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The authors conducted prospective multimodal monitoring of simultaneous brain and heart function to define physiological changes during the human dying process leading to circulatory arrest.

Perturbed B cell responses have been associated with Crohn’s disease. Here, the authors sequence the B cell receptor repertoire in patients with Crohn’s disease and identify shared B cell clones, thus implicating the presence of common Crohn’s disease-associated antigens driving a pathogenic B cell response.

Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibitors in mixed-lineage leukaemia.

The signal transducer and activator of transcription (STAT) family proteins are attractive drug targets but tools to monitor their activation are lacking. Now, STAT biosensors have been developed for real-time tracking in live cells and are applied to screen inhibitors and investigate the effects of cancer-associated mutations.

Watt, Dauber, Szkop and colleagues find that H3K4me3 remodels 5′UTR selection in hypoxia and that this process is independent of HIF-1 transcriptional mechanisms.

Lightbody et al. present SWIFT-seq, a single-cell RNA sequencing approach to profile circulating tumor cells from patients with multiple myeloma and its precursor conditions and leverage it to derive clinical and biological insights into the disease.

The protospacer-adjacent motif specificity of several Cas enzymes is customized using protein language models.

Aging is a risk factor for Parkinson’s disease; however, how DNA damage accumulation, a hallmark of aging, contributes to its pathophysiology remains incompletely understood. Here, the authors identify a blood-based DNA damage signature that is associated with disease progression in patients with Parkinson’s disease.

Genomes of nine brown algal species with different sex determination systems show that U/V sex chromosomes evolved 450–224 Ma and show remarkable conservation of genes within the sex-determining region despite independent expansions of the sex locus in each lineage.

Patient-derived xenografts are important tools for cancer drug development. Here, the authors develop models from 22 non-small cell lung cancer patients. They show genomic differences between models created from different spatial regions of tumours and a bottleneck on model establishment.

Streptococcal S protein activates a peptidoglycan cell wall repair and modification complex to promote resistance of Streptococcus pneumoniae to lysozyme and LL-37, and increase virulence during infection.

The tolerogenic activity of type 1 conventional dendritic cells (cDC1s) is determined by EPOR, which is preferentially expressed in cDC1s and induces antigen-specific FOXP3-expressing regulatory T cells.

How inflammation spreads from the skin to the joints in psoriatic disease is unclear. Here, the authors show that joint-resident fibroblasts can control differentiation of infiltrating skin-derived myeloid precursors that can become inflammatory macrophages.

Birth season has been associated with differences in epigenetic, developmental and health outcomes, but associations to developing metabolome are unclear. Here the authors report a secondary exploratory analysis of The Early Life Interventions for Childhood growth and development in Tanzania (ELICIT) trial showing that in rural Tanzania, an infant’s birth season shapes their metabolism up to 18 months of life, linked to rainfall, food insecurity and breastmilk composition.

A time-resolved high-resolution map of human cardiac remodelling after myocardial infarction, integrating single-cell transcriptomic, chromatin accessibility and spatial transcriptomic data, provides a valuable resource for the field.

This prospective cohort study of patients with cancer incorporated antemortem follow-up visits and rapid autopsy analyses, and reports that spikes—rapidly increasing levels—of circulating tumor cell clusters, observed immediately before and at the time of death, along with tumor masses infiltrating large vessels, were cancer-related events associated with patient mortality.

Combination immunotherapy approaches might be effective in inducing sustained control of HIV by slowing rebound and improving CD8⁺ T cell responses.

Input–output models can predict multiregional brain network dynamics in response to temporally varying patterns of ongoing direct electrical stimulation, with variabilities in prediction accuracy explained by at-rest functional connectivity.

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.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer. Here, the authors develop a NLPHL specific model to identify 34 distinct cell states across 14 cell types that co-occur within 3 lymphocyte predominant ecotypes (LPEs) for 171 cases.

The authors find that 40-Hz flickering light does not suppress Aβ, activate microglia or engage native gamma oscillations. Thus, visual flicker stimulation may not be a viable mechanism for altering AD pathology and modulating deep structures.

Specific pain-sensing nociceptors and chemosensory tuft cells form a circuit to promote type 2 immune responses in the intestine.

Here the authors show that PD-1 controls coinhibitory receptor expression by T_reg cells. The absence of PD-1 expression could induce CD30 expression, thereby enhancing T_reg function and tumor escape, suggesting that CD30 might be a therapeutic target in cases of anti-PD-1 resistance.

Inaccuracies in RNA splicing may play a significant role in aging and disease. Here, the authors present a comprehensive characterization of splicing accuracy across over 14,000 human samples, offering valuable insights into the impact of splicing inaccuracies on aging and neurodegeneration.

Vallentgoed et al. integrate clinical and multiomic data from persons with matched initial and recurrent IDH-mutant astrocytomas to identify progression-associated mechanisms and report a DNA methylation-based signature associated with survival.

From 6,141 Qatari genomes the authors chart structural variants tied to large-scale protein data, biobank traits and everyday health measures. When combined with single nucleotide variants, they find that 1 in 30 participants have a medically actionable genomic finding. The work builds a detailed structural variation reference for Arab ancestries worldwide.

Microflora Danica—an atlas of Danish environmental microbiomes—reveals that although human-disturbed habitats have high alpha diversity, species reoccur, revealing hidden homogeneity.

Neuron-specific DNA methylation and intragenic enhancers target the Rett syndrome protein methyl-CpG-binding protein 2 to regulate genes that delineate closely related neuron types, suggesting breakdown of fine-scale neuronal specification in developmental disorders.

Comparison of paired primary and recurrent glioblastomas at the single-cell transcriptomic level describes molecular and cellular trajectories associated with tumor recurrence, highlighting extensive heterogeneity and microenvironmental co-evolution.

The DNA methylation landscape of triple-negative breast cancer remains to be characterised. Here, the authors analyse tumour methylome profiles and the genomic context of CpG methylation and identify two epigenetic subtypes with distinct transcriptional patterns.

Understanding the mechanisms behind clinical immunity to malaria is crucial for developing effective interventions. Here, the authors demonstrate that clinical immunity to Plasmodium vivax develops rapidly after a single controlled human malaria infection, reducing inflammatory responses and protecting against symptoms, while not significantly affecting parasite load.

HIV’s persistence in diverse tissue reservoirs poses a challenge to cure efforts, necessitating targeted approaches. Here, the authors develop human tissue models of HIV latency and find that inducible reservoirs differ across tissues and CD4⁺ T-cell subsets, highlighting tissue-specific markers and IL-15 as the most effective latency reversal agent.

Spatial multi-omics analysis tools have lagged behind advancements in single-cell technologies. Here, authors introduce TACIT, a scalable tool for automated cell type and state deconvolution from spatial multi-omics datasets, improving accuracy and efficiency over existing methods.

Padawer-Curry et al. show that the hallucinogenic 5-HT2A receptor agonist DOI alters neurovascular coupling in mice, with implications for the interpretation of human fMRI studies of psychedelics.

iGluSnFR4f and iGluSnFR4s are the latest generation of genetically encoded glutamate sensors. They are advantageous for detecting rapid dynamics and large population activity, respectively, as demonstrated in a variety of applications in the mouse brain.

Pertpy serves as a one-stop and performant framework for single-cell perturbation data analysis.

In the adrenal cortex, cholesterol used for steroid production is stored in lipid droplets. The authors demonstrate here the importance of the transcription factor HHEX in maintaining glucocorticoid levels and protecting lipid droplets from androgen-induced lipid depletion.

Alström syndrome (AöS) is a rare genetic disorder characterized by metabolic problems. Here, the authors show that in AöS models, defects in cilia and autophagy lead to ACBP accumulation, which drives obesity. An anti-ACBP antibody reduces weight gain and metabolic dysfunction, highlighting ACBP as a therapeutic target for this ciliopathy.

Immune features and T cell characteristics that correlate with post-intervention control of HIV-1 viraemia inform the development of combination immunotherapies that may enhance the ability to elicit durable HIV remission.

Genes encoding key epigenetic regulators, including Lysine Demethylase 6A (KDM6A), are frequently mutated in bladder cancer. Here, the authors show that loss of KDM6A promotes formation of extrachromosomal circular DNA (eccDNA), genomic instability, and metabolic reprogramming, driving resistance to cisplatin chemotherapy while simultaneously enhancing sensitivity to immune checkpoint inhibitors.

The transcription factor ATF6 causes an enrichment in long-chain fatty acids in the colonic epithelium, which leads to changes in the gut microbiota and contributes to the development of colorectal cancer in humans and mice, thereby linking endoplasmic reticulum stress responses to lipid metabolism and tumorigenesis.

A model trained to generate spatial proteomics profiles and predict the expression of 40 biomarkers directly from histopathology slides is shown to improve survival and treatment response prediction in patients with lung cancer.

Peanut oral immunotherapy (POIT) can treat peanut allergy, but only a subset of patients achieve lasting remission. Here, the authors show that POIT efficacy is associated with the gut microbiome’s functional capacity, specifically bile and amino acid metabolism and protein degradation.

Clonal haematopoiesis of indeterminate potential is driven by somatic mutations in hematopoietic stem/progenitor cells and may progress to myelodysplastic syndromes (MDS). Here authors show that the two conditions share a similar pattern of bone marrow remodeling, characterized by the emergence of inflammatory mesenchymal stromal cells and IFN-responsive T cells, reinforcing their shared etio-pathology.

scooby achieves DNA sequence-based single-cell level modeling of RNA-sequencing coverage and ATAC-sequencing insertion profiles by adapting a deep learning model that predicts bulk RNA-sequencing coverage.

The status of immune cells within human pancreatic lymphatic tissues during the onset and progression of type 1 diabetes (T1D) is underexplored. Here, by flow cytometry and CITEseq, the authors profile pancreatic, mesenteric, and splenic lymphatic tissues from individuals with varying clinical statuses and identify tissue-specific immune responses associated with T1D autoimmunity.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

While the photoreceptor outer segments in the bird outer retina have access to oxygen, the inner retina operates under chronic anoxia, supported by anaerobic glycolysis in the retinal neurons.

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.

The role of lateral inhibition for perception and neural computation remains unsolved. Del Rosario et al. show that distinct types of cortical interneurons in V1 drive lateral inhibition that causes subtraction or division of visual sensitivity.