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The synOptopatch approach enables all-optical access to synaptic communication via mutually exclusive expression of an optogenetic actuator and a voltage sensor in pre- and postsynaptic neurons, respectively.

Transcription factor NF-ĸB is a key regulator of immunity in mammals, but its function in protists like Capsaspora and choanoflagellates is not known. Here, Leah Williams et al. characterize and compare the structure, activity, and regulation of NF-ĸB from Capsaspora and one choanoflagellate, providing further insight into the origins of NF-ĸB.

The MuvB protein complex regulates genes that are differentially expressed through the cell cycle, yet its precise molecular function has remained unclear. Here the authors reveal MuvB associates with the nucleosome adjacent to the transcription start site of cell-cycle genes and that the tight positioning of this nucleosome correlates with MuvB-dependent gene repression.

Acquired resistance to immune checkpoint inhibitors represents an important clinical challenge. Here, in a pancreatic ductal adenocarcinoma model of acquired resistance to immunotherapy, the authors show that plasticity-induced repression of Irf6 is associated with tumor cell-intrinsic resistance to cytotoxic T-cell activity.

Transient receptor potential (TRP) proteins are Ca²⁺-permeable cation channels activated by a range of chemical and physical stimuli. Here the authors describe a cryo-EM structure of the full-length TRPV2 channel that provides insight into the regulation of the TRPV subfamily of channels.

Aminoacyl-tRNA synthetases translate the genetic code. These enzymes harbor signature catalytic motifs dating from their ancient ancestors. A natural variation of one of the stated motifs was discovered and linked to antibiotic hyper-resistance.

Das et al. show that the copper transporter CTR1 functions as a redox sensor in endothelial cells. CTR1 is modified after redox stress, which induces CTR1–VEGFR2 complex formation and promotes VEGFR2 signalling and angiogenesis.

Statins are promising for breast cancer therapy; dipyridamole can potentiate their effects, but is contraindicated in some cases. Here, the authors develop a pharmacogenomics pipeline to predict other compounds that potentiate statins, and validate the top candidates in cell line screens and 3D cultures.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Rhabdomyosarcoma (RMS) is a pediatric malignancy of skeletal muscle lineage with an aggressive subtype caused by translocations involving PAX3- /PAX7-FOXO1 chimeric transcription factors. Here the authors show that the BRG1-containing BAF complex is overexpressed and acts largely independently of the PAX3-FOXO1 chimera on chromatin to result in a myogenic differentiation blockade in this malignancy.

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.

Investigating the inner structure of baryons is important to further our understanding of the strong interaction. Here, the BESIII Collaboration extracts the absolute value of the ratio of the electric to magnetic form factors and its relative phase for e + e − → J/ψ → ΛΣ decays, enhancing the signal thanks to the vacuum polarisation effect at the J/ψ peak.

Wildfires are becoming increasingly frequent in several regions around the world due to climate change, posing serious health risks, especially for respiratory diseases. This study examines the respiratory health risk and burden of wildfire-specific PM_2.5 pollution across eight countries and territories.

RNA sensing-mediated payload expression provides a specific, versatile, simple and generalizable means of detecting and manipulating animal cells with broad potential applications.

A pan-cancer analysis identifies 129 transposable-element-driven promoter-activation events involving 106 oncogenes. At the AluJb-LIN28B locus, deletion of the transposable element eliminates oncogene expression.

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.

SARS-CoV-2 neutralizing antibodies are readily detected with a biosensor.

The acidophilic fungus Acrodontium crateriforme is present in traps of the carnivorous plant Drosera spatulata and promotes prey digestion.

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.

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.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

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.

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 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.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

The semileptonic decay channels of the Λc baryon can give important insights into weak interaction, but decay into a neutron, positron and electron neutrino has not been reported so far, due to difficulties in the final products’ identification. Here, the BESIII Collaboration reports its observation in e+e- collision data, exploiting machine-learning-based identification techniques.

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.

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.

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.

Topological superconductors are potentially important for future quantum computation, but they are very rare in nature. Here, the authors observe topological surface states acquiring a nodeless superconducting gap with similar magnitude as that of the bulk states in 2M-WS₂, suggesting an intrinsic topological superconductor.

p53 inactivation is nearly universal in small-cell lung cancer (SCLC), but its tumor suppressive role in this cancer type is poorly understood. Here the authors show that intertumoral heterogeneity in SCLC influences the biological mechanisms of p53-mediated tumor suppression and identify a role for cyclophilins in p53-dependent necrotic cell death.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

Low-energy structures (LES) in the photoelectron momentum distribution, typically observed in linearly polarized tunneling ionization, are caused by Coulomb effects. The authors demonstrate that the LES induced by specific recollisions persists at any laser ellipticity, provided the nonadiabatic regime is reached with sufficiently large nonadiabaticity.

Observations of γ-rays with energies up to 1.4 PeV find that 12 sources in the Galaxy are PeVatrons, one of which is the Crab Nebula.

Silva and colleagues develop a network-based HDAC6 score which could predict sensitivity to the HDAC6 inhibitor ricolinstat in preclinical models, as well as patients with HR⁺/HER2⁻ breast cancer that received ricolinstat in a phase 1b clinical trial.

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.

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.

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.

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.

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.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Measurements of the inelastic cross section of anti-³He allow the estimation of the transparency of the Milky Way to the propagation of these light antinuclei produced in either cosmic-ray collisions or annihilation of dark-matter particles.

The mechanism of the charge density wave transition in quasi one-dimensional blue bronzes is still debated. Here, the authors report evidence of a Luttinger liquid in the normal state of blue bronzes and Holstein polarons below the transition temperature, revealing the important role of electron-phonon coupling in the transition.

Chemical genetic dissection of the SWI/SNF–Polycomb axis in mouse stem cells identifies an unexpected role for mSWI/SNF in repression, providing mechanistic insight into the dynamic ‘tug of war’ between transcriptional activation and repression.

In this Perspective, members of the Aging Biomarker Consortium outline the X-Age Project, an Aging Biomarker Consortium plan for building standardized aging clocks in China. The authors discuss the project roadmap and its aims of decoding aging heterogeneity, detecting accelerated aging early and evaluating geroprotective interventions.