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Neonatal sepsis caused by Escherichia coli is associated with reduced transfer of pathogen-specific maternal antibodies and, in a mouse model, can be prevented by maternal preconceptual colonization with probiotic E. coli.

Here proteomic chromatome analysis shows metabolic enzymes widely localize to chromatin in cancer in a tissue-specific manner. Nuclear enzymes affect DNA damage/repair and transcription, revealing non-canonical nuclear metabolic roles in cancer.

Metastasis-associated oncofetal cell states emerge at the earliest stages of colorectal cancer and spatial profiling shows stereotypic patterning of fibroblast subtypes resembling normal tissue architecture, resulting in distinct regional microenvironments that dictate the timing and positioning of oncofetal plasticity.

In this phase 1/2 trial, patients with Ewing sarcoma received trabectedin and low-dose irinotecan at concentrations known to inhibit the activity of the transcription factor EWS::FLI1, leading to encouraging clinical response rates.

MitoCatch is a cell-type-specific mitochondrion-targeting system that links mitochondria and the cell surface by protein binders and delivers mitochondria into the target cell.

Salladay-Perez and colleagues explore senescence induction in human and mouse macrophages using multiomic profiling. They characterize a p21⁺TREM2⁺ senescent macrophage population, which they functionally implicate in inflammaging and liver disease.

Contaminants such as CO₂ and H₂S present in natural gas and biogas streams must be removed before use; existing strategies to do so can be rather complex. Here, the authors use a fluorinated porous metal–organic framework to remove CO₂ and H₂S from CH₄-rich feeds in a single step, potentially simplifying the process.

After being internalized by cells, nanoparticles can, in rare events, acquire a biomolecular condensate corona. These complexes can reach the extracellular space, where they can deliver their acquired proteins and RNA content to other cells.

DNA damage burden and inadequate repair in CUX2⁺ cortical layer 2/3 excitatory neurons contributes to selective vulnerability in neuroinflammatory injury.

Emerging multidrug-resistant Neisseria gonorrhoeae is a global health threat in the treatment of gonorrhoea. This study reports the discovery and characterization of a promising antigonorrhoea agent that addresses antibiotic resistance.

The two species of African elephants are facing severe declines. Here, authors assess their continent-wide genomic diversity, identifying differences in their evolutionary histories and highlighting the formative role of gene flow.

Post-translational redox modification of protein cysteine residues has emerged as a mode of immune cell regulation. Now, a deep redox proteomics study identifies redox-regulated and druggable cysteines in immunological proteins.

The excitatory neuron diversity and specialized connectivity of complex, multilayered mammalian neocortex are driven by mammalian-specific cis-regulatory elements bound by ZBTB18, deletion of which disrupts gene expression and results in projection patterns resembling those of non-mammalian brains.

Synthetic super-enhancers enable specific delivery of anticancer payloads, achieving tumour elimination after a single dose in a mouse model of aggressive glioblastoma.

Guan, Ocampo and colleagues report the discovery and mechanistic dissection of Al3Cas12f, a metagenome-derived miniature nuclease that retains notable genome-editing capacity. They engineer an RKK variant, which boosts editing and helps overcome the potency threshold that has limited compact editors.

ALS/FTD-linked mutations in UBQLN2, a protein quality control factor, impair degradation of enzymes essential for mitochondrial lipid catabolism, leading to metabolic dysfunction and neurodegeneration.

A technique called condense-seq has been developed to measure nucleosome condensability and used to show that mononucleosomes contain sufficient information to condense into large-scale compartments without requiring any external factors.

Epigenetic programming of myeloid and CD4⁺ T cells promotes decay of the SIV reservoir in rhesus macaques and a similar molecular pathway is found in HIV elite controllers.

This study demonstrates that overexpression of irisin, an exercise-induced myokine, ameliorates obesity and insulin resistance in high-fat-diet-fed mice by increasing local IL-33 production and preserving ST2⁺ regulatory T cells in white adipose tissues.

Antibodies against SARS-CoV-2 continue to evolve 6 to 12 months after infection in patients who have recovered from COVID-19, increasing in potency and breadth with time.

Paracrine signalling between tuft cells and enterochromaffin cells is a key mode of immune–sensory and gut–brain communication, and accounts for the pattern of gastrointestinal symptoms that occurs during parasite infections.

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.

Store-operated Ca²⁺ entry is essential for cellular signalling, yet excessive calcium influx drives disease. Here, authors develop genetically encoded CRAC channel inhibitory binders (CRABs) to precisely modulate Ca²⁺ signalling, with therapeutic potential in channelopathies and cancer immunotherapy.

Emmett and colleagues evaluate the frequency, magnitude and clinical significance of early prostate-specific membrane antigen (PSMA) upregulation in patients with metastatic castrate-resistant prostate cancer treated with enzalutamide with or without ¹⁷⁷Lu-PSMA-617.

Inducible base editors enhance cancer genomic screens in vivo.

In vivo adenine base editing corrects a common Pex1 pathogenic allele in mouse models of Zellweger spectrum disorder, rescuing liver pathology, fatty acid levels, body weight and peroxisome function.

This study reveals a non-canonical immunomodulatory function for the enzyme iNOS, based on the direct interaction in mitochondria with the itaconate-producing protein IRG1, which limits itaconate production in mouse and human macrophages

To evade the immune system, Trypanosoma brucei relies on a specialized ‘expression site body’. Protein condensates within this nuclear compartment modulate expression of virulence genes via a targeted RNA decay mechanism.

FLT3-ITD mutations drive relapse in acute myeloid leukemia (AML) despite targeted therapies. This group studies therapeutic potential and resistance mechanisms of FLT3-ITD inhibition with QUIZartinib and Omacetaxine Mepesuccinate (QUIZOM) in preclinical and clinical AML specimens.

Microbially derived 10-oxostearic acid (10-oxoSA) interacts with PPARα in the colon to alleviate gut inflammation in acute and chronic mice models.

Tandem duplications are a common class of structural variation in evolving genomes but are rare in healthy cells, and the DNA repair mechanisms that suppress their formation remain poorly defined. Here, the authors identify TONSL as a conserved factor that suppresses tandem duplications across species.

Murthy and colleagues discussed recent research on the effect of a tucanitib–trastuzumab–capecitabine regimen in patients with HER2⁺ breast cancer and leptomeningeal metastasis.

In this study, the authors present optimization and efficacy testing of apolipoprotein-based lipid nanoparticles for delivering various nucleic acid therapeutics in vivo to immune cells and their progenitors in the bone marrow.

Gut microbial changes promoted by weaning in mice result in epigenetic modification in intestinal stem cells with long-lasting impact on host immunity.

Betrancourt, Cinko et al. identify ANKIB1-mediated K11 ubiquitination and OPTN recruitment as a shared mechanism for driving immune signalling by cGAS, TLR3 and TLR4, with functional relevance in interferonopathy and herpes simplex virus-1 protection.

SWI/SNF complexes are mutated in 20% of cancers, yet the underlying mechanisms are poorly understood. Here, the authors identify a compensatory mechanism of chromatin regulation that becomes essential in cancers carrying mutations that broadly inactivate SWI/SNF.

Dutta et al. demonstrate that the tumor suppressor complex BRCA1–BARD1 physically interacts with the RNA–DNA helicase Senataxin (SETX) and upregulates the activity of SETX to resolve harmful R-loops crucial for the avoidance of transcription–replication conflicts.

Age-related microbiome changes increase medium-chain fatty acid-producing bacteria, driving GPR84-mediated myeloid inflammation, impaired vagal signalling and hippocampal dysfunction; targeting this gut–brain pathway restores memory in aged mice.

The transcription factor ATF4 is shown to regulate double-stranded DNA repair within vulnerable CUX2⁺ upper-layer 2/3 cortical neurons, enabling their survival during development.

Here authors show in a human stem cell–derived model, neural cultures from children with MPSIIIA exhibit hyperactive excitatory synapses associated with excitation–inhibition imbalance, altered network dynamics, and broad dysregulation of genes involved in synaptic homeostasis.

Time-restricted eating (TRE) and daily calorie restriction both led to significant weight loss in women with polycystic ovary syndrome compared to controls. Thus, TRE is a safe and effective alternative to calorie restriction for weight management in this population.

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.

In patients with acute heart failure, personalized dosing of a diuretic led to treatment intensification in the majority of patients and improved natriuresis, but had no effects on time to all-cause mortality or heart failure rehospitalization.

BRD2 is key for RNA polymerase II recruitment at promoters, becoming critical in the absence of BRD4 or upon pause-release inhibition. Depletion of MOF or deletion of BRD2’s intrinsically disordered region mimics transcriptional defects caused by BRD2 loss.

Transmission of Plasmodium falciparum relies on the development of gametocytes, which undergo extensive cellular remodelling. Here, the authors demonstrate that the PfGID E3 ubiquitin ligase complex affects gametocyte development by regulating key proteins, producing defective cells that cannot infect mosquitoes.

FRIL is an antiviral legume lectin that recognizes complex type N-glycans. Here, authors discover a process to activate the inert recombinant lectins, and engineer a shift of FRIL’s glycan recognition to high mannose N-glycans.

Endosomal Toll-like receptors (TLRs) are central to the innate immune response but their overactivation can cause systemic inflammation and disease. Now, new small molecules targeting the interaction between Munc13-4 and syntaxin 7 essential for endosomal maturation impair overactivation of endosomal TLR-dependent pathways and inflammation.

A new cerebrospinal fluid biomarker, AcTau174, was elevated in frontotemporal lobar degeneration with TAR DNA-binding protein (FTLD-TDP), distinguishing this pathology from FTLD-Tau, and was associated with disease severity and progression in FTLD-TDP.