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Prostate cancer often does not progress to invasive disease and thus markers predicting the course of the disease progression are critical for optimal treatment choices. Here the authors show that variants at two genetic loci correlate with the aggressiveness of prostate cancer.

The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.

In a GWAS study of 32,438 adults, the authors discovered five novel loci for intracranial volume and confirmed two known signals. Variants for intracranial volume were also related to childhood and adult cognitive function and to Parkinson's disease, and enriched near genes involved in growth pathways, including PI3K-AKT signaling.

Mark Daly and colleagues present a statistical framework to evaluate the role of de novo mutations in human disease by calibrating a model of de novo mutation rates at the individual gene level. The mutation probabilities defined by their model and list of constrained genes can be used to help identify genetic variants that have a significant role in disease.

Unlike ubiquitous axial-flow turbines, cross-flow turbines have rotation axes perpendicular to the flow they sit in. This study presents a control scheme that optimizes blade angular velocity as a function of blade position with no extra degrees of freedom, yielding a 59% increase in power output.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

The MT₁ melatonin receptor differs markedly from 5-HT receptors and shows atypical ligand entry; its structure with various ligands sheds light on receptor specificity.

Adult forms of inflammatory bowel disease (IBD) are of a polygenic nature, but paediatric and very early onset (VEO) IBD also occur as monogenic forms. Here, using whole exome sequencing, the authors explore both the monogenic and polygenic contribution to VEO-IBD and characterize a rare somatic mosaic VEO-IBD patient.

Keratin 16 is an epithelial protein highly expressed at pressure bearing sites and during wound healing and cancer. Here the authors show that K16 interacts with the inactive protease Rhbdf2, associated with Tylosis with oesophageal cancer, and that this interaction drives increased keratinocyte proliferation.

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.

The heterogeneity of androgen receptor (AR) gene alterations across metastases in prostate cancer remains unresolved. Here, the authors characterise AR genomic complexity across spatially separated lethal metastases from 10 prostate cancer patients and investigate how AR alterations evolve.

Structural and functional studies show that the MT₂ melatonin receptor, unlike the MT₁ receptor, contains an extracellular opening for ligand entry, shedding light on receptor subtype specificity.

Though tractography is widely used, it has not been systematically validated. Here, authors report results from 20 groups showing that many tractography algorithms produce both valid and invalid bundles.

Exome sequencing of 175 autism spectrum disorder parent–child trios reveals that few de novo point mutations have a role in autism spectrum disorder and those that do are distributed across many genes and are incompletely penetrant, further supporting extreme genetic heterogeneity of this spectrum disorder.

The mechanism by which cell geometry regulates cell signalling is reported to be modulated by lipid rafts within the plasma membrane, which are now shown to be responsible for geometry-dependent mesenchymal stem cell differentiation.

Identification of markers of drug response is essential for precision therapy. Here the authors introduce an algorithm that uses prior information about each gene’s importance in AML to identify the most predictive gene-drug associations from transcriptome and drug response data from 30 AML samples.

The crystal structure of active mouse SMO in complex with the SAG21k agonist and a stabilizing intracellular binding nanobody reveals the structural basis of SMO regulation by PTCH1.

PHF8 is a JmjC domain-containing protein, the gene for which has been linked to X-linked mental retardation (XLMR). These authors demonstrate PHF8 to be a histone demethylase with activity against H4K20me1. It has a role in regulating gene expression as well as in neuronal cell survival and craniofacial development in zebrafish. The results suggest there may be a link between histone methylation dynamics and XLMR.

The most comprehensive architectural model to date of the nuclear pore complex reveals previously unknown local interactions, and a role for nucleoporin 358 in Y-complex oligomerization.

Meredith Yeager, Stephen Chanock and colleagues analyze mosaic loss of the Y chromosome in three prospective cohorts and observe association with age and smoking but not with cancer survival. They also identify common variation at TCL1A associated with increased risk of mosaic loss of the Y chromosome.

Mark Seielstad and colleagues report results of a large genome-wide association and replication study of ulcerative colitis. The work identifies several new risk loci for this disease and provides further insight into the shared pathogenesis of ulcerative colitis and Crohn's disease.

p63 and PAX6 act to specify limbal stem or progenitor cells (LSCs), and WNT7A controls corneal epithelium differentiation through PAX6; loss of WNT7A or PAX6 induces LSCs into epithelium, and transduction of PAX6 in skin epithelial stem cells converts them to LSC-like cells and transplantation in a rabbit corneal injury model can replenish corneal epithelial cells and repair damaged corneal surface.

A high-quality sequence assembly of the zebrafish genome reveals the largest gene set of any vertebrate and provides information on key genomic features, and comparison to the human reference genome shows that approximately 70% of human protein-coding genes have at least one clear zebrafish orthologue.

Rosalind Eeles, Christopher Haiman and colleagues report genome-wide association and meta-analyses of prostate cancer in populations of European, African, Japanese and Latino ancestry. They identify 23 new susceptibility loci, including one associated with early-onset prostate cancer.

Elise Robinson, Mark Daly and colleagues present an analysis of genetic data from autism spectrum disorder (ASD) and population-based studies and find evidence for genetic correlations between ASDs and typical variation in social behavior and communication traits. These results may inform genetic models of ASDs and other neuropsychiatric disorders.

Single-cell transcriptomics analysis of malignant ascites samples from patients with high-grade serous ovarian cancer reveals inter- and intra-patient heterogeneity in malignant cells, cancer-associated fibroblasts and macrophages.

Using a combination of remote-sensing technologies, lipidomics and gene-based biomarkers, the authors demonstrate a coupling between viral infection of an Emiliania huxleyi bloom and the export of organic and inorganic carbon from the photic zone.

The authors propose a new conceptual model of critical illness that moves away from the current syndrome-based framework in favor of more precise biological descriptors—spurred by mounting translational evidence and insights from Coronavirus Disease 2019 (COVID-19) research.

The authors report two new engineered AAV capsids that efficiently deliver genes throughout the adult central and peripheral nervous systems after intravenous administration. Complementing these capsids is an AAV toolbox that enables cell morphology and genetic manipulation studies of defined neural cell types in transgenic or wild-type animals.