Search

Antimony selenide is a promising photovoltaic material, but the presence of point defects degrades performance. Here, the authors use positron annihilation spectroscopy combined with theory to detect and identify vacancy-type point defects.

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.

Trastuzumab deruxtecan (T-DXd) is a HER2-targeted antibody drug conjugate. Through integrated laboratory and clinical studies, the authors identify significant ERBB2 (the gene that encodes the HER2 protein) mutational heterogeneity in patients with urothelial cancer and co-mutation and amplification of ERBB2 as a potential biomarker of exceptional response to T-DXd.

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 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.

The authors report a meta-analysis of methylome-wide association studies, identifying 15 significant CpG sites linked to major depression, revealing associations with inflammatory markers and suggesting potential causal relationships through Mendelian randomization analysis.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

A NutNet experiment in 57 grasslands across six continents shows that when herbivores are excluded from grasslands with a long coevolutionary history of grazing plant diversity is reduced, while in grasslands without a long grazing history the evolutionary history of the plant species regulates the response of plant diversity.

A genome-wide association meta-analysis of individuals with clinically assessed or self-reported depression identifies 44 independent risk loci. Comparisons with other psychiatric disorders and candidate gene analyses provide new insights into major depressive disorder.

Radioresistance remains a challenge in the treatment of bladder cancer. In this study, the authors show in mice that radiation increases deposits of neutrophil extracellular traps (NETs) via a TLR4-dependent mechanism and that NETs-targeting strategies can improve the response to radiotherapy.

The GREGoR consortium provides foundational resources and substrates for the future of rare disease genomics.

The mechanisms that enforce T cell quiescence are incompletely understood. Slfn2 has now been identified as another participant in this process, functioning as a critical regulator of T cell– and monocyte-mediated immunity.

Here, the authors show that pharmacological and genetic mineralocorticoid receptor antagonism reduces intestinal fibrosis in mice and that NGAL is involved in mineralocorticoid receptor-mediated intestinal fibrogenesis.

A genome-wide association study in ~3 million individuals identifies 3,952 independent variants associated with educational attainment. A polygenic index explains 12–16% of variance for this trait and contributes to risk prediction for ten diseases.

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.

The mechanisms by which debris flows acquire mass and momentum as they entrain material are unclear. Large-scale experiments suggest that the pore pressure of wet bed sediment increases as the flow moves over the bed, leading to reduced friction and progressive scouring of the base.

On the centenary of the first human EEG recording, more than 500 experts reflect on the impact that this discovery has had on our understanding of the brain and behaviour. We document their priorities and call for collective action focusing on validity, democratization and responsibility to realize the potential of EEG in science and society over the next 100 years.

A genetic study identifies hundreds of loci associated with risk tolerance and risky behaviors, finds evidence of substantial shared genetic influences across these phenotypes, and implicates genes involved in neurotransmission.

Platelet hyperreactivity is associated with cardiovascular events in patients with PAD. Here the authors derive and validate a circulating platelet genetic signature to discriminate platelet hyperreactivity and cardiovascular risk.

The authors demonstrate how avian H5N1 influenza A virus polymerase interacts with human ANP32B to facilitate the replication of the viral genetic information in mammalian hosts, revealing insights into cross-species transmission.

Sepsis induces a period of immunosuppression which can be problematic in the face of subsequent infectious challenge. Here the authors show the presence of PD-L1 expressing regulatory plasma cells that can inhibit T cells in a murine model and in patients with sepsis.

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.

An analysis of the localization and intensity of intracortical microstimulation in three participants with cervical spinal cord injury shows that overlapping projected fields from multiple electrodes produce sensations that are more easily localizable.

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.

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.

Analysis of exomes and transcriptomes from 100 African American patients with acute myeloid leukemia identifies ancestry-related variation in mutation profiles and survival. Refined risk classification suggests clinical relevance of these ancestry-associated differences.

A chemoproteomic screen is used here to identify MTH1 as the target of SCH51344, an experimental RAS-dependent cancer drug; a further search for inhibitors revealed (S)-crizotinib as a potent MTH1 antagonist, which suppresses tumour growth in animal models of colon cancer, and could be part of a new class of anticancer drugs.

Analyses of tumor and bone marrow tissue from patients with glioblastoma demonstrate the presence of extracerebral niches that contained tumor-reactive and memory T cell subsets, including early stem-like phenotypes and stages, indicating antitumor CD8⁺ T cell differentiation in cranial bone marrow.

Here, the authors present Paraphase, a HiFi-based informatics method that resolves highly similar genes located in segmental duplications. They apply Paraphase to 316 paralogous genes and summarize extensive genetic diversity across populations.

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology.

Patient-derived xenografts are important tools for cancer drug development. Here, the authors develop models from 22 non-small cell lung cancer patients. They show genomic differences between models created from different spatial regions of tumours and a bottleneck on model establishment.

Influenza viruses carry their own RNAdependent RNA-polymerase that is highly conserved and a promising anti-viral target. Combining functional and structural data, Keown et al. characterise the inhibitory effect of nanobodies on 1918 pandemic H1N1 influenza strain polymerase complex and identify sensitive sites interfering with polymerase activity in vitro.

A machine learning approach is presented to identify dominant patterns in disease progression in amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and Parkinson’s disease. The nonlinearity of ALS progression has important clinical implications.

The non-coding RNA RNU4-2, which is highly expressed in the developing human brain, is identified as a syndromic neurodevelopmental disorder gene, and, using RNA sequencing, 5′ splice-site use is shown to be systematically disrupted in individuals with RNU4-2 variants.

Structural and biochemical studies of influenza virus RNA polymerase in complex with host acidic nuclear phosphoprotein 32 (ANP32) show how ANP32-mediated polymerase dimerization enables the replication of influenza viral RNA in a host-dependent manner.

In a combined computational and multi-center clinical study to investigate the effects of adipose fat tissue infiltration on ventricular arrhythmias, Sung et al. show that infiltrating adipose tissue, as opposed to scar, is the main cause of infarcted-related ventricular arrhythmias by slowing cardiac conduction in critical sites.

The authors conducted a genetic meta-analysis of depression and found 269 associated genes. These genes highlight several potential drug repositioning opportunities, and relationships with depression were found for neuroticism and smoking.