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Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

Here the authors show that the m¹G9 post-transcriptional methylation differentially regulates the stability of the native and the MELAS variants of human mt-Leu(UAA) tRNA, contributing to mitochondrial pathology.

The GLASS Consortium studies the evolutionary trajectories of 222 patients with a diffuse glioma to aid in our understanding of tumour progression and treatment failure

Genome-wide association analyses identify new risk loci for heart failure and its subtypes, extending understanding of the underlying biological pathways and disease mechanisms.

Independent of antigen presentation, migratory CCR7⁺ dendritic cells orchestrate the influx, proliferation and cytotoxic action of natural killer cells to control cancer cell growth in the leptomeninges.

A method, RARE-seq, for sensitive detection of cell-free RNAs in blood is demonstrated to have diverse clinical applications including diagnosing and characterizing human cancers, and tracking response to RNA therapeutics.

Here, the authors characterize the epigenetic status of hybrid ecDNA in HPVOPC, identifying HPV oncogenes E6/E7 in hybrid ecDNA are flanked by somatic DNA enhancers with strong cis-interaction. It can be targeted with ecDNA disrupting therapeutics.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

Semistructured interviews and focus groups with experts in biodiversity finance in Europe identify opportunities and barriers to upscaling private investment in biodiversity, and emphasize that public policy is the key to enabling progression.

This study describes structures of the transcription factor brachyury revealing the mechanism of DNA recognition. They identify fragments using X-ray fragment screening and optimize these into potent ligands with potential as cancer therapeutics.

Robbins and colleagues show that cigarette smoke-induced endothelial dysfunction enables atherosclerotic plaque macrophages to drive abdominal aortic aneurysm formation in a mouse model of atherosclerosis.

A genome-wide association study identifies 17 genetic loci that are associated with the risk of myeloproliferative neoplasms (MPNs), and shows that the modulation of haematopoietic stem cell function drives MPN risk.

Saloner et al. used large-scale cerebrospinal fluid proteomics to uncover molecular signatures in frontotemporal dementia, revealing RNA splicing and synaptic protein candidate markers for genetic and sporadic disease progression.

In a randomized phase 3 trial, the combination of the BET inhibitor pelabresib with the JAK inhibitor ruxolitinib resulted in a significantly higher spleen volume reduction from baseline versus placebo with ruxolitinib in patients with JAK inhibitor-naive myelofibrosis.

The neural mechanisms underlying the antidepressant effects of nitrous oxide remain poorly understood. This study reveals that specific activation of layer V pyramidal neurons in the cingulate cortex rescues stress-associated hypoactivity states and is driven by inhibition of calcium-sensitive potassium channels rather than NMDA-receptor antagonism.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

Mucosal melanoma is a rare melanoma subtype that is poorly characterised. Here, the authors sequenced human, canine, and equine melanoma samples and performed a cross-species analysis, which revealed candidate driver genes, recurrent copy number alterations in regions syntenic between species, extensive intra-tumour heterogeneity and potential germline predisposing alleles

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Whole-genome sequencing of chronic lymphocytic leukemia from 485 patients identifies putative coding and noncoding drivers of disease. Genomically defined subgroups show distinct clinical and biological characteristics.

Tropical forest landscapes are increasingly being modified by human activities. Here the authors apply a causal inference approach to Neotropical forest data to disentangle the role of landscape-level and local drivers and reveal replacement of ‘loser’ by ‘winner’ tree species with distinct functional profiles.

Derailed differentiation of human-specific progenitors of the developing cerebellar rhombic lip is the cause of group 4 medulloblastoma, the most common childhood brain tumour. 

An integrated transcriptome, genome, methylome and proteome analysis of over 200 lung adenocarcinomas reveals high rates of somatic mutations, 18 statistically significantly mutated genes including RIT1 and MGA, splicing changes, and alterations in MAPK and PI(3)K pathway activity.

Next generation sequencing allows the identification of oncogenic driver genes in pancreatic cancer. Here, in an effort to identify additional causal genes, the authors develop a high throughput in vivoscreen and identify genes that whilst infrequently mutated in pancreatic cancer contribute to tumour formation.

Global trends in biodiversity are subject to regionally heterogeneous diversification processes. Here, the authors examine Late Cretaceous ammonoids, modelling the impact of sampling bias and potential biotic and abiotic drivers on our understanding of their biodiversity trends towards the Cretaceous-Paleogene boundary.

Wastewater treatment plants are important reservoirs of antibiotic resistance genes (ARGs). Here, the authors analyze ARGs in a global collection of samples from wastewater treatment plants across six continents, providing insights into biotic and abiotic mechanisms that appear to control ARG diversity and distribution.

Following spinal cord injury, gamified physical therapy that incorporates closed-loop vagus nerve stimulation can aid restoration of arm and hand function.

By bringing together whole exome and genome sequencing data from five cohorts, the authors assess the contribution of rare germline variants to prostate cancer risk and severity, further validating previously reported genes, and implicating a role for genes not previously reported.

Peer review information

Nature Communications thanks the anonymous reviewer(s) for their contribution to the peer review of this work. A peer review file is available.

A study identifies the AT1 cell as a cell of origin for lung adenocarcinoma, and demonstrates that expression of oncogenic KRAS in differentiated AT1 cells reprograms them back into AT2 stem cells that generate indolent lepidic tumours.

Genc and colleagues show developmental increases in neurite density and reductions in soma radius with in vivo MRI data. Combined with ex vivo gene expression data, this supports the model of protracted intra-cortical myelination throughout the adolescent period.

Warthi et al. generated an alpha 8 integrin-cre driver that enables gene targeting preferentially in vascular smooth muscle cells (SMCs) and showed in a proof-of-principle study, that using the Itga8-CreER^T2 knock-in mouse for selective ablation of the Srf gene caused vascular defects but not a lethal visceral myopathy observed in an SMC-specific Myh11-CreER^T2-driven Srf loss.

Nageotte nodules in the dorsal root ganglia were first described 100 years ago, but little is known about them. Here, the authors link Nageotte nodules to neurodegeneration in diabetic neuropathy in humans and describe their molecular composition.

How the brain maintains a stable world model while swiftly adapting to environmental changes remains unclear. Here, the authors propose that the cerebellum drives cortical dynamics, enabling rapid task acquisition, switching, and consolidation.

Authors perform an analysis of the patient data and risk factors to evaluate unfavorable outcomes and adverse events in adults with pulmonary tuberculosis treated with a 4-month rifapentine based regimen. Low rifapentine exposure was the most clinically significant risk factor for treatment failure and tuberculosis relapse.

Virus infection is known to be a trigger for exacerbations in chronic obstructive respiratory disease (COPD). Here the authors investigate how formation of neutrophil extracellular traps (NETs) contribute to the exacerbation of COPD through release of dsDNA using animal models and samples from human participants.

Nociceptin is an opioid peptide regulating important brain functions, including motivation and 2stress responses. Here, the authors develop and validate a genetically encoded sensor as a tool for high-resolution detection of endogenous nociceptin in living animals.

The decision to form a fruiting body have been studied extensively, however, the mechanical events that trigger the creation of multiple cell layers is poorly understood. Here the authors find M. xanthus cells adjust their reversal frequency to control mechanical stresses that triggers layer formation in the colonies.

Alterations in oncogenes and tumor suppressor genes are a hallmark of cancer, yet how they interact remains poorly understood. Here, the authors describe a quantitative functional cancer genomics platform in genetically engineered mice, and uncover complex interactions between tumor suppressors and KRAS, BRAF, and EGFR oncogenes across more than 100 different lung tumor genotypes.

Here the authors describe a method for remote magnetothermal stimulation of neurons that achieves subsecond behavioural responses in Drosophila fruit flies by combining magnetic nanoparticles with TRPA1-A, a rate-sensitive thermoreceptor. Tuning the properties of magnetic nanoparticles to respond to different magnetic field strengths and frequencies enables multichannel thermal magnetogenetic stimulation.

Combination of drugs within cancer treatment is a popular way to overcome resistance and increase efficacy. Here, the authors analyse over 5000 targeted agent combinations in non-small cell lung cancer to identify potentially effective drug strategies.

This Pediatric Cell Atlas study analyzes temporal cortex single-nucleus RNA sequencing datasets from eight diverse donors from 4 to 50 years of age, describing gene expression dynamics over the course of brain maturation.

A rare case of asymptomatic dominantly inherited Alzheimer’s reveals confined tau pathology and unique proteomic features, highlighting potential resilience mechanisms decades beyond expected onset.

The role of the immune system in tissue regeneration remains poorly understood. Here, in bone marrow transplantation and organoid culture models, T-cell-derived Interferon-γ is shown to promote STAT1-dependent intestinal stem cell c-MYC expression and epithelial regeneration.

Transfer of faecal microbiota from hepatocellular carcinoma patients to mice promotes carcinogenesis via live gut pathogenic Klebsiella pneumoniae translocating to the liver.

Using mouse lines in which subsets of neurons are genetically labelled, the authors provide generalized anatomical rules for connections within and between the cortex and thalamus.

Mosquito salivary glands and malaria parasites exhibit daily rhythms, which impact blood feeding and sporozoite gene expression.

The DREPAGLOBE lentiviral-based gene therapy for sickle cell disease is safe. However, its efficacy depends on the number of infused hematopoietic stem cells (HSCs) and intrinsic, engraftment impairing inflammatory alterations in HSCs.