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The T cell receptor β-chain is expressed in two isoforms, TRBC1 and TRBC2, with clonally expanded mature T cell lymphomas expressing one of them exclusively, while healthy T cells randomly express either TRBC1 or TRBC2. Here authors show structure-based design of a TRBC2-specific antibody, and depletion of malignant T cells carrying TRBC1 or TRBC2 with CAR-T cells against the cognate receptor chain in murine models.

Rashan, Bartlett and colleagues show that mammalian 4-hydroxy fatty acids are primarily catabolized by ACAD10 and ACAD11 (atypical mitochondrial and peroxisomal acyl-CoA dehydrogenases, respectively) that use phosphorylation in their reaction mechanisms.

Recent numerical simulations indicate that well-defined topological defects arise in the dynamics of glasses. Here, the authors report the presence of topological defects in the vibrational eigenspace of an experimental two-dimensional colloidal glass.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

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.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Biodiversity change can impact ecosystem functioning, though this is primarily studied at lower trophic levels. Here, Schuldt et al. find that biodiversity components other than tree species richness are particularly important, and higher trophic level diversity plays a role in multifunctionality.

Tools to promote more environmentally friendly behaviours increasingly include nudges but evidence about their effectiveness is mixed. Using an online experiment, this study tests whether reflective strategies increase the effectiveness of nudges in promoting more sustainable diets.

Studying membrane contact sites at high spatiotemporal resolution is still challenging. Here, authors introduce a series of dynamic chemogenetic reporters to visualize these subcellular regions and study the associated calcium signals.

Along with a back-to-back published paper from Zielisnki and co. in this issue of Nature Immunology, this paper shows that NaCl affects CD8⁺ T cell function by counteracting the exhaustion of these cells in the tumor microenvironment.

The mechanisms underlying many genetic variants associated with human traits are often unknown. Here, the authors identify the developmental stage-, organ-, tissue- and cell type-specific associations between genetic variation and gene expression in cardiac tissues, and describe how these associations affect complex cardiac traits and disease.

Filamin C is a key actin-binding protein involved in cardiomyopathies and musculoskeletal disorders. Here, Wang et al reveal that it interacts with the heat shock protein HSPB7 under biomechanical stress, forming a stable hetero-dimer which is regulated by phosphorylation.

The role of brain interactions in encoding goal-directed learning signals remains unclear. Here, the authors show that information gain is encoded through synergistic and higher-order interactions and is broadcast to the prefrontal reward circuitry.

Clathrin light chains (CLCa and CLCb) are major constituents of clathrin-coated vesicles. Here authors find and structurally characterize the selective interaction between CLCa and the actin motor protein myosin VI which act together to generate the force that leads to invagination and fission at the apical surface.

Low sample numbers often limit the robustness of analyses in biomedical research. Here, the authors introduce a method to generate realistic scRNA-seq data using GANs that learn gene expression dependencies from complex samples, and show that augmenting spare cell populations improves downstream analyses.

Cryo-EM structures of the S. cerevisiae condensin holo complex reveal that ATP binding triggers exchange of the two HEAT-repeat subunits bound to the SMC ATPase head domains, potentially leading to an interconversion of DNA-binding sites in the catalytic core of condensin that might form the basis of its DNA translocation and loop-extrusion activities.

Pesticides affect a diverse range of non-target species and the magnitude of this hazard remains only partially understood. Wan et al. found that insecticides, fungicides and herbicides have negative effects on non-target plants, animals and microorganisms within terrestrial and aquatic systems.

In a case series of five children with treatment-refractory neuroblastoma, it was feasible to manufacture and administer donor-derived GD2-specific CAR T cells and clinical responses were seen in four patients.

Airway epithelial repair, a key process in the recovery from lung injury, requires a metabolic shift from glycolysis to fatty acid oxidation (FAO). Pharmacological FAO promotion enhances epithelial differentiation, suggesting new therapeutic options.

NK cells play an important role in anti-tumour immunity, however, the immune-hostile microenvironment often impairs their function. Here authors show that cancers disable autophagy in NK cells, and by restoring this process, intra-tumour NK cells could be re-invigorated.

Repeat expansion disorders are found in all major global populations, and their frequency is up to three times higher than typically quoted, suggesting underdiagnosis or incomplete penetrance.

Some individuals present with multiple synchronous colorectal tumours, but the genetic understanding of this is unclear. Here, the authors use a sequencing strategy to show that the synchronous tumours are genetically independent and the patients harbour rare germline damaging mutations in genes associated with the immune system.

Leukaemia therapy may benefit from the use of antigens that are less restricted to individual donors. Here the authors engineered T cells with a TCR specific for a CD1c restricted lipid leukaemia antigen and show that they can protect against disease progression in mouse leukaemia xenograft models.

Warming temperatures and interactions between plants are the main drivers of changes in Arctic plant communities in response to climate change, and there is no evidence of overall biotic homogenization.

This study assesses the capacity for sexual and asexual reproduction and the chronological life span across 1,011 genome-sequenced budding yeast isolates and shows the remarkable impact of domestication on budding yeast evolution.

Metabolic reprogramming is associated with cancer development and therapy resistance. Here, the authors show that downregulation of the serine biosynthesis enzyme PHGDH in a fraction of patients is associated with relapse in platinum-treated ovarian cancers and to NAD⁺ and PARP activity upregulation.

Scolaro et al. identify the enzyme cytidine deaminase (CDA) as upregulated in immunotherapy-resistant tumors and find it contributes to the UDP pool, which in turn modulates tumor-associated macrophages to instruct an immune-evasive TME.

Nuclear factors rapidly scan the genome for targets, but the role of nuclear organization in such search is uncharted. Here, by combining single molecule tracking of nuclear proteins with high resolution imaging of the nucleus, the authors investigate the search mechanism used by factors such as p53.

As wood growth in deciduous tree stems halts during winter, it has been assumed that wood growth in coarse roots follows the same pattern. This study on the growth of stem and coarse roots of four European tree species challenges the assumption of winter halt in below-ground wood growth of temperate deciduous trees.

CRISPR–Cas9-based saturation genome editing in a humanized mouse embryonic stem cell line was used for comprehensive functional characterization of single nucleotide variants in a region of BRCA2, and shows good agreement with existing variant classifications and high predictive power.

Replication stress has been associated with transient remodelling of replication intermediates into reversed forks, followed by efficient fork restart. Here the authors systematically analyse the role of RAD51 paralogs in these transactions, providing insights on the mechanistic role of different complexes of these proteins.

Analysis of the encoding of natural images by very large populations of neurons in the visual cortex of awake mice characterizes the high dimensional geometry of the neural responses.

Here, the authors provide guidance on the prevention, diagnosis and management of anticancer therapy nephrotoxicity in adult patients. They also define a research agenda focused on preventing and mitigating anticancer therapy toxicity, maximizing early detection of nephrotoxicity and enabling optimal drug dosing in patients with kidney disease.

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.

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.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

OPA1 regulates the formation of the distinct mitochondrial morphology observed in T helper 17 cells, which influences cytokine expression via LKB1.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Absorption lines of iron in the dayside atmosphere of an ultrahot giant exoplanet disappear after travelling across the nightside, showing that the iron has condensed during its travel.

CD8⁺ T cells that are primed by hepatocytes differentiate into dysfunctional T cells, which can be rescued by treatment with IL-2.

During speech, neurons in the subthalamic nucleus transiently couple with cortex oscillations. Speech sound errors occur when this coupling is delayed. These findings enhance understanding of information processing in human brain during speech.

Tumour-derived prostaglandin E₂, signaling through its receptors EP₂ and EP₄, is shown to restrain the responses of tumour-infiltrating stem-like TCF1⁺CD8⁺ T lymphocytes, and modulation of T cell EP₂ and EP₄ can restore anticancer immunity.