Search

nELISA miniaturizes the sandwich immunoassay and transforms it into a massively scalable platform for quantitative proteomics.

Here authors show Trisomy 21 alters fetal brain development by increasing activity of the RNA-editing enzyme ADARB1, leading to premature RNA editing of key genes involved in early synaptic signaling.

Using single-cell tissue imaging and spatial proteomics to study mitochondria–lipid droplet coupling in hepatocytes, PLIN5 phosphorylation is identified as a mediator of lipid flux and nutrient stress responses.

Xia, Zhang, Peng, Chen et al. find that Leydig cells and macrophages show bidirectional mitochondrial transfer through extracellular vesicles, ensuring Leydig cells have functional mitochondria. The exchange is needed for testosterone production.

Telomeres need to open from a close state which protects the chromosome ends to allow extension by telomerase. Here the authors reveal distinct roles of TPP1 and POT1 in telomerase recruitment and telomere protection using siingle-cell telomerase activity assay.

Lipoproteins are major cell-surface components in archaea, but their functions and the lipidation mechanisms are unclear. Here, Hong et al. identify two proteins required for attachment of proteins to unique archaeal membrane lipids via thioether bonds, and demonstrate their importance in archaeal physiology.

Chan et al. generate a high-resolution spatiotemporal atlas of healing hearts and reveal cellular networks of lesion repair, including macrophage–fibroblast interactions that control late-stage fibrosis and immune niches that induce cardiomyocyte de-differentiation.

Plastics are major marine pollutants, and while research suggests that they can release potential harmful additives into seawater, how environmental conditions influence this is unknown. Here the authors determine that byproducts released from microplastics are less under deep-sea conditions versus surface.

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.

Gao, Nowak-Imialek, Chen et al. generate porcine and human stem cells that possess expanded developmental potency for both embryonic and extra-embryonic cell lineages.

Rebecca Fitzgerald and colleagues used genome sequence analyses to study the progression from premalignant Barrett's esophagus to esophageal adenocarcinoma (EAC) and found that the majority of recurrently mutated genes in EAC were also mutated in precursor lesions and that only mutations in TP53 and SMAD4 were stage specific.

The complexity of epithelial cell states in the fibrotic niche in the context of chronic kidney disease remains incompletely understood. Here the authors integrate snRNA and ATAC-seq with high-plex single-cell molecular imaging to generate a spatially-revolved multiomic atlas of human kidney disease.

DIA-MS has emerged as a widely used technological platform for quantitative protein profiling. Here, the authors develop MSFragger-DIA, a robust and fast tool to directly identify peptides from DIA spectra. It demonstrates excellent performance across applications from large-scale tumor studies to single-cell proteomics.

Triacetic acid lactone (TAL) is a platform chemical with a wide range of applications. Here, the authors report the discovery of a polyketoacyl-CoA thiolase from Burkholderia sp. RF2-non_BP3, termed as BktBbr, which has unusually high in vivo and in vitro activity for production of TAL.

Pericytes play an essential role in blood brain barrier (BBB) integrity. Here, the authors generate pericyte-like cells (PCs) from human pluripotent stem cells (hPSCs) which display functional properties and also promote BBB recovery in a mouse model of cerebral artery occlusion.

The ability to oxidise hydrocarbons aerobically has been described in bacteria but not yet in archaea. Here, Leu et al. analyse metagenomic datasets from various environments and provide evidence supporting potential aerobic hydrocarbon oxidation ability in an archaeal lineage within the class Syntropharchaeia.

A microglial state, featuring lipid droplets and secretion of neurotoxic factors, is shown to be most prominent in people with Alzheimer’s disease who have the APOE4 genotype.

How carvedilol, a β1-blocker, activates β2-adrenoceptors, is unclear. Here, the authors resolve this enigma and show that carvedilol drives all of its detectable cellular β2-adrenoceptor signals by slow and low efficacy G protein activation.

Telomerase-independent telomere lengthening is a potential target for cancer therapy, but molecules specific to this pathway have remained elusive. Henson et al. show that DNA circles of (CCCTAA)_n are specific intermediates of alternative lengthening of telomeres and present a sensitive assay to detect them.

Chromatin topology can impact gene regulation. Here, Wu et al. show that evolutionary changes in chromatin structure, particularly CTCF loops, can drive distinct transcriptional landscapes and isoform diversity contributing to human-specific traits.

Fan and colleagues show that FLASH radiation promotes proinflammatory polarization of tumor-associated macrophages, which in turn increases T cell influx in medulloblastoma and synergizes with CAR-T cell therapy.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Dick and colleagues identify human LT-HSC subsets with distinct quiescent states. They link these differences to INKA1-mediated downregulation of the transmembrane protein CD112 and its interaction with the protein deacetylase SIRT1. INKA1 is inversely correlated with the histone H4K16Ac mark, which then distinguishes ‘latent’ CD112^lo LT-HSCs from CD112^hi LT-HSCs that are more readily activated in response to hematopoietic stress.

Immunotherapy has yet to demonstrate efficacy for patients with glioblastoma. Here, the authors employ human single-cell RNA-seq, spatial transcriptomics, and a preclinical mouse model to show that glioblastoma cell-derived synaptogenic factor Thrombospondin-1 promotes neuronal circuit remodeling and regional immunosuppression, highlighting a potential therapeutic target.

The PI3K/Akt/mTOR pathway has been previously implicated in fibrosis and a pan-PI3K/mTOR inhibitor is currently under clinical evaluation for the treatment of IPF. Here the authors show that the mTORC1/4E-BP1 axis is critical for TGF-β1-induced fibrogenesis in in vitro and ex vivo models and that canonical PI3K/Akt signalling is dispensable.

Compared to the oxygenation of Earth’s atmosphere, little is known about the build up of dissolved oxygen in the oceans. Vanadium isotopes in shales suggest shallow oceans equilibrated with a newly oxygenated atmosphere in just a few million years.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Adipose tissue-resident regulatory T (T_reg) cells are important for maintaining normal metabolic function and adiposity. Li and colleagues demonstrate that insulin signaling directly controls adipose T_reg cell development and functionality

Mantle cell lymphoma (MCL) is a form of B-cell non-Hodgkin lymphoma with a high degree of genetic and clinical heterogeneity. Here, using a multi-omics approach, the authors investigate genetic alterations in association with the tumour microenvironment to identify potential therapeutic vulnerabilities.

A highly potent and selective small-molecule catalytic inhibitor of the protein lysine methyltransferase NSD2 shows therapeutic efficacy in preclinical models of KRAS-driven pancreatic cancer and lung cancer.

There is still a need for effective HIV vaccines. In this phase I clinical trial, the authors show that an HIV-1 vaccine candidate, ConM SOSIP.v7, is well-tolerated in HIV-negative adults and that it elicits a strain-specific neutralising antibody response that differed between female and male participants.

Here the authors report asperigimycins, fungal ribosomally synthesized and post-translationally modified peptides with a heptacyclic scaffold. After chemically modifying them for nanomolar anticancer activity, CRISPR screening identifies SLC46A3 as a key transporter for their uptake in cells.

Growth hormone (GH) is a major modulator of physical growth and metabolism that is under tight regulatory control. Here the authors describe the signaling profile of GPR101, an orphan receptor that enhances GH secretion principally via constitutively activated Gs-PKA and Gq/11-PKC pathways.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A first-in-human phase I clinical trial demonstrates the feasibility and safety of non-viral precision genome-engineering of a personalized adoptive cell transfer anticancer therapeutic.

Embryos at the 2-cell (2C) stage are totipotent, and overexpression of Dux transcription factor convert embryonic stem cells (ESCs) to a 2C-like state. Here the authors show that DUX-mediated 2C-like reprogramming is associated with DNA damage at CTCF sites and CTCF depletion promotes 2Clike conversion.

mRNA vaccines must be rigorously analysed to measure their integrity and detect contaminants, which can be time-consuming and costly. Here, authors describe a method to analyse mRNA vaccine quality using long-read sequencing and a custom bioinformatic pipeline.

The impact of breakage fusion bridge (BFB) cycles on tumour heterogeneity and clinical outcomes remains poorly understood. Here, the authors develop OM2BFB, an algorithm to detect and reconstruct BFB amplifications using optical genome maps and use it to study BFB events across 2557 primary tumours and cancer cell lines.

Type 1 regulatory T cells (Tr1) represent a major obstacle that compromises naturally occurring and therapeutically induced tumour-specific immunity.

The immunosuppressive role of regulatory T (Treg) cells largely depends on their virtue of expressing the transcription factor FOXP3. Here the authors show that the E3 deubiquitinase USP21 stabilizes FOXP3 by mediating its deubiquitination and helps to maintain the expression of Treg signature genes and Treg lineage stability in mice.

In preclinical studies, the FDA approved TSP-1 antagonist gabapentin has been shown to disrupt neuronal-glioma interactions, slowing glioblastoma progression. Here, authors report a retrospective cohort study demonstrating a survival benefit associated with gabapentin in patients with newly diagnosed glioblastoma.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.