Search

In chemical-genetic and lipidomics analyses, the clinical candidate oncology drug tegavivint induced an unconventional form of nonapoptotic cell death that required the lipid metabolic enzyme trans-2,3-enoyl-CoA reductase.

Group-IV color centers in diamond show promise for spin-photon interfaces, but precise positioning and activation are challenging. Here the authors combine site-controlled ion implantation with laser annealing and in-situ photoluminescence monitoring to create and tune individual tin vacancy centers in diamond.

Seo et al. present an approach to regulate the formation and optoelectronic quality of the SnO₂ electrodes, improving electroluminescence and efficiency in perovskite solar cells.

A common but untested expectation is that nutrient enrichment causes biotic homogenization. However, a globally standardized nutrient addition experiment in grasslands shows proportionally similar species loss across scales and no biotic homogenization after up to 14 years of treatment.

In order to locate the voltage-dependent gate in the MthK potassium channel, intracellular quaternary ammonium blockers are used for electrophysiology and crystallographic analyses. The data conclusively show that the inactivation gate is located at the selectivity filter and not at the cytoplasmic bundle crossing entrance.

At present, there are no countermeasures against the GI genogroup of noroviruses. The authors characterize a protective human antibody that broadly recognizes this genogroup.

Face stimuli that are perceived as emotionally expressive rather than neutral are associated with specific neural responses in V1. Here the authors show that valence information perceived from facial expressions is computed in the amygdala and fed back to V1 via direct anatomical projections.

The efficacy of CAR-T cells against solid tumors is still limited by immunosuppressive factors. Here, the authors show that engineering of CAR T cells with A1R enhances their efficacy against solid tumors in vitro and in vivo.

A CRISPR knock-in strategy that uses endogenous gene regulatory mechanisms can engineer ‘armoured’ CAR T cells that secrete proinflammatory cytokines directly within a tumour without causing toxicity, leading to prolonged survival in mice.

Fear conditioning results from the association that develops between a neutral conditioned stimulus and an aversive unconditioned stimulus (UCS), which is thought to be supported by plasticity in the amygdala. Here, the authors find that information about the UCS is conveyed to the amygdala by neurons in the periaqueductal gray.

Combining brain imaging, genetics and behavioral data, this study shows that distinct brainwide distributions of serotonin receptors explain the known division of serotonin effects on human impulsivity and aversive processing.

Current cell annotation methods using high-plex spatial proteomics data are resource intensive and demand iterative expert input. Here, the authors present MAPS (Machine learning for Analysis of Proteomics in Spatial biology), an approach that facilitates rapid and precise cell type identification with human-level accuracy from spatial proteomics data.

FAM72A differentially controls mutation rates by regulating uracil processing at different stages of the cell cycle, thereby regulating somatic hypermutation and class-switch recombination in B cells.

Polo-like kinase 3 (Plk3) has a tumor suppressive role through the induction of apoptosis, however, the mechanism underlying its activation is unclear. Here, in pancreatic cancer, the authors show that activation of Plk3 is dependent on its cleavage into p41Plk3, by the metalloendopeptidase nardilysin.

¹³⁴Ce and ¹³⁴La have great potential as companion diagnostic isotopes for radiotherapeutics labelled with α-emitting ²²⁵Ac and ²²⁷Th. Now, by controlling the Ce^III/Ce^IV redox couple, the large-scale production, purification and characterization of ¹³⁴Ce- and ¹³⁴La-based radiolabels has been achieved and their use for in vivo positron emission tomography is demonstrated.

Disassembly of three-dimensionally ordered materials generates nanoparticles with new structural and physicochemical properties. Here the authors show a fragmentation strategy applied to a perovskite material leading to nanostructures with improved catalytic activity in the methane combustion.

The contribution of astrocytic Ca²⁺ signaling to the modulation of sensory transmission in different brain states remains largely unknown. Here, the authors show two types of Ca²⁺ signals in the mouse barrel cortex with distinct function in sensory transmission during sleep and arousal states.

Enzymatic recycling is an emerging technology to circularize the ubiquitous polyester poly(ethylene terephthalate). Here the authors evaluate and implement multiple process changes to improve the scalability and viability of this recycling technology. Process modeling demonstrates that these changes could enable cost competitiveness and greatly reduce overall life cycle impacts.

Visium spatial transcriptomics, single-nucleus RNA sequencing and co-detection by indexing are used to identify distinct spatial microregions in tumours and their microenvironment across six diverse solid cancer types.

PIGEON is a statistical framework that uses summary statistics from genome-wide interaction studies to estimate how genes and environments jointly influence human complex traits.

GDF8 and activin A are the dominant negative regulators of muscle mass in animal models. This two-part, randomized, placebo-controlled Phase 1 trial suggests that GDF8 and activin A are also the dominant negative regulators of muscle mass in humans.

Vagus nerve stimulation (VNS) is emerging as a potential treatment for several chronic diseases. Here, the authors describe a VNS method using intermittent interferential current stimulation (i²CS) that allows precise control of organ-specific fiber activation in swine.

Mammary gland resident macrophages are known to be crucial components of the mammary stem cell niche. Here, the authors show that CXCR4⁺ macrophages form a niche that regulates the tumor-initiating activity of breast cancer cells and induces early immune evasion through the recruitment of regulatory T cells.

Gain-of-function mutations in CTNNB1 (encoding for b-catenin) leading to deregulated Wnt/β-catenin signaling are frequently observed in patients with hepatocellular carcinoma (HCC). Here the authors show that inhibiting b-catenin with lipid nanoparticles encapsulating siRNA targeting CTNNB1 impairs tumor growth and promotes anti-tumor immunity in preclinical HCC models.

Extracellular proteasomes are found in the Arabidopsis apoplastic fluid and shown to participate in biotic defense by proteolytically digesting pathogen proteins into microbe-associated molecular pattern epitopes specifically recognized by the pathogen-triggered innate immune response system.

Mathieu Lupien, Jason Moore and colleagues show that breast cancer risk–associated SNPs commonly disrupt the binding of FOXA1 to chromatin, thereby directly affecting gene expression.

Computationally designed genetically encoded proteins can be used to target surface proteins, thereby triggering endocytosis and subsequent intracellular degradation, activating signalling or increasing cellular uptake in specific tissues.

Here, the authors show that signal transducer and activator of transcription 3 (STAT3) has dual functions in small cell lung cancer as its deletion inhibited primary tumor growth but boosted metastatic spread. These seemingly opposing functions are a result of the requirement of STAT3 for stimulator of interferon genes–interferon signaling in metastasis and the authors show how it can be targeted in mice.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Understanding conserved functional genomic properties between human and mouse provides important context for mouse model studies. Here, the authors present a genome-wide conservation score integrating epigenomic, transcription factor binding, and transcriptomic data from mouse and human genomes.

Metastasis-initiating cells can reawaken from a dormant state that initially allowed them to survive, triggering metastatic outgrowth. Here, authors show that loss of Brd7 promotes an immunosuppressive tumor microenvironment that drives breast cancer metastatic reawakening from dormancy in the lung.

In this article, Batten and colleagues measure fast neurotransmitter release in patients undergoing awake brain surgery. As volunteers play an economic game with human and computer partners, dopamine and serotonin track social context and value statistics.

Elucidation of the mechanism by which zeta inhibitory peptide erases memories, involving endocytosis of AMPA receptors on potentiated synapses, provides insight into more general mechanisms of memory maintenance and response to traumatic brain injury.

Viruses and bacteria are known to subvert the immune system using mimic or inhibitory proteins. Here the authors show that the protein Ank5 from the bacterium Orientia tsutsugamushi inhibits nuclear translocation and promotes proteasomal degradation of the MHC class I gene transactivator NLRC5.

Myostatin and activin A are the two primary negative regulators of muscle mass. Blocking these circulating ligands during GLP-1 therapy induces improved body composition through preservation of lean mass and enhanced fat mass loss in obese primates.

Transcriptomic and proteomic analyses of cells and matrix along the fibrotic trajectory in mouse lung identified PI16 as an anti-fibrotic factor with potential for therapeutic application in humans.

The brain and body are necessarily connected. Here the authors show that brain blood flow and electrical activity are coupled with systemic physiological changes in the body.

Several independent lines of evidence demonstrated long-term potentiation induction by a structural function of calmodulin-dependent protein kinase II rather than by its enzymatic activity.

The bispecific molecule tebotelimab, which blocks both PD-1 and LAG-3, is well tolerated as a monotherapy and in combination with the anti-HER-2 antibody margetuximab and elicits encouraging clinical activity in solid tumors with high LAG-3 levels and/or expression of IFN-γ-regulated genes.

The pulvinar nucleus is involved in modulating visual information. Fischer and Whitney use brain imaging to study the pulvinar during visual attention, and find that the positions and orientations of attended objects are precisely encoded in the pulvinar, while information about ignored objects is gated out.

Coagulation factor VIII deficiency in hemophilia A disrupts clotting and prolongs bleeding. Here, the authors show that vagus nerve stimulation bypasses this defect and improves hemostasis in hemophilia A mice through a mechanism requiring acetylcholine-secreting ChAT⁺ T lymphocytes in spleen and α7nAChR on circulating platelets.

This study elucidates how long-range chromatin loops are altered during short- and long-term changes in neural activity, and analyzes the interplay between the 3D genome and the linear epigenome during activity-dependent transcriptional responses.

We developed PRINT, a computational method that identifies footprints of DNA–protein interactions from bulk and single-cell chromatin accessibility data across multiple scales of protein size.

Deep X-ray limits are placed on the source of the closest fast radio burst, FRB 20200120E, ruling out an ultraluminous X-ray source or a young extragalactic pulsar embedded in a Crab-like nebula as its origin.

A diverse collection of potent neutralizing antibodies against the SARS-CoV-2 spike protein have been isolated from five patients with severe COVID-19 and high serum neutralization titres.

A study that tracked mammal populations before, during and after a severe storm in Mozambique’s Gorongosa National Park finds that behavioural responses and survival are linked to body size, with increased mortality of small species owing to limited mobility and changes in food availability.