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Here the authors report asperigimycins, fungal ribosomally synthesized and post-translationally modified peptides with a heptacyclic scaffold. After chemically modifying them for nanomolar anticancer activity, CRISPR screening identifies SLC46A3 as a key transporter for their uptake in cells.

This study reveals how human small ubiquitin-like modifier (SUMO) E1 recruits its E2 partner UBC9 and transfers SUMO1 through large structural changes, uncovering key mechanisms that ensure specificity and fidelity in SUMOylation, an essential protein modification pathway.

Complex diseases often involve subtle subtypes, making their detection vital for personalized medicine. Here, the authors show that the PHet (Preserving Heterogeneity) method reliably uncovers disease-specific subtypes using small sets of features

The long-spined sea urchin has colonized areas along the Tasmanian coast owing to climate-induced changes in ocean currents, forming barrens that threaten marine species. This study shows how a government-supported strategy of overfishing this sea urchin could help conservation and fisheries outcomes.

A long-period radio transient with coincident radio and X-ray emission and observational properties unlike any known Galactic object has been observed by the Australian Square Kilometre Array Pathfinder.

Poly(carboxybetaine) lipids enhance mRNA lipid nanoparticles efficacy and reduce their immunogenicity, being promising alternatives to poly(ethylene) glycol lipids used in traditional mRNA lipid nanoparticle formulations.

Coherent radio emission with a long (nearly 6.5 h) period has been detected from both magnetic poles of a rotating compact object, offering insights into the evolution and emission mechanism of compact radio transients.

Long-period radio transients emit powerful polarized signals lasting minutes to an hour. The discovery of ASKAP J1935+2148, a source showing diverse emission modes that resemble neutron-star behaviour, challenges existing ideas of these phenomena.

Multiple omics platforms and deep single-cell profiling in the I4 astronauts reveal both conserved and distinct immune system disruptions across missions, provide a single-cell immune reference for future missions.

AI models integrating molecular dynamics data improve pathogenicity prediction in PMM2 mutations, which can outperform existing tools and helps in classifying variants of uncertain significance aiding genomic translational medicine.

Using the MeerKAT radio telescope, the authors have discovered a neutron star with an ultra-long spin period of 76 s. Though it resides in the neutron star graveyard, it emits radio waves and challenges our understanding of neutron star evolution.

Exome sequencing of 851 trios from more than 2,500 individuals finds 187 genes with de novo mutations that contribute to meningomyelocele (spina bifida) and highlights critical pathways required for neural tube closure.

A study of human and mouse models of pancreatic cancer finds that inhibiting the lipid kinase PIKfyve interferes with the cancer’s lipid homeostasis, making it a potential target for drug development.

Multiple myeloma (MM) cancer cells can develop different resistance mechanisms to therapies inducing DNA-damage. Here, the authors show that the mitochondrial DNA repair protein DNA2 promotes MM cells survival after DNA damage-induced metabolic reprogramming.

Combining microfluidics with combinatorial indexing enables rapid mapping of genome accessibility in hundreds of thousands of single cells.

Cytokines are immune signaling molecules that are frequently dysregulated in disease. Here, the authors create engineered cytokine ‘adaptors,’ molecular switches that simultaneously block a target cytokine while inducing local activation of alternative cytokine receptors.

A study describes chromatin accessibility and paired gene expression across the entire developing human brain during the first trimester in the context of gene regulation and neurodevelopmental disease.

The precise mechanism by which gut microbiota influence the immunotherapy response of tumors in anatomically distant locations remains debated. In this study, using organoids and animal models, Zhang and colleagues show that Bifidobacterium-derived extracellular vesicles synergize the anti-tumor effect of anti-PD-1 via modulation of key cytokines, immune response and oncogenic pathways, and increase in tumor-infiltrating CD8 + T cells.

Type 2 Long QT syndrome is a cardiac disease associated with hundreds of individual mutations within the Kv11.1 potassium channel. Here, the authors systematically investigate the trafficking defects associated with different types of Kv11.1 mutations and to what extent they can be corrected pharmacologically.

Transcriptomic and proteomic analyses show that high levels of the extracellular-matrix protein osteopontin are associated with the attenuated foreign-body response elicited by breast silicone implants wrapped with acellular dermal matrix.

Diketopiperazine (DKP) natural products have diverse structures and biological functions. Here, the authors elucidate the biosynthetic pathway for indole alkaloid DKP nocardioazine B which includes DKP stereoisomerization by an unusual aspartate/glutamate racemase homolog and N- and C-methylation by a dual function methyltransferase.

The Signac framework enables the end-to-end analysis of single-cell chromatin data and interoperability with the Seurat package for multimodal analysis.

Here the authors provide the biospecimen collection methodology from the SpaceX Inspiration4 mission, including venous blood, capillary blood, saliva, urine, stool, skin biopsy, body swab, and environmental swab samples.

Disease risk variants can exert their influence on phenotypes by altering epigenome function. Here, Pelikan et al. show that variants inducing allelic imbalance in histone marks in lymphoblastoid cell lines from lupus patients are enriched in autoimmune disease haplotypes and influence gene expression.

Mouse models often combine mutant alleles to accelerate cancer development, limiting oncogenic diversity. Here the authors show that sporadic MYC activation in Vk*MYC mice is sufficient to induce tumors with a variety of secondary mutations that mirror the genetic heterogeneity of human myeloma.

Combining droplet-based ATAC-seq and mitochondrial DNA sequencing reveals clonal variation in human cells and tissues.

Fine-mapping of blood cell traits in the UK Biobank identifies putative causal variants and enrichment of fine-mapped variants in accessible chromatin of hematopoietic progenitor cells. The study provides an analytical framework for single-variant and single-cell analyses of genetic associations.

An integrated data and sample repository for clinical, cellular and multi-omics research from diverse spaceflight missions known as Space Omics and Medical Atlas (SOMA) is presented.

A number of natural occurring small-molecule splicing modulators are known. Here, the authors combine chemogenomic, structural and biochemical methods and show that these compounds also target the spliceosome-associated protein PHF5A and propose a potential modulator binding site in the PHF5A–SF3B1 complex.

Fuel cells are promising for various applications but need durable electrocatalysts. Here, the authors present a solution-phase derived Pt-Mg alloy endowed with a Pt-rich shell and an intermetallic core, showing high durability and activity.

Keypoint-MoSeq is an unsupervised behavior segmentation algorithm that extracts behavioral modules from keypoint tracking data acquired with diverse algorithms, as demonstrated in mice, rats and fruit flies. The extracted modules faithfully reflect human-annotated behaviors even though they are obtained in an unsupervised fashion.

Radio pulses from a rare, radio-loud magnetar, XTE J1810−197, are seen to have undergone a conversion in their polarization state. This change can be linked to the magnetar’s magnetic field geometry, and has commonalities with an effect also seen in fast radio bursts.

The results of the Fifth RNA-Puzzles contest highlights advances in RNA three-dimensional structure prediction and uncovers new insights into RNA folding and structure.

The transfer of electronic energy through a photosystem can harm the photosynthetic apparatus when not balanced with CO₂ fixation. Here, the authors show that CO₂ modulates electronic energy transfer in cyanobacteria by binding to and enhancing the activity of the light-harvesting complex.

In vivo lensless imaging can be achieved via a phase mask that creates diffraction patterns with high-contrast contours, as shown for the imaging of calcium dynamics in the cortex of mice and of microvasculature in the oral mucosa of volunteers.

Screening a large barcoded library of unique CD19-specific chimaeric antigen receptors with diverse intracellular domains allows for the discovery of receptors that elicit enhanced antitumoural functions.

In a large-scale study involving 389 board-certified dermatologists and 459 primary-care physicians from 39 countries, the impact of a deep learning-aided decision support system on physicians’ diagnostic accuracy was tested across 46 skin diseases and for both light and dark skin tones.

Genomics analyses reveal that in vitro culture of CAR T cells can lead to reactivation of a latent herpesvirus, which might be involved in complications in patients receiving associated cell therapies.

Chromatin accessibility, gene expression and protein levels are measured in the same single cell.

Due to the pulsed nature of X-ray free electron laser (XFEL) instruments the majority of protein crystals, which are injected using continuous jet injection techniques are wasted. Here, the authors present a microfluidic device to deliver aqueous protein crystal laden droplets segmented with an immiscible oil and demonstrate that with this device an approx. 60% reduction in sample waste was achieved for data collection of 3-deoxy-D-manno-octulosonate 8-phosphate synthase crystals at the EuXFEL.

Single-cell analyses of immune cells from patients with pathogenic, single large-scale mitochondrial DNA (mtDNA) deletions including Pearson syndrome describe heteroplasmy dynamics consistent with purifying selection, as well as T-cell state-specific regulatory mechanisms and metabolic vulnerabilities.

Low bandgap tin–lead perovskites are crucial to making efficient all-perovskite tandem solar cells but have so far shown poor stability. By removing the hole transport layer and improving film morphology, Prasanna et al. demonstrate a low-gap perovskite solar cell that is stable for 1,000 h under heat, light and atmospheric conditions.

Photometric recordings and optogenetic manipulation show that dopamine fluctuations in the dorsolateral striatum in mice modulate the use, sequencing and vigour of behavioural modules during spontaneous behaviour.

Metamaterials enable the realization of unique material properties such as coupling between strain and momentum in a fluid—known as Willis coupling. Here, Muhlesteinet al. use homogenization theory to better understand Willis coupling in acoustic metamaterials and demonstrate the unusual material response.

It is assumed that single-cell analyses capture one barcode per cell. Here, the authors show that up to 21% of cell barcodes on the 10X Chromium scATAC-seq assay may be derived from barcode multiplets.

Evidence for the abundant presentation of class II neoantigens by a human B-cell lymphoma.

Using single-cell lineage tracing, the authors identify TCF15 as a novel regulator of haematopoietic stem cell quiescence and self-renewal.