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Disparities in risk and outcomes of pediatric acute lymphoblastic leukemia (ALL) are apparent between different ancestries. Here the authors identify genetic variants with African ancestry-specific risks for developing pediatric B-cell ALL that are also linked to greater 5-year mortality risk.

Colorectal cancer is often diagnosed at later stages, leading to poor prognosis. Here, the authors utilise analysis of rectal mucus specimens using host and microbial analysis to detect cancer lesions.

Klebanoff and colleagues report that survival and persistence of CAR-T and CAR-NK cells are regulated by a FAS ligand–FAS autoregulatory circuit, showing that disabling FAS signaling enhances their antitumor efficacy in preclinical models.

Observations of a 3-million-year-old pre-main-sequence star with a misaligned disk reveal a giant orbiting planet; the system is ideal for studying the early formation and migration of planets.

Chaperomes are dynamic assemblies of proteins that regulate cellular homeostasis but specific cellular stresses remodel chaperome components into a stable chaperome network called the epichaperome, which might offer a new cancer target.

A series of early-time, multiwavelength observations of an optical transient, AT2022cmc, indicate that it is a relativistic jet from a tidal disruption event originating from a supermassive black hole.

Genetic variants associated with susceptibility to pancreatic cancer have been identified using genome wide association studies (GWAS). Here, the authors combine data from over 9000 patients and perform a meta-analysis to identify five novel loci linked to pancreatic cancer.

Memory formation requires gene transcription, but the link between synaptic activity and transcription is not fully understood. Brd4 regulates transcription in other cell types and Brd4 family inhibitors are in clinical trials for cancer. The authors show that Brd4 is important for activity-dependent gene transcription in neurons and memory consolidation.

Loss of the tumour suppressor gene PTEN leads to the activation of pro-tumourigenic signalling pathways. Here, the authors analyse sequencing data from a large cohort of colorectal cancer patients harbouring PTEN mutations and identify distinct patterns of associations with genomic and clinical features.

Joshi, Gomes et al. employ a chemical modulation approach of the cellular interactome to a hyperconnectivity state and show association with the increased response of pancreatic cancer cell lines to specific drugs, including those that target the MAPK-pathways and PI3K-mTOR pathway. To achieve this, the authors employ chemical modulation of the interactome via epichaperome inhibition with the small molecule PU-H71.

Adverse life events have been associated with reduced survival in cancer patients. Here, the authors explore the mechanism responsible and show that chronic stress in mice activates a signalling cascade in macrophages and tumour cells, which results in restructuring of the tumour lymphatic system, promoting metastasis.

Hubble Space Telescope, Keck telescope and Spitzer satellite data reveal the formation of the dense stellar core of a massive galaxy occurring three billion years after the Big Bang.

Activating oncogenic mutations in KRAS and NRAS are common in colorectal cancer, which is a heterogenous disease. Here, the authors show that the RAS mutation spectrum is markedly different between colon and rectal cancer, and also different based on age of diagnosis and microsatellite instability.

Competitive binding of 53BP1 and BRCA1 determines DNA repair pathway choice at double-strand breaks. New work shows that acetylation of H4K16 by TIP60 tips the balance in favor of BRCA1 by limiting 53BP1 binding, thereby promoting repair through homologous recombination over nonhomologous end joining.

A manifold learning method called T-PHATE is developed for high-dimensional time-series data. T-PHATE is applied to brain data (functional magnetic resonance imaging) where it faithfully denoises signals and unveils latent brain-state trajectories which correspond with cognitive processing.

Evidence is found for a distant galaxy growing inside-out within the first 700 million years of the Universe. The galaxy has a dense central core comparable in mass density to local massive ellipticals, and an extended star-forming disc.

Alison Klein and colleagues report a genome-wide meta-analysis to identify loci associated with pancreatic cancer risk. They identify associated variants at 17q25.1, 3q29, 7p13 and 2p13.3.

The inhibitor PU-H71 preferentially targets tumor-enriched Hsp90 complexes. Affinity purification using PU-H71 reveals cancer-specific protein networks in chronic myeloid leukemia and that the abundance of tumor-specific Hsp90 clients in cells can predict sensitivity to Hsp90 inhibitors.

Cytoplasmic polyadenylated transcripts have been poorly characterized, particularly in cancer. Here the authors identify a lineage-specific requirement of the cytoplasmic polyadenylation binding protein 4 (CPEB4) in malignant melanoma and show that it controls melanoma drivers MITF and RAB27A.

Hundreds of mRNA binding proteins (mRBPs) have been described in mammalian cells. Here, the authors identify RBPs differentially regulated in melanoma, and show the RBP CELF1 controlling a distinct set of protumorigenic factors.

Longitudinal genomic and transcriptomic profiling of 1,143 patients with multiple myeloma by the Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study yields an improved copy number and gene expression subtype scheme, most notably a high-risk proliferative subtype associated with complete loss of RB1 or MAX.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

JWST observations of a massive galaxy at a redshift of 2.45 show a powerful outflow of neutral gas, with a mass outflow rate that is sufficient to shut down star formation.

ctDNA is a known poor prognostic factor for multiple cancer types, but variant-specificity is unknown. Here, the authors show variant-specific association of ctKRAS levels with survival in previously untreated metastatic pancreatic ductal adenocarcinoma patients in multiple cohorts.

The spectral properties of a short gamma-ray burst indicate that, contrary to expectations, it arose from the collapse of a massive star rather than from a compact binary merger. This discovery also confirms that most collapsars do not produce ultra-relativistic jets.

The SARS-CoV-2 protein ORF8 functions as a mimic of histone H3 to disrupt host cell epigenetic regulation.

The authors report 1.3 mm observations of dust emission from strongly lensed galaxies where star formation is quenched, demonstrating that gas depletion is responsible for the cessation of star formation in some high-redshift galaxies.

The tidal disruption event AT2019dsg is probably associated with a high-energy neutrino, suggesting that such events can contribute to the cosmic neutrino flux. The electromagnetic emission is explained in terms of a central engine, a photosphere and an extended synchrotron-emitting outflow.

Aguirre-Ghiso and colleagues report that the pluripotency transcription factor ZFP281 promotes dormancy of early disseminated breast cancer cells in the lung by driving a mesenchymal-like gene expression program.

The structure of the yeast nuclear pore complex, determined at sub-nanometre precision using an integrative approach that combines a wide range of data, reveals details of its architecture, transport mechanism and evolutionary origins.

Jones et al. examine the generalizability of the valence–dominance model of social judgements of faces in 41 countries across 11 world regions. They find evidence of both generalizability and variation, depending on the analytical method.

James Webb Space Telescope early release observations used to search for intrinsically red galaxies from the first 750 million years of cosmic history find six candidate massive galaxies, possibly including one of roughly 10¹¹ solar masses.

Microbes inhabit built environments and could contribute to degradation of surfaces especially in damp conditions. Here the authors explore how communities of microbes and their metabolites affect four types of built surfaces under varying environmental conditions.

In this paper, Korb and colleagues find that Arc can shuttle in and out of the nucleus in an activity-dependent manner. The authors further demonstrate that the nuclear translocation of Arc participates in homeostatic plasticity by promoting the formation of PML nuclear bodies, which in turn decreases GluA1 transcription, eventually contributing to the downscaling of synaptic strength.

Clinical exome and transcriptome sequencing of 500 adult patients with metastatic solid tumours of diverse lineage and biopsy site, as part of the Michigan Oncology Sequencing (MI-ONCOSEQ) Program.

Visible-light-mediated photocatalytic generation of carbon-centred radicals from alkyl, alkenyl and aryl iodides, which then undergo subsequent hydrogen-atom abstraction or reductive cyclizations, is reported. The protocol is characterized by the use of inexpensive reagents, mild conditions, exceptional functional group tolerance, and good to high yields.

A single-cell approach is used to follow the heritable stochastic changes to DNA methylation that occur in primary chronic lymphocytic leukaemia and healthy B cells, allowing the tracing of cell lineage histories and evolution during treatment with ibrutinib.

Drinking behaviour in mice is regulated by a signal derived from the water and salt content of the gastrointestinal tract that is transmitted to forebrain neurons that control thirst via the vagus nerve.

Feedback from the oral cavity to thirst-promoting neurons in the subfornical organ (SFO) during eating and drinking is integrated with information about blood composition, providing a prediction of how oral consumption will affect fluid balance and leading to changes in behaviour.

As guidelines, therapies and literature on cancer variants expand, the lack of consensus variant interpretations impedes clinical applications. CIViC is a public-domain, crowd-sourced and adaptable knowledgebase of evidence for the clinical interpretation of variants in cancer, designed to reduce barriers to knowledge sharing and alleviate the variant-interpretation bottleneck.

The International Childhood Cancer Outcome Project group, involving survivors and other relevant stakeholders, develop a set of core outcomes to measure the quality of care for 17 types of childhood cancers.

Whole-genome whole-population sequencing is used to examine the dynamics of genome-sequence evolution in Saccharomyces cerevisiae populations for 1,000 generations; this reveals patterns of sequence evolution driven by pervasive genetic hitchhiking and interference, and shows that beneficial mutations that escape drift and increase in frequency typically occur in cohorts.

Genetically engineered ‘lymphoreporter’ mouse strains are used to track melanoma dissemination in vivo, identifying midkine as a tumour-secreted factor that acts at a distance, preparing pre-metastatic niches and serving as an indicator of poor prognosis in patients.

Here, the authors summarize the evidence concerning the neurological health of individuals affected by the 11 September 2001 terrorist attacks and present the outcome of a meeting convened by the US National Institute for Occupational Safety and Health that aimed to generate recommendations for future research in this population.