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This large meta-analysis of 11 GWAS identified 7 genetic loci associated with strabismus, esotropia and exotropia. Mendelian randomisation provided genetic evidence of the causal link between maternal smoking to increased strabismus risk in offspring.

This study explores four decades of biodiversity change across the tree of life in Germany’s terrestrial and aquatic ecosystems by sequencing standardized biota samples from a long-term pollution monitoring archive.

A study describes the assembly and analysis of a haplotype-resolved pangenome of bulbous barley with the potential to improve domesticated barley and illustrates its use in evolutionary research and trait mapping.

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 advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

A pangenome analysis of 76 wild and domesticated barley accessions in combination with short-read sequence data of 1,315 barley genotypes indicates that allelic diversity at structurally complex loci may have helped crop plants to adapt to agricultural ecosystems.

Multi-ancestry genome-wide analyses identify new risk loci for age-related macular degeneration. Ancestry-specific analyses identify distinct effects at major risk loci, including smaller effect sizes for CFH risk alleles in haplotypes of African ancestry.

The Middle Palaeolithic of southwest Asia witnessed interactions and knowledge sharing between archaic and modern humans ~130,000–80,000 years ago. These interactions led to increased behavioural complexity and consolidation of a uniform behavioural set across Homo groups in the region.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

The evolutionary origin of habenular asymmetries is elusive. Here they show morphological and molecular conservations indicative of an ancient origin in vertebrates and identify Wnt signaling as a core mechanism underlying their formation and diversification.

The specifics of the pediatric immune response that gives rise to antibodies capable of neutralising diverse HIV-1 strains is not fully understood. Here the authors characterise the immune environment of Simian-HIV infected paediatric macaques and link to antibody neutralisation induction.

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.

Here, the authors look at present day and medieval genome samples from Northern France to piece together demographic history and population structure across Brittany and the Loire basin.

Puissant and colleagues identify a myeloid-restricted PIK3CG/p110γ–PIK3R5/p101 axis as a therapeutic vulnerability in acute myeloid leukemia and develop a proteolysis-targeting chimera to potently degrade PIK3CG and suppress AML progression.

Differences in virulence across the Listeria monocytogenes species are determined by the fine-tuning of SigB pathway responsiveness and reflect host adaptation.

Jean-Pierre Bourquin, Martin Stanulla and colleagues report whole genome, whole exome and transcriptome sequencing of TCF3-HLF fusion–positive acute lymphoblastic leukemia. Drug response profiling in patient-derived xenografts identified sensitivity to the BCL2-specific inhibitor ABT-199 (venetoclax) as a new option for treating this fatal disease.

Human TNF is required for respiratory-burst-dependent immunity to Mycobacterium tuberculosis in macrophages but seems to be largely redundant physiologically.

MCM8-9 and HROB function together in DNA damage response. Here, the authors describe the mechanism of DNA unwinding by MCM8-9 and its activation by HROB. HROB makes direct contacts with both MCM8 and MCM9 and promotes DNA unwinding downstream of MCM8-9 loading and hexameric ring formation on DNA.

The identification of T cell epitopes is a critical step in understanding the immune response to infection and in designing vaccine based approaches. Here the authors introduce a frame work of antigen discovery called MHCvalidator and Epitrack to identify new antigenic features for T-cell COVID-19 vaccines and characterise a novel non-canonical epitope from a truncated Spike variant and mutation of an immunodominant epitope in the BNT162b4 vaccine.

It is found that carbon export fluxes to the deep ocean from a highly productive, naturally iron-fertilized region of the sub-Antarctic Southern Ocean are two to three times larger than the carbon export fluxes from an adjacent high-nutrient low-chlorophyll area not fertilized by iron. These findings support the hypothesis that increased iron supply to the glacial sub-Antarctic may have directly enhanced carbon export to the deep ocean.

“In subarachnoid hemorrhage (SAH), therapies are limited and clinical outcomes remain disappointing. The authors show a contribution of the urotensin II system in microvascular changes, vasospasm, neuroinflammation and cognitive deficits post-SAH, primarily through meningeal cells and border-associated macrophages

Distinguishing between different proteins that each bind to the same type of glycan is challenging. Here, the authors demonstrate that an enzymatically synthesised library of Lewis^x ‘glycofluoroforms’ that feature site-specific fluorination can discriminate closely related proteins.

Cytidine nucleotide triphosphate (CTP) is a key precursor involved in the metabolism of DNA, RNA and phospholipids. In this study, the authors examine the physiological consequences of CTP synthase (Ctps) 1 and 2 deletion in vivo and demonstrate that Ctps1 protects mice from fatal autoimmunity.

Combined hepatocellular-cholangiocarcinomas (cHCC-CCA) are challenging to diagnose, as they exhibit features of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICCA). Here, the authors use deep learning to re-classify cHCC-CCA tumours into HCC or ICCA based on histopathology images.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

In both focal segmental glomerulosclerosis (FSGS) and crescentic glomerulonephritis (CGN), kidney injury is characterised by the invasion of glomerular tufts by parietal epithelial cells (PECs). Here Lazareth et al. identify the tetraspanin CD9 as a key regulator of PEC migration, and find its upregulation in FSGS and CGN contributes to kidney injury in both diseases.

Hantaan virus polymerase is a central enzyme that performs hantavirus genome replication and transcription. Here, the authors unveil the structure of the full-length Hantaan virus polymerase in monomeric, dimeric and hexameric apo forms, revealing the multimerization capability of this enzyme.

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

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Efficient statistical emulation of melting land ice under various climate scenarios to 2100 indicates a contribution from melting land ice to sea level increase of at least 13 centimetres sea level equivalent.

Crenarchaeota, which comprise the most abundant clade of organisms on Earth, are believed to be responsible for the majority of ammonia oxidation in terrestrial and marine environments. But recent studies have suggested that not all species are autotrophic. Using a comprehensive dataset, it is now shown that a significant proportion of marine crenarchaeota lack the genes required for ammonia oxidation, suggesting that they are heterotrophs.

Mapping of a mutation in a tomato deficient in the plant cuticle component cutin yields the first cutin synthase, as shown via accumulation of polymer precursors and in vitro oligomerization of synthetic substrates.

The 2004 Sumatra earthquake was one of the largest events to occur in a subduction zone in the past 50 years. Seismic reflection data for this subduction zone reveal thrust faults cutting across the entire oceanic crust. This observation, coupled with the hypocentres of aftershocks, suggests that the megathrust—the interface between the Indo-Australian plate and the Sunda plate—currently lies in the oceanic mantle.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

Jamel Chelly and colleagues identify mutations in the E3 ubiquitin ligase gene NEDD4L that cause a syndrome of periventricular nodular heterotopia associated with neurodevelopmental disorders, cleft palate and toe syndactyly. The authors show that the mutations affect the mTORC1 and AKT pathways and cause defects in mouse brain development.

This experimental study shows how the interplay between bacteria-phage coevolution and competition among bacterial genotypes results in increased diversity of bacterial CRISPR immunity.

A high-quality reference for the sunflower genome (Helianthus annuus L.) and analysis of gene networks involved in flowering time and oil metabolism provide a basis for nutritional exploitation and analyses of adaptation to climate change.