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Improved imaging methods are crucial to map pancreatic ductal adenocarcinoma (PDAC). Here, the authors analyse PDAC samples using spatial transcriptomics and proteomics, identify claudin-4 as a potential theranostic target, and develop an imaging agent to track claudin-4 in primary and metastatic PDAC tumours.

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.

Benchmarking of scATAC-seq protocols demonstrates the effects of data quality on downstream analyses.

Wenzel et al. detect radio signatures of two forms of cyanopyrene, a small molecular sheet of carbon, which can be used as indicators of the abundance of pyrene. Their findings suggest that small polycyclic aromatic hydrocarbons must be formed in or transported to the cold interstellar medium.

A diverse, multidisciplinary panel of 386 experts in COVID-19 response from 112 countries provides health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

A trans-ancestry genome-wide association study of serum urate levels identifies 183 loci influencing this trait. Enrichment analyses, fine-mapping and colocalization with gene expression in 47 tissues implicate the kidney and liver as key target organs and prioritize potential causal genes.

Plasma turbulence is the main driver to deteriorate the performance of fusion power plants. This work presents an unprecedented comparison of plasma turbulence between experiment and simulation, proving that the gyrokinetic model GENE reached a high level of maturity to predict core turbulence.

Two below-threshold surface code memories on superconducting processors markedly reduce logical error rates, achieving high efficiency and real-time decoding, indicating potential for practical large-scale fault-tolerant quantum algorithms.

Extinction threatens to erode the Tree of Life. Here, the authors calculate extinction risk for jawed vertebrates, predicting a loss of 86–150 billion years (11–19%) of evolutionary history through the next 50–500 years and indicating that cartilaginous fish, ray-finned fish, and turtles are most at risk from a phylogenetic perspective.

RNA binding proteins (RBPs) regulate various RNA processes, yet their interactions remain poorly understood. Here, authors generate a comprehensive map of RBP interactions using multimodal data, uncovering context-specific functions and revealing complex post-transcriptional regulatory networks.

Modelling diverse ecological phenomena across scales with a single mathematical framework is challenging. Here, the authors draw on density functional theory to develop a framework that bridges between mechanistic theories at fine scales and statistical models at large scales.

Using a sample of more than 1 million individuals, Hatoum et al. identify genomic loci associated with general and substance-specific addiction risk.

 A transcriptomic cell-type atlas of the whole adult mouse brain with ~5,300 clusters built from single-cell and spatial transcriptomic datasets with more than eight million cells reveals remarkable cell type diversity across the brain and unique cell type characteristics of different brain regions. 

Genome-wide analyses identify common variants associated with 11 distinct neuropathology endophenotypes, providing insights into the mechanisms underlying the genetic risk of Alzheimer’s disease and related dementias.

Follicular lymphoma can transform to a more aggressive histology. Here, the authors use bulk and single cell analysis to create a 26 marker panel which could be used to profile FL samples and predict the risk of transformation using flow cytometry.

Defective protein quality control is a key feature of neurodegeneration. Here, the authors show that mutations in Nemf/NEMF, a component of the Ribosome-associated Quality Control complex, have a neurodegenerative effect in mice and may underlie neuromuscular disease in seven unrelated families.

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 genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

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.

The measurement of the total cross-section of proton–proton collisions is of fundamental importance for particle physics. Here, the first measurement of the inelastic cross-section is presented for proton–proton collisions at an energy of 7 teraelectronvolts using the ATLAS detector at the Large Hadron Collider.

Bahmani, Cha, Alavi, Dixit et al. evaluate an AI-facilitated precision medicine learning platform they built, Stanford Data Ocean. The platform, which provided 3594 costfree certification accesses across 93 countries, demonstrates positive training outcomes across bioinformatics topics for low and middle income learners.

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.

The molecular characteristics of myocarditis associated with immune checkpoint inhibitors are described and potential biomarkers of onset and severity are identified.

Manual injection, which remains low-throughput and labor-intensive, is a technical bottleneck for large-scale genetic studies of C. elegans. Here, the authors report a robotic microinjection system which facilitates injection speed while maintaining injection quality which is comparable to experienced experts.

The plumage of Cretaceous birds has previously been described only from compression fossils and isolated feathers in amber. Here, Xing et al.describe two 99 million year old bird wings found preserved in amber, enabling new insight into the evolution of feather arrangement, pigmentation, and structure.

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.

The origins of alpine plant diversity are unclear. Here, the authors provide a time-calibrated molecular phylogenetic tree for Saxifraga, a diverse alpine plant clade, and show that upslope biome shifts into the alpine zone occurred more often than dispersal between alpine regions.

Stephanie London, Martin Tobin and colleagues report meta-analyses of genome-wide association studies for forced vital capacity (FVC), a spirometric measure of pulmonary function that reflects lung volume. They identify six regions newly associated with FVC and demonstrate that candidate genes at these loci are expressed in lung tissue and primary lung cells.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

The essential role of ORAI1 channels in receptor-evoked Ca²⁺ signaling is well understood, but the roles of ORAI2 and ORAI3 remained obscure. Here authors show that ORAI2 and ORAI3 channels multimerize with ORAI1 to expand the range of sensitivity of receptor-activated Ca²⁺ signals, reflecting their enhanced basal STIM1-binding and heightened Ca²⁺-dependent inactivation.

Past genome-wide associate studies have identified hundreds of genetic loci that influence body size and shape when examined one trait at a time. Here, Jeff and colleagues develop an aggregate score of various body traits, and use meta-analysis to find new loci linked to body shape.

Over half the world’s rivers dry periodically, yet little is known about the biological communities in dry riverbeds. This study examines biodiversity across 84 non-perennial rivers in 19 countries using DNA metabarcoding. It finds that nutrient availability, climate and biotic interactions influence the biodiversity of these dry environments.

The question of whether recombination rate increases with maternal age is controversial, with conflicting prior evidence. Here, Martin et al.analyse nine cohorts in the largest SNP-based analysis of this question and find a small positive increase with maternal age in the number of crossovers.

Thyroid dysfunction is involved in many diseases. Here, the authors provide insights into the genetics and biological pathways influencing important thyroid function parameters, showing potential causal effects on many clinical outcomes.

In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.

Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.

Using a single-nucleus multi-omics approach, a study jointly profiles the reorganization of the epigenome and the three-dimensional chromatin conformation during the development of the human hippocampus and prefrontal cortex.

Power exhaust is one of the biggest challenges stopping fusion energy. This article shows experimental evidence for strategically shaping the power exhaust region as a solution to this challenge, utilising physics understanding to strike a balance between engineering complexity and power exhaust benefits, consistent with reduced models and simulations.

Chronic myelomonocytic leukaemia is classified as proliferative (pCMML) or dysplastic based on the white blood cell counts but biological differences are unclear. Here, the authors show genetic, transcriptomic and epigenomic differences between these two subtypes establishing that pCMML is RAS-pathway driven and that inhibiting RAS-driven PLK1 expression is a viable therapeutic target.

Durable agonism of NPR1 achieved with a novel investigational monoclonal antibody could mirror the positive hemodynamic changes in blood pressure and heart failure identified in humans with lifelong exposure to NPR1 coding variants.

Stathmin-2 is lost in amyotrophic lateral sclerosis. Here the authors show that stathmin-2 has an essential role in the maintenance of axon structure, with its loss from adult motor neurons resulting in axonal collapse and muscle denervation.

Glycolytic enzymes are challenging drug targets due to their highly conserved active sites and phosphorylated substrates. Here, the authors identify fast acting allosteric inhibitors of Trypanosoma brucei phosphofructokinase that block trypanosome glycolysis and provide cure evidence in murine model.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

In cancer, neoantigen (NeoAg)-specific CD8⁺ T cells capable of direct tumor recognition have been extensively studied but little is known of the role of NeoAg-specific CD4⁺ T cells. Here Schoenberger and colleagues analyze an oligoclonal CD4⁺ T cell response to a naturally arising murine tumor NeoAg at the level of TCR usage and functionality.

How the segmental innervation of upper limb muscles recovers after spinal cord injury is not fully understood. Here the authors show associations between corticospinal tract sparing and upper extremity recovery in spinal cord injury.

A survey of sharks and rays on coral reefs within 66 marine protected areas across 36 countries showcases that the conservation benefits of full MPA protection to sharks almost double when accompanied by effective fisheries management.