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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.

A study examines the effects of mutations that occur naturally in T cell cancers, reporting that such mutations can potentially be exploited to increase the potency of T cell therapies.

Cells can sense mitochondrial damage through signalling via an unimported mitochondrial targeting sequence.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

For parallel computers to simulate our brains, we must face the fact that human beings have a better claim on the title Homo seriatim than Homo sapiens – we're more consistently serial than wise.

Opposing forces generated by exopolysaccharide trail binding versus type IV pilus retraction generate a high cyclic diGMP–high cyclic AMP state in Pseudomonas aeruginosa that promotes social motility.

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.

Deep X-ray limits are placed on the source of the closest fast radio burst, FRB 20200120E, ruling out an ultraluminous X-ray source or a young extragalactic pulsar embedded in a Crab-like nebula as its origin.

Two ‘outrigger’ telescopes were added to CHIME, leading to the localization at detection of FRB 20210603A. The burst originated from deep within the star-forming disk of its host galaxy.

Squeezed light field microscopy (SLIM) combines ideas from tomography and compressed sensing with light field microscopy to enable volumetric imaging at kilohertz rates, as demonstrated in blood flow imaging in zebrafish and voltage imaging in leeches and mice.

FRB 20221022A, detected by the Canadian Hydrogen Intensity Mapping Experiment Fast Radio Burst project, shows a pronounced change in polarization during the burst, providing important clues into the nature of the source.

Most atom-based quantum networks emit photons at non-telecom wavelengths, requiring lossy conversion for long-distance links. A scalable approach for generating direct entanglement between atoms and telecom-band photons has now been demonstrated.

Aarrestad et al. show that, in contrast to psychedelics, the nonhallucinogenic psychoplastogen tabernanthalog promotes neuroplasticity through 5-HT_2AR activation without immediately increasing extracellular glutamate levels or immediate early gene expression.

Insufficient AHR activation has been suggested in SLE, and augmenting AHR activation therapeutically may prevent CXCL13⁺ T_PH/T_FH differentiation and the subsequent recruitment of B cells and formation of lymphoid aggregates in inflamed tissues.

Dietary n-6 PUFAs enhance adipose tissue expandability through the PPARγ–LPCAT3 membrane remodelling axis.

Transposons are DNA sequences that can mobilize, causing deleterious mutations. This work uncovers a novel structure in RNA polymerase IV allowing it to dock with four CLSY recruitment factors and silence transposons throughout the genome.

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.

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.

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.

Exoelectrogenic microorganisms provide a sustainable approach for power generation and wastewater treatment. Here the authors report a redox-mediated microbial flow fuel cell, realizing efficient electron/mass transport and high power output.

The Kondo effect usually refers to increased electrical resistance in metals due to spin-spin interactions between localized magnetic impurities and conduction electrons. Here the authors report a Kondo-like coupling between a light-induced exciton and localized impurity spins in Nd-doped hybrid perovskite.

Retrosynthesis prediction is a fundamental problem in organic synthesis. Here, inspired by simplified arrow-pushing reaction mechanisms, the authors develop a graph-to-edits framework, Graph2Edits, based on graph neural network for retrosynthesis prediction.

Proteins can be both stabilized and destabilized by pressure. Here the authors analyse the factors contributing to both negative and positive protein volume change upon denaturation, and shed light on the molecular determinants allowing proteins to be stable at high pressures.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

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.

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.

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.

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.

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.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

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.

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.

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.

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.

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

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.

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.

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.

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.

Submillimetre surveys have discovered a population of luminous, high-redshift, dusty starburst galaxies, which go through a phase of very rapid star formation, resulting in approximately equal extragalactic optical and far infrared backgrounds (FIRB). Devlin et al. report an extragalactic survey at 250, 350 and 500 µm; they determine that all of the FIRB comes from individual galaxies, with galaxies at redshift z ≥ 1.2 accounting for 70 per cent of it.

The detection of scintillation caused by inhomogeneous plasma near a fast radio burst indicates an emission process that occurs within or just beyond the magnetosphere of a compact object.

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.

The degree of ligand ordering on colloidal inorganic nanocrystal surfaces has long been a topic of interest. Here, the authors show that a well-known powder X-ray diffraction feature observed in prior works, frequently assigned to excess ligands, corresponds to bound and ordered capping ligands.

Iceberg gouging of continental slopes can initiate submarine landslides, potentially far from the iceberg source region, according to observations and geotechnical analysis of an event in a Baffin Island fjord.