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Upstream open reading frames (uORFs), located in 5’ untranslated regions, are regulators of downstream protein translation. Here, Whiffin et al. use the genomes of 15,708 individuals in the Genome Aggregation Database (gnomAD) to systematically assess the deleteriousness of variants creating or disrupting uORFs.

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.

Pine Island Glacier terminates in a rapidly melting ice shelf and ocean conditions are believed to influence its contribution to sea level rise. Here, the authors show that variability in these ocean conditions is driven by a combination of changes in ocean circulation and local surface heat fluxes.

Primary immunodeficiency can predispose patients to mycobacterial disease. Casanova and colleagues identify novel human mutations in the enzyme SPPL2A that result in selective accumulation of CD74 in a dendritic cell subset and lead to their death and the failure to mount effective T_H1 responses.

Methicillin-resistant strains of Staphylococcus aureus appeared in European hedgehogs in the pre-antibiotic era as a co-evolutionary adaptation to antibiotic-producing dermatophytes and have spread within the local hedgehog populations and between hedgehogs and secondary hosts.

Authors utilize a number of models (mathematical, in vitro and in vivo infection) to analyse pre-clinical and Phase I clinical trial data, in regard to potential risk of resistance associated with a Plasmodium falciparum inhibitor, cabamiquine.

By simulating the implementation of airport-based wastewater surveillance sites at the global level, a modeling study shows how this early warning system would perform in identifying sources of pandemic outbreaks, in time and space, and what the optimal location of monitoring sites would be.

The genetic basis of atopic dermatitis is not fully understood. Here, the authors find 91 genetic loci associated with atopic dermatitis in a GWAS of >1million individuals, which highlight the importance of systemic immune regulation.

IL-27RA–IL-27 has a critical role in the immunity to EBV, and this defence is hijacked by Epstein–Barr virus to promote the expansion of infected transformed B cells

The James Webb Space Telescope has detected water ice in the cold debris disk (analogous to the Kuiper belt) around the star HD 181327.

Trehalose polyphleates are surface-exposed glycolipids that are required for successful infection by phages BPs and Muddy when infecting Mycobacterium abscessus and M. smegmatis.

The preferential susceptibility of oncolytic viruses to certain antibiotics can be exploited to accelerate the engineering of oncolytic viruses expressing transgenes for immunomodulatory cytokines.

Somatically determined preferential allelic expression of select genes that when mutated cause inborn errors of immunity corresponds with disease phenotypes, suggesting that the penetrance and expressivity of monogenic disorders is also dependent on the ‘transcriptotype’.

Multi-nucleotide variants (MNV) are genetic variants in close proximity of each other on the same haplotype whose functional impact is difficult to predict if they reside in the same codon. Here, Wang et al. use the gnomAD dataset to assemble a catalogue of MNVs and estimate their global mutation rate.

Herpes simplex virus-1 encephalitis is linked to variants in a small nucleolar RNA, suggesting a new mechanism for antiviral immunity in cortical neurons.

An analysis of 38 ancient genomes from the aurochs, the extinct ancestor of modern cattle, provides insight into the population ancestry and domestication of this species.

La-substitution in BiFeO₃ enables an electric field-driven conversion of a multi-domain into a single ferroelectric domain accompanied by a single variant spin cycloid. A single domain multiferroic generates 400% larger non-local inverse spin Hall voltage at the output.

SARS-CoV-2 evolution poses a risk to vaccine and antiviral drug efficacy. Here, Gagne et al. report the development of a variant-agnostic protein, RBD-62, with enhanced ACE2 binding obtained through in vitro evolution and show that RBD-62 inhalation protects nonhuman primates against SARS-CoV-2 Delta challenge.

This study uses gene expression predictors for the dorsolateral prefrontal cortex and other brain regions to perform a transcriptomic imputation analysis of schizophrenia, identifying 413 genic associations across 13 brain regions and 36 significantly enriched pathways.

Springtails are omnipresent soil arthropods, vital for ecosystems. In the first global assessment of springtails, this study shows a 20-fold biomass difference between the tundra and the tropics, with distinct temperature-related patterns for diversity and metabolism that suggest climate change may restructure the functioning of soil biodiversity.

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.

X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases such as chronic kidney disease (CKD). Here, the authors perform a sex-stratified, cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits, with results including identification of four novel loci associated with the CKD-defining trait eGFR.

Tropical seagrasses in Patagonia during the Miocene imply a broader paleogeographic distribution than previously recognized, particularly in high South American latitudes indicating warmer sea surface temperatures, based on the seagrass botanical affinities.

At a time when protecting the environment is urgent, dealing with inherent uncertainties in the responses of biodiversity to disturbances is essential. This study promotes a promising tool to assess the vulnerability of species assemblages to guide protection efforts even if species response and disturbance regimes are poorly documented.

Analyses of 34 ancient genomes from northeastern Siberia, dating to between 31,000 and 600 years ago, reveal at least three major migration events in the late Pleistocene population history of the region.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

Theta oscillations are essential to temporal encoding in the hippocampus; they clock hippocampal activity during awake behaviour and rapid eye movement (REM) sleep. Although these 4–10-Hz oscillations are widely believed to be synchronized throughout the hippocampus, they are now demonstrated to form waves that travel across the hippocampal circuit, making the organization of time in the hippocampus similar to that on Earth—a progression of local time zones.

Results from 316 Bombus terrestris colonies at 106 agricultural sites across eight European countries find pesticides in bumble bee pollen to be associated with reduced colony performance, especially in areas of intensive agriculture.

The heterogenous nature of rheumatoid arthritis renders the prediction of responsiveness to biological treatments difficult. Here the authors analyze bulk RNA-seq data from the STRAP trial (n = 208) to build a machine-learning model for predicting responses to etanercept, tocilizumab and rituximab with AUCs around 0.75 to potentially assist in therapy planning.

Sepsis may promptly develop into lethal organ failure, so early diagnosis and treatment planning are essential. Here the authors use machine learning to develop a six-gene signature, termed Sepset, for initial diagnosis, and integrate Sepset into a microfluidic-based bench-side platform for predicting the prognosis of suspected sepsis suitable for the clinic.

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.

Current ultrasound transducers are bulky and rigid. Here, the authors describe a new way to realize large-area and mechanically flexible ultrasound arrays on polymer foils suited for wearable ultrasound applications

The authors show that DCAF1, a substrate receptor of CUL4 and EDVP E3 ligases, can be recruited by PROTACs to degrade the cancer drug target, WDR5. They also report the crystal structures of PROTAC ternary complexes that reveal a significant role for loops in DCAF1 substrate recognition, a potential mechanism behind the diverse substrate specificity of DCAF1.

Duchenne muscular dystrophy is a progressive degenerative disease of muscles caused by mutations in the dystrophin gene. Here the authors use AAV vectors to deliver microdystrophin to dogs with muscular dystrophy, and show restoration of dystrophin expression and reduction of symptoms up to 26 months of age.

How arable farming affects soil fungal biogeography is poorly understood. Here, the authors find that prevalent fungal groups become more abundant, whereas rare groups become fewer or absent in arable lands across Europe, suggesting a biotic homogenization due to arable farming.

An outstanding discrepancy between observations and models of stellar limb darkening is resolved here by the inclusion of stellar surface magnetism in models. This will enable an improved characterization of transiting exoplanets.

There is growing evidence that the intestinal microbiota can affect host behaviour. Here, De Palma et al. show in mice that early-life stress (maternal separation) induces changes in host physiology that alter the gut microbiota, which then triggers anxiety-like and depression-like behaviour later in life.

The roles played by thrombin in the human intestinal mucosa are unclear. Here, the authors show that the commensal microbiota modulates epithelial production of active thrombin, which controls biofilm growth and contributes to protection of the mucosa from bacterial invasion.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.