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Sharing of whole genome sequencing (WGS) data improves study scale and power, but data from different groups are often incompatible. Here, US genome centers and NIH programs define WGS data processing standards and a flexible validation method, facilitating collaboration in human genetics research.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

Here, the authors describe biallelic loss-of-function variants in human SHARPIN in individuals with autoinflammation and immunodeficiency, termed sharpenia. They also successfully treat one of these individuals with TNF inhibitors.

The interface between two oxide materials can play host to numerous exotic phenomenon. Here, the authors observe a four order of magnitude change in the conductance at a lanthanum-aluminate–strontium-titanate interface controlled by surface protonation, which can be reversed by exposure to light.

Metamaterials using split-ring resonators can display negative refractive index, yet the same effect for closed rings has remained elusive. Kanté et al.overcome this by using closely spaced coupled nanorings that exploit symmetry breaking to show broadband negative refractive index at optical frequencies.

How the dauer, an alternative developmental stage in nematodes, exhibits distinct behavioral traits remains unclear. Here, the authors reveal the neural circuitry underlying these distinctions by reconstructing the dauer connectome and comparing it with other stages.

Genome-wide analyses identify variants associated with sinus node dysfunction, distal conduction disease and pacemaker implantation, implicating ion channel function, cardiac developmental programs and sarcomeric structure in bradyarrhythmia susceptibility.

Previous studies identified an association between the 2q35 locus and breast cancer. Here, the authors show that a SNP at 2q35, rs4442975, is associated with oestrogen receptor positive disease and suggest that this effect is mediated through the downregulation of a known breast cancer gene, IGFBP5.

A distinct population of CD4 T cells resides in specific regions of the steady-state brain, and these T cells are programmed in the periphery by the microbiome to coordinate adaptive behaviour.

A new approach that uses complementary metal oxide semiconductor field effect transistor compatible technology is reported, and demonstrates the specific label-free detection of below 100 femtomolar concentrations of antibodies as well as real-time monitoring of the cellular immune response.

Bottom gates in epitaxial graphene structures can now be fabricated through a technique based on nitrogen implantation. This is an important achievement to increase both the versatility of the material for fundamental studies and the potential for its use in devices.

Hyperactivation of inflammasome-induced IL-1β can cause immunopathology and is a feature of autoinflammatory diseases. Here, the authors show how ubiquitination of IL-1β limits its activity by targeting it for proteasomal degradation and preventing its cleavage by caspase-1.

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.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Plunge into a profusion of brilliant summer reads suggested by regular reviewers and editors, far away from the lab and lecture hall.

The orbital-to-spin moments ratio for individual atomic planes of an iron crystal is studied, revealing local variations at subatomic scales.

The PUF RNAbinding domain has an eight-repeat structure with the ability to bind an eight-base RNA sequence. Here the authors generate a comprehensive library of variants of a PUF domain to find an RNA binding code and design PUF domains that recognize an arbitrary RNA sequence.

Van Hove singularities have the potential to drive unconventional magnetic states in Kagomes. Here, the authors provide experimental and theoretical results suggesting a van Hove singularity-assisted spin density wave in the Kagome metal CeTi₃Bi₄.

The recently discovered spin-triplet superconductor UTe₂ is found to display a number of other ‘re-entrant’ superconducting phases under ultrahigh magnetic fields.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Here the authors identify age-associated changes in the epithelial cell compartment of the thymus that form high-density nonproductive microenvironmental niches that contribute toward thymic involution and inhibit its repair following injury.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

The peptide/histidine transporter 1, PHT1 (SLC15A4), is required for TLR-IRF5 activation via the adaptor protein TASL. Here, the authors determined the structure of PHT1 in the outward-open conformation and present a model of the PHT1-TASL complex where the first 16 residues of TASL bind into the central cavity of PHT1.

tag-Targeted Protein Degrader (tTPD) systems are powerful tools for preclinical target validation. Here the authors extend the tTPD platform by developing NanoTACs that degrade NanoLuc tagged substrates and benchmark each tTPD system using an interchangeable tag reporter system.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

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.

Many pathogens encode transporters that extract heme directly from host proteins. In this study, the authors demonstrate the utility of de novo-designed proteins in understanding the mechanism behind this process and how it can be inhibited in pathogenic E. coli.

The electronic and photonic contributions to the power conversion efficiency in solar cell devices are often hard to disentangle. Here Bercegol et al. develop a purely optical method to quantitatively decouple and assess the electronic and photonic processes in halide perovskite solar cells.

Trees come in all shapes and size, but what drives this incredible variation in tree form remains poorly understood. Using a global dataset, the authors show that a combination of climate, competition, disturbance and evolutionary history shape the crown architecture of the world’s trees and thereby constrain the 3D structure of woody ecosystems.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Acquired resistance limits the efficacy of PARP inhibitors (PARPi) in high grade serous ovarian cancer (HGSOC). Here, the authors show that inhibition of RNA polymerase I transcription using CX-5461 increases the therapeutic efficacy of PARPi and overcomes PARPi resistance in PDX models of HGSOC.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

It is not entirely understood how network plasticity produces the coding of predicted value during stimulus-outcome learning. Here, the authors reveal a reinforcing loop in distributed limbic circuits, transforming sensory stimuli into reward prediction coding broadcasted by dopamine neurons to the brain.

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.