Search

This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

A subset of inflammatory group 3 innate lymphoid cells, here termed iILC3s, infiltrate the central nervous system and promote neuroinflammation and disease progression in a mouse model of multiple sclerosis.

Evolutionarily conserved gene modules mediate neurodegenerative dementia in a variety of mouse models and in postmortem brain tissue from patients.

Analyses of expression profiles from whole blood of 31,684 individuals identify cis-expression quantitative trait loci (eQTL) effects for 88% of genes and trans-eQTL effects for 37% of trait-associated variants.

Integrin α-β heterodimers recognize ligands with RGD peptide motifs, but how they differentiate between the numerous RGD-containing proteins is unknown. Here, Springer and colleagues elucidate the structural basis for ligand binding specificity of the integrin β subunit.

Lidar survey of the Maya lowlands uncovers the monumental site of Aguada Fénix, which dates to around 1000–800 bc and points to the role of communal construction in the development of Maya civilization.

O’Sullivan and colleagues show that liver-resident type 1 ILCs have enhanced protective effector responses to secondary challenge with mouse cytomegalovirus, dependent on the viral glycoprotein m12.

Single-nucleus and single-cell RNA sequencing plus spatial profiling with four methods of core biopsies from 60 patients with metastatic breast cancer reveal patient-specific gene expression programs of breast cancer metastases that are maintained across time, site of metastasis and spatial profiling method, with spatial phenotypes correlating with microenvironmental features.

Peter Balint-Kurti, Qin Yang and colleagues report that ZmCCoAOMT2, which encodes a caffeoyl-CoA O-methyltransferase, is a gene within the quantitative trait locus qMdr_9.02, which confers resistance to southern leaf blight and gray leaf spot. Their findings suggest that resistance might be caused by differences in levels of lignin and other metabolites in the phenylpropanoid pathway.

Microbes can establish mutualistic interactions with plants and insects. Here, Kim et al. show that Streptomyces bacteria can protect strawberry plants and honeybees from pathogens, can move into the plant vascular tissue from soil and from flowers, and are transferred among flowers by the pollinators.

Thomas and colleagues examine preinfection baseline parameters of cellular and serologic immunity. Their findings collectively show that peripheral cell composition provides better correlates of immune protection from symptomatic influenza infection than vaccination, demographics or serology alone.

As proof of principle, an analysis using a suite of human-aligned immunocompetent mouse models of hepatocellular carcinoma identifies a promising therapeutic candidate, cladribine, which acts in a highly effective subtype-specific manner in combination with standard-of-care therapy.

The role of ecosystem structure in microbial activity related to greenhouse gas production is poorly understood. Here, Taş and colleagues show that microbial communities and ecosystem function vary across fine-scale topography in a polygonal tundra.

Diagnosing acute infections based on transcriptional host response shows promise, but generalizability is wanting. Here, the authors use a co-normalization framework to train a classifier to diagnose acute infections and apply it to independent data on a targeted diagnostic platform.

The OX40-OX40L axis is a crucial component of the costimulatory requirement of CD4 T cell responses. Here, the authors show context and cell type specific expression of OX40L for driving Th1 cell generation during acute and chronic models of infection.

One way to improve the performance of supercapacitors is to use hybrid carbon nanomaterials. Here the authors show a bioinspired electrode design with graphene petals and carbon nanotube arrays serving as leaves and branchlets, respectively. The structure affords excellent electrochemical characteristics.

Oncolytic measles virus (MV) vaccine strains have shown preclinical antitumor activity against glioblastoma (GBM). Here the authors report the results of a phase 1 trial of intratumoral administration of a MV strain engineered to express the carcinoembryonic antigen in patients with recurrent GBM including assessment of viral replication and proinflammatory remodeling of the treated tumors.

MLLT3 is identified as a crucial regulator of the self-renewal of human haematopoietic stem cells, and helps to maintain an active chromatin state in haematopoietic stem-cell regulatory genes during culture.

A new hominin species, Australopithecus deyiremeda, which lived between 3.5 and 3.3 million years ago, at around the same time as species such as Au. afarensis (‘Lucy’), is discovered in Ethiopia; its morphology suggests that some dental features traditionally associated with later genera such as Paranthropus and Homo emerged earlier than previously thought.

A network-based method and computational tool, PIUMet, reveals disease-associated molecular pathways from untargeted metabolomics data without requiring mass-spectral feature identification.

Regulatory small RNA (sRNA) interact with mRNAs to regulate their stability, transcription, and translation via diverse mechanisms. Here, Mediati et al. apply RNase III-CLASH to multidrug-resistant Staphylococcus aureus to characterise the network of RNA–RNA interactions associated with RNase III and identify a regulatory mRNA 3′UTR, named vigR-3′UTR, involved in the regulation of genes relevant for vancomycin sensitivity.

A substudy nested within a double-blind cluster-randomized controlled trial in Bangladesh shows that drinking chlorinated water had relatively minor impacts on children’s gut microbiome development in this setting.

Keng et al. characterize the mouse hepatocellular carcinoma genome by using tissue-specific recombinase expression to restrict mobilization of the Sleeping Beauty transposon to the liver. High throughput sequencing of >100,000 insertions sites in mouse tumor nodules identifies potential therapeutic targets.

A high-throughput virtual screening approach is used to select molecules with efficient, thermally activated delayed fluorescence. The good performance of several selected emitters in organic LED applications has also been confirmed experimentally.

Fibroblastic reticular cells support lymph-node function and adaptive immunity. McGeachy and colleagues show that the cytokine IL-17 is needed to trigger metabolic changes required for the proliferation and survival of these cells in reactive lymph nodes.

Mark Walker and colleagues report the whole-genome sequencing of 132 group A Streptococcus (GAS) isolates of a sequence type that has been associated with scarlet fever. The isolates were obtained from 58 clinical cases of scarlet fever and 83 cases without scarlet fever during the course of a recent epidemic in Hong Kong.

There is increasing evidence that epigenetic mechanisms contribute to therapeutic resistance in cancer. Here the authors study AML patient samples and a mouse model of non-genetic resistance and find that transcriptional plasticity drives stable epigenetic resistance, and identify regulators of enhancer function as important modulators of resistance.

In mammals, hypoxia causes dilation of small arteries for increased metabolic demand. Keller et al used novel transgenic mice to show alpha hemoglobin in endothelium, once thought only in red blood cells, can regulate hypoxic-mediated dilation.

We evaluated the use of chimeric antigen receptor-modified T cells targeting GD2 (GD2-CART) for H3K27M⁺ diffuse midline glioma (DMG), finding that intravenous administration of GD2-CART, followed by intracranial infusions, induced tumour regressions and neurological improvements in patients with H3K27M-mutant pontine or spinal DMG.

Splicing dysfunction has been observed in Alzheimer’s disease but it remains unclear whether splicing defects have a causal role. Here the authors generate a mouse model with perturbed U1 snRNP activity, recapitulating RNA splicing defects, neuron hyperexcitability, neurodegeneration and synergy with the amyloid cascade when crossed with 5xFAD mice.

Synthetic promoters can be superior to native ones but the design is challenging without knowledge of gene regulation. Here the authors develop a pipeline that allows for screening a synthetic promoter library to identify high performance promoters in potentially any given cell state of interest.

SPI1 fusion genes in T-cell acute lymphoblastic leukemia (T-ALL) are commonly found with co-occurring NRAS mutations. Here, the authors show that the combination of these oncogenes is necessary to drive T-ALL in a murine model and that the oncogenic activity of the SPI1 fusion is dependent on β-catenin.

Fenebrutinib, an oral Bruton’s tyrosine kinase inhibitor, reduces disease activity in patients with chronic spontaneous urticaria refractory to antihistamines, suggesting that this treatment type could be an alternative to standard of care anti-IgE therapy.

Genome-wide data from 400 individuals indicate that the initial spread of the Beaker archaeological complex between Iberia and central Europe was propelled by cultural diffusion, but that its spread into Britain involved a large-scale migration that permanently replaced about ninety per cent of the ancestry in the previously resident population.

It is known that there are sex differences in the incidence and prognosis of certain cancers, including melanoma. In this study, the authors utilize a melanoma model to reveal that castrated mice have a higher metastatic burden associated with androgen dependent impaired neutrophil function.

Exhausted T cells arise when chronic activation triggers functional defects. Here the authors show that chronic antigenic stimulation in both tumour and infection models induces the expression of EGR2, which drives and stabilises exhausted cell epigenetic and transcriptional identity.

Oxygen in shallow shelf waters rose linearly with atmospheric oxygen in the Neoproterozoic era, potentially driving the first radiation of marine animals, but widespread ocean oxygenation came later, according to reconstructions of oxygen levels and marine productivity.

Field surveys suggest peatlands in the central Congo Basin are globally significant carbon stocks, storing approximately 28% of the world’s tropical peat carbon.

The effect of diet-induced obesity on intestinal B cell populations is not well understood despite emerging evidence of a critical role for the intestinal immune system in contributing to insulin resistance. Here, the authors show important functions of IgA in regulating metabolic disease and for intestinal immunity in modulating systemic glucose metabolism.

The GEOCARBSULF model provides the most detailed reconstructions of Phanerozoic O₂, but its predictions are not supported by geochemical data. Here, a GEOCARBSULF model rebuilt from first principles, with the addition of an amended sulphur cycle and the latest isotope records, supports a Paleozoic Oxygenation Event.

An exploratory analysis of IL-15 superagonist treatment in people living with HIV and taking antiretroviral therapy shows increased T cell activation and viral transcription alongside a sustained reduction in inducible HIV provirus from blood cells.

T cells are involved in the bone loss induced by parathyroid hormone (PTH), but their origin is unknown. Here, the authors show that the intestinal microbiota is required for PTH to induce bone loss and describes mechanisms for microbiota-mediated gut–bone crosstalk in mouse models of hyperparathyroidism.

3-finger toxins are unique to the venoms of caenophidian snakes. This study traces the evolution of these toxins in snakes, highlighting a key shift from membrane-bound to secretory proteins. This transformation, involving the loss of a membrane-anchoring domain and changes in gene expression, paved the way for their venomous function.

Cyclin-dependent kinase (CDK) inhibitors are widely used both in the clinic and for basic research aimed at dissecting the specific cellular functions of specific CDKs. Here, the authors report the development of a panel of fluorescent reporter probes and provide a comprehensive profile of the inhibitory activity of several CDK inhibitors towards all 21 CDKs in living cells.

The design of synthetic biology circuits remains challenging due to poorly understood design rules. Here the authors introduce STORM and NuSpeak, two deep-learning architectures to characterize and optimize toehold switches.