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

Sequencing analysis of tamoxifen-associated uterine cancers and further in vivo analyses suggest that the drug tamoxifen can activate the PI3K pathway in the absence of oncogenic mutations.

This study shows that aboveground plant diversity is only weakly related to belowground mycorrhizal fungal diversity, although these relationships can be stronger at regional scales. Therefore, conservation efforts centered only on plant diversity may overlook critical fungal diversity hotspots.

Using RFdiffusion, a general method for targeting intrinsically disordered proteins and regions for protein design has been developed.

Machine-learning algorithms trained on 25,000 geolocated soil samples are used to create high-resolution global maps of mycorrhizal fungi, revealing that less than 10% of their biodiversity hotspots are in protected areas.

Observations from a borehole in the Kamb Ice Stream suggest that discrete subglacial discharge events dominate channel melt and sediment transport.

The bacterial anti-phage defense systems known as ‘Zorya’ consist of a membrane protein complex (ZorAB) and soluble components of unclear function. Here, the authors solve cryo-EM structures of the ZorAB complex and show that the soluble component ZorE displays nickase activity and acts as an effector module.

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.

The application and therapeutic success of CAR-T cell approaches are limited by the development of T cell exhaustion. Here, Stewart et al discover a role for IL-4 in driving CD8⁺ CAR-T cell exhaustion and demonstrate the improvement of CAR-T cell effectivity with interruption of IL-4 signalling.

Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.

MERS-CoV ORF4b antagonizes host innate immune response, partially via blocking nuclear import adapter IMPα activity and preventing nuclear translocation of NF-κB. Here, Munasinghe and Edwards et al. biochemically and structurally define the interaction between ORF4b and IMPα-family members and find a non-canonical interaction between ORF4b NLS and IMPα2 and IMPα3.

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.

Systematic base-editing and computational screens identify specific cysteine residues on VPS35 in the retromer complex as key sensors that decrease mitochondrial translation in response to reactive oxygen species signals.

Quantum computers may help to solve classically intractable problems, such as simulating non-equilibrium dissipative quantum systems. The critical dynamics of a dissipative quantum model has now been probed on a trapped-ion quantum computer.

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.

Symbiotic fungi control network-level structure and flows to meet trade demands.

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.

Deep learning methods have been used to design proteins that can neutralize the effects of three-finger toxins found in snake venom, which could lead to the development of safer and more accessible antivenom treatments.

A de novo-designed protein that precisely assembles a chlorophyll dimer has been developed. The design matches the conformation of the native ‘special pair’ of chlorophylls that functions as the primary electron donor in natural photosynthetic reaction centers. In the designed protein, excitonically coupled chlorophylls participate in energy transfer. The proteins were also redesigned to assemble into 24-chlorophyll nanocages.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A new elpistostegalian from the Late Devonian period has been discovered that shows disparity in the group and represents a previously hidden ecological expansion, a secondary return to open water, near the origin of limbed vertebrates.

Justin Rubio and colleagues report results of a genome-wide association study of multiple sclerosis using cases from Australia and New Zealand. Their findings confirm several published risk loci for MS and identify two new risk loci on chromosomes 12 and 20.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

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.

Engineering enzymes to utilize the noncanonical redox cofactors such as nicotinamide mononucleotide (NMN + ) is challenging. Here, the authors report a growth-based selection platform for NMN + -reducing enzyme engineering and show its application in developing a phosphite dehydrogenase with improved catalytic efficiency.

In mitosis, genome integrity is maintained by DNA polymerase theta-dependent repair of DNA double-strand breaks, which is regulated by Polo-like kinase 1 activity.

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.

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 study provides a comprehensive transcriptomic atlas of the human gastrointestinal tract across the lifespan, highlighting inflammation-induced changes in epithelial stem cells that alter mucosal architecture and promote further inflammation.

Genomic and transcriptomic analysis of 393 non-small cell lung cancer patients treated with checkpoint inhibitors identifies molecular features associated with response.

Cui et al. find that arginine depletion and inflammation reduces nuclear localization of arginyl-tRNA synthetase, which influences alternative splicing via condensate-like serine/arginine repetitive matrix protein 2, and regulates cellular metabolism and response to inflammation.

New research examines disparities in renewable energy development on American Indian reservations relative to adjacent lands. Results highlight barriers contributing to these disparities and the scope for poverty alleviation, if eliminated, is quantified.

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

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.

The MAVEN spacecraft observed brightening in the Lyman-α line correlated with solar wind activity, which can be attributed to auroral activity by solar wind protons interacting with the Martian neutral hydrogen corona. Proton aurorae are normally seen at Earth only.

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.

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.

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.

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.

An autoimmune-prone state of steady-state cytokinopathy, hyperactivated CD4 T cells and ongoing B cell activation contributes to a breach in immune tolerance in individuals with Down’s syndrome.

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.

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.