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Tergaonkar and colleagues identify a noncanonical interaction between the NF-κB transcription factor family member p52 and the ETS family member ETS1. They find that the p52–ETS1 complex is required for splenic germinal center B cell formation and T cell-dependent antibody responses.

Understanding the mechanisms of chemoresistance in multiple myeloma (MM) remains elusive. Here, the authors identify a long non-coding RNA termed as PLUM that is overexpressed in NF-ĸB mutant high-risk MM and interacts with EZH2 to mediate PRC2 complex formation promoting chemoresistance via the activation of the UPR pathway.

The skin has a remarkable ability to grow under stretch, though the underlying mechanisms remain unclear. Here, the authors show that the mechanosensor Piezo1 coordinates metabolic and immune responses to drive tension-induced skin growth.

Neovascular eye diseases cause blindness, but underlying drivers are unclear. Here, the authors show that PRL3 promotes pathological angiogenesis, and that targeting PRL3 with an antibody therapy could offer a new treatment for ocular neovascularization.

How changes in brain blood vessels lead to a chronic reduction in blood flow and, consequently, to vascular dementia is poorly understood. Here, the authors show that venous endothelial dysfunction driven by EPAS1 promotes abnormal vascular remodeling and contributes to cognitive decline.

The interplay between tau and amyloid-β (Aβ) in the development of Alzheimer’s disease is not fully understood. It has now been shown that tau’s microtubule-binding repeat regions, which contain a combination of hydrophobic and hydrophilic sections, interact with Aβ to form hetero-assemblies, which can modify Aβ amyloidogenesis and alleviate Aβ-induced cytotoxicity.

Achieving diverse neuromorphic functions with ultralow energy consumption in a single device is a major challenge. Here, the authors demonstrate reconfigurable memristors enabling adaptive neuromorphic computing and high-accuracy spatiotemporal signal recognition at attojoule energy scales.

Li et al. uncover a lysosomal surveillance response whereby intestinal lumen deacidification induces a transcriptional programme that boosts lysosomal activity and improves protein aggregate clearance in multiple worm disease models, extending healthspan.

Fibroblasts from old mice are heterogeneous, which affects the ability of these fibroblasts to reprogram into induced pluripotent stem cells in vitro and influences wound healing rate in vivo.

Here, Zhang et al. succeed in creating a heavily distorted oxygen deficient film of lanthanum cobaltite. The new phase of LaCoO_2.5 has several unique properties, most notably, a Curie temperature of 284 K, significantly larger than the films from which it was derived.

Here, the authors sample air and surfaces in hospital rooms of COVID-19 patients, detect SARS-CoV-2 RNA in air samples of two of three tested airborne infection isolation rooms, and find surface contamination in 66.7% of tested rooms during the first week of illness and 20% beyond the first week of illness.

Free-standing nitrogen-doped amorphous monolayer carbon consisting of mixed five-, six- and seven-membered rings was prepared through the polymerization of pyrrole within the confined interlayer cavity of a removable layered-double-hydroxide template.

Membrane fouling during electrodialysis, nanofiltration and ultrafiltration processes results in a reduction in the dye/salt fractionation efficacy. Here, authors devise an electro-driven filtration process using tight ion-conductive ultrafiltration membrane for one-step, stable dye/salt fractionation.

Structural variations (SV) contribute to inter-individual variability. Here, the authors describe a first-generation multi-ancestry Asian SV catalogue containing 73,035 SVs from 8392 Singaporeans to provide insights into Asian SV diversity.

So-called two-dimensional superconductivity has been reported in several material systems but just how thin a system can be and maintain a superconducting state has been difficult to determine. Da Jiang and colleagues demonstrate that Bi2Sr2CaCu2O8+xcontinues to be superconducting even when it is just half a unit cell thick.

Wood and colleagues report that the XPO1 inhibitor selinexor activates PI3Ky-dependent AKT signaling in AML via upregulation of P2RY2 and demonstrate a synergistic effect of combining selinexor with inhibition of prosurvival AKT signaling.

Tracing cellular changes in complex biological systems is challenging. Here, authors present a flexible framework that integrates multi-sample data with in-house algorithms to infer comparative and spatiotemporal cell-gene patterns, advancing understanding of cellular dynamics.

Direct reprogramming of closely-related lineages can generate hematopoietic stem cells. Here, the authors show hematopoietic transcription factors Scl, Lmo2, Runx1 and Bmi1 can reprogram fibroblasts into induced hematopoietic progenitors (iHPs), which are engraftable blood progenitors.

Here, the authors show that low-intensity exercise training in mice before sleep yields greater benefits than after waking for muscle contractile performance and systemic glucose tolerance, a phenomenon abolished by muscle-specific knockout of circadian clock genes Rev-erbα/β.

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.

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.

Current methods to subtype brain tumors rely on invasive biopsies. Here, the authors develop a digital platform to regeneratively convert and catalytically enhance signals from rare circulating RNAs for blood-based characterization of brain tumors.

In a multicenter, open-label, randomized phase 2 trial, neoadjuvant chemoradiation with PD-1 blockade elicited a pathological complete response rate superior to that with neoadjuvant chemoradiation alone in patients with locally advanced rectal cancer.

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.

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.

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.

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.

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.

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.

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.

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

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.

Ferroelectric phase stability is a pivotal challenge for fluorite-structure ferroelectrics. Using electron microscopy, a ferroelastically protected reversible polar-to-non-polar phase transition in ZrO₂ is observed and the critical strain state to break the reversibility is measured.

Conventional magnetic biosensing technologies have limited ability to detect magnetic field dimensionality. Here, the authors develop a platform which uses DNA hydrogels to spatially engineer a 3D magnetic response and demonstrate its use in the direct and programmable detection of RNA and protein biomarkers.

Manual injection, which remains low-throughput and labor-intensive, is a technical bottleneck for large-scale genetic studies of C. elegans. Here, the authors report a robotic microinjection system which facilitates injection speed while maintaining injection quality which is comparable to experienced experts.

Puissant and colleagues identify a myeloid-restricted PIK3CG/p110γ–PIK3R5/p101 axis as a therapeutic vulnerability in acute myeloid leukemia and develop a proteolysis-targeting chimera to potently degrade PIK3CG and suppress AML progression.

Previous studies have proposed conflicting models of visual perceptual learning. Leveraging deep neural network modelling, human functional MRI imaging and multiunit recordings in macaques, Cheng et al. introduce a neural geometry approach to reconcile past findings. They propose a unified theory of visual perceptual learning.