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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.

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.

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.

Subcellular compartmentalization of the glycolytic enzyme PFKM regulates cell fate and metabolic switch during skeletal muscle differentiation.

It remains unclear whether rRNA modifications can be naturally altered in response to antibiotics in bacteria. Here, the authors analyzed direct RNA nanopore sequencing data with an analytical pipeline Nanoconsensus, to investigate whether bacterial rRNA modifications are modulated upon exposure to various antibiotics.

Schober and colleagues show that effector CD8⁺ T cells undergo metabolic shutdown, CD8⁺ central memory T cells are the most metabolically active, and naive-like memory T cells are quiescent during the acute phase of the immune response and represent the dominant population of memory CD8⁺ T cells after yellow fever vaccination in humans.

Verhaege et al. identify a conserved fibroblast barrier population at the base of the choroid plexus that compartmentalizes brain–CSF interfaces and is disrupted by inflammation, revealing a new site of central nervous system immune entry and barrier regulation.

A platform using matched patient-derived lung tumouroids and healthy lung organoids enables accurate examination of patient responses to CAR T therapy and offers a faithful framework for improved CAR T design.

An in-depth analysis of tissue biopsies from patients with multiple myeloma and CAR T cell therapy-associated immune-related adverse events (CirAEs) after treatment with commercial BCMA-targeted CAR T cell therapy shows that CD4⁺ CAR T cells mediate off-tumor toxicities and that high CD4:CD8 ratio at apheresis, robust early CAR T cell expansion, ICANS and ciltacabtagene autoleuce treatment are independently associated with the development of CirAEs.

The systemic discovery of metal–small-molecule complexes from biological samples is a difficult challenge. Now, a method based on liquid chromatography and native electrospray ionization mass spectrometry has been developed. The approach uses post-column pH adjustment and metal infusion combined with ion identity molecular networking, and a rule-based informatics workflow, to interrogate small-molecule–metal binding.

The identification and optimization of bifunctional small-molecule protein degraders remain labor-intensive processes largely restricted to proteins with well-defined ligandable pockets. Here, the authors present a polymer-based strategy, HYbrid DegRAding Copolymer (HYDRAC): modular copolymers that densely display target-binding peptides in conjunction with peptide-based or small molecule-derived degrons in a multivalent fashion, enabling selective degradation of disease-relevant proteins.

Approved antibody–drug conjugates (ADCs) remain constrained by a limited repertoire of payloads with restricted modes of action. Here, the authors present phosphoramidate-based self-immolative linker units that facilitate stable attachment in serum and traceless drug release in the target cell from aliphatic and aromatic alcohols with various modes of action.

Beta-glucan is an inducer of trained immunity, an epigenetic and metabolic reprogramming of the innate immune cells conferring immunological memory. Here the authors show that glucan-induced trained immunity enhances response to a cancer vaccine platform in colorectal cancer models, by inducing epigenetic and metabolic rewiring of macrophages that promotes an NK-cDC1 axis boosting anti-tumor immunity.

In this work, the authors reveal that three non-ribosomal peptides targeting a common protein quality system differentially alter the Mycobacterium tuberculosis proteome, providing new insight into the molecular mechanisms behind their antimycobacterial activity.

Tissue stiffness mediated by Piezo1 is shown to regulate the expression of diffusive guidance cues in the developing Xenopus laevis brain, revealing a crosstalk between mechanical signals and long-range chemical signalling.

Antigen presentation in skull bone marrow by hematopoietic stem and progenitor cells induces myelopoiesis and generates CD4⁺ regulatory T cells in a mouse model of ependymoma, promoting immune tolerance. Treatment with anti-GM-CSF antibody has antitumor effects that are augmented by immunotherapy.

Yashinskie, Zhu and colleagues show that p53 activation triggers increased synthesis and accumulation of phospholipids, with enhanced activation of autophagy and lysosomal catabolism programmes and increased reliance on lipid headgroup recycling.

Morales-Sanfrutos, Etxeberria-Ugartemendia, Barroso-Gomila and colleagues map the elution profiles of small extracellular vesicles along density gradients from human biofluids and cell lines, distinguishing extracellular vesicle content from co-isolation components.

Here, the authors show that complexes formed by bacterial chromosome segregation protein ParB are stabilized by condesin SMC. They examine the impact of SMC on ParB dynamics, DNA binding and its CTPase activity, providing insights into the nature of ParB complexes.

Becker et. al developed a proteomic proximity labeling platform named POCA, which makes use of a photosensitizer for singlet oxygen production and protein capture in the presence of amine, enabling profiling of interactomes of proteins and lipids in living cells.

Benito-Martínez, Salavessa and colleagues show that keratin intermediate filaments and microtubules control the three-dimensional perinuclear position of melanin-containing organelles, shielding the DNA from photodamage.

The impact of ACKR3 constitutive activity is unknown. Here, the authors suppress basal ACKR3 activity using inverse agonistic nanobodies to stabilize an inactive conformation and revealing a role for ACKR3 in basal cell motility.

This study reveals that anti-NS1 IgA antibodies in plasma, induced by prior Zika virus infection, activate neutrophils, underlying severe dengue disease upon a subsequent DENV2 infection, uncovering a pathogenic mechanism relevant for vaccines and therapeutics.

The recruitment of RNAPII to gene promoters is initiated by TBP and TFIIB. Here, the authors use cryo-EM to show how the RNAP from the Vaccinia virus recognizes promoters, identifying transcription factor VITF-3 as an atypical TBP/TFIIB pair.

Oxytocin promotes social behaviors, but its cortical targets remain unclear. Here, authors show that oxytocin activates local interneurons in the rat prefrontal cortex, enhancing sociability through top-down control of the basolateral amygdala.

The authors detail human antibodies that neutralize all three serotypes of poliovirus and mimic poliovirus receptor binding, accelerating antiviral development to further efforts to eradicate poliovirus.

Ubiquitination is a versatile modification system in eukaryotic cells. Here, the authors unveil that the ubiquitin ligase HUWE1 can modify drug-like small-molecule substrates, beyond proteins. This discovery may be harnessed to develop specific tool substrates or inhibitors of HECT-type ligases.

Ribosomal translation is coupled to cotranslational protein folding, process assisted by dedicated chaperones. Here, authors present structures of the ribosome-bound yeast Hsp70 chaperone Ssb, identifying its ribosomal binding site and revealing its interactions with a model nascent chain.

Dysregulation of blood vessel size can cause vascular malformations. Here, the authors demonstrate that endothelial cells generate circumferential actomyosin cables to control the size of cells and vessels.

A combination of genome-wide functional screening, imaging and chromatin profiling identifies a new class of highly prevalent genomic elements that help retain extrachromosomal DNA copies in dividing cells and persist across generations.

Multi-omics profiling of monkeypox virus infected human primary cells was used to characterize the infection process and to prioritize potential antiviral drug targets.

Elevated risk of Guillain-Barre syndrome following respiratory syncytial virus vaccination in older adults as been reported in the United States. Here, the authors investigate evidence for this association following rollout of the vaccine in people aged 75-79 years in the United Kingdom.

Some brain lesions recover in multiple sclerosis, while others do not; however, the underlying mechanisms are unclear. Here, the authors show that microglia-derived TGFα orchestrates immune control and tissue repair, and that intranasal delivery of TGFα in the autoimmune encephalomyelitis model promotes lesion resolution.

Formate produced by synthetic methylotrophic E. coli can lead to carbon loss and negatively impact bioproduction efficiency. Here, the authors report the production of formate as a widespread property of NAD-dependent methanol dehydrogenases and identify Mdhs without this overoxidation activity.

CAR-T cell therapy has been shown to be effective in immunotherapy for treatment of several different tumours. Here the authors show pre-specified interim outcomes from a P-BCMA-ALLO1 trial with BCMA targeted CAR-T therapy in multiple myeloma.

Here authors identify GluN2D-containing NMDA receptors on interneurons as a specific target for rapid antidepressant action. Blocking GluN2D restores stress-impaired plasticity and mimics the effects of ketamine with fewer side effects.

Standard of care in patients with unresectable stage III non-small cell lung cancer (NSCLC) is concurrent chemo-radiotherapy followed by immunotherapy. Here, the authors report a phase II trial investigating induction chemo-immunotherapy (atezolizumab, carboplatin and paclitaxel) followed by concurrent chemoradiotherapy and immunotherapy maintenance in patients with stage III NSCLC.

Here, the authors reveal using single-cell RNA sequencing that Parkinson’s disease (PD) patient-derived neuronal cells show altered primary cilia morphology and signaling suggesting cilia dysfunction may underlie PD pathogenesis.

Caspase 8 protein expression is largely absent in small cell lung cancer (SCLC) patients. Here, the authors generate a caspase 8 deletion SCLC mouse model and show that it promotes a neuronal progenitor-like cell state and pre-tumoral immunosuppression triggered by necroptosis that promotes metastasis.

Understanding of the immune microenvironment in pediatric acute T cell lymphoblastic leukemia is limited. By analyzing single-cell transcriptome, surface protein expression and immune repertoire data, the authors here identify non-malignant CD4^-CD8^- TCRαβ T cells that are present in a subset of patients with Rap1 signaling in leukemia cells and are associated with adverse clinical outcome in patients with low minimal residual disease.

Proof-of-concept of a humanised gut-brain axis ex vivo model with physiological coupling of intestinal and blood-brain barrier for mechanistical assessment of butyrate- or fiber-rich diets on the serotonergic system in healthy or diseased states.

Including data from 1,047 patients across 19 inflammatory diseases, a new atlas presents a comprehensive model of inflammation in circulating immune cells.

SARS-CoV-2 Omicron XEC variant, a recombinant of JN.1 progeny, shows increased viral fitness and pathogenicity. Here, the authors show that the nucleocapsid mutation R204P enhances inflammation and suggest a growing role of non-spike mutations in viral evolution.

Mapping protein interactions requires sensitive mass spectrometry. Here, the authors show that the Orbitrap Astral, combined with optimized chromatography, improves detection of low-abundance crosslinks compared with the Eclipse.

Brain-wide recordings in mice reveal that prior expectations are distributed through recurrent loops across all levels of cortical and subcortical processing.

Direct interaction between the small GTPase Rab7a and the cation channel TPC2 has been reported but the functional regulation is less clear. Here, the authors show that Rab7a enhances the activity of TPC2 to promote melanoma progression through the GSK3β/β-Catenin/MITF axis.

By performing a CAR-adapted base-editing screen of phosphatidylinositol-3-kinase delta (PI3Kδ, PIK3CD), Bucher et al. identify mutations affecting endogenous PI3K–AKT signaling that enhances CAR T cell antitumor potency.

Cosgun et al. show that, in B cell leukemia, β-catenin expression is maintained at low levels through glycogen synthase kinase 3B (GSK3β)-mediated phosphorylation. Inhibition of GSK3β results in β-catenin–Ikaros–NuRD complex formation, leading to B-ALL cell death through MYC repression.

The function of DNMT1 (DNA methyltransferase 1) in these subsets of immature, migrating cortical inhibitory interneurons is not fully understood. This study shows that DNMT1 regulates cortical development by orchestrating the migration of postmitotic SST+ interneurons and their signaling to cortical progenitors, with implications for proper cortical architecture and function.