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Zeng et al. show that TDP-43, known for repressing cryptic exon usage in frontotemporal dementia/amyotrophic lateral sclerosis, also controls alternative polyadenylation, impacting expression of disease-linked genes (SFPQ, NEFL and TMEM106B).

CAR-T cell efficacy is often limited by the inability to maintain a memory T cell program. Here, the authors show that intrinsic CXCR4 expression enhances CAR-T cell persistence and memory differentiation in acute myeloid leukemia.

Could astronauts serve as a unique model for human aging research? Manwaring-Mueller et al. review how spaceflight stressors, such as microgravity and radiation, accelerate biological aging pathways and could inform treatments for age-related diseases on Earth.

Here they show that ATF7IP/SETDB1-mediated epigenetic programming governs T lymphoid progenitor trafficking and differentiation, providing important insights into the pathogenesis of human T lymphoid diseases.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Understanding principles that govern protein association with extracellular vesicles should expand their potential as a therapeutic modality. Here, the authors show that by localizing proteins to the plasma membrane and lipid rafts, a variety of proteins can be preferentially loaded into extracellular vesicles.

Children from lower socioeconomic backgrounds often show lower academic achievement, commonly linked to limited resources. Here, the authors show that reduced exploration–a behavior tuned for learning in childhood–helps to explain these learning gaps.

Understanding gene expression involves studying the transcriptional effects of perturbations. Here, the authors monitor RNA transcripts after applying 83 epigenetic compounds, identifying responsive genes enriched with chromatin marks and regulators in line with their mechanisms of action.

The proinflammatory cytokine interleukin-1ß (IL-1ß) plays an important role in host defence against pathogens. Here the authors report a non-canonical pathway for IL-1 ß production in conventional dendritic cells that is induced by IL-21 via STAT3-dependent mechanism.

An abiotic information ratchet mechanism increases selectivity for the correct DNA duplex from 2:1 at equilibrium to 6:1 under energy-dissipating conditions.

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.

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.

T cells are a major cell type involved in systemic lupus erythematosus (SLE). Here, the authors use promoter capture-C and ATAC-seq in human follicular T helper cells to identify SLE genes distant from GWAS loci (via 3D interaction) and validate the function of key regulatory elements and genes in vitro.

Key cardiac transcription factors require precise regulation for heart development and function. Here, the authors show that the miR-200 family controls cardiomyocyte differentiation and maturation, with its loss causing structural heart defects.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

A genomic map of nearly 300,000 potential cis-regulatory sequences determined from diverse mouse tissues and cell types reveals active promoters, enhancers and CCCTC-binding factor sites encompassing 11% of the mouse genome and significantly expands annotation of mammalian regulatory sequences.

Widespread differences in H3K27ac, a key histone modification, are associated with Alzheimer’s disease. H3K27ac differences were enriched in genomic regions containing loci involved in the progression of Aβ and tau pathology.

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.

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.

Aging is a risk factor for blood malignancies, leading to increased myelopoiesis and impaired immunity. Here, the authors show that aging alters cellular and molecular properties of HSC subsets, with changes starting as early as the juvenile stage.

Managing power exhaust in fusion reactors is a key challenge, especially in compact designs for cost-effective commercial energy. This study shows how alternative divertor configurations improve exhaust control, enhance stability, absorb transients and enable independent plasma regulation.

Many loci in the mammalian genome are intermediately methylated. Here, by comprehensively identifying these loci and quantifying their relationship with gene activity, the authors show that intermediate methylation is an evolutionarily conserved epigenomic signature of gene regulation.

Here, the authors describe a noncoding genetic variant in GBA1 specific to people of African ancestry that increases the risk of neurodegenerative diseases by interfering with the splicing of mRNA, resulting in lowered protein levels and activity.

A strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.

DNA methylation is critically involved in X chromosome inactivation (XCI) and dosage compensation, yet some X-chromosomal genes escape XCI. Here, Lujik et al. identify three autosomal genetic loci that associate with differential DNA methylation near genes that variably escape XCI in females.

Differential impact of genetic and environmental influences on DNA methylation may result in sex- and age-related physiological variation and disease susceptibility. By analysing DNA methylome of 2,603 individuals from twin families, here, the authors establish a catalogue of between-individual variation in DNA methylation.

Typhoid fever is caused by the bacterium Salmonella Typhi. Here, Park et al. analyse the genomes of 249 S. Typhi isolates from 11 sub-Saharan African countries, identifying genes and plasmids associated with antibiotic resistance and showing that multi-drug resistance is highly pervasive in sub-Saharan Africa.

There are more than 20 known melanoma susceptibility genes. Here, using a massively parallel reporter assay, the authors identify risk-associated variants that alter gene transcription, and demonstrate that expression of one such gene, MX2, leads to the promotion of melanoma in a zebrafish model.

In this study, the authors examined the relationship between oral antibiotic use and composition and antimicrobial resistance in the gut microbiome in Bangladeshi infants with a high exposure to community-administered antibiotics.

The translation of perovskite solar cells to large-area devices fabricated by industry-relevant manufacturing methods remains a critical challenge. Here, authors report solar modules with serially-interconnected cells produced entirely by industrial roll-to-roll printing under ambient conditions.

Methods connecting genes to their cis-regulatory elements usually requires millions of input cells. Here the authors combine proximity ligation in ChIA-PET and transposase accessibility in ATAC-seq, reporting ChIATAC, to map interactions between open chromatin loci in low numbers of input cells.

Sequencing the microbial species present in complex metagenomic samples is made easier with a method that groups genes by co-abundance.

Genome-wide analysis of self-reported dyslexia identifies 42 associated loci, including 27 not previously associated with cognitive traits. Dyslexia shows genetic correlation with ambidexterity but not neuroanatomical measures of language-related circuitry.

GWAS have identified numerous genetic loci for bone mineral density (BMD) and fracture risk. Here, the authors map these variants to putative target genes using ATAC-seq and Capture C of human osteoblasts and confirm ING3 and EPDR1 as BMD genes in in vitro osteoblast differentiation experiments.

Artificial stacking of van der Waals materials is an effective method to design and investigate emergent physical properties in condensed matter systems. Here, the authors characterize the natural twisted layer structure of CrI₃, showing its dependence on the sample fabrication process and its implications for the magnetic properties of the material.

Animals tracking objects can adapt their movements to optimise sensory coding. Using fish that sense objects as perturbations to an electric field, Clarke et al. reveal that the optimal object distance maintained by the fish is encoded within the firing properties of electrosensory neurons.

A catalogue of human long non-coding RNA genes and their expression profiles across samples from major human primary cell types, tissues and cell lines.