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In this work, the authors demonstrate the application of multi-parameter photon-by-photon hidden Markov modeling (mpH²MM) on alternating laser excitation (ALEX)-based smFRET measurements. The utility of mpH²MM in identifying and quantifying dynamic biomolecular sub-populations is demonstrated in three different systems.

The patch-clamp technique enables probing of the gating behavior of individual ion channel proteins, but unambiguous analysis of single-channel datasets is challenging. Here, the authors present a deep learning approach for extracting Markov models from single-channel recordings.

Mitochondrial DNA from horses at the Middle Pleistocene archaeological site of Schöningen reveals insight into the evolutionary history of horses and advances techniques for the analysis of ancient DNA retrieved from highly degraded samples.

Observations of the shape, topography, crustal thickness and surface composition of the South Pole–Aitken impact basin on the Moon suggest a southward impact trajectory and the excavation of a discontinuous remnant magma ocean from beneath the crust.

META-SiM brings foundation model power to single-molecule time traces, excelling across diverse analysis tasks. Paired with the web-based META-SiM Projector and entropy mapping, it rapidly reveals hidden molecular behaviors inaccessible by other means.

Understanding how cells discriminate between stimuli is an ongoing challenge. Here, the authors propose a mathematical framework for inferring the mutual information encoded in temporal signaling dynamics and use it to study how information is transmitted over time in response to different stimuli in NFκB, MAPK and p53 signaling pathways.

It has been proposed that language meaning is represented throughout the cerebral cortex in a distributed ‘semantic system’, but little is known about the details of this network; here, voxel-wise modelling of functional MRI data collected while subjects listened to natural stories is used to create a detailed atlas that maps representations of word meaning in the human brain.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Synthetic microbial consortia are collections of strains which can segregate metabolic tasks for efficient use in biomaterials, biomanufacturing, and biotherapeutics. Here, the authors present a method to maintain and tune the ratio of two co-cultured bacterial strains via growth medium manipulation.

A rhynchocephalian skeleton around 3–7 million years older than the oldest currently known lepidosaur fossil provides important insight into the origin of lizards and snakes.

Zhao et al. used single-cell and spatial multiomics data analysis of human and mouse lung adenocarcinoma tumors and cell lines to reveal TP53 mutation-associated changes in cancer cells and their microenvironment.

The zebra finch robust nucleus of the arcopallium (RA) directs singing by providing descending projections to brainstem motor neurons. The authors show that electrophysiological characteristics of RA neurons rely on resurgent Na+ currents that emerge early during song development only in males.

Genomic and biochemical analyses of prokaryotic sulfur metabolism identify diverse microorganisms with the capacity to oxidize sulfide using iron(iii).

Apollo is a GPU-accelerated simulator of within-host viral evolution, spanning host populations, tissues, and cells. It scales to millions of viral genomes and supports complex demographic and population genetic models.

sciCSR is a computational workflow that leverages single-cell RNA sequencing data to predict B cell dynamics and class-switch recombination events.

Individual decisions drive the dynamics of collective systems. Here, the authors use an immersive-reality experiment to show that group incentives reduce social information use and improve performance in naturalistic collectives.

Robbie Waugh and colleagues report that the EARLINESS PER SE (EPS2) locus is associated with spring growth habit and environmental adaptation in barley. Resequencing the barley homolog of CENTRORADIALIS, located within the EPS2 locus, in 216 spring and 207 winter barley accessions identified haplotypes at HvCEN that correspond with winter or spring growth habit.

HiScanner, a tool for identification of copy number alterations from single cell whole-genome sequencing data, uncovers cell-type-specific somatic mosaicism in human brain and offers a way to track clonal evolution at the single cell resolution.

Cancer stem cells (CSCs) comprise a putative population that can drive growth and resistance. Here, in glioblastoma models the authors show that rather than being a distinct clonal entity, the CSC population represents a plastic state adoptable by most cancer cells via reversible state transitions induced by the microenvironment.

A computational model called Centaur, developed by fine-tuning a language model on a huge dataset called Psych-101, can predict and simulate human nature in experiments expressible in natural language, even in previously unseen situations.

Gene editors designed using artificial intelligence can undertake precision editing of the human genome.

The network of the fly brain is highly recurrent and displays rich-club organization, with a large population (30%) of preferentially connected neurons.

Zeinert et al. provide cryo-EM structures of the E. coli Mg²⁺ importer MgtA: unexpectedly, this P-type ATPase is a dimer with an uncommon transmembrane ion-binding site and knotted N-terminus, which are functionally important features.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

SNARE-dependent membrane fusion underlies neurotransmission in the nervous system. Here, the authors demonstrate how, in mammalian neurons, the synaptic protein tomosyn controls secretion by increasing the energy barrier for fusion.

Emperor penguins colony occupancy is variable and chiefly estimated with remote sensing images at end of the breeding season. Here, the authors provide a phenological model that can extrapolate occupancy from sparse data and can predict phenological events, breeding pairs and fledging chicks.

The Fermi-LAT Collaboration reports a significant γ-ray detection (5.2σ) from the coronae of radio-quiet active galactic nuclei, revealing compact (~10 gravitational radii) and extended (~2.7 × 10⁶ gravitational radii) corona regions, challenging existing models.

Using sequencing and haplotype-resolved assembly of 65 diverse human genomes, complex regions including the major histocompatibility complex and centromeres are analysed.

The authors use systematic monitoring across the former USSR to investigate phenological changes across taxa. The long-term mean temperature of a site emerged as a strong predictor of phenological change, with further imprints of trophic level, event timing, site, year and biotic interactions.

Fluorine-19 NMR analysis combined with molecular dynamics and Monte Carlo simulations captures the activation ensemble and associated dynamics of adenosine A_2A receptor-mediated coupling to cognate and noncognate G proteins.

Genomic surveillance has been important for tracking the evolution and spread of SARS-CoV-2. Here, the authors analyse ~300,000 SARS-CoV-2 genomes from two years of sequencing in the Latin America and Caribbean regions and describe the emergence and spread of different lineages over time.

Here, the authors detect clade 2.3.4.4b H5N1 viruses in elephant seals associated with a mass mortality event in Argentina, show that the viruses belong to a clade primarily seen in marine mammals in South America and that they carry mammal-adaptation mutations suggestive of potential mammal-to-mammal transmission.

Using a new phylogeny of Pseudosuchia (crocodile-line archosaurs), the authors use diversification analyses and information theory to show that the interplay of abiotic and biotic processes over hundreds of millions of years shaped evolutionary history and diversification dynamics in this clade.

The dynamics of SARS-CoV-2 transmission in the Middle East have been relatively under-studied. Here, the authors integrate genomic and travel data and show that introductions to the region were initially driven by intercontinental air travel, after which regional land travel became a more important driver.

Folding of abundant, complex proteins can begin during their synthesis. Here, Sabbarini et al. show that the conserved protein Ypl225w (Chp1) functions as a co-translational chaperone for eEF1A and identify a role for NAC in the process as a recruitment factor.

Here, the authors study the effects of expression quantitative trait loci on enhancer activity and promoter contacts in primary monocytes isolated from male individuals, suggesting an inherent genetic link between the activity of enhancers, their contacts to target gene promoters and gene expression.

The mechanisms that accommodate variable external dependencies in evolution are not clear. Here, the authors show that switches between external and internal metabolic controls of carotenoid-producing networks in birds are linked to shifts in evolutionary rates, with internalization of control resulting in bursts of evolutionary diversification.

Chlamydia trachomatis forms membrane-bound inclusions inside the host cell that are decorated with IncA, a SNARE-like protein that promotes the fusion of inclusions. Here, Cingolani et al. show that the protein folds into a non-canonical four-helix bundle and identify an intramolecular clamp required for membrane fusion.

Cohesin functions must be tightly regulated. Here Prusén Mota et al. show that the cohesin regulator SORORIN is conserved beyond the animal kingdom and they provide the first organismal in vivo evidence that SORORIN antagonizes WAPL.

How DNA repair proteins locate their target sites on DNA is still a matter of debate. Here the authors characterize by single-molecule fluorescence imaging the modes of scanning adopted by bacterial endonuclease V as it moves along linear DNA tracks.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Detailed data on SARS-CoV-2 dynamics in Africa remain limited. Here, the authors use longitudinal serology and SARS-CoV-2 sequencing data from Ethiopia between August 2020 and July 2022 to characterise circulating variants, identify infection pathways, and explore cross-immunity properties.

During DNA metabolism, single-stranded DNA intermediates are often generated that are protected from degradation by binding of ssDNA-binding (SSB) proteins. Bacterial SSB protein forms a tetramer that wraps ssDNA using its four subunits. Here it is shown that tetrameric SSB protein can spontaneously migrate along ssDNA; this diffusional movement introducing a new model for the redistribution of the SSB protein, while remaining bound to ssDNA during recombination and repair processes.

Using Kepler, this study identifies a compact multiplanetary system that is not flat, where gravitational interactions cause its planets’ periods to change by nearly a day per cycle and their orbital planes to tilt back and forth.