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.

This year marks the 200th anniversary of the birth of Henry Walter Bates, an English naturalist who formally introduced ‘mimicry’ as a scientific concept. We asked a range of researchers working on mimicry across biological systems to reflect on emerging questions in the field.

JWST data reveal a multi-galaxy merger 800 Myr after the Big Bang, likely a progenitor of massive quiescent galaxies seen at later times. Its extended [O iii] halo offers direct evidence of early metal enrichment via tidal stripping.

Hepatitis C virus lacks an effective vaccine, partly due to the absence of suitable animal models for testing. Here, the authors develop a live-attenuated vaccine, using synonymous mutagenesis in rodent hepacivirus, and demonstrate induction of a protective T cell response and protection from chronic infection in rats.

The SLC45A4 gene encodes a neuronal polyamine transporter and is linked to pain response in humans and mice.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Analysing camera-trap data of 163 mammal species before and after the onset of COVID-19 lockdowns, the authors show that responses to human activity are dependent on the degree to which the landscape is modified by humans, with carnivores being especially sensitive.

Many bacteria use the second messenger cyclic diguanylate (c-di-GMP) to control motility, biofilm production and virulence. Here, the authors identify a thermosensitive enzyme that synthesizes c-di-GMP and modulates temperature-dependent motility, biofilm development and virulence in the opportunistic pathogen Pseudomonas aeruginosa.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

The Mass Spectrometry Query Language (MassQL) is an open-source language that enables instrument-independent searching across mass spectrometry data for complex patterns of interest via concise and expressive queries without the need for programming skills.

Jayavelu, Samaha et al., apply machine learning models on hospital admission data, including antibody titers and viral load, to identify patients at high risk for Long COVID. Low antibody levels, high viral loads, chronic diseases, and female sex are key predictors, supporting early, targeted interventions.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

Human iPSC-CMs are invaluable for cardiac disease modeling and regeneration. Here, authors developed an optimized suspension culture protocol to efficiently and reproducibly differentiate hiPSCs into cardiomyocytes and cardiac organoids.

When monkeys are infected with a virus similar to HIV, treated with antiretroviral therapy (ART), and are administered a ‘combo therapy’ made of antibodies against molecules that inhibit immune responses, they control viral rebound when ART is discontinued for more than 6 months

Osteosarcomas (OS) are aggressive bone tumors which have no actionable recurrent driver mutations. Here the authors identify aberrant expression of EZHIP in a subset of OS patients as an oncogenic driver, which exhibits vulnerability to epigenetic therapies.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Mass photometry is a label-free optical approach capable of detecting, imaging and accurately measuring the mass of single biomolecules in solution. Here, the authors demonstrate the potential of mass photometry for quantitatively characterizing sample heterogeneity of purified protein complexes with implications for structural studies specifically and in vitro studies more generally.

A screening approach finds VH-domain antibodies that bind the SARS-CoV-2 Spike protein receptor-binding domain at its interface with host ACE2. Bi-paratopic and multivalent binders have high affinity and potency.

A device architecture based on indium arsenide–aluminium heterostructures with a gate-defined superconducting nanowire allows single-shot interferometric measurement of fermion parity and demonstrates an assignment error probability of 1%.

Clonal evolution in multiple myeloma (MM) needs to be understood in both the tumor and its microenvironment. Here the authors perform single-cell multi-omics profiling of samples from MM patients at different stages, finding transitions in the immune cell composition throughout progression.

Integrated analysis of transcriptome, open chromatin region and chromatin conformation capture data from subjects with acute myeloid leukemia (AML) harboring defined transcription factor and signaling molecule alterations provide insights into the subtype-specific regulatory network in AML.

Corona phase molecular recognition (CoPhMoRe) involves the deposition of a heteropolymer onto a nanoparticle surface, providing a recognition site for a given analyte. Here, the authors show that CoPhMoRe can be used to selectively detect proteins (fibrinogen) with high selectivity, including in a complex serum environment.

Siles Alvarado and Schuler et al. examine the long-term dynamics of SARS-CoV-2 antibodies in individuals with varying COVID-19 severities over 12 months. While anti-N antibodies decline, anti-RBD antibodies persist, offering insights into the evolving immunity post-COVID.

High-speed programmability of spatially-structured light imparts faster control upon atomic qubits. Here, the authors demonstrate reconfigurable GHz-rate modulation on sixteen visible-wavelength channels, used here to address color centers in diamond.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

Oxygen in shallow shelf waters rose linearly with atmospheric oxygen in the Neoproterozoic era, potentially driving the first radiation of marine animals, but widespread ocean oxygenation came later, according to reconstructions of oxygen levels and marine productivity.

Alteration of the epigenetic landscape has been implicated in several disease processes, where targeting histone modifiers may have therapeutic applications. Here the authors report a bifunctional small molecule inhibitor that simultaneously targets the deacetylase (HDAC1) and demethylase (LSD1) activities of the CoREST complex.

Acute respiratory distress in macaques and baboons recapitulates COVID-19 disease progression in humans, making them suitable as models to test vaccines and therapies.

The mechanisms underlying deep pressure sensing are not fully understood. Here the authors demonstrate that while two individuals lacking Aβ fibers demonstrate impaired deep pressure sensing, seven individuals with PIEZO2 loss of function mutations display normal deep pressure responses.

The base-calling algorithm SNPSeeker detects single-nucleotide polymorphisms with frequencies that are below the error rate of the sequencing platform. It is thus well suited to analyze data from large pooled samples and find rare variants that may contribute to diseases or complex traits.

A comparison of specimens collected from the same locations but nearly a century apart shows that an alpine chipmunk has suffered reduced genetic diversity and gene flow as a result of climate-driven habitat loss in Yosemite National Park, USA. This study highlights one important impact of climate change on biodiversity

Data from 42 chronosequence sites show a geater abundance of legumes in seasonally dry forests than in wet forests, particularly during early secondary succession, probably owing to legumes’ nitrogen-fixing ability and reduced leaflet size.

Ian Blair and colleagues use genome-wide linkage analysis and whole exome sequencing to identify mutations in the CCNF gene in large cohorts of amyotrophic lateral sclerosis and frontotemporal dementia patients. In addition to validating the mutations in international cohorts, the authors also show that mutant CCNFgene product affects ubiquitination and protein degradation in cultured cells.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

This Review Article discusses the physical, chemical and ecological features of the phycosphere, the microenvironment surrounding individual phytoplankton cells, and its importance during phytoplankton–bacteria interactions in aquatic ecosystems.

Actin is critical to the survival of the parasite Toxoplasma gondii. In this study, Hvorecny and Sladewski et al. show that T. gondii actin forms intrinsically dynamic filaments in vitro due to differences in assembly contacts in the D-loop.

A new approach for whole-genome sequencing of plasma circulating tumor DNA allows for dynamic monitoring of disease burden and ultra-sensitive detection of minimal residual disease.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Mantis shrimps are known to display large pitch, yaw and torsional eye rotations. Here, the authors show that these eye movements allow mantis shrimp to orientate particular photoreceptors in order to better discriminate the polarization of light.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.