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Inborn errors of the alternative NF-κB pathway in humans impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases

This study characterizes the three-dimensional (3D) genome architecture of 15 primary human cancer types from The Cancer Genome Atlas. The analyses identify different archetypes of enhancer usage and enhancer rewiring events due to different classes of mutations and structural variants.

The plant cuticle provides a barrier between internal leaf tissues and the environment. Here the authors develop a mathematical model of water movement through the cuticle and describe a prominent role for cellulose in controlling the dynamics of moisture diffusion and adsorption.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

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.

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.

Cross-species transcriptomics on vulnerable neuronal populations unravels the transcription factor CREB3 and its regulatory network as resilience markers of ALS. Genetics and epidemiology further identify the protective rare variant CREB3R119G.

The ability to synthesise lemniscular molecules to allow for the study and application of their chiroptical properties is a notable technical challenge. Herein, the authors report the design and synthesis of enantiomers of a [5]helicenoid derived molecular lemniscate, in which two homochiral helicenes are linked via the formation of two azine motifs.

In this work, the researchers realize the current-induced motion of Néel type chiral domain walls via spin-transfer-torque in the pristine van der Waals ferromagnet Fe₃GeTe₂ and via spin-orbit-torques in heterostructures with platinum or tungsten.

Distinguishing band and Mott insulators experimentally represents a longstanding challenge. Here, the authors demonstrate a momentum-resolved signature of a dimerized Mott-insulator in the out-of-plane spectral function of Nb₃Br₈.

A method for de novo design of peptide macrocyles called RFpeptides has been developed. RFpeptides is an extension of RoseTTAFold2 and RFdiffusion and combines structure prediction and protein backbone generation for rapid and custom design of macrocyclic peptide binders.

The magnetoresistance suggests an exotic topological phase in LaBi, but the evidence is still missing. Here, Nayaket al. report the existence of surface states of LaBi through the observation of three Dirac cones, confirming it a topological semimetal.

Phylogenetic statistical analyses, biophysical models and information from the fossil record show that an evolutionary signal of natural selection acted to increase the flight efficiency of pterosaurs over millions of years.

Spin manipulation in memory devices typically requires large electrical currents, limiting performance. Here the authors demonstrate magnetization switching in ferromagnetic films by depositing chiral molecules, making use of a proximity effect without needing magnetic or electric fields.

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.

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.

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.

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.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

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.

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.

This work reveals a mechanism of cGAS- and STING-dependent type I IFN induction in response to biofilm-associated Candida albicans DNA packaged in extracellular vesicles.

Measurements from the heavily shielded Orion spacecraft during the uncrewed Artemis I mission show dose-rate reductions due to shielding and orientation for Van Allen belt crossings and quantify the interplanetary cosmic-ray radiation in a human-rated spacecraft.

The number of single-cell RNA-seq datasets generated is increasing rapidly, making methods that map cell types to well-curated references increasingly important. Here, the authors propose an accurate method for mapping single cells onto a reference atlas in seconds.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Results from the phase 2 MATCH01 clinical trial of autologous monocyte-derived macrophage therapy for liver cirrhosis revealed no liver-related severe adverse events or deaths in the treatment group.

Analysis of human tumor datasets shows that all features that appear significantly associated with immunotherapy response and survival may be collapsed into five latent factors: tumor mutation burden, T cell effective infiltration, TGF-β activity in the microenvironment, prior treatment and tumor proliferative potential.

A 50 microRNA-based dynamic risk score for stratifying individuals with and without type 1 diabetes was developed using samples obtained from multicenter and multiethnic cohorts.

Studies of the genetic association between vitamin D and cancer risk have typically been underpowered. Here the authors analyse this using Mendelian Randomisation with more than 70 vitamin D variants obtained from the UK Biobank and large-scale data from various consortia, confirming null associations between vitamin D and most cancers.

Traditional approaches in spatial transcriptomics often rely on preliminary data grouping, which can overlook subtle expression patterns in tissues. Here, the authors present Spatial Gradient Screening, a tool which facilitates the detection of histology-associated gene expression patterns without prior data grouping.

T cell responses can be generated to either pathogen infection or from priming with a vaccine. Here the authors compare T cell generation, phenotype and single cell transcriptome of participants vaccinated with a mpox vaccine or infected with the virus showing that the virus induced T cells showed more effective function and phenotype.

The genomic landscape of diffuse gliomas remains to be characterised. Here, the authors perform whole genome sequencing of 403 tumours and identify recurrent coding and non-coding genetic mutations, their associations with clinical outcomes and potential therapeutic targets.

Payton et al. develop small-molecule inhibitors of kinesin KIF18A able to selectively kill cancer cells with high chromosomal instability and demonstrate that the inhibitors are therapeutically beneficial in cancer patient-derived in vivo models.

Using HDX-MS, X-ray crystallography, cryo-EM, and MD simulations, the authors examined the conformational dynamics of GAD65 in its apo- and holo- states and its interaction with the autoimmune polyendocrine syndrome type 2-associated autoantibody b96.11.

The spatial architecture of multiple myeloma remains to be explored. Here, the authors perform bulk and single cell sequencing for samples from newly diagnosed patients and reveal gene signatures associated with focal lesions and spatial heterogeneity in the tumour microenvironment.

The authors seek to understand the precise roles of microglia in the early human brain by coculturing brain organoids with primitive-like macrophages generated from the same human induced pluripotent stem cells (iMac).

Application of a nanopore sequencing workflow for real-time analysis of brain tumors results in molecular classification within a 30-minute intraoperative window, followed by comprehensive profiling within 24 hours.