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Climate change will impact the global economy. Here, the authors propose a framework to evaluate its effect on economies across multiple regional and temporal scales, and project decreased financial stability in a northern temperate economy.

The molecular factors influencing patient response to endocrine therapy are poorly understood. Here Stone et al.characterize the DNA methylome of endocrine response and show that methylation of oestrogen receptor-associated enhancers underpins endocrine sensitivity in human breast cancer.

Single-cell and spatial transcriptomics analysis of stricturing Crohn’s disease highlights cellular heterogeneity in fibrotic tissue and identifies neighborhoods of fibroblasts and immune cells contributing to this severe disease complication.

Injectable electrodes could improve technologies for deep-brain stimulation. Plus, how dinosaurs got big (and small) and your views on climate activism at scientific events.

A central question in cancer research is how specific driver mutations are acquired and maintained during cancer development. Here Temko et al. use public sequencing data to infer the effect of mutation and selection on a set of driver mutations and suggest that selection frequently dominates.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

COVID-19-related travel restrictions were imposed in China around the same time as major annual holiday migrations, with unknown combined impacts on mobility patterns. Here, the authors show that restructuring of the travel network in response to restrictions was temporary, whilst holiday-related travel increased pressure on healthcare services with lower capacity.

Pathologically activated neutrophils, termed myeloid-derived suppressor cells, in the tumour microenvironment spontaneously undergo ferroptosis, which negatively regulates anti-tumour immunity through the release of oxygenated lipids, therefore limiting the activity of human and mouse T cells.

Methods that analyze intra-tumor genetic heterogeneity often do not preserve the spatial context of tumor subclones. Here, the authors present BaseScope, a mutation-specific RNA in situ hybridization assay and spatially map colorectal cancer and adenoma KRAS, BRAF and PIK3CA driver gene mutant subclones.

Quantification of genomic responses to environmental stimuli by current genome-scale assays is limited to indirect measurements or requires knowledge of the transcription factors involved. Here, the authors use genome-wide high-throughput reporter assays to agnostically map enhancer activity in response to glucocorticoid treatment across the human genome.

Modulation of the cholinergic pathway and spleen function can reduce inflammation with invasive implants. Here, the authors show that non-invasive ultrasound stimulation of the spleen reduces disease severity in a mouse model of inflammatory arthritis, partly via altering B and T cell function.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

Axons have always been assumed to be cylindrical. Using in silico modeling and cryopreservation of tissues, Griswold et al. demonstrate that unmyelinated axons of the mammalian central nervous system exhibit pearls-on-a-string morphology through their entire length.

Functional roles of natural acetylcholine (ACh) dynamics are not fully understood. This study reveals dynamic changes in ACh release across the mouse striatum during learning and extinction, identifying how and where release dynamics shape brain plasticity to gate learning and promote extinction of cue-reward associations.

FDNC4 is a poorly characterized homologue of FNDC5/irisin, a myokine induced by exercise. Here the authors show that FDNC4 increases macrophage survival in growth factor deprivation, inhibits phagocytosis and transcriptional responses to M1 and M2 polarizing stimuli, and protects mice from DSS-induced colitis.

The accumulation of senescent cells drives age-related diseases. In this study, the authors show that senolytic CAR T cells can rejuvenate metabolic function and fitness in old mice and that a single dose is sufficient to lead to long-term preventive effects.

Borrelia burgdorferi, the causative agent of Lyme disease, is transmitted by the tick Ixodes scapularis. Here, the authors show that a tick secreted protein (PIXR) modulates the tick gut microbiota and facilitates B. burgdorferi colonization.

Drugs targeting cardiovascular disease (CVD) can have negative consequences for liver function. Here, the authors combine genome wide analyses on 69,479 individuals to identify loss-of-function variants with beneficial effects on CVD-related traits without negative impacts on liver function.

Much of what is known about nervous system development is based on chemical signaling. In this study, Koser et al. demonstrate that developing neurons also respond to mechanical signals and that local tissue stiffness is a regulator of neuronal growth in vivo.

Polar microalgae have high zinc demand. Here, the authors use quantitative proteomics and transcriptomics of polar and non-polar model algae combined with cellular physiology to show that zinc plays an important role in supporting photosynthetic growth in eukaryotic polar phytoplankton.

The United Arab Emirates will launch a Mars mission. Plus: a promising new HIV vaccine and a placental microbiome plot twist.

Injection of donor apoptotic cells induces graft tolerance in mice. Here the authors combine this approach with short immunosuppressive therapy to achieve long-term tolerance to allogeneic islets and restoration of normoglycemia in diabetic nonhuman primates, and delineate cellular and molecular correlates of tolerance induction.

Immune dN/dS is the ratio of nonsynonymous to synonymous mutations in the MHC-bound immunopeptidome. Application of immune dN/dS to cancer datasets shows that it distinguishes immune evasion and escape and predicts response to immunotherapies.

Peng et al. find that immunodominant cytotoxic T lymphocytes (CTLs) specific for NP_105–113-B*07:02 are associated with reduced COVID-19 severity. Mechanistically, NP_105–113-B*07:02-specific CTLs show potent antiviral functionality and may represent rational T cell vaccine targets.

Inflammatory skin diseases are frequently associated with dysregulation of cutaneous immunity. Here the authors perform human challenge with house dust mite allergen in patients with atopic dermatitis and explore the molecular network determining tolerance versus inflammation and identify a role for metallothioneins in the modulation of allergen induced inflammation.

Targeting extracellular matrix (ECM) remodelling is a feasible avenue to prevent cancer aggressiveness and metastasis. In this study, Kay et al. show that metabolic flux in cancer-associated fibroblasts is coupled to enhanced proline synthesis by PYCR1 to support elevated production of collagen-rich ECM, thus contributing to cancer spreading.

Interleukin (IL)-1α is a critical inflammatory cytokine and yet its intracellular role is poorly understood. Here, the authors use proximity labelling of pro-IL-1α and assess its interactome, and dissect the presence and impact on a conserved nuclear interaction and its impact on the immunobiology and evolutionary convergence/divergence between species.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

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.

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.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

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.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

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.

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

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.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Despite growing interest in environmental metabolomics, we lack conceptual frameworks for considering how metabolites vary across space and time in ecological systems. Here, the authors apply (species) community assembly concepts to metabolomics data, offering a way forward in understanding the assembly of metabolite assemblages.

Some patients with HIV-associated tuberculosis develop an immune reconstitution inflammatory syndrome (TB-IRIS) in response to antiretroviral therapy. Here the authors identify genes differentially expressed in patients likely to progress to TB-IRIS and find activation of Toll-like receptor and inflammasome pathways.

Based on the identification of CD4⁺ T cell clones specific for distinct epitopes in the SARS-CoV-2 proteins, Long and colleagues characterize how mutations in these epitopes lead to loss of recognition by the CD4⁺ T cells elicited by natural infection or vaccination.

Unmet need exists for a vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV). Here the authors report the establishment and evaluation, in mice and primates, of a series of MERS-CoV immunogens and show that they can serve as promising leads for vaccine development.