Search

Mehl and colleagues present a protocol for selecting aminoacyl-tRNA synthetase (RS)/tRNA pairs from a publicly available MaPylRS active site mutant library for specific and efficient incorporation of noncanonical amino acids into proteins.

Mauthe et al. find that protein aggregate clearance requires fragmentation of the aggregate by a chaperone module and a proteasomal regulatory particle for recruitment and clustering of selective autophagy receptors to initiate phagophore formation.

Neuroimmune communication in Alzheimer’s disease (AD) is poorly understood. Here, the authors show that CD103–CD8+ resident memory T cells induce neurotoxicity and neuroinflammation in AD via the granzyme K–PAR-1 axis.

In vivo loss-of-function CRISPR screens were performed to identify genes influencing CAR T cell persistence and function in human multiple myeloma, highlighting CDKN1B as a promising target.

Using mouse pancreatic cancer models, Tsanov et al. show that reactivation of SMAD4 at metastatic sites promotes tumor growth in the lung through RUNX1 but restrains metastatic growth through KLF4 in the liver, influenced by organ-specific epigenetic states.

Human papillomavirus (HPV) DNA testing is the preferred method for cervical cancer screening, but existing tests are inaccessible for resource-limited settings. Here, authors develop a low-cost, simple HPV DNA assay suitable for bedside testing and demonstrate strong performance in Mozambique.

CAR-T cells have been found to be less effective as treatment for solid tumours. Here the authors, utilising B7H3 as an antigen, consider how changes in B7H3 binders lead to functional changes of CAR-T cells and differences in tumour outcomes in humanised mouse tumour models.

Modulating pro-inflammatory immune cell kinetics after myocardial infarction is a critical step to prevent heart dysfunction. In this study, the authors show that Ezh2 pharmacological inhibition, acting as an epigenetic checkpoint in monocytes and macrophages, prevents myocardial infarction-induced cardiac dysfunction.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

Drug and target discovery for advanced liver disease are hampered by a lack of suitable models for clinical translation. Here the authors present a human liver cell-based system modeling a clinical prognostic signature allowing to propose nizatidine for treatment of advanced liver fibrosis and hepatocellular carcinoma prevention.

B. thuringiensis spores contain uncharacterized protein filaments that extend from the surface of the exosporium. Here, the authors show that these filaments feature conserved β-barrel neck domains and promote spore clustering through protein contacts and filament bundling, and reveal a mechanism for biofilm-like spore aggregation.

Constitutional mismatch repair deficiency (CMMRD) is associated with high cancer incidence early in life. Here, the authors perform a genomic analysis of CMMRD-associated tumors and find mutational patterns influenced by the affected mismatch repair gene, tumour type, and treatment history.

Lung cancer is characterized by an immunosuppressive microenvironment, limiting responses to immunotherapies. Here the authors report the design of a pH-responsive nanomedicine for the co-delivery of a T-type calcium channel inhibitor and of a small molecule targeting CD47, promoting anti-tumor immune responses in orthotopic lung cancer preclinical models.

Metabolic enzymes of the tricarboxylic acid cycle, such as 2-oxoglutarate dehydrogenase, are differentially expressed in absorptive and secretory lineages, guiding cell fate establishment and offering insights for targeted regenerative therapies.

A liver-intrinsic mechanism is presented that suppresses effective anti-hepatitis virus B responses in mice and humans by rendering virus-specific CD8 T cells refractory to activation causing loss of effector functions.

Biofluorescence is widespread in fishes. Here, the authors compile data on biofluorescence presence across teleost fishes and demonstrate that it may have originally evolved in eels 112 million years ago, but evolved numerous other times as well, often in association with coral reefs.

Here, the authors show how in β-thalassemia, a perturbed bone marrow microenvironment leads to altered hematopoiesis. Reduced TGFβ reduces autophagy levels, in turn reducing dormancy and priming of haematopoietic stem cells and multipotent progenitors towards erythroid lineage.

Barreby et al. identify a distinct subpopulation of human resident liver myeloid cells that expresses factors that act in a protective fashion against oxidative stress associated with NAFLD.

The authors investigate the mechanical behavior of origami tessellations composed of trapezoid faces, which are more general but less studied compared to parallelogram faces. They develop analytical expressions for the deformation modes and test the model’s validity through laboratory scale experiments.

The composition of lipid nanoparticles for the delivery of tumour-antigen-encoding mRNA can be optimized via a screening method to enhance antitumour activity via the modulation of the immune activity of helper T cells.

An in vivo base editing approach targeting the PRNP gene led to a 52% increase in the lifespan of mouse models inoculated with the most common sporadic and genetic types of human pathogenic prion isolate.

Microbes that colonise ice sheet surfaces are important to the carbon cycle, but their biomass and transport remains unquantified. Here, the authors reveal substantial microbial carbon fluxes across Greenland’s ice surface, in quantities that may sustain subglacial heterotrophs and fuel methanogenesis.

Wooden artefacts from waterlogged deposits in Zambia dating back 477 ka indicate hitherto unknown sophistication in woodworking at an early date.

A genome-scale gain-of-function screen using overexpression of nearly 12,000 open reading frames (ORFs) identifies positive regulators of human T cell function and suggests that ORF-based screens could be applied clinically to improve T cell therapies.

Imaging non-repetitive loci in living cells remains challenging. Here, the authors engineered an inducible system whereby biomolecular assemblies can be guided to specific genomic loci by a nuclease-defective Cas9, allowing the simultaneous imaging and manipulation of the loci.

The cell of origin for high-grade serous carcinoma (HGSC) remains to be determined. Here, the authors characterize the different cell types and states of the mouse uterine tube and identify transitional pre-ciliated cells as a cancer-prone cell state, which could be targeted therapeutically.

Here, van der Lans et al describe an antigen-agnostic approach to identify antibodies against Klebsiella pneumoniae. Functional analysis of these antibodies indicates that their capacity to activate complement depends on their antigenic target.

Liver X receptor drives epithelial Areg-mediated intestinal regeneration, while preventing tumour growth through adaptive immune responses.

Chimeric antigen receptor (CAR) T cells specific for an antigen, BCMA, have shown efficacy in controlling multiple myeloma in some patients, but responses vary. Here the authors show that, by over-expressing a granzyme B-NOXA fusion protein in anti-BCMA CAR T cells, cancer cells are rendered more susceptible to apoptosis induction and CAR T-mediated killing.

Combining single-cell RNA-sequencing with high-resolution multiplexed error-robust fluorescence in situ hybridization reveals in detail the cellular interactions and specialization of cardiac cell types that form and remodel the human heart.

Tumour-derived prostaglandin E₂, signaling through its receptors EP₂ and EP₄, is shown to restrain the responses of tumour-infiltrating stem-like TCF1⁺CD8⁺ T lymphocytes, and modulation of T cell EP₂ and EP₄ can restore anticancer immunity.

The molecular regulation of endothelial cells (ECs) in metastasis remains unclear. Here, the authors use single-cell RNA-seq to examine the reprogramming of lung ECs in mouse models of melanoma metastasis, revealing that PIM3 protects capillary integrity and that its inhibition increases vascular leakage and metastatic colonisation.

Familial adenomatous polyposis (FAP) is an inherited gastrointestinal syndrome associated with duodenal adenoma formation. Here the authors show that IL17A-producing NKp44- group 3 innate lymphoid cells accumulate in FAP duodenal tissue and are associated with duodenal adenoma formation in patients with FAP.

Quiescent populations are a likely key source of treatment resistance in glioblastoma. Here, the authors characterize KAT5 as a critical mediator of quiescence and adoption of progenitor-like states.

Fishing has had a profound impact on global reef shark populations, and the absence or presence of sharks is strongly correlated with national socio-economic conditions and reef governance.

Ligand detection is an essential component of pre-clinical drug development. Here, the authors develop an assay directly coupling protein ligand binding to the luminescence intensity of NanoLuc luciferase; enabling a compound discovery strategy for a broad spectrum of potential drug targets.

A peptide display method was developed, revealing that a kinase important for infection by Salmonella and related pathogens detects specific human antimicrobial peptides, possibly reflecting bacterial adaptation to distinct host locations.

Hervé, Scelfo et al. show that chromosome mis-segregation induces mTORC2- and ATR-mediated p53 activation through a mechanosensitive checkpoint at the nuclear envelope triggered by altered heterochromatin content and increased nuclear membrane tension.

Liver resident CD8 T cells have an essential role in immunopathology in a mouse model of nonalcoholic steatohepatitis, by becoming auto-aggressive following sequential transcriptional and metabolic activation steps .

3D-printed models of the penis can facilitate the study of penile physiology and the repair of penile defects, as shown via a reconstructed and implanted corpus cavernosum that restored erectile function and mating capacity in rabbits and pigs.

Multi-omic profiling of matched brain and peripheral tissues offer rare opportunities to uncover extra-CNS drivers of Alzheimer’s pathobiology. Here, authors report an Alzheimer’s linked CD83(+) microglia subtype that is associated with immunoglobulin IgG4 production in the transverse colon.

Here the authors show that DNA translesion synthesis affects primordial germ cell DNA demethylation and plays a role in the development of embryonic germ cells.

Spatial transcriptomics aims to pair omic data with tissue structure. Here the authors report Spatially PhotoActivatable Colour Encoded Cell Address Tags (SPACECAT) to track and isolate live cells by location; this enables spatially informed downstream assays like scRNA-seq and flow cytometry.

A neuron-specific activity-dependent DNA repair mechanism is identified, the impairment of which may lead to neurodevelopmental disorders, neurodegeneration and ageing.

Marking of recently activated T cells may help further our understanding of immunity against Mycobacterium tuberculosis (Mtb). Here the authors use Nur77-GFP reporter mice infected with Mtb and systems data approaches to implicate OX40 as a marker for recently activated, functionally and transcriptome-wise distinct CD4 T cells, and as a potential target for immunotherapy.