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.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Aging, chronic high-fat diet feeding, or housing at thermoneutrality induces brown adipose tissue (BAT) involution. Here, the authors demonstrate that physiologic aging induced involution and thermogenic dysfunction result from pyroptotic signalling activation.

Chemical language models trained on known metabolites can identify previously unknown metabolites from mass spectrometry-based metabolomics data with high accuracy.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Vertical transmission is thought to favour beneficial host–microbe interactions, but these may also be context dependent. Here Bruijning et al. show with a model that variable environments can select for bet-hedging by hosts via imperfect vertical transmission of microbes.

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.

Organisms vary in their nitrogen and phosphorus content, shaping ecological and evolutionary processes. This study shows that nitrogen deposition is a consistent global factor associated with plant and animal stoichiometry.

Quantifying lipid and water content in tissues non-invasively is difficult, and no method exists to quantify lipids in blood non-invasively. Here the authors develop an imaging approach called shortwave infrared meso-patterned imaging (SWIR-MPI) to detect and spatially map tissue water and lipids in preclinical models.

The timing of respiratory syncytial virus seasonal epidemic peaks in Japan shifted in 2016-17. Here, the authors use mathematical modelling to evaluate the hypothesis that this change in timing may be due to an increase in use of childcare facilities following a policy change

Metabolic and proteomic profiles derived from fossilized skeletal remains of animals enable inferences regarding physiological health and disease as well as diet to provide reconstructions of ancient soil, vegetation and palaeoclimate characteristics.

The solute carrier transporter protein SLC25A44 regulates uptake of branched-chain amino acids in mitochondria of brown adipose tissue in which they are utilized for thermogenesis.

The study of statistical correlations is central to the description of complex quantum objects. Measurements of density correlation functions of ultracold molecules are now possible through the realization of a molecular quantum gas microscope.

The variability in clinical outcomes of SARS-CoV-2 infection is partly due to deficiencies in production or response to type I interferons (IFN). Here, the authors describe a FIP200-dependent lysosomal degradation pathway, independent of canonical autophagy and type I IFN, that restricts SARS-CoV-2 replication, offering insights into critical COVID-19 pneumonia mechanisms.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

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.

Frugivory evolved multiple times in mammals, including bats. Here, the authors use integrative single-cell sequencing on fruit and insect bat kidneys and pancreases and identify cell population, gene expression and regulatory differences associated with frugivory that also relate to diabetes.

Green subsidies (carrots) are now becoming a more politically acceptable climate policy option compared with corrective regulations (sticks). However, researcher show that carrots without quick and appropriate sticks will not be sufficient to reach the deep decarbonization goal in the long run.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

Whole-ecosystem manipulations of Caribbean islands occupied by brown anoles, involving the addition of competitors (green anoles) and/or top predators (curly-tailed lizards), demonstrate that predator introductions can alter the ecological niches and destabilize the coexistence of competing prey species.

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.

Liver and adipose tissue are shown to use different metabolic routes to generate NADPH for de novo lipogenesis, with the liver relying on a unique cytosolic serine catabolic pathway involving the enzyme SHMT1.

Hepatitis B virus is an almost uniquely human-tropic pathogen for which model systems are scarce. Here, the authors determine key residues within the HBV receptor that form a barrier in the HBV life cycle in primates and identify marmosets as a model candidate for infection with simian-tropic HBV.

Combining high-resolution mapping of foliar and herbivore faecal sodium concentrations across Africa, the authors show that plant-derived sodium availability constrains megaherbivore densities at a continental scale.

Controlled breaking of a chemical bond by mechanical forces can provide key insight into reaction mechanisms. Here the authors, using atomic force microscopy and computations, measure the forces involved in breaking a single dative bond between a CO molecule and a ferrous phthalocyanine complex.

Scanning tunnelling microscopy is used to image pristine electrostatically defined quantum Hall edge states in graphene with high spatial resolution and demonstrate their interaction-driven restructuring.

Here they generate endogenous optogenetic RhoGEFs and use them to quantitatively direct and study epithelial furrowing via cell shortening, uncovering design principles for morphogenetic furrowing including a role for tissue mechanics in furrow asymmetry.

Wildfire particulate matter emitted from the 2023 Canadian wildfires contributed to a reduction in temperature of 3 °C over New York and New Jersey area, according to real-time particulate matter monitoring combined with transport modelling.

Genotype-phenotype data from over 450,000 individuals was analyzed to discover 205 genomic loci where an allele associated with increase adiposity was associated with a lower cardiometabolic disease risk to an individual.

Cleavable bonds are a central strategy for polymer deconstruction, but controlling the rate of breakdown remains difficult because it is dictated by intrinsic bond cleavage kinetics. Now it has been shown that bio-inspired conformationally preorganized neighbouring groups enable programmable polymer deconstruction without changing the cleavable bond itself or compromising material properties.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

In this paper, the authors describe the energy state-dependent regulation of the PVN^GLP-1R to DVC circuit, resulting in altered food intake and metabolic health, mediated by GLP-1 receptor signalling.

Here the authors use mRNA display to discover peptide inhibitors of BamA, an essential factor that catalyzes the membrane insertion of bacterial outer membrane proteins. They show that three peptides are antibacterial and inhibit BamA activity by a unique mechanism.

WD 0032–317B is a 75–88-Jupiter mass companion orbiting a hot white dwarf with a period of 2.3 h. It has a day-side temperature of about 8,000 K and a day–night difference of ~6,000 K. WD 0032–317B is amenable to detailed characterization and can be used as a proxy for strongly irradiated ultra-hot giant planets.

Garnet-type LLZO electrolytes are considered among the most promising solid-state electrolytes for all-solid-state batteries; however, numerous challenges need to be addressed before they are integrated into a cell. By precipitating amorphous zirconium oxide onto grain boundaries, increased ionic conductivity is observed and dendrite growth is suppressed.

Using intracranial electroencephalography from patients with epilepsy during spatial attention tasks, this study shows that high-frequency bursts facilitate fast communications in brain networks and support attentional information routing.

The SLFN14 nuclease cleaves RNA for translational regulation through a poorly defined mechanism. Here the authors report a cryo-EM structure of SLFN14 to reveal RNA interfaces, demonstrate broad site-specificity in the absence of tRNA modifications, and highlight analogy to prokaryotic nucleases.

Conditional cysteine restriction in mice causes substantial weight loss, exceeding that seen with essential amino acid restriction, by activating the integrated stress and oxidative stress responses, and by unexpectedly depleting coenzyme A, leading to metabolic inefficiency.

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.

High near-surface nitrogen-fixation rates that promoted the recent growth of the Great Atlantic Sargassum Belt were tied to greater upwelling of phosphorus from the equatorial Atlantic, according to coral-bound nitrogen isotope records from the Caribbean.

A giant planet candidate roughly the size of Jupiter but more than 14 times as massive is observed by TESS and other instruments to be transiting the white dwarf star WD 1856+534.

Li, Platt et al. examine cross-reactivity of antibodies induced by the adult-specific pneumococcal conjugate vaccine V116 within serogroups 6 and 15. Antibodies demonstrated cross-reactivity to non-vaccine serotypes 6 C and 15B, suggesting broader coverage may be available beyond the 21 V116 serotypes following vaccination.

Noel et al. show aberrant updating of expectations in three distinct mouse models of autism spectrum disorder. Brain-wide neurophysiology data suggest this stems from excess units encoding deviations from prior mean and a lack of sensory prediction errors in frontal areas.

As solid tumours develop, cancer cells shed energetically expensive tissue-specific functions, enabling uncontrolled growth despite a limited ability to produce ATP.

A brightness dip in the extragalactic X-ray binary M51-ULS-1 can be well fit by a planet transit model in which the eclipser is most likely Saturn-sized. The locations of possible orbits are consistent with the survival of a planet bound to a mass-transfer binary.