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The identification of cellular targets for natural products that potently inhibit the growth of cancer cell lines implicates oxysterol-binding proteins in the growth of cancer cells. These natural products, termed ORPphilins, also affect sphingomyelin biosynthesis.

Brogan et al. uncover a signalling pathway in which levels of the nucleotide second messenger c-di-AMP increase in response to defects in cell wall synthesis. This regulatory pathway decreases turgor pressure and protects the cell from lysis.

Here the authors investigate the underlying genetic mechanisms for pathogenic variant carrier phenotype heterogeneity using exomes and clinical phenotypes from the UK and Mt. Sinai BioMe Biobanks and observed translational potential for all three mechanisms.

Natural forest regeneration is key to biodiversity conservation and climate change mitigation. Here the authors present a high-resolution time-series map of the age of regenerating tropical moist forests and find that most are ≤5 years old, with forest characteristics and geography explaining patterns better than climate or human pressure.

Natural killer T (NKT) cell defects have been implicated in several diseases such as autoimmunity, asthma and cancer, but will targeting them really be of clinical benefit? Here, the authors investigate this question and conclude that more careful studies are needed before the true clinical potential of NKT cell-targeted therapies can be determined.

Polio remains a public health concern in Pakistan and Afghanistan and continuous surveillance is essential. Here, the authors analyse genetic sequence data collected from 2012-2023 and perform phylogeographic analyses to investigate virus spread, transmission routes, and trends in viral diversity and persistence.

Rashan, Bartlett and colleagues show that mammalian 4-hydroxy fatty acids are primarily catabolized by ACAD10 and ACAD11 (atypical mitochondrial and peroxisomal acyl-CoA dehydrogenases, respectively) that use phosphorylation in their reaction mechanisms.

Zhang et al. provide evidence that, during meiosis, recombination proteins assemble into active droplets, the coarsening of which partially explains the phenomenon of crossover interference.

An expert-elicitation process identifies current methodological barriers for monitoring terrestrial biodiversity, and how technological and procedural development of robotic and autonomous systems may contribute to overcoming these challenges.

The antiviral protein SP140 negatively regulates Ifnb1 mRNA stability by directly repressing the expression of the immune regulator RESIST.

In chemical-genetic and lipidomics analyses, the clinical candidate oncology drug tegavivint induced an unconventional form of nonapoptotic cell death that required the lipid metabolic enzyme trans-2,3-enoyl-CoA reductase.

Subducted slabs may experience transient weakening during mineral phase transitions, consistent with slab stagnation in the mantle transition zone, according to a synchrotron beamline study of the quartz-to-coesite and olivine-to-ringwoodite phase transitions.

Plankton models have crucial applications in ecosystem management and climate change projections. This Perspective suggests that stronger alignment of plankton models with empirical knowledge is needed and recommends steps to close the gap between empirical research and modelling.

Manipulating the chemical composition of proteins and peptides has been central to the development of polypeptide-based therapeutics and to help address fundamental biological questions. This Review describes how nature-inspired protein ligation strategies have been repurposed as chemical biology tools.

Many SARS-CoV-2 infections may go undetected through conventional PCR or lateral flow tests. Here, the authors analyse the utility of analysing longitudinal nucleocapsid antibody trajectories to improve identification of prior SARS-CoV-2 infections using surveillance data from the UK.

Some surveys of intelligence have suggested that the mean IQ is rising; others, that it is decreasing alarmingly. The explanation seems to be that the educational level of the populations has changed.

How lung epithelial and endothelial cells develop into alveoli is a major knowledge gap, with implications for lung repair in preterm infants. Here, the authors establish a transcriptomic atlas of human neonatal lung disease, identifying semaphorins as pivotal mediators of organogenesis and injury.

Multiple types of cell elongation have been described in bacteria, but little is known about how these strategies vary across species. Here, the authors use fluorescent D-amino acids to track the spatiotemporal dynamics of bacterial cell elongation, revealing unsuspected diversity of elongation modes among closely related species of the family Caulobacteraceae.

A large international panel of experts reach consensus on a new standard for reporting settings in psychedelic trials, identifying 30 key non-pharmacological factors to strengthen the rigor of psychedelic research.

A 50 microRNA-based dynamic risk score for stratifying individuals with and without type 1 diabetes was developed using samples obtained from multicenter and multiethnic cohorts.

In this study, the authors performed single-cell RNA-sequencing across various isogenic mutant FUS and TDP43 neurons. Mitochondrial dysfunction emerged as pathway unique to motor neurons demonstrating shared toxic gain of-function mechanisms, uncoupled from protein mislocalization.

Recent evidence suggests the existence of a neural pathway specialized for social perception projecting between the well-established “what” and “where” pathways. A new study of neuropsychological patients demonstrates that this social pathway is causally essential for recognizing dynamic facial expressions.

Cell cycle control depends on phosphorylation of many proteins by the kinase Cdk1. Here, the authors show that phosphorylation of Cdk1 substrates is influenced by a phosphate-binding pocket on the surface of the cyclin regulatory subunit.

Deep phenotyping of responses to carbohydrate meals and mitigators revealed interindividual differences in postprandial glycemic responses that reflect underlying metabolic physiology, such as insulin resistance and beta cell dysfunction.

Gradients of cell recognition molecules wire a sensorimotor interface in Drosophila.

Differences in the Pace of Aging are important for many health outcomes but difficult to measure. Here the authors describe the Dunedin Pace of Aging Calculated from NeuroImaging measure, an approach that uses a single brain image to measure how fast a person is aging and can help predict mortality or the risk of developing chronic disease.

Trees come in all shapes and size, but what drives this incredible variation in tree form remains poorly understood. Using a global dataset, the authors show that a combination of climate, competition, disturbance and evolutionary history shape the crown architecture of the world’s trees and thereby constrain the 3D structure of woody ecosystems.

Chromatin structure is thought to regulate transcription factor access by modulating DNA accessibility. Here, the authors show that in living human cells, euchromatin and heterochromatin are fully accessible, while centromeric chromatin remains partially inaccessible.

How signaling pathways recruit SWI/SNF chromatin remodeling complexes is not known. Here the authors suggest a ubiquitin directed mechanism targeting SWI/SNF for Wnt pathway dependent transcription, important for development and cancer.

Around 1 in 136 pregnancies is lost due to a pathogenic small sequence variant genotype in the fetus.

Cities affect biological evolution, but traditionally researchers focus on the biophysical influence of urban environments. Instead, this Review explores how the social processes of religion, politics and war drive wildlife evolution by shaping urban conditions.

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.

The West African–South American lineage of Vibrio cholerae contains multiple distinct anti-phage defence systems that provide resistance to various phage families, including vibriophage ICP1, a key predator of pandemic strains.

JWST observations suggest that both pebbles and planetesimals played an important role in forming the giant exoplanet WASP-121 b beyond the H₂O ice line. They also indicate that strong vertical mixing likely drives the nightside atmospheric chemistry.

In this study, the authors analyse 2,409 nasopharyngeal swabs from 300 infants in Botswana to investigate the impacts of respiratory virus infection on the colonisation dynamics of bacterial respiratory pathobionts.

Here, the authors investigate the intrinsic ultrafast transport dynamics in mono- and multi-layered MoSe₂ by studying suspended crystals that do not suffer from detrimental substrate effects. They identify four sequential transport regimes, including a phase of negative diffusion and slow exciton propagation.

Light at low power densities can be used to manipulate ferromagnetic domains in the two-dimensional van der Waals ferromagnet Fe₃GeTe₂. This capability could be used to engineer the behaviour of Fe₃GeTe₂-based devices.

Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) of the salivary gland are rare tumours. Here the authors report that BCA and BCAC patients possess distinct genomic profiles despite histopathological similarities, and identify a recurrent FBXW11 missense mutation (p.F517S) which leads to accumulation of β-catenin in BCA and higher expression of Wnt/β-catenin targets.

Biofluorescence is widespread in fishes. Here, the authors compile data on biofluorescence presence across teleost fishes and demonstrate that it may have originally evolved in eels 112 million years ago, but evolved numerous other times as well, often in association with coral reefs.

Levantine Phoenicians made little genetic contribution to Punic settlements in the central and western Mediterranean between the sixth and second centuries bce; instead, the Punic people derived most of their ancestry from a genetic profile similar to that of Sicily and the Aegean, with notable contributions from North Africa as well.

Adoptive transfer of regulatory T (Treg) cells holds promise for the treatment of inflammatory diseases, but maintaining a therapeutic capacity is challenging. Here, the authors show that engineering Tregs to express an IL-2 partial agonist enhances Treg persistence and suppression of inflammation in mouse models, representing a potential optimization for Treg therapy.

Partitioning of FtsN and the septal peptidoglycan synthesis complex between an active synthesis track and an inactive denuded glycan track coordinates opposing peptidoglycan synthesis and degradation activities in E. coli.

N-terminal acetylation dysregulation in the heart causes severe arrhythmia and cardiomyopathy. The authors show that stem cell models demonstrate ion channel trafficking defects and sarcomeric disarray as the underlying mechanisms, with gene therapy reversing both phenotypes

Charge transfer is facilitated in molecular systems through orbital coupling. Here the authors use core-hole-clock spectroscopy to show that electron transfer from an argon atom caged in a fullerene can be up to two orders of magnitude faster than for the isolated atom.

Picks include a rogue gene-editor, a wunderkind physicist and a DNA detective who helped catch a serial killer.