Search

Acetyl-CoA synthetases have been proposed as targets for development of new antimicrobial drugs. Here, Jezewski et al. identify isoxazole-based compounds with activity against the pathogenic fungus Cryptococcus neoformans, and describe their mechanism of action as inhibitors of fungal acetyl-CoA synthetases.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Cannulae are heat-resistant protein nanotubes found on the surface of thermophilic archaea. Here, the authors report the structures of cannulae at the atomic level with insight into their high stability and mechanism of assembly, which has potential impact for biomaterials design.

Perineural invasion and cancer-induced nerve injury of tumour-associated nerves are associated with poor response to anti-PD-1 therapy, which can be reversed by combining anti-PD-1 therapy with anti-inflammatory interventions.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Indonesian cattle are unique due to their history of admixture involving both zebu and banteng. Here, Wang et al. identify ~3.5 million novel introgressed SNP variants and provide a genomic map of banteng introgression within and across many cattle breeds, each with unique introgression histories.

Introduction of structured neutron waves carrying orbital angular momentum (OAM) in small-angle neutron scattering experiments provides novel approaches to the characterisation of material properties. Here the authors demonstrate the retrieval of phase information in far-field intensity profiles by means of an interferometric technique using helical neutron waves.

In most metals the optical Hall effect is very small at visible wavelengths, and usually can only be observed at low frequencies. Here, Am-Shalom et al present a technique involving a large amplitude modulation of the external magnetic field, allowing for the measurement of the optical Hall effect in a range of metals at visible wavelengths.

A combination of mouse model data and data from a randomized phase 2 trial in patients with breast cancer in remission demonstrates feasibility, safety and a reduction in residual tumor cells following treatment with hydroxychloroquine and/or everolimus.

RNA splicing is an important mechanism for gene regulation. Here, the authors present a core logic that links sequence variation and splice-site choice across eukaryotes.

In a phase 3 trial for Huntington’s disease, pridopidine did not meet its primary endpoints but was safe and favored in some prespecified subgroup analyses.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

Observations of a luminous quasar from the high-resolution spectrometer Resolve aboard XRISM revealed highly inhomogeneous wind structure outflowing from a supermassive black hole, which probably consists of up to a million clumps.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

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.

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.

STAAR is a powerful rare variant association test that incorporates variant functional categories and complementary functional annotations using a dynamic weighting scheme based on annotation principal components. STAAR accounts for population structure and relatedness and is scalable for analyzing large whole-genome sequencing studies.

Space debris laser ranging, and satellite laser ranging are currently performed with slightly different setups. Here, the authors show a single setup with a Megahertz laser for both high-precision satellite laser ranging and space debris laser ranging.

The authors introduce a new spectroscopic technique for studying Higgs modes in superconductors and apply it to a cuprate superconductor. The method involves a soft quench of the Mexican-Hat potential, populating Higgs modes of different symmetries, which are then probed by non equilibrium anti-Stokes Raman scattering.

An ex vivo model and pre-clinical study in a brain-dead recipient provide enzyme-converted O organs to avoid hyperacute rejection in ABO-incompatible kidney transplant patients.

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.

The structure-function relationships of a β-helix, a folding motif formed by parallel β-strands arranged in a helical repetitive pattern, remain poorly understood and underexploited. Here, the authors reconstitute a protein β-helix by design from an elementary sequence of 18 amino acids, which self-assembles into a self-contained multifunctional motif exhibiting a range of biological functions.

Here, the authors show the emergence of valley-polarized Floquet-Bloch states in 2H-WSe₂ upon below-band-gap driving using circularly polarized light.

Vector magnetometers measure magnetic fields for diverse applications. Here, the authors present a high-resolution vector atomic magnetometer achieving precise field and angular measurements, addressing key metrology challenges while retaining the accuracy and calibration benefits of scalar sensors.

The diversity of ponerine ants varies widely across the globe. This study finds that the origin and early colonization in Gondwana’s tropical regions mainly shaped this distribution, while differences in diversification and dispersal have balanced regional diversity over time.

The accretion geometry of X-ray binary Cygnus X-3 is determined here from IXPE observations. X-ray polarization reveals a narrow funnel with reflecting walls, which focuses emission, making Cyg X-3 appear as an ultraluminous X-ray source.

A hybrid epoxy–acrylate resin is reported for the digital light processing 3D printing of bioinspired metamaterial structures with precisely patterned hard and soft domains.

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.

Standard approaches for identifying pleiotropic genetic variants may lead to spurious results. Here the authors present a new statistical method and show that it uncovers five genes linked to metabolites in METSIM participants, which were previously undetected by existing methods.

Hippocampal neurons adapt to experience through changes in gene expression and chromatin accessibility. Here, authors show that novel environment exposure induces region- and cell-type specific transcriptional changes coordinated by FOS/AP-1.

Using visible-light-induced crosslinking, a local stiffening approach is developed for ex vivo mouse and human lung tissue as an early lung injury model, directing epithelial cell mechanosensing, differentiation and nascent protein deposition.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

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

ACE2 and TMPRSS2 have received recent attention as entry factors for SARS-CoV-2. Here the authors analyze nasal airway transcriptome data from 695 children determining ACE2 and TMPRSS2 expression is induced by viral and type2 inflammation, respectively, and both exhibit eQTLs that vary across world populations.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Asteroid interiors are key to understand their formation and evolution. Here, the authors show that numerically simulated low-cohesion and low-friction structures with several high-cohesion internal zones can explain asteroid Bennu’s geophysical characteristics and the absence of the moons.

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.

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.

In Drosophila, the physical structure of the eye has a key role in the directional tuning of motion-sensitive neurons, showing how navigational behaviour is tightly associated with anatomy.

Sepsis is a global challenge and a significant burden in Sub-Saharan Africa. Here, Chenoweth et al profile host gene expression signatures from a cohort in Ghana to define molecular phenotypes and identify potential targets to improve patient outcomes.

The feasibility of Floquet engineering in graphene has been called into question due to its fast decoherence processes. Measurements of graphene’s photoemission spectrum now support the generation of Floquet states in this material.

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.

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.

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.