Communications Biology最新文献

The first truly terrestrial apex predators were carnivorous synapsids, which emerged in the Permian over 260 million years ago and evolved against a backdrop of harsh ecological change. In many ways, these predators mirrored feeding modes and evolutionary trends seen in their much later descendants, the flesh-eating mammals; could apparent resemblances indicate evolutionary constraints on form, or were they shaped by natural selection? Here we show that the skulls of carnivorous Permian synapsids were shaped primarily by adaptation, their shapes reflecting trophic function, and with similarities between distant relatives arising by convergence through natural selection. Conversely, we find no evidence for constraint in terms of the direction or rate of evolution based on patterns of topological modularity. These findings illustrate methods of identifying evolutionary processes in deep time and emphasise the role of competition and adaptation over intrinsic constraints in macroevolution.

Significant changes occur in brain structure and cognition during adolescence. Investigating their association can provide insight into brain-based cognitive development, yet previous studies are limited by narrow measures, small samples, and lacking focus on age-dependence. Using a large cohort (n = 8534, age 9-15) with structural MRI and diffusion imaging, we derive 16 regional metrics and integrate them via morphometric similarity networks to characterize 16,563 brain features. We apply large-scale models to investigate their associations with seven cognitive subtests and general intelligence (g), as well as age-dependence. Brain areas most strongly associated with cognition also show the greatest age-dependence of the associations, primarily in the frontal, temporal, and occipital lobes. Stronger and more age-dependent associations with cognition are observed for structural MRI measures and global hub measures, compared with diffusion-derived metrics and local measures, respectively. Overall, our study provides a comprehensive and reliable characterization of adolescent brain structure-cognition associations.

Mono-ADP-ribosylation, a modification of both proteins and nucleic acids, is implicated in innate immunity. Intracellularly, this modification is catalyzed by PARP enzymes, some induced in response to interferons. Mono-ADP-ribosylation is reversed by hydrolases including proteins with macrodomains, which are conserved across all kingdoms of life. Macrodomains encoded by certain positive-sense single-stranded RNA viruses, such as Chikungunya virus and SARS-CoV-2, antagonize host MARylation to enhance viral replication and suppress the immune response. While macrodomain hydrolase activity is essential for CHIKV replication, in SARS-CoV-2 it predominantly contributes to immune evasion, underscoring viral macrodomains as potential antiviral drug targets. Efforts to develop macrodomain inhibitors include computational modeling, crystallography-based methods, and in vitro assays. However, tools to study macrodomain activity directly in cells remain rare. Here, we established a cell-based assay using PARP15 isoform 1, which we found forms nuclear foci dependent on its ADP-ribosyltransferase activity. Enzymatically active macrodomains dissolve these foci, enabling hydrolase activity monitoring in living cells. Using stable cell lines, this system allows the screening of macrodomain inhibitors while simultaneously addressing cell permeability, toxicity, and physiological relevance. Adaptable to various macrodomains, our platform offers a versatile tool to study macrodomain function in living cells, analyzing mutants, and advancing drug discovery efforts.

Aquatic ecosystems are major reservoirs of antibiotic resistance genes (ARGs) and hubs for microbial interactions that can facilitate their spread through horizontal gene transfer (HGT). While mobile genetic elements (MGEs), including plasmids and viruses, are recognized as important drivers of ARG mobility, the extent to which water column stratification constrains their vertical dissemination remains unresolved. Here, we analysed depth-resolved metagenomic data from stratified freshwater and marine systems to assess the role of HGT in ARG spread. We found that ARG diversity is consistently lower in marine than freshwater environments and that only a small fraction of ARGs is mobilized by plasmids and viruses. Importantly, we detected no evidence for recent HGT-mediated dissemination of ARGs across depth layers, despite genetic compatibility among co-occurring bacteria. Instead, ARGs appear largely confined to lineage-specific inheritance and within-layer persistence. These findings suggest that stratification acts as a barrier, limiting vertical ARG transfer while promoting within-layer accumulation. Given projections of intensified and prolonged stratification under climate change, our results imply reduced vertical connectivity of ARGs in aquatic environments, with potential consequences of further mitigation in its dynamics by water stratification.

Primates' decision-making in economic contexts follows distinctive patterns, as initially described by Prospect Theory. Social animals, such as monkeys, live in hierarchically structured groups where individual status may influence cognitive processes, including economic decisions. We leveraged a unique dataset from a semi-free ranging macaques' group, which had continuous access to gambling tasks over several years, yielding hundreds of thousands of trials and longitudinal assessments of social hierarchy. Our findings reveal a dynamic relationship between social hierarchy and decision parameters: middle-ranking individuals displayed reduced risk aversion for potential gains but not losses. Longitudinal analyses suggested that changes in social rank were followed by corresponding shifts in risk attitudes, implying that social position, rather than inherent traits, influences decision-making patterns. While sex had no significant impact, age was primarily associated with variations in loss aversion. These results underscore the flexibility and adaptive nature of primates' cognitive biases and provide key insights into how social structures influence risk behavior, with potential implications for understanding decision-making processes in other social species, including humans.

The neuromuscular junction (NMJ) is the peripheral synapse controlling muscle contraction. Although aging and neurodegeneration result in NMJ denervation and synaptic dismantling, early indicators of this process remain elusive. Here, we analyzed the organization and dynamics of postsynaptic nicotinic acetylcholine receptors (nAChR) following muscle denervation. Using fluorescent conjugates of α-bungarotoxin (BTX), we found that loss of nAChR stability preceded morphological disintegration. Early after denervation, the combined use of receptor labeling and lectin staining revealed a rearrangement of long-lasting or newly inserted receptors that resulted in a novel compartmentalized postsynaptic pattern in which stable, pre-existing nAChRs concentrated centrally, while newly inserted, dynamic receptors localized peripherally. Small ectopic, highly dynamic nAChR clusters emerged since early denervation. Additionally, intracellular ring-like nAChR aggregates emerged since early denervation stages and were distributed in perinuclear regions, co-localizing with the lysosomal marker LAMP1, consistent with a degradative fate. Altogether, specific combinations of nAChR dynamics and morphologies serve as early markers of NMJ dismantling. These novel criteria to assess NMJ integrity may help define therapeutic windows to promote reinnervation in degenerative neuromuscular conditions.

The latent features of RNA sequences are crucial for our understanding of their functions. Thus, Transformer-based nucleotide language models have received widespread attention; however, the O(n²) complexity of Transformer limits their ability to process long sequences. In this work, we propose RNAret, an RNA language model based on Retention Network, which achieves training parallelism, low computational overhead, and long-sequence processing through a retention mechanism, with O(n) complexity. We pretrain RNAret using a self-supervised masked language modeling approach on 29.8 million RNA sequences. Experiments demonstrate the merit of RNAret as an RNA language model, achieving superior performance on a range of tasks, including RNA-RNA interaction prediction, RNA secondary structure prediction, and mRNA/lncRNA classification. RNAret shows strong potential for extracting latent features from RNA sequences and advancing our understanding of RNA biology.

Actions are the building blocks of our dynamic visual world, yet the neural computations supporting action perception are not well understood. How does perceptual and conceptual information unfold in the brain when we observe what others are doing? We collected EEG and fMRI data while participants viewed short videos and sentences depicting naturalistic actions. Using representational similarity analysis, we found distinct conceptual representations along the ventral, dorsal, and lateral pathways, with the target of actions specifically encoded in lateral occipitotemporal cortex (LOTC) and posterior superior temporal sulcus (pSTS). Among conceptual features, the target of actions (i.e. whether the action was directed at an object, a person, or the self) explained the most unique variance in EEG responses. Finally, EEG-fMRI fusion revealed rapid processing along the lateral and dorsal pathways. Together, our results disentangle the perceptual and conceptual components of action understanding and characterize the underlying spatiotemporal dynamics in the human brain.

In sessile animals, body surface-associated water currents are essential for integrating feeding, cleaning, and boosting metabolic exchange across colonies or communities of solitary individuals. The evolutionary origins of surface currents and their distribution among cnidarians remain poorly understood. Here, we investigated directional surface currents by tracking moving fluorescent beads on live specimens. We show that surface-associated flows are widespread among cnidarians, including anthozoans, scyphozoans, and cubozoans, but vary in complexity. The structural organization of these currents, as well as flow regimes, correlates with animal size, coloniality, and feeding strategy, highlighting their evolutionary significance across diverse lifestyles and morphologies. Notably, we observed a consistent absence of cilia-driven surface flows in octocorals, hydrozoans, and staurozoans. Moreover, surface flow was also stage-dependent, being absent in medusae but present in polyps of the same species. This suggests that the muscle-mediated motility of a cnidarian medusae might reduce the necessity for surface-mediated hydrodynamic control in cnidarians. Overall, the patchy distribution of cilia-driven surface currents implies repeated evolutionary gains and losses under selective pressure in multiple systematic groups.

Disruption of the circadian clock as well as reduced NAD⁺ levels are both hallmarks of aging. While circadian rhythms and NAD⁺ metabolism have been linked in heart disease, their relationship during cardiac aging is less clear. Here, we show that aging leads to disruption of diurnal gene expression in the heart. Long-term supplementation with the NAD⁺ precursor nicotinamide riboside (NR) boosts NAD⁺ levels, reprograms the diurnal transcriptome, and reverses naturally occurring cardiac enlargement in aged female mice. In addition, drastic reduction of NAD⁺ levels in cardiomyocytes impairs PER2::luc oscillations, which is rescued by NR supplementation. Finally, we demonstrate that changes to the cardiac transcriptome due to NR treatment partially depend on the activity of SIRT1. These findings reveal an essential role for NAD⁺ in regulation of the cardiac circadian clock upon aging, which opens up new avenues to counteract age-related cardiac disorders.