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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.

Traumatic brain injury is associated with changes to the metabolome. Here the authors show that acute traumatic brain injury has distinctive serum metabolic patterns which may suggest protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.

In preclinical studies, Hutt, Loi and colleagues find that mice treated with checkpoint blockade have impaired ovarian function and reserve, associated with increased immune infiltrate, raising considerations about fertility implications for female patients.

Nanostructured fibres with highly aligned and alternating crystalline and amorphous domains created from triblock copolymers exhibit excellent mechanical properties, multi-trigger actuation, high-performance contraction and on/off rotation.

A multi-ancestry meta-regression study analyses diverse genome-wide association studies and genome loci associated with tobacco and alcohol use.

 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. 

Deep brain stimulation has been investigated as a potential treatment for cognitive impairments in Alzheimer’s disease. Here the authors carry out post hoc analysis of multi-center cohorts to investigate the anatomical and functional correlates of effective deep brain stimulation, and find that stimulating circuit of Papez, fornix and bed nucleus of the stria terminalis, and a multi-region functional network, were associated with clinical improvement.

Peripheral nerves slowly regrow after injury, but often fail to form functional synapses. Here, authors use NANOG, a pluripotency factor, to induce denervated muscle to a pro-regenerative state improving muscle reinnervation after nerve transection.

Comprehensive molecular profiles are required to understand and treat sarcomas, which comprise more than 70 different subtypes. Here, the authors profile the genomic landscape of 7494 sarcomas across 44 histologies using targeted panel sequencing and identify potential therapeutic targets.

Youth engagement in agriculture in low- and middle-income countries offers social and economic opportunities, and supports food security. Agriculture skills training is key for youth engagement, yet programmes are not well evaluated for effectiveness in employment outcomes.

By implementing random circuit sampling, experimental and theoretical results establish the existence of transitions to a stable, computationally complex phase that is reachable with current quantum processors.

Here the authors identify 33 individuals with a dominant neurodevelopmental disorder due to heterozygous missense or loss-of-function variants in the gene encoding Densin-180, a scaffold protein present at postsynaptic sites in neurons of the central nervous system.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

To selectively internalize proteins into the endosomal system, eukaryotic cells rely on clathrin adaptors such as the clathrin assembly lymphoid myeloid leukaemia protein (CALM), but details regarding the underlying mechanism remain unexplored. Here, the authors characterize the effect of CALM on lipid packaging density and membrane remodelling through a combination of in vitro studies, neutron reflectometry, grazing incidence X-ray diffraction, atomic force microscopy and solid-state nuclear magnetic resonance, and show that CALM’s amphiphilic N-terminal helix embeds into the membrane to stabilize protein docking.

Sweet corn is one of the most important vegetables in North America and has undergone different selection pressures than non-sweet cultivars. Here, the authors report its genome assembly and reveal the evolutionary history of modern sweet corn through population genomic analyses.

Quasicrystals exhibit long-range order without periodicity. The authors report an approach for quasicrystal fabrication and show through in situ imaging and corresponding simulations the formation of a single decagonal quasicrystal arising from coalescence of multiple quasicrystals in a liquid.

Circulating tumor cells (CTCs) are clinically useful for detecting and monitoring cancer, but they are rare in blood. Here, the authors use a highthroughput microfluidic device to massively enrich CTCs from leukapheresis products to uncover single cell molecular features in prostate and other cancers.

Niemann–Pick disease is characterized by the cellular accumulation of sphingomyelin. Blumberg and colleagues use both mouse models and materials from patients with Niemann–Pick disease to show that sphingomyelin accumulation inhibits CD1d-restricted NKT cell activation and development.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

A new phylogenomic tree for butterflies is constructed using 391 genes from 2,300 species, representing 92% of genera. It suggests that butterflies originated around 100 million years ago in what is now the Americas and originally fed on Fabaceae.

A genomic and transcriptomic analysis of 2,754 childhood acute lymphoblastic leukemias identifies 376 putative driver genes, and associations between disease subtypes and prognosis.

Pretomanid has been approved for use in cases of multi-drug resistant pulmonary tuberculosis, yet the penetration of this antibiotic into other target tissues is not well established. Authors provide insight on pretomanid pharmacokinetics in the central nervous system, using positron emission tomography in animal models, and human studies.

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.

Functional MRI studies across ages show that the classic homunculus of the motor cortex in humans is in fact discontinuous, alternating with action control-linked regions termed the somato-cognitive action network.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

The WNT/b-catenin pathway is essential for bloodbrain barrier (BBB) and blood-retina barrier (BRB) function. A bioengineered FZD4-selective WNT surrogate demonstrated systemic efficacy during BRB and ischemic stroke BBB dysfunction in mice.

The slow maturation of human neurons is regulated by epigenetic modification in nascent neurons, mediated by EZH2, EHMT1, EHMT2 and DOT1L.

Palaeoproteomics offers an opportunity to resolve molecular phylogenies especially in contexts where ancient DNA does not preserve. Here collagen sequences resolve sloth phylogenies differently from morphology-based estimates, illuminating the utility of proteomics in systematics.

HIV exposed but uninfected infants may face an increased risk of serious infection and mortality. In this work, the authors utilise a cohort from rural Zimbabwe to explore the biological mechanisms underlying infant mortality.

Andrew Morris, Mark McCarthy, Michael Boehnke and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes, including 26,488 cases and 83,964 controls from populations of European, east Asian, south Asian and Mexican and Mexican American ancestry. They identify seven loci newly associated with type 2 diabetes and examine the genetic architecture of disease across populations.

Studies of cell heterogeneity in white matter in primates have been limited to date. Here the authors describe a marmoset brain cell atlas that bridges rodent and human data, revealing strong gray-white matter glial segregation.

Different molecular subtypes defined by specific gene rearrangements have been described for acute lymphoblastic leukaemia (ALL). Here, the authors show that ZNF384 fusion activates FLT3 expression conferring a therapeutic vulnerability for ZNF384- rearranged ALL subtype.

Microglia play key roles during early neurodevelopment. Here the authors show that microglia are important mediators of ocular dominance plasticity (ODP). Microglia respond to monocular deprivation during the visual critical period, and disrupting microglial P2Y12 purinergic receptor abrogates ODP.

In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer’s disease, and functional analysis suggests it interacts with amyloid-beta.

Dawe et al. report a protein tethering method for recruiting Centromeric Histone H3 to synthetic repeat arrays. Newly recruited Centromeric Histone H3 organized functional centromeres that supported independent chromosome segregation for several generations.

The production of microparticles with complex geometries for biotechnological use historically requires sophisticated fabrication techniques. Here, the authors create complex particle geometries by exploiting the metastable region of the phase diagram of thermally responsive intrinsically disordered proteins within microdroplets.

It is hoped that simulations of molecules and materials will provide a near-term application of quantum computers. A study of the performance of error mitigation highlights the obstacles to scaling up these calculations to practically useful sizes.

The translational elongation factor eIF5a may have a function in T cell protein translation. Here the authors show that hypusination of eIF5a or deletion of eIF5a alters the profile of mRNA translation in T cells and that eIF5 regulates the proliferation and effector function of these T cells.

Skeletal ryanodine receptor controls calcium mobilization indispensable for muscle contraction. Here, authors combine cryo-EM and molecular dynamics to uncover the structural basis of the intricate regulation of this channel by calcium and magnesium.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

Populations of the cave fish Astyanax mexicanus exhibit a variety of traits that evolved repeatedly and independently from its surface counterparts. Here the authors present a de novo genome assembly for A. mexicanusand identify candidate genes for eye loss and reduced pigmentation.

A campaign-level field experiment shows how digital advertising may have affected differential turnout in the 2020 US presidential election, particularly among early voters.

Post-translational modification of microtubules by detyrosination is prevalent in failing human cardiomyocytes and inhibits cardiomyocyte contraction, suggesting a new therapeutic strategy for improving heart function.

Multi-ancestry genome-wide association meta-analyses identify risk loci for cannabis use disorder. Genomic structural equation modeling and genetic correlation analyses show overlap with several other traits, including impulsivity and psychopathology.

Association analyses in over 1 million individuals identify 535 new loci influencing blood pressure traits. The results provide new insights into blood pressure regulation and highlight shared genetic architecture between blood pressure and lifestyle exposures.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.