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The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

Intraspecies response to climate change is expected to align with genetic affinity. Using the American pika as a case study suggests that divisions of species distributions best explain intraspecific heterogeneity in climate relationships.

The genetic architecture underlying brainstem regions and how this links to common brain disorders is not well understood. Here, the authors use MRI and GWAS data from 27,034 individuals to identify genetic and morphological brainstem features that influence common brain disorders.

Nociceptin is an opioid peptide regulating important brain functions, including motivation and 2stress responses. Here, the authors develop and validate a genetically encoded sensor as a tool for high-resolution detection of endogenous nociceptin in living animals.

There is an urgent need for biomarkers for type 2 diabetes progression that provide a deeper understanding of the disease process. Here, the authors identify biomarkers in three molecular classes, replicate them in other cohorts and explore top protein biomarkers in detail in functional studies.

The SPECULOOS project detected an Earth-sized planet in a short orbit around a nearby Jupiter-sized star. This planet, SPECULOOS-3 b, is one of the most promising rocky exoplanets for detailed emission spectroscopy characterization with JWST.

JWST–NIRSpec spectroscopic confirmation of two luminous galaxies is presented, proving that luminous galaxies were already in place 300 million years after the Big Bang and are more common than what was expected before JWST.

A multi-ancestry meta-regression study analyses diverse genome-wide association studies and genome loci associated with tobacco and alcohol use.

Patients with partial recombination-activating gene (RAG) deficiency (pRD) present variable late-onset autoimmune clinical phenotypes. Walter and colleagues identified a restricted primary B cell antigen receptor repertoire enriched for autoreactivity and clonal persistence in pRD. They described dysregulated B cell maturation with expansion of T-bet⁺ B cells revealing how RAG impacts stringency of tolerance and B cell fate in the periphery.

The competitive dynamics of mitochondrial haplotypes juxtaposed within the same cell are poorly studied. Here the authors show, in the context of a transmissible cancer, that one haplotype has recurrently entered cancer cells by horizontal transfer and appears to have a ‘selfish’ selective advantage.

Three covalent hybrid inhibitors of SARS-CoV-2 main protease (Mpro) have been designed and compared to Pfizer’s nirmatrelvir (PF-07321332), providing atomic and thermodynamic details of their binding to the enzyme, and antiviral potency.

Phenotypic variation and diseases are influenced by factors such as genetic variants and gene expression. Here, Barbeira et al. develop S-PrediXcan to compute PrediXcan results using summary data, and investigate the effects of gene expression variation on human phenotypes in 44 GTEx tissues and >100 phenotypes.

Conditional Degron Tags are a valuable tool to validate and study novel therapeutic targets. Here, the authors compared 5 orthogonal tags across 16 unique proteins and provide a panel of vectors for users to systematically screen the tags with their own protein of interest.

The association between obesity and breast cancer biology remains understudied in humans. Here, using a large retrospective data collection, the authors identify obesity associated changes in the genomic, transcriptomic profile, and the tumor microenvironment of primary untreated breast tumors.

Vectorial optoelectronic metasurfaces are described, showing that light pulses can be used to drive and direct local charge flows around symmetry-broken plasmonic nanostructures, leading to tunable responses in terahertz emission.

Most testicular germ-cell tumours are exquisitely sensitive to platinum-based chemotherapies, but little is known about why 10% are resistant. Here, the authors explore the potential underlying mechanisms by probing the genomic landscape of platinum-resistant disease.

In an inpatient, randomized controlled crossover trial, participants consumed 550–700 kcal day⁻¹ fewer calories when following a plant-based, low-fat diet with a high glycemic load compared with an animal-based, low-carbohydrate diet with a low glycemic load; weight loss was comparable between the two diets and there were no significant differences in hunger or enjoyment of the meals.

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology.

Here, the authors use sedimentary DNA, pollen, fungal spores, chironomids, and microcharcoal from an alpine lake core to reconstruct vegetation across 12,000 years. They find that vegetation responded to climate in the early Holocene, followed by a shift to human activity from 6000 years onward corresponding with an increase in deforestation and agropastoralism.

A longitudinal analysis of viral expansion and clearance rates in 60 individuals sampled daily during acute infection reveals high inter-individual variation in infectious virus shedding, which may contribute to superspreading.

Deep phenotype and genome-wide genetic data from 500,000 individuals from the UK Biobank, describing population structure and relatedness in the cohort, and imputation to increase the number of testable variants to 96 million.

In this work, the authors develop a platform called AGILE or AI Guided Ionizable Lipid Engineering, which streamlines ionizable lipid development. Using AGILE, they rapidly design, synthesize, and evaluate ionizable lipids for mRNA delivery.

Quantum computation will depend on fault-tolerant error correction, which requires the chance for errors to occur to be below a certain threshold. Here the authors use gate set tomography as a means to rigorously characterize error rates of single-qubit operations of a qubit encoded in a trapped ion.

A new GWAS of schizophrenia (11,260 cases and 24,542 controls) and meta-analysis identifies 50 new associated loci and 145 loci in total. The common variant association signal is highly enriched in mutation-intolerant genes and in regions under strong background selection.

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.

A genome-wide association study of cerebral ventricle phenotypes finds 62 unique loci and reveals a genetic overlap between ventricular and neuropsychiatric traits.

Interaction of photons with Rydberg atoms can be used to modify quantum states of light. Here the authors demonstrate a controlled nonlinear quantum behavior of multi-photon subtraction in a cascaded system based on Rydberg superatoms.

A genome-wide association study of the human hypothalamus discovers 23 unique loci and examines genetic associations with neuropsychiatric behaviours and disorders.

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.

This very large genome-wide association study identifies hundreds of new genetic variants influencing adult height in at least 180 loci enriched for genes involved in skeletal growth defects. The results show that the likely causal gene is often located near the most strongly associated variant, that many loci have multiple independently associated variants and that associated variants are enriched for likely functional effects on genes.

The spatial and physical nature of tumour growth remains unclear. Combining whole-tumour images from clear cell renal cell carcinoma with genomic data, the authors show more aggressive subclonal growth and metastasizing subclones in the tumour centre.

The independent control of substrate stiffness and tethering of extracellular matrix to substrates for mechanical signalling investigations remains challenging. Here the authors present StemBond hydrogels, with stable ECM tethering that can be varied independently of stiffness, and use these to modulate the function of mouse and human pluripotent stem cells.

This study shows that Epac2, a cAMP-activated Rap-GEF, acts downstream of D1/D5 dopamine receptor signaling to regulate dendritic spines and synaptic transmission. The authors also show that rare mutations of the EPAC2 gene that are associated with autism cause defects in Epac2-mediated spine remodeling.

A spectroscopic thermal phase curve of GJ 1214b obtained with the JWST in the mid-infrared is reported and a planet with a high metallicity atmosphere blanketed by thick and reflective clouds or haze is found.

King Richard III was a controversial English King whose remains are presumably deposited in Grey Friars in Leicester. Here the authors sequence the mitochondrial genome and Y-chromosome DNA of the skeletal remains and living relatives of Richard III and confirm that the remains belong to King Richard III.

Organogenesis is orchestrated by biochemical and biophysical stimuli. Here, Ma et al. generate a micro-patterned surface that provides mechanical cues which, when combined with biochemical signals, drive human pluripotent stem cells’ differentiation into beating cardiac microchambers resembling primitive hearts.

Metabolic pathways are increasingly recognized as crucial determinants of T cell function. Here the authors show that the balance between IFNγ and IL-10 production in human CD4 T cells is modulated by the cholesterol biosynthetic pathway.

The origin of the unique turtle lung ventilatory apparatus is poorly understood. Here the authors show an increase in body wall rigidity early in evolution that allowed the abdominal muscles to become specialized for breathing and the ribs to eventually form the iconic turtle shell.

When the packing fraction is increased sufficiently, loose particulates jam together to form a rigid solid in which the constituents are no longer free to move. Although in typical granular materials and foams the thermal energy is too small to produce structural rearrangements, thermal motion becomes relevant when the particles are small enough. Here, colloidal experiments and computer simulations are used to investigate the overlap distance between neighbouring particles beyond the zero-temperature limit, revealing some surprising behaviour.

The stability over time of the zonal jets on the giant planets has been debated. An analysis of observations from the Cassini spacecraft reveals an acceleration of wind velocities in Saturn’s high-altitude equatorial jet between 2004 and 2009, by 20 m s⁻¹ at tropopause level and by 60 m s⁻¹ in the stratosphere.

An information-theory-inspired re-analysis of Cassini mass spectrometry data reveals the presence of HCN and partially oxidized organics within the plume of Enceladus. Ongoing redox chemistry may create a habitable environment.

During microbial infection, proteins are modified by the ubiquitin-like protein ISG15. Here, the authors uncover RNF213 as a sensor for ISGylated proteins on the surface of lipid droplets, showing that RNF213 has antiviral properties but also directly targets intracellular bacteria in infected cells.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

Identification of host factors associated with severe influenza infection could provide insights into treatment options. Here, the authors provide transcriptomic analyses of blood from >100 influenza infected patients and show that changes in circulating neutrophils are associated with severe influenza infection.

Analysis of 100 consecutive personalized bacteriophage therapy cases supports the use of personalized and sometimes pre-adapted, bacteriophage preparations, often in combination with antibiotics.