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Surprisingly consistent replication failure of gray matter correlates of childhood maltreatment raises questions about publication bias in prior literature and about prevailing models linking maltreatment to brain structure in adult populations.

Small CRISPR Cas9 proteins have potential in gene therapies but generally have poor editing efficiency or specificity and often recognize sub-optimal PAM sequences. Here the authors characterise four small nucleases and use protein engineering to create effective in vivo editors.

The antisense oligonucleotide rugonersen has acceptable safety and tolerability in children with Angelman syndrome and shows partial normalization of electroencephalogram abnormalities and clinical improvements relative to natural history.

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.

Here, using long-read RNA sequencing, SILAC proteomics, and cryo-EM, the authors show that loss of mitochondrial methylation impairs rRNA processing and ribosome maturation, leading to unprocessed rRNA accumulation and defective monosome assembly.

A laser–plasma accelerator provides proton beams for the precise irradiation of human tumours in a mouse model. This work advances translational research with ultrahigh proton dose rates at laser-driven sources.

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

Here, the authors characterize the spectroscopic and transport properties of heterojunctions composed of quasi-metallic and semiconducting graphene nanoribbons (GNRs) with different widths, showing a predominant quantum tunnelling mechanism. The GNR heterojunctions can also be used to realize adsorbate sensors with high sensitivity.

Neutralization of the SARS-CoV-2 Omicron variant is markedly impaired in sera from recipients of two doses of the COVID-19 vaccine BNT162b2 or from convalescent individuals, but is robustly increased in both groups following a booster vaccine dose.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Single-molecule fluorescence currently requires specialized imaging equipment due to the low signal of a single emitter. Here the authors introduce NanoAntennas with Cleared HOtSpots (NACHOS) to boost the signal sufficient for detection of a single emitter by a smartphone, opening the door to point-of-care applications.

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.

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.

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.

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.

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.

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous and aggressive type of T-cell lymphoma. Here, the authors perform single-cell analyses of human and murine PTCL-NOS tumors, and identify a subtype defined by the loss of SMARCB1 that could be targeted with HDAC-inhibitor combination therapies.

Comprehensive characterisation of RNA-protein interactions requires different levels of resolution. Here, the authors present an integrated mass spectrometry-based approach that allows them to define the Drosophila RNA-protein interactome from the level of multisubunit complexes down to the RNA-binding amino acid.

Dewald et al. show a high Spike-IgG seroprevalence (95%) in a multicenter study with 1,411 participants. They determined a substantially reduced serum neutralization against the SARS-CoV-2 VOCs BA.4/5 and BQ.1.1. and explored predictive factors of neutralizing activity.

Schwaz, Austria, experienced SARS-CoV-2 outbreaks caused by variants of concern in early 2021 and conducted a mass vaccination campaign in response, with 70% of the adult population vaccinated after 5 days. Here, the authors show that this campaign resulted in reduced infections and hospitalisations.

The complex equilibria of sulfur compounds at the liquid-vapor interface play key roles in atmospheric processes. Here, using X-ray photoelectron spectroscopy, Raman spectroscopy, and molecular dynamics simulations the authors determining pKa values and tautomer ratios at the air-vapor interface in a liquid microjet.

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.

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.

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.

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.

X-ray triggered non-local processes, such as Intermolecular Coulombic Decay, are shown here to selectively probe solvation-shell molecules in solution and provide new information on their electronic structure and on ion-pair formation.

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.

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.

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.

The state of the Main Marmara Fault (fault segment of the North Anatolian Fault) is widely discussed, towards whether it is creeping or locked. The authors here present seafloor geodetic measurements which indicate a complete locking of the fault in the central part of the Sea of Marmara. This provides significant information for the assessment of both seismic and potential tsunami hazard to Istanbul.

A chemical screen identified BET bromodomain inhibitors as promoters of keratinocyte regenerative function and skin wound healing. Specifically, low-dose transient treatment with BET inhibitors imposes an activated, migratory state in keratinocytes.

Nitrogen availability in soils is predominantly controlled by microorganisms, yet our understanding of their organic nitrogen use is limited. Mooshammer et al.show that microbial nitrogen use efficiency is dependent on resource stoichiometry and substrate type.

Sound and Vision: In-situ synchrotron x-ray imaging with simultaneous acoustic monitoring captures grain scale damage mechanisms and unlocks the relationship between seismic and aseismic processes during catastrophic failure of porous rock.

HER2 acts an oncogenic driver in numerous cancers. Here, the authors design an anti-HER2 biparatopic and tetravalent IgG fusion with inhibitory effects in a xenograft model.

A mass spectrometry–based approach is used to investigate the mechanisms by which different NUP98 fusion proteins cause leukemia, revealing that the fusion proteins share common interactors and alter the composition of nuclear condensates.

A single cell type in the Drosophila visual system implements motion-opponent inhibition at multiple consecutive circuit levels. This neural architecture enables high stimulus selectivity without compromising sensitivity under noisy conditions.

It has been commonly believed that the driving force at the donor-acceptor heterojunction is vital to efficient charge separation in organic solar cells. Here Zhong et al. show that the driving force can be as small as 0.05 eV without compromising the charge transfer rate and efficiency.