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Native state proteomics of PV interneurons revealed unique molecular features of high translational and metabolic activity, and enrichment of Alzheimer’s risk genes. Early amyloid pathology exerted unique effects on mitochondria, mTOR signaling and neurotransmission in PV neurons.

Distinguishing local hydrological, cave internal, and regional monsoon signals in speleothem records resolves disagreements among proxy reconstructions and illuminates the Holocene evolution of summer and winter monsoon in Southeast Asia.

A population genomic analysis of 1,854 Listeria soil isolates collected across the contiguous United States identifies geographically prevalent phylogroups with increased pangenome openness and recombination, as a result of adaptation to variable environments.

Light can provide ultrafast ways of spin manipulation in magnetic materials, but existing methods are limited by long thermal recovery or low temperature. Here, the authors demonstrate ultrafast spin precession via optical charge-transfer processes in exchange-coupled Fe/CoO at room temperature.

A single-cell atlas of the human lungs, integrating data from 2.4 million cells from 486 individuals and including samples from healthy and diseased lungs, provides a roadmap for the generation of organ-scale cell atlases.

The broad infrared spectrum of water in the OH stretching region shows how significantly a water molecule is distorted when within a hydrogen-bonding network; it also raises the question of what the spectrum of a single OH oscillator would be. Now, the spectral signatures of isolated OH oscillators embedded in cold water cages have been measured using vibrational spectroscopy.

Bond et al. show that inducible PolG mutation in muscle causes mtDNA damage and muscle wasting. This is driven by the integrated stress response (ISR) and reduction in folate intermediates, linking impaired folate metabolism with ISR/disease induction.

Recent prior influenza A infection is associated with elevated hemagglutinin-inhibiting antibody responses and greater breadth of reactivity to influenza strains following vaccination, suggesting that infection history boosts vaccine responses.

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.

Rather than assuming that relatives of older people will step up to fill systemic gaps in health care, communities need research and policies that align with families’ existing routines.

Puissant and colleagues identify a myeloid-restricted PIK3CG/p110γ–PIK3R5/p101 axis as a therapeutic vulnerability in acute myeloid leukemia and develop a proteolysis-targeting chimera to potently degrade PIK3CG and suppress AML progression.

Genetic variation in the IFNλ locus has been associated with clearance of hepatitis C virus. Here, the authors show that a single amino-acid variant of IFNλ4 affects its antiviral activity and that patients carrying the impaired variant have better viral clearance rates.

In Alzheimer’s disease (AD) tau and neurodegeneration have complex regional relationships. Here, the authors show neuronal hypometabolism discordant with tau burden defines functional resilience or susceptibility to Alzheimer’s pathology via limbic/cortical axes. Susceptible groups have faster cognitive decline and evidence of non-Alzheimer’s pathologies.

Drug and target discovery for advanced liver disease are hampered by a lack of suitable models for clinical translation. Here the authors present a human liver cell-based system modeling a clinical prognostic signature allowing to propose nizatidine for treatment of advanced liver fibrosis and hepatocellular carcinoma prevention.

A 3.7 Å resolution structure for the yeast U4/U6.U5 tri-snRNP, a complex involved in splicing, allows a better appreciation of the architecture of the tri-snRNP, and offers new functional insights into the activation of the spliceosome and the assembly of the catalytic core.

Genome-wide association meta-analyses identify more than 350 loci associated with atrial fibrillation. A polygenic score derived from these results improves atrial fibrillation risk prediction compared to published clinical and polygenic scores.

An interim report from the GAIN/iCat2 study shows that molecular profiling of pediatric solid malignancies clarifies diagnostic classifications and provides opportunities for matched targeted therapy.

The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease.

Local microbiome composition influences treatment efficacy of chemotherapy in colon cancer via modulation of tolerogenic versus immunogenic ileal intestinal epithelial cell death, which in turn influences follicular helper T cell priming.

High-resolution spatial maps of the global abundance of soil nematodes and the composition of functional groups show that soil nematodes are found in higher abundances in sub-Arctic regions, than in temperate or tropical regions.

Many heritage sites are threatened by rising sea levels under climate change as they lie within the coastal zone. A continental assessment of exposure of 284 African heritage sites shows that 20% of sites are currently at risk, which more than triples under moderate and high emission scenarios.

The results of the Fifth RNA-Puzzles contest highlights advances in RNA three-dimensional structure prediction and uncovers new insights into RNA folding and structure.

The arginine methyltransferase PRMT5 is over-expressed in cancer and has a role in the maintenance of stem cells. Here, the authors show that PRMT5 inhibitors can block the growth of patient derived glioblastoma stem cell cultures in vitro and in vivo, suggesting that PRMT5 inhibition may be a useful therapeutic strategy

The expression of therapeutic protein targets in circulating tumour cells isolated from blood samples of patients with cancer can be tracked at the single-cell level by antibody-mediated magnetic labelling and microfluidic sorting.

JWST mid-infrared images of the nearby star Fomalhaut reveal a complex system of dusty rings and disks, created as debris from planetesimal collisions. These structures suggest the presence of a complex and probably dynamically active planetary system.

The spatial and frontal QRS-T angles are electrocardiographic (ECG) predictors for arrhythmia. This work used genetic analyses to identify associated loci and pathways, and explore their relationships with other ECG traits and cardiovascular disease.

Current isolation-based approaches for cell type-specific proteomics pose several challenges. Here, the authors present an approach for in vivo cell type-specific protein labeling to characterize proteomic differences between neurons and astrocytes in their native state in adult mouse brain.

The transfer of ubiquitin (UB) to cellular targets is mediated sequentially by three groups of enzymes, UB activating enzyme (E1), UB conjugating enzyme (E2) and UB ligase (E3). Here the authors provide evidence that the two mammalian E1 enzymes, Uba1 and Uba6, exert biologically distinct functions.

To investigate the molecular foundation of sporadic Alzheimer’s disease (AD), Beckmann et al. constructed multiscale causal networks on a large human AD multi-omics dataset, detecting AD-associated networks and their top predicted regulator, VGF, with extensive validation in the 5xFAD mouse model.

This study determines the structure of the spliceosomal tri-snRNP complex (containing three small nuclear RNAs and more than 30 proteins) by single-particle cryo-electron microscopy; the resolution is sufficient to discern the organization of RNA and protein components involved in spliceosome activation, exon alignment and catalysis.

An integrated analysis of over 100 single-cell and single-nucleus transcriptomics studies illustrates severe acute respiratory syndrome coronavirus 2 viral entry gene coexpression patterns across different human tissues, and shows association of age, smoking status and sex with viral entry gene expression in respiratory cell populations.

The clinical management of metastatic melanoma requires predictors of the response to checkpoint blockade. Here, the authors use immunological assays to identify potential prognostic/predictive biomarkers in circulating blood cells and in tumor-infiltrating lymphocytes from patients with resected stage III melanoma.

A genomic epidemiology approach describes the population structure of Salmonella monophasic Typhimurium ST34 from Vietnam, and identifies Southeast Asia as a potential hub for the emergence and international spread of multidrug resistant Salm. ST34.

A deep learning system able to identify the most common skin conditions may help clinicians in making more accurate diagnoses in routine clinical practice

RNA delivery for disease treatment often has low uptake efficiencies and cytotoxicity. Here the authors produce extracellular vesicles from red blood cells for in vivo cargo delivery.

Endurance exercise is associated with an increased risk of atrial fibrillation. Here, the authors show the adipokine TNFα is a crucial mediator of exercise-induced atrial fibrillation and irreversible atrial remodelling characterized by fibrosis and inflammation.