Search

Exome-wide analysis identifies rare and low-frequency coding variants associated with body mass index. Gene-based meta-analysis and functional studies implicate 13 genes, eight of which are novel, and neuronal pathways as factors in human obesity.

A genome-wide association study suggests 41 previously unreported loci on top of the 23 known loci that influence the disease risk for lumbar disc herniations. Many of these loci harbour genes implicated in disc structure and inflammation, as well as genes related to the nervous system and nerve function.

Genetic mutations are usually the source of debilitating disease. But, for a number of rare inherited blood and skin disorders, spontaneous DNA changes can repair and even reverse disease symptoms. Mike May explores the therapeutic potential of this 'natural gene therapy'.

Super-resolution imaging of multiple target proteins in the same sample can provide important information of cellular nanostructure, but has not been routinely achieved. Here, the authors present a fully automated 3D STORM approach using a re-staining protocol to image 15 targets in single cells and 16 targets in neuronal tissue.

Botanic gardens are using good garden design to attract and educate the public. Mike Maunder explains how they can thrive both as businesses and as institutions of learning.

Traumatic brain injury is associated with changes to the metabolome. Here the authors show that acute traumatic brain injury has distinctive serum metabolic patterns which may suggest protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.

Ice core records of gradually declining atmospheric carbon dioxide (CO₂) for the period 1450–1700 CE support modelled scenarios of large-scale reorganisation of land use in the Americas following New World-Old World contact.

Ocean alkalinity enhancement (OAE) is seen as a promising method for CO₂ removal as it alters the surface carbon equilibrium, driving the transfer of CO₂ into the ocean. Here the authors computationally map the spatiotemporal efficiency of OAE to identify locations and timing for optimal OAE deployment.

Combining single-cell cytometry datasets increases the analytical flexibility and the statistical power of data analyses. Here, the authors present a method to robustly integrate cytometry data from different batches, experiments, or even different experimental techniques.

DNA-PAINT image acquisition is limited by speed. Here the authors use the neural network DeepSTORM to predict fluorophore positions from high emitter density DNA-PAINT data in order to achieve image acquisition in one minute; they demonstrate multi-colour and large-area imaging of semi-thin neuronal tissue.

Genetic screens are important tools to identify host factors associated with viral infections. Here, Flint et al. perform a genome-wide CRISPR screen using infectious Ebola virus (EBOV) and show that the host transferase GNPTAB is required for EBOV infection and a potential target for antiviral therapies

The first lasing results at SwissFEL, an X-ray free-electron laser, are presented, highlighting the facility’s unique capabilities. A general comparison to other major facilities is also provided.

Nanoscopy of non-adherent cells is currently not possible, due to their movement in solution. Here the authors immobilize and manipulate fixedE. coli by multiple optical traps; their holographic optical tweezers enable dSTORM imaging of orthogonal planes via 3D realignment of the sample.

Sequence assemblies for the genomes of 16 widely used inbred laboratory mouse strains highlight considerable strain-specific haplotype variation and allow for the identification of regions with the greatest sequence diversity between strains.

This meta-analysis of genome-wide association studies identifies four genetic loci associated with circulating leptin levels independent of adiposity. Examination in mouse adipose tissue explants provides functional support for the leptin-associated loci.

The authors define the cenotectic — the low-temperature stability limit for a liquid under arbitrary thermodynamic conditions — and measure it for several aqueous solutions of relevance to extraterrestrial oceans using isochoric freezing/melting.

DBlink uses deep learning to capture long-term dependencies between different frames in single-molecule localization microscopy data, yielding super spatiotemporal resolution videos of fast dynamic processes in living cells.

Berkane et al. investigated the activation process of selective autophagy of the ER. They show that that phosphorylation of FAM134 proteins by CK2 is a prerequisite for the formation of large micro-clusters of high-density at the ER membrane.

Two-dimensional (2D) membranes are emerging candidates for osmotic energy conversion but the trade-off between ion selectivity and conductivity remains the key bottleneck. Here, the authors demonstrate a fully crystalline imine-based 2D polymer membrane capable of combining excellent ionic conductivity and high selectivity for osmotic energy conversion.

To promote the recovery of the currently declining global trends in terrestrial biodiversity, increases in both the extent of land under conservation management and the sustainability of the global food system from farm to fork are required.

John Perry, Ken Ong and colleagues analyze genotype data on ∼370,000 women and identify 389 independent signals that associate with age at menarche, implicating ∼250 genes. Their analyses suggest causal inverse associations, independent of BMI, between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men.

Analogue regulation of gene expression is important for normal function in mammals but existing genetic technologies are designed to achieve ON/OFF control. Here the authors develop synthetic microRNA silencing-mediated fine-tuners (miSFITs) to precisely control target gene expression levels.

Here, the authors describe the global distribution of crAssphage, its presence in Old-World and New-World primates, and its association with gut bacterial communities and dietary factors, providing insights into the origin, evolution and epidemiology of human gut crAssphage.

The oxidoreductase (NXR) multiprotein complex is a key enzyme in the nitrogen cycle. A detailed structural and biochemical characterization of NXR from the anammox bacterium Kuenenia stuttgartiensis shows that this complex is a filament-forming protein that catalysers both nitrite oxidation and nitrate reduction, and elucidates the mechanisms governing complex assembly and function.

Genome assembly of durum wheat cultivar Svevo enables genome-wide genetic diversity analyses highlighting modifications imposed by thousands of years of empirical selection and breeding.

There is currently no disease-modifying treatment for Parkinson’s disease, a common neurodegenerative disorder. Here, the authors use genetic variation associated with gene and protein expression to find putative drug targets for Parkinson’s disease using Mendelian randomization of the druggable genome.

Optical observations of Dimorphos, a satellite of the asteroid 65803 Didymos, before, during and after the impact of the DART spacecraft, from a network of citizen science telescopes across the world are reported.

Azole antifungals are used to treat lung diseases caused by the pathogenic fungus Aspergillus fumigatus, but resistance is rising. Here, the authors generate a library of >100 protein kinase mutants of A. fumigatus, and show that loss of function or pharmacological inhibition of kinase YakA results in hypersensitivity to azoles and reduced pathogenicity.

Top predators can reduce local mesopredator abundance either through direct predation or behavioural changes. Here, Newsome and colleagues demonstrate at a landscape scale across three continents that mesopredator populations are suppressed at the core, but less so on the periphery, of top predators’ ranges.

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.

Schork et al. identify novel variants contributing to shared risk among psychiatric disorders and suggest that these variants act through the disruption of early neurodevelopment.

Rebecca Fitzgerald and colleagues used genome sequence analyses to study the progression from premalignant Barrett's esophagus to esophageal adenocarcinoma (EAC) and found that the majority of recurrently mutated genes in EAC were also mutated in precursor lesions and that only mutations in TP53 and SMAD4 were stage specific.

The genetic basis of metabolic diseases is incompletely understood. Here, by high-throughput phenotyping of 2,016 knockout mouse strains, Rozman and colleagues identify candidate metabolic genes, many of which are associated with unexplored regulatory gene networks and metabolic traits in human GWAS.

A multi-model framework that accounts for climate, water, energy, food, biodiversity and economic activity in Australia reveals that a sustainable society that enjoys economic improvement without ecological deterioration is possible, but that specific political and economic choices need to be made to achieve this.

An integrative genomic analysis of several hundred endometrial carcinomas shows that a minority of tumour samples carry copy number alterations or TP53 mutations and many contain key cancer-related gene mutations, such as those involved in canonical pathways and chromatin remodelling; a reclassification of endometrial tumours into four distinct types is proposed, which may have an effect on patient treatment regimes.

Analysis of antibody responses to COVID-19 vaccines encoding variant-specific spike, with or without ancestral spike, suggests no loss of neutralization of the ancestral virus with variant-only vaccines, which may simplify future vaccine updates.

PIK3CA mutations and ARID1A loss co-exist in endometrial neoplasms. Here, the authors show that these co-mutations drive gene expression profiles correlated with differential chromatin accessibility and ARID1A binding in the endometrial epithelium, resulting in partial EMT and myometrial invasion.

Primary biliary cirrhosis is an autoimmune liver disease with poor therapeutic options. Here Cordell et al. a perform meta-analysis of European genome-wide association studies identifying six novel risk loci and a number of potential therapeutic pathways.

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.