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The processes influencing the Van Allen belt – a layer of charged particles inside the Earth’s magnetosphere – are poorly understood. Using CRRES and NASA’s Van Allen Probes data, Mann et al.suggest that ultra-low frequency waves may play a larger role in accelerating particles than previously thought.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Analysing camera-trap data of 163 mammal species before and after the onset of COVID-19 lockdowns, the authors show that responses to human activity are dependent on the degree to which the landscape is modified by humans, with carnivores being especially sensitive.

Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

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.

Experimental knowledge of magnetoelectric (ME) activity from magnetic multipole moments has so far been limited. Here, Kimura et al. show that a magnetic square cupola cluster such as Cu₄O₁₂ realized in Ba(TiO)Cu₄(PO₄)₄is a promising structural unit carrying ME-active magnetic quadrupole moments.

The coexistence of ferromagnetism and ferroelectricity in a multiferroic material often arises from complex magnetoelectric couplings. Here, the authors observe switching of domains in Mn₂GeO₄using neutron diffraction and develop a phenomenological theory to explain their results.

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

Small molecule antagonists of CCR6 are potential drugs for autoimmune disorders. Here the authors present inactive structures of CCR6 bound by different allosteric antagonists from two series simultaneously, offering multiple approaches to inhibit CCR6.

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.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

The lineage relationship between blood and endothelial cells has been difficult to examine due to the multiphasic timing of hematopoiesis in the embryo. Here the authors use using in vivo barcoding technology to assess cell ancestry and show that blood and endothelial cells emerge through common (haemangioblast) or separate (mesenchymoangioblasts and haematomesoblasts) progenitors in the yolk sac.

A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.

Mark Daly, Manuel Rivas and colleagues used next-generation sequencing to study the coding exons of 56 genes from regions previously associated with Crohn's disease. Follow-up analyses in independent case-control series confirmed association of many newly discovered rare variants with disease risk.

In lung adenocarcinoma, antibodies against endogenous retroviruses promote anti-tumour activity, and expression of endogenous retroviruses can predict outcomes of immunotherapy.

GPAT1 is a mitochondrial outer membrane protein that catalyzes the first step of glycerolipid biosynthesis. Cryo-EM structures and functional studies of human GPAT1 uncover the molecular architecture and mechanism of this important acyltransferase.

Single particle cryo-electron microscopy of membrane proteins is limited by their small size and difficulty to orient. Here the authors generate recombinant antibodies against the 12 kDa fusion partner BRIL domain from apocytochrome b562 to use them as plug and play fiducial marks for structure determination of BRIL fused membrane proteins.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

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.

Exome sequence analysis of more than 5,000 schizophrenia cases and controls identifies a polygenic burden primarily arising from rare, disruptive mutations distributed across many genes, among which are those encoding voltage-gated calcium ion channels and the signalling complex formed by the ARC protein of the postsynaptic density; as in autism, mutations were also found in homologues of known targets of the fragile X mental retardation protein.

The pressure dependence and magnetic field dependence of the specific heat of a quantum magnet, SrCu₂(BO₃)₂, demonstrate that its phase diagram contains a line of first-order transitions terminating at a critical point, in analogy with water.

Results of the TRACERx study shed new light into the association between body composition and body weight with survival in individuals with non-small cell lung cancer, and delineate potential biological processes and mediators contributing to the development of cancer-associated cachexia.

David Altshuler and colleagues report genotyping or sequencing of ∼150,000 individuals from several population-based cohorts, identifying 12 rare protein-truncating variants in SLC30A8, encoding a pancreatic islet zinc transporter. Carriers of these rare protein-truncating variants in SLC30A8 show reduced risk of type 2 diabetes and reduced glucose levels.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

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.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

During apoptosis, Bak undergoes major conformational changes that lead to mitochondrial permeabilization. Here, the authors characterize changes that occur within the Bak N-terminus using a series of antibodies and a novel tethering approach, demonstrating that dissociation of the α1 helix is a key early step in the unfolding of Bak.

Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.

In response to activation of death receptors, a multimeric signalling complex assembles in which FADD binds caspase 8 and FLIP through structurally similar binding surfaces. Majkut et al.show that each surface preferentially binds to one of the two proteins, resulting in the formation of a trimeric intermediate.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

Sequencing of over 600 genes in a large collection of lung adenocarcinoma samples provides an overview of somatic mutations and signalling pathways altered in cancer genes in this tumour type.

With a comprehensive analysis of sequencing data, DNA copy number, gene expression and DNA methylation in a large number of human glioblastomas, The Cancer Genome Atlas project initiative provides a broad overview of the genes and pathways that are altered in this cancer type.

Bennu’s surface has experienced continuous changes, mostly induced by its accelerating spin rate, which could have resulted in a collapse of its interior in the past. This scenario is also supported by the heterogeneity of Bennu’s internal mass distribution.

Vicinity of small bodies might be dangerous to the spacecrafts and to their instrumentation. Here the authors show the operational environment of asteroid Bennu, validate its photometric phase function and demonstrate the accelerating rotational rate due to YORP effect using the data acquired during the approach phase of OSIRIS-REx mission.

Bennu’s surface presents evidence of a variety of particle sizes, from fine regolith to metre-sized boulders. Its moderate thermal inertia suggests that the boulders are very porous or blanketed by thin dust. Bennu’s boulders exhibit high albedo variations, indicating different origins and/or ages.

Current outcomes are reported from the ongoing National Lung Matrix Trial, an umbrella trial for the treatment of non-small-cell lung cancer in which patients are triaged according to their tumour genotype and matched with targeted therapeutic agents.

Signatures of phyllosilicate-like hydrated minerals are widespread on Bennu’s surface, indicating significant aqueous alteration. The lack of spatial variations in the spectra down to the scale of ~100 m indicates both a relatively uniform particle size distribution and a lack of compositional segregation, possibly due to surficial redistribution processes.

A survey of T cell repertoire evolution in the tumors, healthy tissue and blood of patients with early-stage untreated lung cancer offers an opportunity to monitor and identify neoantigen-specific T cells for personalized immunotherapy.

In a phase 2 trial, the combination of chemotherapy with durvalumab, an anti-PD-L1 antibody, exhibited promising clinical activity in patients with previously untreated, unresectable mesothelioma, with additional analyses providing insights into genomic and immunologic features potentially associated with response.

A robust, cost-effective technique based on whole-exome sequencing data can be used to characterize immune infiltrates, relate the extent of these infiltrates to somatic changes in tumours, and enables prediction of tumour responses to immune checkpoint inhibition therapy.