct from dominant ReNU syndrome and associated with reduced RNU4-2 transcript levels, consistent with a loss-of-function mechanism.

Conventional type 1 dendritic cells (cDC1) can boost the precursor exhausted T cell population thought to be essential for efficacy of immune checkpoint therapy. Here the authors enhance this cellular network using Flt3L to expand cDC1s and then map the movement of T cells and DCs between tumors and lymph nodes.

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

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.

Single-variant and ultrarare variant burden analyses leveraging exome sequencing data from 22 cohorts identify new risk genes for amyotrophic lateral sclerosis and show cumulative effects of several rare variants on disease risk.

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.

Femtosecond laser pulse-induced coherent helicity switching of magnetic vortices in permalloy disks on picosecond timescales is reported.

The authors mapped the continental-scale fraction of age-dependent leaf area index and revealed a widespread increase in the fraction of photosynthetically efficient young leaves across the majority of Amazon rainforests over the past decades.

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.

A fully automated methodology based on rubrics capturing a broad range of cognitive and intellectual demands is illustrated using LLMs and tasks, demonstrating a new way to evaluate the capabilities of AI systems and anticipate their performance.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

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

Magnon transport is confined to a plane by sandwiching BiFeO₃ between layers of non-polar antiferromagnetic LaFeO₃, resulting in efficient magnon transport and a higher voltage output through spin–charge conversion that can be controlled using electric fields. These results have implications for electric-field-controlled spin-based memory and logic elements.

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.

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.

Here the authors present a compendium of avirulence genotypes for epidemiologically significant strains of wheat stem rust based on nuclear phased genome assemblies and functional assays to inform resistance gene deployment and pathogen surveillance.

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.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

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.

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.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

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.

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.

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.

This paper conducted a priority-setting exercise to identify ten questions that define the future direction of blue carbon science. It highlights key gaps, emerging challenges and opportunities for advancing climate mitigation, ecosystem management and evidence-based policy.

In this study, the authors show that the monoclonal antibody, FNI9, potently inhibits neuraminidases across H5N1 viruses spanning almost 30 years of evolution, protects mice from lethal challenge, and targets an H5N1-conserved NA epitope predicted to have low mutational escape and high fitness cost.

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.

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.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Bansal, Olechnowicz et al. examine levels of inflammatory and neurology-related proteins in individuals with long COVID. They find that vaccination and breakthrough infections are linked to differential plasma levels of a subset of proteins compared to initial infection suggesting an altered immune response outcome upon re-exposure.

Genome-wide association analyses using data from 19 biobanks identify variants influencing risk of thyroid diseases and yield polygenic risk scores associated with features of aggressive thyroid cancer.