Search

Mechanisms of inefficient vaccine protection against pathobionts such as S. aureus (SA) are still unclear. Here the authors show that prior SA exposure induces non-protective CD4⁺ T cells, which impair IsdB vaccine protection by IL-10 secretion and IL-17A suppression, whereas IL-17A promoting adjuvant CAF01 overcomes this dilemma.

The secondary bile acid 3β-hydroxy-deoxycholic (isodeoxycholic) acid, produced by gut bacteria, promotes the generation of colonic extrathymic regulatory T cells, whose immunosuppressive activities are known to be essential for intestinal health.

End-stage heart failure remains a major clinical challenge with limited effective treatments. Here, the authors present a concept for a soft robotic total artificial heart with a biocompatible inner lining that shows native-like functions

Retroviral integration of DNA into the host genome is a point of no return in the replication cycle but how efficient integration can take place remains unclear. Here the authors demonstrate that consecutive nucleoprotein intermediates are increasingly stable, resulting in a net forward rate.

Magnetic reconnection is a fundamental energy release mechanism in space and laboratory plasmas. Here, the authors show persistent magnetic null-point reconnection in the solar corona at a scale of about 390 km.

The role of TRPV1 in the CNS is not fully understood. Here the authors show that TRPV1 is expressed specifically in somatostatin-positive OLM interneurons of the hippocampus, where it promotes excitatory innervation of these cells.

Mixed Lineage Kinase Domain-Like (MLKL) pseudokinase is phosphorylated by RIPK3 kinase prior to cell death by necroptosis. Here, the authors use monobodies that bind to the MLKL pseudokinase domain as tools, which allowed them to determine the crystal structures of the MLKL pseudokinase domain in two distinct conformations. By combining their structural data with cell signalling assays and MD simulations they provide evidence that endogenous MLKL preassociates with its upstream regulator RIPK3, and that MLKL disengages from RIPK3 following the induction of necroptosis.

Bubbles, long studied for their diverse dynamics across industrial, biological, and medical applications, continue to reveal unexpected behaviors. This study introduces galloping bubbles, a novel self-propulsion mechanism driven by shape oscillations in a vibrated fluid chamber, offering potential for applications in fluid transport, cleaning, and active matter.

Using a composite bioinformatics approach, the DNA:DNA:RNA triplex-forming lncRNAs HIF1α-AS1 was identified in human endothelial cells which recruits an epigenetic silencing complex to limit expression of triplex target genes.

Wolf et al. show that N-Ank proteins combine their curvature-sensing ankyrin repeat array and N-terminal amphipathic helix to shape membranes, and ankycorbin shapes membrane protrusions in developing neurons.

Deep brain stimulation is a neuroelectronic therapy for Parkinson’s disease. Here, the authors present the bidirectional capability of reduced graphene oxide to deliver high-density focal stimulation and to record high-fidelity signals enabling the visualization of local modulation of multiunit biomarkers.

A generalizable framework to prospectively engineer cis-regulatory elements from massively parallel reporter assay models can be used to write fit-for-purpose regulatory code.

An analysis of the localization and intensity of intracortical microstimulation in three participants with cervical spinal cord injury shows that overlapping projected fields from multiple electrodes produce sensations that are more easily localizable.

Small-molecule ligands have been developed that covalently attach to their cognate RNA aptamers in vitro and in living cells. This strategy opens up new avenues for RNA imaging applications (for example, FRAP), for direct fluorescence detection of RNA pull-downs or for covalent RNA-targeted drug design.

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.

Pyramidal cells are classically thought to comprise the excitatory output of the subiculum. Here, the authors show the existence of “ovoid cells”, excitatory subiculum neurons with specialized gene expression, morphology, projections, and function.

The epigenetic mechanisms underlying pancreatic ductal adenocarcinoma (PDAC) are not fully elucidated. Here, the authors reveal a druggable super-enhancer-mediated RNA-binding protein cascade that supports PDAC growth through enhanced mRNA translation.

van Lengerich et al. developed a human TREM2 antibody with a transport vehicle (ATV) that improves brain exposure and biodistribution in mouse models. ATV:TREM2 promotes microglial energetic capacity and metabolism via mitochondrial pathways.

The loading of two different protein therapeutics onto extracellular vesicles can be optimized by genetically engineering the parent cells, as shown for extracellular vesicles displaying decoy receptors for two pro-inflammatory cytokines.

The extraembryonic yolk sac is a major location for developmental hematopoiesis, but it is unclear whether non-bone marrow sources contribute during adulthood. Here they show that embryonically derived endothelial-macrophage progenitor cells located in the aorta are a bipotent source of macrophage and endothelial cells later in life.

Tau aggregates are associated with several neurodegenerative disorders. In this work, I. Saha and colleagues show that valosin-containing protein (VCP) recruited to Tau fibrils disaggregates them. However, this process comes at a cost: it generates seeding-active Tau species as byproduct.

Allura Red AC is a dye used in food products. Here the authors report that chronic, long-term exposure to Allura Red AC increases susceptibility to experimental colitis in mice dependent on the serotonin biosynthetic enzyme TPH1, while intermittent exposure more typical for the human setting did not increase susceptibility to experimental colitis.

Stretchable sensor networks with multiplexing designs can result in misrecognition due to electrical signal interferences from the sensing nodes and internal circuits. Here, Shao et al. show an untethered triboelectric electronic skin with an elastic composite-based shield layer for lower misrecognition rate.

FDA-approved RAF inhibitors poorly inhibit BRAF dimers, which limits their clinical efficacy in tumors expressing BRAFV600E mutant monomers. Here the authors identify FDA-approved Ponatinib as an effective inhibitor of BRAF monomers and dimers and designed PHI1, an inhibitor with a unique mode of action and selectivity for oncogenic BRAF dimers.

Whether antigen processing and presentation differs between pathogen-derived antigens and self-antigens is not clear. Here the authors use a reductionist cell-free approach to study antigen processing, uncovering differences in antigen sensitivity to digestion by cathepsins and resistance to DM.

Ventricular arrhythmia is a leading cause of death in patients with diabetes. Here the authors show that inflammasome activation and ILK-1β production in cardiac macrophages cause arrhythmia in diabetic mice, which can be successfully treated using agonists to IL-1β receptor or NLRP3 inhibitors.

Plectasin, a natural host defence peptide of fungal origin, uses a calcium-sensitive supramolecular killing mechanism to block bacterial cell wall synthesis.

G49, a dual glucagon/glucagon-like peptide-1 receptor agonist, triggers an inter-organ crosstalk between adipose tissue, pancreas and liver, leading to brown fat activation with the final outcomes of increased energy expenditure and body weight loss.

Proteomic, transcriptomic, and genomic analysis has shown osteosarcoma (OS) to be a complex and heterogenous disease but revealed little about its carcinogenesis or potential therapeutic targets. Here, the authors profile the RNA interactome, transcriptome and proteome of cells derived from OS patients, identifying a targetable vulnerability to translation inhibition.

Characterization of RNA-binding proteins (RBPs) in tissues has been hampered by technical constraints. Here, the authors describe ex vivo eRIC, a method for global profiling of RBPs active in mammalian organs, and report comprehensive RBP atlases from mouse brain, kidney and liver.

Selective activation of the hepatoportal nerve plexus via peripheral focused ultrasound stimulation improves glucose homoeostasis and enhances glucose tolerance and utilization in rodent models of diabetes and in swine.

The fast-spinning primary of the Didymos near-earth asteroid binary system was found to have a degraded top shape by the DART (NASA) mission. Here, authors find that these surface features observed in the asteroid are more likely to have been caused by collisional effects than by the YORP effect.

How downstream regulators of Wnt/β-catenin signalling control the fate of intestinal epithelial stem cells (IESCs) is unclear. Here, the authors show that the transcriptional co-factors interacting with the N- and C-terminal domains of β-catenin differentially regulate Wnt target gene activation, in turn differentially affecting the murine IESC proliferation and differentiation.

Aß are extracellular deposits relevant in Alzheimer’s disease (AD). This study shows that Aß plaques are hubs of endothelial disassembly that induce non-productive angiogenesis. This process is aided by the microglia and unchained by reduced presenilin function, a trait of AD, in endothelial cells.

Dietary lipids are linked to the development of inflammatory bowel diseases through unclear mechanisms. Here, the authors report that dietary polyunsaturated fatty acids trigger intestinal inflammation resembling aspects of Crohn’s disease, which is restricted by glutathione peroxidase 4 in the intestinal epithelium.

Dystrophic Epidermolysis Bullosa is an uncurable monogenetic skin disease. Here, Neumayer et al. develop a cGMP-compatible CRISPR- and iPS cell-based approach that produces gene-corrected, autologous skin composite grafts for definitive treatment.

Homologous recombination ensures genome integrity during meiotic recombination. Here the authors reveal that factors SWS1 and SWSAP1 are critical for meiotic homologues recombination, particularly in promoting assembly of RAD51 and DMC1 on early recombination intermediates.

DNA aptamers that specifically bind to the T-cell marker CD8 and can be displaced by a complementary oligonucleotide enable the isolation, at high purity and yield, of CD8⁺ T cells for chimeric antigen receptor T-cell therapies.

The regulatory mechanisms governing peptidoglycan-degrading autolysins remain poorly understood. In this work, Alvarez et al. show that lytic transglycosylase activity is inhibited by LD-crosslinks in Vibrio cholerae and other bacteria, providing resistance against predatory enzymes of both bacterial and viral origin.

Cancer cells can be dependent on mitochondrial respiration to survive. Here, in pancreatic cancer cells, the authors show that monounsaturated fatty acids-linked ether lipids maintain mitochondrial redox homeostasis and modulate sensitivity to inhibition to electron transport chain complex I.

Dormant replication origins begin DNA synthesis under replication stress and are inactive in unperturbed cells. Here, the authors show that phospho-RecQL4 helicase blocks dormant origins’ activation by the Treslin/MTBP complex, facilitating its redistribution to activate dormant origins upon stress.

Bone marrow-derived cells can rapidly enter the systemic circulation, but how this is achieved is unclear. Grüneboom et al. identify tiny capillaries, termed trans-cortical vessels (TCVs), that connect the bone marrow cavity to the systemic vasculature, and show that the majority of blood in long bones passes through TCVs.

Gringhuis and colleagues show that the extent of type I IFN responses induced by fungal stimulation in human DCs modulate the activation of TGF-β and the production of pathogenic or non-pathogenic T_H17 cells.

Cutibacterium acnes phylotypes can be catalogued based on their association with acneic or healthy skin. Here, Hajam et al show that the functional divergence of a hyaluronidase enzyme expressed by the phylotypes is a major determinant of acne severity.

Timblin et al. demonstrate that LPS or hydroxyoestrogen-induced mitochondrial stress triggers mitohormesis in macrophages, restraining inflammatory gene activation by suppressing oxidative metabolism.