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Multi-ancestry genome-wide and transcriptome-wide association studies of aortic stenosis identify more than 200 independent risk loci and provide insights into its genetic architecture.

Here, as part of the Sherlock-Lung study, the authors profile the microbiomes of 940 lung cancers in never smokers finding no significant associations with demographic and clinical features, suggesting lung bacteria are unlikely to have a sizable role in lung cancer.

Lung adenocarcinomas bearing the ID2 mutational signature display increased LINE-1 retrotransposon activity, which contributes to their fast evolutionary dynamics and aggressive phenotype.

In this Tools of the Trade article, Yohan Lee (Stachowiak lab) describes a method to generate free-standing planar lipid membranes for the study of membrane-associated protein phase separation.

Here the authors introduce INSPECT, a live-cell imaging method for mapping protein interactions. They reveal how Cdc42–FMNL locks cell polarity while Rac1–ROCK triggers turning, exposing the intrinsic program that drives spontaneous cell migration.

An analysis of data from the Sherlock-Lung study provides insight into the mutational processes that contribute to lung cancer in never smokers, and looks at the possible role of factors such as air pollution and passive smoking.

Electrochemical energy can be produced by using solar energy to oxidize water, providing an abundant source of electrons, which are needed in fuel synthesis. The operation of an efficient and stable semiconductor nanocomposite anode, made of a protective TiO₂ layer that protects a silicon substrate during photoelectrochemical water oxidation in both dark and light conditions, is now reported.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Using a freestanding planar lipid membrane system, the authors show that liquid-like protein condensates on one side of a lipid membrane colocalize with those on the opposite side, suggesting a mechanism of information transfer across biological membranes.

Genome-wide analysis of chronic obstructive pulmonary disease identifies 82 loci, 35 of which are new. Integration of gene expression and genomic annotation data shows enrichment of signals in lung tissue, smooth muscle and several lung cell types.

The regulation of KRAS oncoprotein stability remains to be completely determined. Here the authors identify that USP9X-mediated deubiquitination of KRAS protein is dependent on scaffolding protein NDRG3, suggesting KRAS-NDRG3 interaction as a targetable vulnerability in KRAS-driven cancers.

The lithium solvation structure in the electrolyte solution for lithium-ion batteries has not been fully understood. Here, the authors show ultrafast fluxional exchange of carbonate solvent molecules in and out of lithium-ion solvation sheath utilizing coherent two-dimensional infrared spectroscopy.

Analysis of 2,096 single-cell clones from three tissues of 31 healthy donors characterizes mitochondrial DNA mosaicism and highlights the following two origins of mtDNA variants: heteroplasmy in the fertilized egg and postzygotic mutations.

Adult human tissues from diverse sites around the body are used to reconstruct cellular phylogenies from early development, using somatic mutations as an internal barcode.

By comparing human induced pluripotent stem cell-derived spinal and ocular motor neurons, the authors identify low levels of a natural 5-lipoxygenase inhibitor in amyotrophic lateral sclerosis (ALS) spinal motor neurons. Functional analogs of 5-lipoxygenase inhibitors can ameliorate in vitro and in vivo ALS phenotypes.

Whole-genome sequencing of lung cancer in never smokers identifies different copy number subtypes and shows a lack of tobacco smoking signatures, even in cases exposed to secondhand smoke.

Designing an efficient platform that enables verbal communication without vocalization remains a challenge. Here, the authors propose a silent speech interface by utilizing a deep learning algorithm combined with strain sensors attached near the subject’s mouth, able to collect 100 words and classify at a high accuracy rate.

In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.

Responsive hydrogels containing multichannel information have potential in miniature devices, but their fabrication can be challenging. Here, the authors report the creation of hydrogel materials with each pixel containing three-channel information for printing of distinct images in one location.

ARID1A, which is often mutated in human endometrial cancer, is a component of the SWI/SNF chromatin remodelling complex. Here, the authors show that Arid1a mutations in the mouse endometrium and primary human endometrial epithelial cells cause widespread reprogramming of gene transcription and result in a loss of response to TGFβ.

A cross-ancestry genome-wide association meta-analysis of lung cancer including 61,047 cases and 947,237 controls identifies five new cross-ancestry susceptibility loci and highlights ancestry-specific effects of common and rare variants on lung cancer risk.

The chromosome 15q25.1 locus is a leading susceptibility region for lung cancer. Here, the authors interrogate three GWAS cohorts with 42,901 individuals to investigate potential pathological pathways such as gated channel activity and neuroactive ligand receptor interaction in lung cancer etiology.

A comparison of the molecular, cellular and functional characteristics of three congruent patient-specific cell types for the modelling of Charcot−Marie−Tooth 1A reveals commonly upregulated chemokines.

Pulmonary function is influenced by environmental factors, lifestyle, and genetics. Here, in a multiethnic GWAS meta-analysis for pulmonary function traits, the authors identify over 50 additional genetic loci, a subset of which are specific for European, African, Asian, or Hispanic/Latino ancestry.

Future optical devices, e.g., for AR and VR, will require sophisticated flat metaoptics with unique optical functionalities. The authors demonstrate a metaobjective based on electrically switchable metallic polymer metalenses, whose optical states and focal length is adjustable via CMOS compatible voltages.

The role of impaired lung function in lung cancer etiology is complex due to the relation of cigarette smoking to both conditions. Here, supported by Mendelian randomization analysis the authors find a link between pulmonary function impairment and lung cancer risk beyond smoking, implicating immune-related pathways

Christopher Amos and colleagues perform genome-wide association analysis for lung cancer using cohorts genotyped on the OncoArray and combing these with existing data. They identify 18 loci, 10 of which are new, finding heterogeneity across the different lung cancer subtypes, and explore candidate genes through eQTL analysis in lung tissue.

Zika virus infection is associated with neurological disorders, yet few studies have directly examined its impact on the peripheral nervous system. Oh et al. show that Zika virus can infect peripheral neurons in the mouse in vivo, as well as human peripheral neurons in vitro, leading to increased cell death and transcriptional dysregulation.

An approach that combines a pH-sensitive synaptic biomarker expressed in vivo with the ex vivo staining of oligodendrocyte precursor cells enables quantification of synapse engulfment by oligodendrocyte precursor cells at single-cell and population-level resolution.

Michael Cho and colleagues report a genome-wide association study of risk for chronic obstructive pulmonary disease (COPD) in a large, multi-ancestry cohort. They identify 22 genome-wide significant loci, including 13 not previously associated with COPD and 4 not previously associated with any lung function trait.