Search

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.

Lasing with multi-pass gain is achieved in a diamond-based X-ray cavity at the European XFEL, opening a path to next-generation X-ray science.

How aperiodic 1/f noise drives ripple activity in human brain and impacts on ripple detections is not fully understood. Here authors show that ripple detections should be driven by the 1/f noise, which indexes different brain states and cognitive demands.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Guided by density functional theory, a commercially viable refractory alloy is developed, which exhibits excellent room-temperature ductility and strength, and high strength at elevated temperatures.

Using chemical photoswitchable reagents to exert purely wavelength-dependent control over biological systems in deep tissue and in vivo requires a concentration-independent design paradigm. Here, such photoswitchable ligands are realized by ensuring that E/Z isomers have opposing efficacies yet similarly high affinity, allowing them to probe transient receptor potential C4 and C5 channel functions up to the tissue level.

During development of eutherian females, one of the X-chromosomes is silenced. Here, authors show that alleles on the inactive X-chromosome are dynamically expressed along neural differentiation enhancing resilience of female neural tissue.

Genome-wide analyses identify 13 loci associated with susceptibility to infection with SARS-CoV-2 Omicron variants, including variation in ST6GAL1, previously associated with influenza susceptibility, and other genes involved in glycosylation processes.

Transcription factor osr2 is identified as a specific marker and regulator of mural lymphatic endothelial cell (muLEC) differentiation and maintenance, and muLECs and border-associated macrophages share functional analogies but are not homologous, providing an example of convergent evolution.

A proposed theoretical explanation for the electronic behaviour of moiré graphene is the coexistence of light and heavy electrons. Now local thermoelectric measurements hint that this model could be accurate.

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.

The structural mechanism of a natively isolated GRP94 folding intermediate tethered to a CCDC134-bound translocon is described, revealing how the nascent chain remodels the translocon to control N-glycosylation by OST.

How cells respond to replication-derived DNA damage that is carried over into mitosis is not well understood. Here, the authors show that CIP2A with TOPBP1 mediates the mitotic recruitment of the SLX4/MUS81/XPF nuclease complex to replication stress-induced DNA lesions to maintain genome integrity.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

Ferroptosis is an iron-dependent lipid peroxidation-mediated form of cell death that holds promise for targeting treatment-resistant cancer cells. Here, the authors show that AMPK-mediated lipid droplet dynamics modulates the response to ferroptosis inducers in melanoma.

Hydrogen oxidation in alkaline media is limited by slow reaction kinetics. Here, the authors develop a family of bimetallic catalysts by theoretical analysis and reveal that RuIr achieves superior activity and durability through synergistic adsorption of hydrogen and hydroxyl intermediates.

Methane emissions have a large short-term impact on temperature, which can be potentially offset by nature-based solutions that provide temporary carbon storage. This research demonstrates such matching could minimize intertemporal welfare trade-offs and avoid various risks for permanent removal.

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.

Age-related macular degeneration (AMD) is a common cause of vision loss with a large genetic risk in older individuals. Here, for a high-risk AMD subtype, the authors identify an association with a chromosome 10 risk region containing a long non-coding RNA.

How the brain represents high-level musical meaning is unclear. Here, the authors reconstruct heard music from fMRI data and show that both music- and text-derived semantic features are predictive of activity in the auditory cortex.

Protein motion in crowded environments governs cellular transport and reaction rates. Here, the authors use megahertz X-ray Photon Correlation Spectroscopy to reveal anomalous diffusion of ferritin, linking hydrodynamic and direct interactions to cage-trapping at microsecond time scales.

IL-17A, a cytokine important for tissue repair, can impair healing when increased, contributing to keratinocyte dysfunction in type 2 diabetic wounds. Here, the authors show that IL-17A drives this dysfunction via JMJD3-mediated epigenetic changes, and that blocking this pathway improves wound healing.

Borgs are large extrachromosomal elements of anaerobic methane-oxidizing archaea. Here, via in silico protein structure prediction of ~10,000 Borg proteins, the authors reveal that Borgs share numerous features with giant eukaryotic viruses, suggesting that Borgs have a viral-like lifestyle and evolutionary convergence of large extrachromosomal elements across the Domains of Life.

The predicted increase in frequency of droughts and rising temperatures in Europe will lead core populations of a temperate plant to an evolutionary dead-end unless they acquire genetic alleles that are present only in extreme edge Mediterranean, Scandinavian, or Siberian populations.

Using generative AI, Insilico Medicine developed an oral PROTAC that potently inhibits and degrades PKMYT1, a synthetically lethal target in cancer, demonstrating high selectivity and strong antitumor efficacy in preclinical models.

This study describes how a dynamical model can connect three areas of work in economic complexity: regression models of country diversification, classic accounts of economic development, and methods to estimate an economy’s complexity.

Pancreatic ductal adenocarcinoma is defined by a fibroinflammatory microenvironment, which influences both disease progression and therapy response. In this Review, Arnold et al. outline our current understanding of the complex interplay between the stromal elements of the tumour microenvironment in pancreatic ductal adenocarcinoma and present ways we might use this knowledge to develop better therapeutic strategies for patients with pancreatic cancer.

Even if net-zero emissions are reached well before 2100, West Antarctic ice-sheet retreat could still drive multi-meter sea-level rise by 2300. Emission reductions in the coming years are critical to limit long-term ice loss from Antarctica.

Mutations in elongation factor G protect bacteria from aminoglycoside antibiotics through unknown mechanisms. Here, the authors show that the mutations selectively slow the movement of antibiotic-bound ribosomes along mRNA, which prevents error-prone protein synthesis and thus membrane damage and antibiotic uptake.

The authors develop a computational method to design small DNA-binding proteins (DBPs) that target specific sequences. Designed DBPs show structural accuracy and function in both bacterial and mammalian cells for transcriptional regulation.

The notion that catalysts are static entities that barely change under operation is still prevalent although it is often not true. Here, a range of operando and in situ techniques reveals the dynamic nature of Co₃O₄ during the oxidation of 2-propanol to acetone, unveiling a network of interconnected solid-state processes, such as exsolution, diffusion or void formation, that govern the catalytic performance.

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.

Somatic instability plays a role in Huntington’s disease. Here, the authors show that lowering HTT levels by transcriptional repression suppresses somatic instability. This can also be done without affecting HTT levels by direct CAG repeat binding.

The Zika viral protease NS2B-NS3 is a crucial target for antiviral drug development due to its role in processing viral polyproteins. Here, the authors utilize crystallographic fragment screening and deep mutational scanning to identify binding sites for resistance-resilient inhibitors.

The authors couple calculations of historical heatwave intensity at present and future global temperatures with exposure–response functions to quantify mortality from extreme heat events in Europe. They project tens of thousands of excess deaths, with limited attenuation from existing adaptations.