Search

Fluid shear stress plays a role in medulloblastoma metastasis through a PIEZO2-actomyosin-GLUT1 signalling cascade.

Here the authors reveal how an incoherent feedforward C/EBPα–Notch circuit times lung cell fate, guiding alveolar development, repair after injury, and shifts between protective and reparative states.

This paper presents TDAC-seq, a targeted chromatin-accessibility-profiling method using cytidine deaminases and long-read sequencing, to resolve the effects of CRISPR edits on single chromatin fibers.

Zhang et al. show that bone marrow fatty acid metabolism fuels expanded leukocyte production after myocardial infarction and, based on mouse, pig and human data, suggest that lipolysis in marrow adipocytes provides fatty acids to hematopoietic stem cells.

Payton et al. develop small-molecule inhibitors of kinesin KIF18A able to selectively kill cancer cells with high chromosomal instability and demonstrate that the inhibitors are therapeutically beneficial in cancer patient-derived in vivo models.

A purpose-built implantable system based on biomimetic epidural electrical stimulation of the spinal cord reduces the severity of hypotensive complications in people with spinal cord injury and improves quality of life.

Commensal Candida albicans enhances the virulence and dissemination of Salmonella enterica subsp. enterica serovar Typhimurium.

This research investigates aperiodic neural activity in depressed individuals versus healthy controls using resting state electroencephalography recordings. Findings reveal significant differences in aperiodic exponent and offset, influenced by lifetime depressive episodes, highlighting the relationship between depression heterogeneity and neural mechanisms.

Perivascular and leptomeningeal macrophages, collectively termed here parenchymal border macrophages, are shown to regulate flow dynamics of cerebrospinal fluid, implicating this cell population as new therapeutic targets in neurological diseases such as Alzheimer’s.

Lipids shed by pathogenic mycobacteria have been shown to inhibit NPC1, a lysosomal membrane protein deficient in most cases of a rate inherited lysosomal storage disorder Niemann-Pick disease type C (NPC). Here, authors utilise lipid extracts from clinical Mycobacterium tuberculosis strains, and non-tubercular mycobacteria to investigate their ability to inhibit the NPC pathway.

An understanding of the molecular mechanisms promoting the generation of immunoregulatory and tumour-promoting monocytes and macrophages is key to breaking the cycle of tumour myelopoiesis and developing more effective myeloid-targeting therapies.

By comparing the genome-wide profile of H4K16ac in AD with younger and elder controls, the authors propose a mechanism for how age is a risk factor for AD: a histone modification, whose accumulation is associated with aging, is dysregulated in AD.

Nelson et al. report that the APOE-R136S mutation protects against APOE4-promoted Alzheimer’s disease pathologies, including phosphorylated Tau accumulation, neuroinflammation and neurodegeneration, in mouse and human neuron models.

Understanding the tumor microenviroment is important before it can be exploited therapeutically. Here, the authors use single cell sequencing to study stromal cells in mouse tumors and identify a subset of interferon-licensed cancer associated fibroblasts that appear after anti-TGFβ treatment.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Ellis and colleagues show that combination of EZH2 inhibition and anti-PD-1 can increase antitumor immune responses in typically ‘immune cold’ prostate cancer, by increasing EZH2-regulated dsRNA–STING–ISG response signaling.

A pangenome of the Cannabis genus including 193 genomes demonstrates high variability in most of the genome but low diversity in cannabinoid synthesis genes and provides a resource for future genetic studies and crop optimization.

The authors show that chronic neonatal hypoxia reduces GABA_A receptor–mediated signaling to oligodendrocyte precursor cells in the cerebellar white matter and enhances their proliferation, delays oligodendrocyte maturation and disrupts myelination. Following hypoxia, treatment with a GABA uptake blocker restores myelination.

Biological sex affects all aspects of animal physiology. Using the model C. elegans, the authors show that metabolomes are highly sex-specific and include a vast space of yet unidentified metabolites that may control development and lifespan.

Fatty acid desaturation is central to metazoan lipid metabolism. Here, using C. elegans as a model, the authors show that both endogenous and microbiota-dependent small molecule signals converge to promote lipid desaturation via the nuclear receptor NHR-49/PPARα.

Machine learning classifiers generated using chronic neural measurements in individuals with obsessive-compulsive disorder accurately predicted clinical status and deep brain stimulation response.

CD40 is typically understood as a costimulatory molecule. Here, the authors show CD4⁺ T cell-induced CD40 signaling in conventional type 1 dendritic cells results in complicated gene expression that can enhance CD8⁺ T cell priming by various underappreciated and independent mechanisms.

Using differences among strains as a model for inter-individual variation, this paper identifies a conserved metabolicadaptation in C. elegans that compensates for genetic variation.

Pancreatic ductal adenocarcinoma is characterized by a highly immunosuppressive tumour microenvironment. Here, the authors show that specialized subsets of tumour-infiltrating dendritic cells induce distinct CD4⁺ T cell programs and specifically identify a CD103^–CD11b⁺ subset which induces tumor-promoting FoxP3^– Type-1 regulatory T cells.

Bacteria reprogram tick metabolism impacting vector fitness and susceptibility to bacterial infection.

SARS-CoV-2 infection is milder in children, but direct comparison with adults is rare. Here the authors show that immune responses are higher in children, retained for 12 months or longer and can neutralize Alpha, Beta and Delta variants.

The yields of edited primary human lymphocytes can be increased substantially, with respect to those obtained via electroporation, by delivering a CRISPR ribonucleoprotein alongside an amphiphilic peptide identified via screening.

Mohanakrishnan et al. identify a distinct subset of post-arterial capillaries, termed type R. They show that type R capillaries contribute to trabecular bone formation in the diaphysis and respond to anti-osteoporosis treatments.

Positron emission tomography measurements of nutrient uptake in cells of the tumour microenvironment reveal cell-intrinsic partitioning in which glucose uptake is higher in myeloid cells, whereas glutamine is preferentially acquired by cancer cells.

Cleavage Under Targets & Tagmentation is a rapidly expanding technique, but thorough evaluation and benchmarking against established ChIP-seq datasets are required. This study shows that CUT&Tag recovers ~54% of ENCODE peaks for H3K27ac/H3K27me3 in K562 cells, with CUT&Tag peaks mapping to key cell type-specific regulatory regions.

Skeletal muscle regeneration declines during aging but the underlying processes are incompletely understood. Here the authors generated single-cell and spatial transcriptomics data from uninjured and injured muscles across mouse lifespan and observed age-specific immune cell dynamics and an elevation of senescent-like muscle stem cells in aged muscles.

Structural and single-molecule analyses show the CTPase, KorB, is a sliding DNA clamp that interacts with a clamp-locking protein KorA to inhibit gene expression over distances of more than 1 kb in the multi-drug resistance RK2 plasmid.

Computationally designed genetically encoded proteins can be used to target surface proteins, thereby triggering endocytosis and subsequent intracellular degradation, activating signalling or increasing cellular uptake in specific tissues.

Here, the authors show that PRMT1 targeting inhibits clear cell renal cell carcinoma cells through perturbation of RNA metabolism and down-regulation of DNA repair pathways, resulting in the accumulation of unresolved R-loops and DNA damage.

Mercey et al. demonstrate that without deuterosomes, multiciliated cells still develop the proper number of centrioles with normal step-wise kinetics, independent of the growing platform.

Studies on the essentiality of Ku in human cells reveal that Ku interacts with diverse double-stranded RNA molecules, including antisense Alu, and enables tolerance of Alu sequence expansion in primates.

Mouse B cells can be reprogrammed via Cas12a to express human antibodies that when affinity-matured in recipient mice generate broader and more potent antibody variants.

Untargeted comparative metabolomics revealed serotonin biosynthesis and metabolism pathways in nonneuronal tissues that contribute to established serotonin-dependent phenotypes in C. elegans.

Using single-molecule techniques, the authors find that the methyl-CpG-binding protein MeCP2, whose mutations cause Rett syndrome, exhibits distinctive behaviors when bound to nucleosomes versus free DNA, thus directing its multifaceted functions on chromatin.

Comprehensive genomic profiling of human H3K27M mutant diffuse midline gliomas, combining single-cell RNA sequencing and ATAC sequencing with bulk ChIP sequencing and other data, proposes distinct oligodendrocyte populations as potential cells of origin.

Anti-TNF CAR macrophages show anti-inflammatory efficacy in both acute and chronic inflammatory disease mouse models.

Experimental removal of corallivorous snails from corals in the Caribbean Sea shows that this local management action can improve coral resilience to severe warming through reducing bleaching severity and post-bleaching tissue mortality.

This manuscript describes the structure of an endocannabinoid analog-bound CB1 complex and reveals the structural determinants of ligand efficacy. The activation mechanism, unique to CB1, that is exploited by allosteric modulators is also outlined.

A synthetic hydrogel has been developed to mimic the physicochemical properties of pancreatic tissue and is shown to support the culture of pancreatic cancer organoids, revealing the role of laminin–integrin interactions in their growth.

Familial dysautonomia is a rare genetic disease caused in part by neurodegeneration. Here, the authors show that the gut-metabolism axis is altered in both patients and transgenic mice and that disease pathology is ameliorated by controlling microbiome divergence.

Single-nucleus RNA-seq was used to profile 11 retinas with varying stages of age-related macular degeneration and 6 control retinas. The authors identified shared glial states across neurodegeneration, indicating that the retina provides a human system for investigating therapeutic approaches in neurodegeneration.

Mechanical forces, along with gene regulatory networks and cell-cell signalling, play an important role in the complex organization of tissues. Here the authors describe devices that actively apply mechanical force to developing neural tube, demonstrating that mechanical forces increase growth and enhance patterning.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.