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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.

Knock-in mice conditionally or constitutively expressing Cas12 variants enable a wide range of ex vivo and in vivo applications requiring multiplexed genome engineering.

Cells under environmental stress, including viral infections, accumulate RNA molecules stalled in pre-initiation complexes known as stress granules (SG). Here the authors show that the viral protein Gag counters anti-viral stress responses by inhibiting SG assembly during HIV-1 infection.

Multi-ancestry fine-mapping of breast cancer susceptibility regions identifies candidate causal variants and prioritizes likely effector genes supported by functional genomic evidence.

Analysis of whole-genome sequencing data from hematopoietic stem and progenitor cells taken from patients with myeloma shows how treatment shapes clonal architecture and sheds light on the evolution of treatment-related myeloid neoplasms.

Multiple transcriptome approaches, including single-cell sequencing, demonstrate that escape from X chromosome inactivation is widespread and occasionally variable between cells, chromosomes, and tissues, resulting in sex-biased expression of at least 60 genes and potentially contributing to sex-specific differences in health and disease.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

The gene Pirtencodes a transmembrane domain protein that is expressed in sensory neurons. Tang and colleagues use calcium imaging and electrophysiology to show that Pirt positively regulates the transient receptor potential channel TRPM8, and that deletion of this protein results in impaired cold sensitivity.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

Long-term imaging in the spinal cord is achieved by placing a fluoropolymer membrane on the spinal cord, which reduces fibrosis. This approach, combined with deep-learning-based motion correction, enables months-long imaging of the same neurons.

R9AP is a key receptor for entry of Epstein–Barr virus into human epithelial and B cells, and interacts directly with the viral glycoprotein gH/gL complex to mediate virus–host membrane fusion.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

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.

Geometrical confinement in ultrathin 0.68PbMg_1/3Nb_2/3O₃-0.32PbTiO₃ films induces a dome-shaped stability region of relaxor behaviour in a temperature–thickness relaxor phase diagram.

The Cancer Genome Atlas Research Network report integrated genomic and molecular analyses of 164 squamous cell carcinomas and adenocarcinomas of the oesophagus; they find genomic and molecular features that differentiate squamous and adenocarcinomas of the oesophagus, and strong similarities between oesophageal adenocarcinomas and the chromosomally unstable variant of gastric adenocarcinoma, suggesting that gastroesophageal adenocarcinoma is a single disease entity.

Acylhydrazones are often found in compounds across screening databases, and numerous bioactive acylhydrazones exist. This functional group can isomerize between E and Z in response to light or upon exposure to thiols. Now, E/Z isomerization is found to impact activities of bioactive acylhydrazones and should be routinely analysed.

Malignant cells with mesenchymal features display increased chromatin accessibility, particularly in the pericentromeric and centromeric regions, in turn resulting in delayed mitosis and catastrophic cell division.

A dataset of 3D images from more than 200,000 human induced pluripotent stem cells is used to develop a framework to analyse cell shape and the location and organization of major intracellular structures.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Distinct electronic and optical properties emerge from quantum confinement in low-dimensional materials. Here, combining optical characterization and ab initio calculations, the authors report an unconventional excitonic state and bound phonon sideband in layered silicon diphosphide.

Gaussian Process Spatial Alignment (GPSA) aligns multiple spatially resolved genomics and histology datasets and improves downstream analysis.

The cost-effective use of platinum as a catalyst has led to an evolving set of systems ranging from nanoparticles to single atoms on a variety of solid supports. It has now been shown that the dissolution of platinum atoms in a liquid gallium matrix generates a liquid catalyst that functions at low temperature with high activity.

The geological histories of Archaean regions indicate that stabilization of the Earth’s continents and the formation of cratons was driven by continental emergence and subaerial weathering.

Oblique line scan microscopy achieves nanoscale spatial and sub-millisecond temporal resolution across a large field of view, enabling improved and robust single-molecule biophysical measurements and single-molecule tracking in both cells and solution.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

Benisty, Barson et al. show that motor behaviors are represented by fast changes in the activity magnitude and functional connectivity across the mouse neocortex, which provides insight into the relationship between neural signals and behavior.

This work introduces a k-mer-based approach to customizing a pangenome reference, making it more relevant to a new sample of interest. This method enhances the accuracy of genotyping small variants and large structural variants.

Free-space meta-optics with ultrahigh quality(Q)-factor at visible wavelengths is demanded but very challenging to achieve due to the fabrication imperfections. Here, the authors design an etch-free metasurface with minimized fabrication defects and experimentally demonstrate a million-Q resonance at 779 nm wavelength.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

High-quality genome sequence of cultivated peanut comprising 2.54 Gb with 20 pseudomolecules and 83,709 protein-coding gene models provides insights into genome evolution and the genetic mechanisms underlying seed size and leaf resistance in peanut.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

Our understanding of how compartmentalisation and intercellular communication can tune enzyme reactions is still in its infancy. Here, the authors show that multi-enzyme reactions within semi-permeable compartments have distinct properties compared to reactions in buffer solution.

A remora-inspired mechanical underwater adhesive device adheres securely to a range of soft substrates and maintains performance under extreme pH and moisture conditions, with potential applications in biosensing and drug delivery.

Lin et al. show that MCM8 protects vascular health by mediating nitric-oxide-dependent mitophagy. The common East-Asian MCM8-P276 variant is ineffective in mitophagy, which potentiates cGAS-STING and type I interferon signaling in a mouse model of Kawasaki disease.

Brassica oleracea is plant species comprising economically important vegetable crops. Here, the authors report the draft genome sequence of B. oleracea and, through a comparative analysis with the closely related B. rapa, reveal insights into Brassicaevolution and divergence of interspecific genomes and intraspecific subgenomes.

Oncolytic viruses (OVs) represent a treatment option for patients with cancer. Here the authors propose a tumour-agnostic dual-virus strategy for cancer therapy by generating a vesicular stomatitis virus encoding a truncated version of HER2, combined with a vaccinia virus as a delivery platform for a HER2-targeted T-cell engager.

A whole-genome sequencing analysis of 100 pancreatic ductal adenocarcinomas has discovered known and newly identified genetic drivers of pancreatic cancer; these genetic alterations can be classified into four subtypes, which raises the possibility of improved targeting of clinical treatments.

Benedetti et al. produce a Cancer Atlas of Metabolic Profiles from 988 metabolomic and transcriptomic tissue profiles across 15 studies to analyse and identify gene–metabolite interactions that transcend cancer types.

Exome sequencing and copy number analysis are used to define genomic aberrations in early sporadic pancreatic ductal adenocarcinoma; among the findings are mutations in genes involved in chromatin modification and DNA damage repair, and frequent and diverse somatic aberrations in genes known as embryonic regulators of axon guidance.

The heterogeneity of androgen receptor (AR) gene alterations across metastases in prostate cancer remains unresolved. Here, the authors characterise AR genomic complexity across spatially separated lethal metastases from 10 prostate cancer patients and investigate how AR alterations evolve.

Polydienes are essential in industry but rely on a complex synthesis involving catalysts and solvents. Now it is shown that photo-melt-bulk polymerization enables the solvent- and catalyst-free synthesis of controlled high-molecular-weight polydienes by combining chain growth and the coupling of stable biradicals, advancing sustainable materials development.

Diagnosing acute infections based on transcriptional host response shows promise, but generalizability is wanting. Here, the authors use a co-normalization framework to train a classifier to diagnose acute infections and apply it to independent data on a targeted diagnostic platform.

Antiferromagnets have a variety of attractive features such as rapid operation, lack of stray fields, and insensitivity to external perturbations, that make an exciting prospect for memory and computing applications. Unfortunately, readout of the antiferromagnetic state is challenging. Here, Yan, Mao and coauthors demonstrate an antiferromagnet that can be switched between antiferromagnetic phases via piezoelectric strain with a large difference in the resistance between the two antiferromagnetic phases.

2- arachidonoylglycerol (2-AG), an abundant endocannabinoid in the brain, regulates diverse neural functions. Here, the authors identified four loss-of-function mutations in dicylglycerol lipase β (DAGLB) from six patients with early onset Parkinsonism. In mice, loss of DAGLB in dopamine neurons reduced neuronal activity and impaired locomotor function and augmentation of 2-AG levels boosted neuronal activity and rescued locomotor deficits.

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.