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.

Examining drivers of the latitudinal biodiversity gradient in a global database of local tree species richness, the authors show that co-limitation by multiple environmental and anthropogenic factors causes steeper increases in richness with latitude in tropical versus temperate and boreal zones.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

Human intracranial recordings reveal that during aversive memory retrieval, memory-specific gamma activity patterns, shaped by the amygdala during encoding, are reactivated in hippocampus.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

The authors show that LARP4 drives T cell dysfunction in tumors by promoting hypertranslation of oxidative phosphorylation-related mRNAs, resulting in mitochondrial dysfunction. They also target LARP4 to enhance T cell persistence and anti-tumor activity and provide a CAR T cell strategy for treating solid and liquid tumors.

Rhombohedral-stacked molybdenum disulfide with sliding ferroelectric behaviour can be used to create atomically thin ferroelectric transistors for computing-in-memory device applications.

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.

FANCD2 and FANCI are essential components of the Fanconi anaemia DNA damage repair pathway. Here the authors present the cryo-EM structure of the FANCD2-FANCI complex, providing insight into how the complex is recruited to stalled replication forks.

Screening in Escherichia coli and biochemical experiments show that in Arabidopsis thaliana, OSCA2.1 and OSCA2.2 function as plant sensors of hypo-osmolarity, utilize Ca²⁺ oscillations as second messengers and have crucial roles in pollen germination.

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.

Chest computed tomography (CT) is one of the most common diagnostic tests. Here, the authors combine two AI models to measure from CT coronary artery calcium, left ventricular mass index, and left and right atrial and ventricular volumes, and show their association with cardiovascular mortality.

Molecular switches are ubiquitous in the biochemistry regulatory network. Here, the authors construct synthetic molecular switches controlled by DNA-modifying enzymes such as DNA polymerase and nicking endonuclease to control and cascade assembly and disassembly.

Fluid liberation and migration from subducted oceanic slabs play a critical role in arc magmatism but the volume and origin of the released fluids is unclear and difficult to trace. Here, the authors use Molybdenum isotope ratios to tackle these problems.

In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer’s disease, and functional analysis suggests it interacts with amyloid-beta.

MHC-I mediated antigen presentation is an important element of the anti-tumour immune response. Here authors identify a tumour immune escape mechanism by which the cancer cells express the ubiquitin E3 ligase UHRF1 in the cytoplasm instead of the nuclear expression pattern observed in normal tissues, and this results in degradation of MHC-I and thus diminished antigen presentation and anti-tumour T cell response.

Schief and colleagues show that germline-targeting epitope scaffolds can elicit responses from rare broadly neutralizing antibody precursor B cells with predefined binding specificities and genetic features.

A sequencing chemistry that separates nucleotide identification from nucleotide incorporation achieves high accuracy.

High-resolution spatial maps of the global abundance of soil nematodes and the composition of functional groups show that soil nematodes are found in higher abundances in sub-Arctic regions, than in temperate or tropical regions.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

Here the authors show that immune cell exclusion and immunosuppression in the melanoma microenviromment are driven by nerve growth factor interactions with tropomyosin receptor kinase A on melanoma cells and that a tropomyosin receptor kinase inhibitor can sensitize these tumors to immune checkpoint blockade.

Imputation uses genotype information from SNP arrays to infer the genotypes of missing markers. Here, the authors show that an imputation reference panel derived from whole-genome sequencing of 3,781 samples from the UK10K project improves the imputation accuracy and coverage of low frequency variants compared to existing methods.

The edematous form of severe acute childhood malnutrition (ESAM) presents with more severe multi-organ dysfunction than non-edematous SAM (NESAM). Here the authors assess genome-wide DNA methylation in buccal cells of SAM children and find that ESAM is characterized by hypomethylation at genes associated with disorders of nutrition and metabolism, including fatty liver and diabetes.

A video-based deep learning algorithm—EchoNet-Dynamic—accurately identifies subtle changes in ejection fraction and classifies heart failure with reduced ejection fraction using information from multiple cardiac cycles.

A manufacturable platform for quantum computing with photons is introduced and a set of monolithically integrated silicon-photonics-based modules is benchmarked, demonstrating dual-rail photonic qubits with performance close to thresholds required for operation.

The importance of the post-translational modification by acetylation in regulating protein function is not fully understood. Here, the authors show that acetylation of the transcriptional factor PLZF promotes the assembly of a repressor complex that limits the inflammatory response mediated by NF-κB.

Lakes are essential components of the hydrological and biogeochemical cycles. Here, Pi et al develop a global lake dataset called GLAKES via high-resolution satellite images and deep learning to examine global lake changes over four decades.

Bacteria can grow as free living planktonic cells or as part of surface-associated biofilms. Here the authors show, for the opportunistic pathogen Pseudomonas aeruginosa, that cells recently dispersed from biofilms are physiologically different from, and more virulent than, planktonic and biofilm cells.

The CNV analysis group of the Psychiatric Genomic Consortium analyzes a large schizophrenia cohort to examine genomic copy number variants (CNVs) and disease risk. They find an enrichment of CNV burden in cases versus controls and identify 8 genome-wide significant loci as well as novel suggestive loci conferring either risk or protection to schizophrenia.

Vivianna Van Deerlin and colleagues report that common variants at 7p21 are associated with a subtype of frontotemporal lobar degeneration marked by TDP-43 inclusions. They further show that the risk alleles are associated with elevated brain expression of TMEM106B, which resides at the peak of association on 7p21.

The expression of each of the roughly 22,000 genes of the mouse genome has been mapped, at cellular resolution, across all major structures of the mouse brain, revealing that 80% of all genes appear to be expressed in the brain.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

The E3 ligase Mule has been previously reported to be essential for B cell development and function by modulating p53 ubiquitination and degradation. Here Haoet al. identify KLF4 as a novel ubiquitination target of Mule and show it controls T cell proliferation and autoimmunity.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

Alvarez and colleagues develop a bispecific anti-PD-1–GITR-L agonist that activates T cells via a mechanism distinct from those found with individual PD-1 and GITR-L agonists and demonstrate its antitumor activity in mice and nonhuman primates.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

This study uses gene expression predictors for the dorsolateral prefrontal cortex and other brain regions to perform a transcriptomic imputation analysis of schizophrenia, identifying 413 genic associations across 13 brain regions and 36 significantly enriched pathways.

Counterfeit medicines sold online are a global scourge. Although erectile dysfunction drugs are well known to be heavily counterfeited, illicit vendors are rapidly expanding to other drugs and devices in the sexual health arena. International multidisciplinary cooperation is needed to address key patient safety concerns resulting from such markets.

A solution-processing step has been used to prepare quantum-well structures that comprise a thin layer of perovskite sandwiched between two layers of conjugated oligothiophene derivatives. The band gap of the resulting 2D hybrid perovskites can be fine-tuned by functionalizing the organic component, which also improves the stability of the system.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

Electrochemical routes for the production of hydrogen peroxide would reduce the waste inherent in the current anthraquinone process, and also make distributed and on-site production more feasible. Here, inexpensive reduced graphene oxide is proven to be a stable and selective catalyst for oxygen reduction at remarkably low overpotentials.

Comprehensive analyses of 178 lung squamous cell carcinomas by The Cancer Genome Atlas project show that the tumour type is characterized by complex genomic alterations, with statistically recurrent mutations in 11 genes, including TP53 in nearly all samples; a potential therapeutic target is identified in most of the samples studied.