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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.

Loss-of-function variants in thyroid hormone transporter MCT8 cause a neurodevelopmental and metabolic disorder. Here the authors identify genotype-phenotype relationships, advance insights in MCT8 (dys)function and create a pathogenicity-severity variant classifier.

The development of highly water-permeable membranes is key for the treatment of high salinity waters. Here the authors enhance the water permeability of a metal-organic framework nanoporous membrane via an intra-crystalline defect engineering strategy.

Trefoil factors (TFFs) protect the mucosa and have various reported binding activities, but whether they share a common interaction mechanism has remained unclear. Here, the authors provide structural and biochemical evidence that all three human TFFs are divalent lectins that recognise the same disaccharide.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

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.

Intestinal homeostasis is ensured by stem cell self-renewal and differentiation while alterations of these processes can lead to cancer. In this study, using Drosophilagenetics the authors demonstrate that the loss of the transcription factor Sox21a blocks the differentiation of the intestinal stem cell progeny, which accumulate and form aggressive tumours.

Intestinal cell types are organized into distinct neighbourhoods and communities within the healthy human intestine, with distinct immunological niches.

Here, the authors show that a single substitution in mouse P1, outside of its arginine core and independently of its charge, suffices to alter sperm chromatin structure and associated developmental outcomes.

Han Brunner and colleagues report the identification of de novo nonsense mutations in ASXL1 in individuals with Bohring-Opitz syndrome, which is characterized by intellectual disability, distinctive facial features and multiple congenital malformations.

Analysis of the results of a large clinical trial, EMPEROR-Preserved, shows that the SGLT2 inhibitor empagliflozin improves outcomes for heart failure patients with either mid-range (41–49%) or preserved (≥50%) ejection fraction, supporting the use of this drug for both categories of patients.

Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.

CK1a-mediated progressive phosphorylation of FRQ is an essential aspect of the molecular clock in Neurospora. Here, Lauinger et al.demonstrate that the DEAD box helicase FRH acts as an ATP driven remodelling factor of the CK1a/FRQ complex that provides a pacemaker function by attenuating FRQ phosphorylation.

The wheat Pm3 immune receptors confer resistance against powdery mildew by recognizing isolate-specific avirulence (AVR) effectors of the pathogen. Here, the authors identify and characterize two new AVR genes and demonstrate that Pm3 receptors are determinants of host-specificity for grass mildews.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

Michael Talkowski and colleagues analyze balanced chromosomal abnormalities in 273 individuals by whole-genome sequencing. Their findings suggest that sequence-level resolution improves prediction of clinical outcomes for balanced rearrangements and provides insight into pathogenic mechanisms such as altered gene regulation due to changes in chromosome topology.

Environmental stress on coral reefs is increasing. Authors show a stress-related reduction in residency of grey reef sharks on the remote reefs of the Chagos Archipelago, promoting more diffuse space use and increased time away from the shallow forereefs.

Genome-wide analysis identifies variants associated with the volume of seven different subcortical brain regions defined by magnetic resonance imaging. Implicated genes are involved in neurodevelopmental and synaptic signaling pathways.

Lateral opening of the LptDE transporter in the outer membrane of Gram-negative bacteria is necessary for insertion of lipopolysaccharides. Here, Botte et al. report a cryo-EM structure of a partially opened LptDE transporter, in complex with rigid chaperones derived from nanobodies.

The bicyclic disulfide–containing compound thiolutin has broad antimicrobial activity and targets the essential proteasomal deubiquitinase Rpn11 and other metalloproteases, leading to inhibition of enzymatic activity through a mechanism involving zinc chelation.

Whole-genome sequencing of normal human endometrial glands shows that most are clonal cell populations and frequently carry cancer driver mutations that occur early in life, and that parity has a protective effect.

By integrating healthcare and exome-sequencing data from parent–offspring trios of patients with developmental disorders, 28 genes that had not previously been associated with developmental disorders were identified.

Richard Watanabe and colleagues of the MAGIC consortium report meta-analyses of genome-wide association studies to glucose levels two hours after an oral glucose challenge. They identify variants in GIPR associated with glucose and insulin responses.

Generative Deep Learning holds promise for mining the unexplored “chemical universe” for new drugs. Here, the authors demonstrate the de novo design of phosphoinositide 3-kinase gamma (PI3Kγ) inhibitors for the PI3K/Akt pathway in human tumor cells.

Neurodevelopmental disorders (NDDs) are a heterogeneous group of diseases for which the genetic basis is still unknown in more than half of the cases. Here, the authors report a NDD associated with disruptive variants in the TANC2 gene and show that rols, the TANC2 homolog in flies, is required for synapse growth and function.

Whole-genome sequencing analysis of somatic mutations in liver samples from patients with chronic liver disease identifies driver mutations in metabolism-related genes such as FOXO1, and shows that these variants frequently exhibit convergent evolution.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong ethnic and gender bias. In a transancestral genetic association study, Langefeldet al. identify 24 novel regions associated with risk to lupus and propose a cumulative hits hypothesis for loci conferring risk to SLE.

The contribution of glia to Huntington's disease is unclear. The authors show that human glial progenitor cells (GPCs) expressing mutant huntingtin impair motor performance when engrafted into wild type mice, and wild type human GPCs ameliorate disease phenotypes when engrafted into an HD mouse model.

Whole-genome sequencing of liver microdissections from five healthy individuals and nine with cirrhosis demonstrates the effects of liver disease on the genome, including increased rates of mutation, complex structural variation and different mutational signatures.

A new approach to evolve novel aminoacyl-tRNA synthetase–tRNA pairs with orthogonal substrate specificity is applied to generate a system to site-specifically incorporate phosphothreonine into proteins, enabling functional studies of this post-translational modification.

Phage engineered with tail fibers and CRISPR–Cas reduce Escherichia coli load in animals.