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White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.

Short hairpin RNAs can be used to modulate and regulate gene expression. Here the authors generate chimeric RNAs that interact with the photoreceptor PAL, allowing for optoribogenetic control of cell physiology.

Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.

Zinc finger protein transcription factors are developed for the selective silencing of the mutant huntingtin gene in human neurons in vitro and multiple animal models of Huntington’s disease in vivo while preserving expression of the wild-type allele.

Volcanic ash is often neglected in climate simulations as it is assumed to have a short atmospheric lifetime. Here, the authors show a persistent super-micron ash layer after the Mt. Kelut eruption in 2014 that impacts the stratospheric sulfur burden and chemistry for over the first months after the eruption.

Despite widespread transcription of LncRNA in mammalian systems, their contribution to metabolic homeostasis at the cellular and tissue level remains elusive. Here Pradas-Juni et al. describe a transcription factor–LncRNA pathway that couples hepatocyte nutrient sensing to regulation of glucose metabolism in mice.

This Consensus Statement presents the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines.

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.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

The LHCb experiment at CERN has observed significant asymmetries between the decay rates of the beauty baryon and its CP-conjugated antibaryon, thus demonstrating CP violation in baryon decays.

Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution.

A genome-wide association meta-analysis study here shows novel genetic loci to be associated to body fat percentage, and describes cross-phenotype association that further demonstrate a close relationship between adiposity and cardiovascular disease risk.

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.

A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis.

Genetic variants at multiple loci of chr5p15.33 have been associated with susceptibility to numerous cancers. Here the authors show that the association of one of these loci may be explained by a variant, rs36115365, influencing telomerase reverse transcriptase (TERT) expression via ZNF148.

John Perry and colleagues report the results of a large genome-wide association study meta-analysis to identify variants influencing age at natural menopause. They identify 54 independent signals and find enrichment near genes involved in delayed puberty and DNA damage response.

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma.

The main protease, a key enzyme of SARS-CoV-2, can protect itself from oxidative damage. Here, Reinke, Schubert, and colleagues used XFEL radiation to image the enzyme, revealing the disulfide and NOS/SONOS bonds that form in response to oxygen.

Recent work indicates that drug delivery to the brain can be improved through disruption of the blood brain barrier using low intensity pulsed ultrasound. Here, the authors report a phase I/II clinical trial investigating the combination of a nine-emitter implantable ultrasound device and carboplatin in patients with recurrent glioblastoma.

Mismatch between the ancestry of mitochondrial and nuclear genomes can drive somatic evolution during ageing. Analysis of around 1.2 million mitochodrial somatic mutations in young and old mice shows haplotype-specific mutational patterns and hotspots, and reversion mutations that re-align mito-nuclear ancestry during an organism’s lifespan.

Sven van der Lee, Julie Williams, Gerard Schellenberg and colleagues identify rare coding variants in PLCG2, ABI3 and TREM2 associated with Alzheimer's disease. These genes are highly expressed in microglia and provide additional evidence that the microglia-mediated immune response contributes to the development of Alzheimer's disease.

Far-infrared measurements of galaxies in the early Universe would reveal their detailed properties, but have been lacking for the more typical galaxies where most stars form; here an archetypal, early Universe star-forming galaxy is detected at far-infrared wavelengths, allowing its dust mass, total star-formation rate and dust-to-gas ratio to be calculated.

Extracellular vesicles (EVs) play a crucial role in intercellular communication by transferring bioactive molecules from donor to recipient cells. Here, the authors show that EVs play a crucial role in activating immune responses through cell fusion, shedding light on their impact on inflammation.

This work applies diffusion models to conditional molecule generation and shows how they can be used to tackle various structure-based drug design problems

The efficacy of carbapenem antibiotics can be compromised by metallo-β-lactamases, but a high-throughput screen followed by optimization has now enabled the discovery of indole-2-carboxylates (InCs) as potent broad-spectrum metallo-β-lactamase inhibitors. The results highlight the potential of InC–carbapenem combinations for clinical use as well as mechanism-guided approaches to combatting globally disseminated antibiotic resistant mechanisms.

The authors present the results of a 24-month phase 2 study of AADvac1, a tau vaccine against Alzheimer’s disease. AADvac1 was safe and induced high levels of antibodies. In the whole study sample, there were no significant changes on clinical outcomes.

A study of multisystem inflammatory syndrome in children (MIS-C) shows maintenance of elevated levels of monocyte-activating pathogen-specific IgG not seen in children infected with SARS-CoV-2 who do not develop MIS-C.

The cis-regulatory functions of human accelerated regions of genomic loci and their potential contribution to human brain evolution are revealed.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

Mutations in the Protein Phosphatase PPM1D are oncogenic in certain cancers including diffuse intrinsic pontine glioma (DIPG). Here, the authors show that PPM1D mutations in DIPG induce the silencing of the nicotinic acid phosphoribosyltransferase gene and display synthetic lethality with nicotinamide phosphoribosyltransferase inhibitors.

Experiments in mice show that a population of neurons in the vagal ganglia respond to the presence of glucose in the gut and connect to neurons in the brainstem, revealing the circuit that underlies the neural basis for the behavioural preference for sugar.

Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.

Transcriptional profiling and axonal reconstructions identify two types of pyramidal tract neuron in the motor cortex: one type projects to thalamic regions and produces early and persistent preparatory activity, and the other type projects to motor centres in the medulla and produces motor commands.

The exploitation of non-covalent interactions in carbohydrate chemistry is gaining traction. This Review summarizes recent developments in harnessing non-covalent interactions in selective carbohydrate synthesis, and highlights future directions.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

Evaluation of the effectiveness of COVID-19 vaccines is increasingly challenging due to high levels of exposure to infection and vaccination. Here, the authors use a model-based approach incorporating these factors and estimate that using a variant-matched rather than ancestral booster could prevent nearly twice as many hospitalisations and deaths over one year.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Bedoui and colleagues describe a sequential process of integration of innate and CD40-delivered signals in APCs, which optimizes their capacity to drive antiviral CD8⁺ T cell responses.

Does self-administered mindfulness effectively reduce stress? In a study across 37 sites involving 2,239 participants, four mindfulness exercises significantly reduced short-term, self-reported stress.