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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.

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.

Biopolymers can couple to membrane lipids and condense to prewet membranes. Here a range of membrane perturbations in reconstituted systems and cells show that the prewetting is sensitive to membrane composition and phase transitions and can drive interorganelle contact.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Sequencing of the Arabidopsis thaliana root microbiome shows that its composition is strongly influenced by location, inside or outside the root, and by soil type.

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.

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.

This multi-omic longitudinal analysis of the healthy human peripheral immune system constructs the Human Immune Health Atlas and assembles data on immune cell composition and state changes with age, including responses to cytomegalovirus infection and influenza vaccination.

Viruses generally have compact genomes, resulting in many viral mRNAs with short 5’ untranslated regions. An antiviral complex exploits this feature of viral mRNAs to selectively inhibit viral protein synthesis and repress viral replication.

Hybrid gRNAs significantly increase targeted editing in the liver while simultaneously reducing unwanted bystander editing in humanized mouse models.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

The authors leveraged a large multimodal sample and combined normative modeling and linked independent component analysis to study a cross-modal signature of face processing within the fusiform gyrus in autism.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

Investigation of Zea mays (maize, corn) pollen cellular respiration and pollen-silk (stigma) interactions leads to the development of an accessible protocol that can preserve maize pollen viability for up to seven days at a hybrid seed production scale.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Here the authors dissect the developmental and functional relationship between tumor-responsive cytotoxic T cells in the tumor versus the tumor-draining lymph nodes (tdLNs), finding that stem-like T_PEX cells dependent on MYB in the tdLNs are required for CD8⁺ T cell tumor infiltration and ICB responses.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Gut microbiota are hypothesized to shape the ecology and evolution of animal life but robust estimates of natural selection acting on gut microbiome variation is lacking. This study provides evidence that variation in the gut microbiome is associated with survival in a population of feral horses.

Animal migrations are extensive and crucial for ecosystem health but are in decline. This study identifies 1,787 sites and links among them for 109 marine species, highlighting the need for international cooperation and providing policymakers with essential knowledge for effective conservation.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

Serological analysis and infection outcomes of participants in the multi-center, prospectively enrolled OCTAVE cohort, comprising 2,686 participants with immune-suppressive diseases who recieved two COVID-19 vaccines, reveals specific clinical phenotypes that might benefit from specific COVID-19 therapeutic strategies.

Activated carbon has been widely used for PFAS adsorption, but this method generates secondary solid wastes. The flash Joule heating approach realizes mineralization of PFAS and generation of useful flash graphene in waste granular activated carbon.

Volatile metal pollutants in basaltic volcanic plumes can be deposited up to 100 times faster than refractory species, and may produce disproportionate impacts at proximal locations, according to extensive sampling of Kīlauea’s 2018 eruption plume.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

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.

What is the state of trust in scientists around the world? To answer this question, the authors surveyed 71,922 respondents in 68 countries and found that trust in scientists is moderately high.

Literature produced inconsistent findings regarding the links between extreme weather events and climate policy support across regions, populations and events. This global study offers a holistic assessment of these relationships and highlights the role of subjective attribution.

Glaciers in the Karakoram mountains have been stable in mass, whereas in nearby regions, mass loss has prevailed. Climate model simulations reveal a unique seasonal cycle in Karakoram snowfall that contributes to this pattern.

This study used fine-mapping to analyze genetic regions associated with bipolar disorder, identifying specific risk genes and providing new insights into the biology of the condition that may guide future research and treatment approaches.

Sea otters recolonizing an estuary in California indirectly reduce erosion by reducing burrowing crab abundance, suggesting that restoring predators could be a key mechanism to improve the stability of coastal wetlands and other ecosystems.

Differential gene expression experiments yield quantitative insight into biological activity and may be important in disease classification and treatment. Here, the authors analyse external spike-in RNA controls to provide a standard method to assess and compare experiment performance.

An expert-elicitation process identifies current methodological barriers for monitoring terrestrial biodiversity, and how technological and procedural development of robotic and autonomous systems may contribute to overcoming these challenges.

Cheek swabs are widely used in pediatric epigenetic studies, but changes in their cellular composition with age are unclear. Here the authors show that buccal epithelial cells decline with age until adolescence, then stabilize, while variability increases with age, impacting the precision of tools like the PedBE clock in pediatric epigenetics.

Constantinides et al., perform a recall study from a British South Asian genetic cohort to explore the genetic and phenotypic risk of cholestatic liver disease. 55.6% of participants with rare heterozygous ABCB4/ABCB11 variants or a history of intrahepatic cholestasis of pregnancy showed evidence of liver involvement, highlighting the utility of genetic screening and monitoring.

Here, the authors used electronic healthcare records to analyse the genetic basis of variation in 42 routinely-acquired quantitative blood tests among up to 40,000 British South Asian volunteers from the Genes and Health study. By combining their results with genetic findings from UK Biobank, they explore similarities and differences between ancestries in the genetic basis of these traits.

Accurate chromosome segregation into daughter cells depends on proper compaction and disentanglement. The authors uncover SRBD1 as a key mediator of these essential processes that localizes topoisomerase IIα to mitotic chromosomes.

Genome-wide analysis identifies 30 loci associated with bipolar disorder, allowing for comparisons of shared genes and pathways with other psychiatric disorders, including schizophrenia and depression.

Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.

A common immune signature in the blood of patients with COVID-19, who are otherwise clinically heterogeneous, sheds light into the pathogenesis and clinical progression of the disease.

Perivascular and leptomeningeal macrophages, collectively termed here parenchymal border macrophages, are shown to regulate flow dynamics of cerebrospinal fluid, implicating this cell population as new therapeutic targets in neurological diseases such as Alzheimer’s.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Breaking down the endothelial barrier is a hallmark of systemic inflammatory response syndrome. Here the authors show that palmitoylation, a post-translational modification of proteins, plays a critical role in altering endothelial function during inflammation, and suggest the targeting of palmitoyl acyltransferase DHHC21 as potential disease therapy.