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Streptolysin S (SLS) is a cytolytic toxin and virulence factor produced by mostStreptococcus pyogenesstrains. This Review discusses advances in the study of SLS, the SLS-like peptide family, and its placement within the extended thiazole/oxazole-modified microcin (TOMM) family.

A combination of proteomics and structural analyses reveals the assembly mechanism of transcription factor TFIID in human cells and identifies the chaperonin CCT as a checkpoint in the process.

A ChIP–exo method is used to define the genome-wide positional organization of proteins associated with gene transcription, DNA replication, centromeres, subtelomeres and transposons, revealing distinct protein assemblies for constitutive and inducible gene expression.

Streptococcus pyogenes (also known as group A Streptococcus or GAS) streptolysin S (SLS)-mediated red blood cell lysis occurs through disruption of the function of major erythrocyte anion exchange protein, band 3, leading to Cl^- ion influx.

NuA4 is an essential and conserved histone acetyltransferase (HAT) complex. Using electron microscopy supported by biochemical analyses, insights are now gained into its interaction with the nucleosome core particle (NCP). These data indicate that the Epl1 subunit is essential for NCP interaction, whereas the Yng2 subunit positions the acetyltransferase complex relative to specific histone tails.

Pluripotent cells are defined by their ability to self-renew: to proliferate indefinitely while maintaining their identity. Here, authors use genome-scale CRISPR knockout screens to untangle these two aspects of self-renewal.

Context specificity confounds genetic analysis and prevents reproducible genome engineering. Here, the authors report a pan-CRISPR analysis of specificity in mammalian cells and identify ultra-compact sgRNA subsets for genome-scale screens.

A modularized open-source pipeline for invasive brain signal decoding bridges the gap between closed-loop neuromodulation and clinical brain–computer interface approaches in a large patient cohort.

Histone modification recognition is an important mechanism for gene expression regulation in cancer. Here, the authors identify YEATS2 as a histone H3K27ac reader, regulating a transcriptional program essential for tumorigenesis in human non-small cell lung cancer.

DNA double-strand breaks endanger genome stability. Here, the authors present cryo-EM structures showing how Ku70/80 and DNA-PK bind DNA ends on nucleosomes, offering a mechanistic model for break recognition within chromatin.

The cryo-electron microscopy structure of NuA4 from Saccharomyces cerevisiae bound to the nucleosome illustrates how NuA4 is assembled and provides mechanistic insights into nucleosome recognition and transcription co-activation by a histone acetyltransferase.

Multi-omic profiling of brain tissue from patients with Alzheimer’s disease (AD) identifies gains in H3K27ac and H3K9ac linked to transcription and disease pathways. Increasing H3K27ac and H3K9ac in a fly model of AD exacerbates neurodegeneration.

The ALICE Collaboration provides details on the microscopic mechanism that ends up creating antideuteron in high-energy proton–proton collisions at the Large Hadron Collider.

Proximity-dependent biotinylation maps protein locations using multiple bait proteins, limiting scalability. Here, the authors present GENBAIT, a computational tool that selects optimal baits to reduce the number of experiments required while preserving subcellular organization.

Understanding the kinetics of gene expression involves accurate quantitation of gene expression. This is now undertaken by quantifying nascent-RNA levels and relating this indication of transcriptional activity to mRNA abundance in single yeast cells. Combining these measurements with computational modeling indicates that the tested yeast housekeeping genes are probably expressed through single initiation events, whereas a SAGA-transcribed gene shows behavior consistent with transcriptional bursting.

Kimura, Tanaka et al. perform exome and RNA sequencing in Japanese melanoma patients to investigate genomic and transcriptomic factors associated with clinical efficacy of immune checkpoint inhibitors. Findings reveal the characteristic genomic features and potential biomarkers of melanoma in Japanese patients.

Loss-of-function variants in thyroid hormone transporter MCT8 cause a neurodevelopmental and metabolic disorder. Here the authors identify genotype-phenotype relationships, advance insights in MCT8 (dys)function and create a pathogenicity-severity variant classifier.

A CRISPR-based screening platform was used to identify previously uncharacterized genes that regulate the regulatory T cell-specific master transcription factor Foxp3, indicating that this screening method may be broadly applicable for the discovery of other genes involved in autoimmunity and immune responses to cancer.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

The presence of phenotypic heterogeneity in collectively invading cells suggests cooperation amongst distinct subtypes of cells to promote invasion and metastasis. Here, the authors use chemical biology tools and report metabolic heterogeneity within the lung cancer collective invasion pack.

A strategy involving high-throughput flow cytometry to monitor protein abundance at single-cell resolution in yeast allows a different view of the cellular response to environmental changes than can be obtained with DNA microarrays.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

Using historical aerial photographs and new bed topography data, accelerating changes on Kennicott and Root Glaciers, Alaska since 1938 are documented. These observations inform projections showing 38–63% mass loss by 2100, depending on future climate.

Resting and activated T cell states are established by context-specific regulators and dynamic gene circuits.

Here, the authors show that IRX3 is a transcriptional master regulator of multiple histone- and chromatin-remodeling enzymes and the SUMOylation pathway in adipocyte precursor cells. IRX3 ablation results in a SUMOylation-dependent switch from adipogenic to osteogenic identity.

SWING is a versatile interaction language model that can learn the language of peptide and protein interactions.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Improved muscle function, strength and fatigue measures were observed after electrical spinal cord stimulation in individuals with spinal muscular atrophy.

Overall survival in metastatic non-small cell lung cancer is improved by immunotherapy but individual responses widely vary, and predictive biomarkers are urgently needed. Here authors show that multimodal markers, based on clinical, pathological, radiological, and transcriptomic data are more reliable at patient risk stratification than unimodal markers, considering one type of input data only.

Political instability, recurrent floods and droughts, and unsustainable crop production weakened food security, contributing to the decline of the Tang Dynasty in the late 9th and early 10th centuries CE, according to a multicomponent hydroclimatic vulnerability model.

While CDK4/6 inhibitors (CDK4/6i) have improved outcomes for breast cancer patients, estrogen receptor (ER + ) breast cancers often develop resistance, and triple negative breast cancer (TNBC) show poor sensitivity. Here, the authors identify a vulnerability of CDK4/6i treated ER+ and TNBC on ferroptosis and identify the combination of CDK4/6i and GPX4 inhibition as synergistic.

A comprehensive multi-omics reference atlas of prenatal human skin shows that innate immune cells crosstalk with non-immune cells to perform pivotal roles in skin morphogenesis, including the formation of hair follicles.

The authors develop multimodal machine learning models to infer metastatic recurrence risk for early-stage, hormone receptor-positive breast cancer from H&E images using >6000 cases across three centers, outperforming a nomogram and unimodal methods.