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This study develops a platform that enables simultaneous, multiplexed tracing of 30 nitrogen isotope-labelled metabolites, uncovering differences in pyrimidine synthesis pathway choice between primitive and differentiated cells.

Castro-Dopico et al. report the design of reagents to bridge F-actin and Fcγ receptors, endowing a range of antigen-presenting cells with the ability to cross-present antigens from dead tumor cells and boosting antitumor immunity in preclinical models.

Proteomic data from natural isolates of Saccharomyces cerevisiae provide insight into how these cells tolerate aneuploidy (an imbalance in the number of chromosomes), and reveal differences between lab-engineered aneuploids and diverse natural yeasts.

A common rifampicin-resistance mutation in Mycobacterium tuberculosis alters transcription and creates new metabolic vulnerabilities through transcription attenuation, revealing potential targets to combat drug-resistant tuberculosis.

PTCHD1-AS, which encodes a long non-coding RNA, is associated with the aetiology of autism spectrum disorder in humans through striatal molecular and circuit-level dysregulation.

Combined single-cell transcriptomic and chromatin accessibility sequencing analysis of mouse primary visual cortex across postnatal development reveals that the glucocorticoid receptor drives astrocyte maturation to limit neuronal plasticity.

CASP5 expression is restricted to the human intestinal epithelium, and the CASP5C isoform has a key role in promoting Wnt signalling, which is required for epithelial homeostasis, through binding to dishevelled and cleavage of APC to regulate β-catenin turnover.

Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

The authors have applied an eight-tissue rat multi-omic dataset to analyze the gene regulatory landscape of endurance exercise training, identifying tissue-specific regulatory patterns involved in muscle function, metabolism and immune response.

Here, the authors elucidate TMPRSS2 protease recognition of the SARS-CoV-2 spike S₂′ cleavage site, revealing the molecular basis of activation of membrane fusion, and show that antibodies recognizing the S₂′ site or TMPRSS2 block viral entry by interfering with TMPRSS2 access.

Communication between distant brain regions is mediated by plastic networks of gap junction-coupled astrocytes.

A transient grey matter microgliosis is required for remyelination, the failure of which results in a chronic neuroinflammatory state seen in neurodegenerative disorders.

Functional studies of O-GlcNAcylation have often focused on individual modifications. Now, a systems-level approach has identified simultaneous O-GlcNAcylation events that coordinate cellular activities and tissue-specific functions.

Jacquemyn et al. identify key lipid determinants controlling ectosome shedding from neurons. They find that ectosomes are a major route for the intercellular transport of misfolded α-synuclein, with relevance to Parkinson’s disease pathology.

Peritoneal metastasis of ovarian cancer is often accompanied by the accumulation of ascitic fluid. Here, the authors find that ascites protects ovarian cancer cells against ferroptosis, thus enabling their spread in the peritoneum.

N-desethyl-fluornitrazene is a µ-opioid receptor agonist derived from nitazenes that has supramaximal intrinsic efficacy that produces analgesia with minimal adverse effects in rodent models.

Cas12a2 enables RNA-triggered, sequence-specific killing of eukaryotic cells via widespread DNA shredding, allowing selective elimination of cells on the basis of gene expression, including virus-infected or mutation-bearing cells.

DNA-sequencing data from primary tumours and paired metastases from participants in the TRACERx lung study and PEACE autopsy programme are used to analyse the metastatic diversity of advanced non-small cell lung cancer and the seeding patterns that underpin it.

Androgens have distinct roles in the brain, acting as immune-based tumour suppressors through neuroinflammation and neuroendocrine mechanisms.

Here they show that despite conserved TGFβ signalling, repeated receptor domain multiplications across vertebrates reshape ligand binding and function, revealing unexpected structural plasticity in a core pathway.

Plant community properties affect ecosystem functioning via energy fluxes in food webs, with the leaf and root resource economics of dominant tree species controlling soil food web multifunctionality.

Chimeric Antigen Receptor (CAR)-T cells with high affinity for their targeted epitopes efficiently kill malignant cells at the expense of excessive and potentially harmful immune activation, while lower-affinity targeting shows a safer profile but compromises tumour cell killing. Here the authors show that the combination of high- and low-affinity CARs results in a T-cell product with maintained functionality while reducing cytokine release and CAR-T-cell exhaustion in mouse models.

Natural products inspire the development of pseudo-natural products through combinations of fragments of compound classes that are chemically and biologically distinct. Here, the authors report a library of 244 pseudo-natural products, evaluate them in the cell painting essays and identify the phenotypic role of individual fragments.

Here, the authors show that 2’-O-methylated RNA fragments from ribosomal RNA naturally block TLR7 and TLR8, helping to avoid avoid harmful self-RNA detection and autoimmunity.

Here, the authors show that endothelial cells lining the blood vessels and red blood cells continually exchange glycocalyx sugars on their surface in health and disease. These exchanges enable the prediction of blood vessel damage by studying simultaneous red blood cell damage.

The authors performed computational and experimental analyses to reveal how Smoothened directly inhibits PKA through an intrinsically disordered region, defining a central step in Hedgehog signaling and a mechanism of G-protein-coupled receptor–kinase regulation.

Androgen activity in the male embryonic hindbrain prolongs hindbrain differentiation in male individuals and drives sex differences in the incidence and prognosis of posterior fossa type A (PFA) ependymoma, an aggressive childhood brain tumour.

l-2-Hydroxyglutarate is identified as a legitimate physiological signalling metabolite, and control of its levels is essential for postnatal growth and survival and correct renal development and function.

Authors investigate ancient DNA from animal remains and identify multiple signatures of ancient zoonotic pathogens. They find ancient pathogen genomics from archaeological animal remains may inform zoonotic disease emergence.

This study uses multi-omics approaches to dissect the roles of macrophage populations in the progression of metabolic dysfunction-associated steatohepatitis. GPNMB⁺ macrophages accumulate in the portal tract in advanced disease and may have antigen-presenting capabilities.

Alternative splicing generates diverse protein isoforms, yet the functions of most exons remain unknown. Here, the authors introduce scCHyMErA-Seq, a scalable single-cell CRISPR exon-deletion platform that maps exon-specific transcriptional functions shaping gene expression and cell-cycle states.

The rapid evolution of SARS-CoV-2 challenges antibody therapeutics, but glycan-masked antigens enable isolation of class 3 monoclonal antibodies that potently neutralize diverse Omicron variants and reveal cross-reactive epitopes.

Researchers reveal that TNF alpha unmasks a metabolic impairment in the enteric malate-aspartate shuttle. This dysfunction acts as a key pathological bridge linking intestinal inflammation to the neurodegeneration seen in Parkinson’s disease.

In a first-in-human trial combining the transplantation of CD33-negative CRISPR-edited hematopoietic cells with the CD33-targeted antibody–drug conjugate gemtuzumab ozogamicin, all transplanted patients achieved primary engraftment, and the treatment was well tolerated.

RNA velocity is a widely used method to predict the fate of single cells. Here the authors show that the concept can be adapted to predict the fate of individual human subjects, using RNA velocity of whole blood at a single point in time to predict future clinical outcomes and treatment responses.

Wei et al. perform spatial transcriptomic profiling on synovial tissue biopsy samples from individuals with recent-onset rheumatoid arthritis, finding TGFβ signaling and fibrogenic fibroblast activation drive a treatment-refractory tissue phenotype.

ΨDNA guides are used with Cas12 for precise, programmable targeting of cellular RNA.

Pagani et al. used cross-species fMRI to reveal two autism subtypes, characterized by lower and higher brain connectivity and linked to synaptic and immune-related pathways, respectively.

Here they identify TBL/R1 as regulator of insulin levels and pancreatic β-cell identity. Mice with β-cell TBL/R1 deficiency display diabetes and interactome screens reveal a regulatory network including PAX6, verified in human β-cells.

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

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.

A single-cell spatial atlas identifies a B cell-predominant microenvironment within the profibrotic tubular niche that marks a subset of patients with diabetic kidney disease with rapid progression.

Kancharla, Kelly et al. identify an acridone antimalarial potent across all major parasite life stages. Lead candidate T111 shows oral efficacy, low toxicity, and synergy with tafenoquine, providing a unique mechanism to overcome resistance.

The authors resolve 63 structurally diverse haplotype structures for the 22q11.2 deletion syndrome region. Deletion risk differs depending on structure; individuals of African ancestry are enriched for inverted repeats that predispose to inversion.

Myopathy caused by BAG3 mutation disrupts muscle protein homeostasis and leads to severe muscle weakness. In mouse models, the authors demonstrate that impaired autophagy drives the pathology, while gene therapy targeting the mutated BAG3 improves muscle function.

Lysosome positioning is essential for cell metabolism and stress responses. Here, the authors show that the TMEM55B-associated protein TBC1D9B controls lysosome positioning, autophagy, and starvation-induced degradation by serving as a GTPase activating protein of ARL8B

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Autorino et al. report a feedback loop between Nodal signalling and tissue phase transitions in zebrafish embryos. Nodal alters adhesion, triggering tissue rigidification and reduced porosity, which limits its diffusion and speeds up Lefty expression.

Massively parallel reporter assays promise rapid in vivo characterization of enhancer AAVs. Here, through systematic testing, authors uncover pervasive technical and biological noise, including chimeric AAV species, that exposes fundamental limitations in pooled enhancer screening.

In mice, female aggression is governed by an amygdala–to–medial hypothalamus circuit that is strengthened during pregnancy and is dynamically amplified by oxytocin during lactation.