Pavlovian biases reflect how evolutionarily hard-wired tendencies-automatic approach toward reward cues and withdrawal from threat cues-can interfere with flexible, goal-directed action. Such biases arise through three m...Pavlovian biases reflect how evolutionarily hard-wired tendencies-automatic approach toward reward cues and withdrawal from threat cues-can interfere with flexible, goal-directed action. Such biases arise through three mechanisms: (a) anticipated rewards energize action while anticipated punishments suppress it (response bias), (b) agents learn differently from actions than from inactions (learning bias), and (c) reward/punishment cues themselves drive repetitive behavior, independent of outcomes (perseveration bias). The neural origin of these biases is unclear. Past evidence suggests dorsal anterior cingulate cortex (dACC) and anterior insula (aIns) as part of a "reset network" that rapidly responds to salient information and might contribute to these biases. We used transcranial ultrasonic stimulation (TUS) in 29 healthy participants to interfere with neural activity in these regions and test their causal role in a within-subject, counter-balanced design across three sessions (sham, TUS-dACC, TUS-aIns). Computational modeling revealed a functional differentiation of both regions in Pavlovian biases: while TUS to either region did not affect the response bias, TUS to the aIns decreased people's learning bias, while TUS to dACC increased participants' perseveration bias. Although the dACC and aIns are part of the same network and often co-activate during decision-making tasks, TUS interference reveals their distinct roles: the dACC mediates cue-dependent persistence while the aIns is critical for inferring whether outcomes are self-caused.
Visual selection is often conceptualized as emerging from goal-, stimulus- and history-driven processes within spatial priority maps. Although extensive work detailed the interplay between goal- and stimulus-driven selec...Visual selection is often conceptualized as emerging from goal-, stimulus- and history-driven processes within spatial priority maps. Although extensive work detailed the interplay between goal- and stimulus-driven selection, it is largely unknown how goal- and history-driven processes jointly drive selection. While persistent neural firing likely underlies goal-driven selection, it is generally assumed that activity-silent mechanisms effectuate history-driven selection. Due to these different underlying neural mechanisms, simultaneously tracking goal- and history-driven influences neurally has proven difficult. We here employed EEG decoding techniques to simultaneously track and compare goal- and history-driven influences on search. We first established a history-driven signal: Neural decoding closely tracked the target location from the preceding trial. We further demonstrated simultaneous, distinct neural representations of the current and preceding target locations. Strikingly, even when participants attended an upcoming target location before search could commence, prior target locations were reactivated. Our results show that past experiences are reactivated in an inflexible fashion, and do so even when prior targets are completely task-irrelevant. Together, we demonstrate that goal- and history-driven selection are neurally distinct, and reveal that both influences are represented in parallel.
The tree shrew (Tupaia belangeri), phylogenetically proximal to primates, serves as a critical model for evolutionary neurobiology and disease mechanisms. High-resolution MRI provides a unique opportunity to refine its n...The tree shrew (Tupaia belangeri), phylogenetically proximal to primates, serves as a critical model for evolutionary neurobiology and disease mechanisms. High-resolution MRI provides a unique opportunity to refine its neuroanatomical architecture and facilitate cross-species comparisons. Here, we present a comprehensive, ultra-high-resolution (9.4T) MRI atlas of the tree shrew brain, integrating structural and diffusion imaging to resolve fine-scale anatomical features and whole-brain connectivity gradients. Our comparative analysis characterizes the tree shrew as a distinct evolutionary mosaic: the cerebellum exhibits pronounced volumetric expansion and connectivity gradients recapitulating those of primates, whereas the hippocampus retains rodent-like architectural scaling yet preserves evolutionarily conserved longitudinal functional axes. Moving beyond these regional adaptations, we uncovered a universal organizational principle: geometry-gradient coupling (GGC)-the fundamental constraint of brain shape on functional organization. By systematically linking geometric eigenmodes to connectivity gradients across diverse species (from mice to humans), we demonstrate that despite dramatic morphological divergence, the spatial alignment between brain geometry and functional organization remains evolutionarily invariant. Collectively, these results establish the tree shrew as a pivotal phylogenetic bridge and provide a neuroanatomical benchmark for deciphering the interplay between structural diversity and universal biophysical constraints.
Ben Chehida Y, van der Heijden ESM, Page E
… +18 more, Salazar C PA, Rosser N, Córdova KGG, Sánchez-Prado M, Sánchez-Carvajal MJ, Chandi F, Arias-Cruz AP, Radford M, Lamas G, Jiggins CD, Mallet J, McClure M, Salazar C, Elias M, Bacquet CN, Nadeau NJ, Dasmahapatra KK, Meier JI
Convergent evolution, the repeated evolution of similar phenotypes, is widespread in nature, but there are few studies investigating the genetic mechanisms of convergence across wide evolutionary timescales. The extent t...Convergent evolution, the repeated evolution of similar phenotypes, is widespread in nature, but there are few studies investigating the genetic mechanisms of convergence across wide evolutionary timescales. The extent to which the same genetic mechanisms contribute to convergent evolution could reveal whether the pathway towards these fitness optima is flexible or constrained to follow a particular route, informing us about the predictability of evolution. Wing color pattern mimicry in Lepidoptera is a well-known example of convergent evolution, but as studies are restricted to a few closely related species, it is difficult to make general inferences about the predictability of evolution in this system. Here we study convergent evolution in multiple mimetic neotropical lepidopteran lineages that diverged between ~1 and 120 Mya, including seven species of Ithomiini and Heliconius butterflies and a day-flying Chetone moth. Across butterfly lineages that diverged up to ~30 Mya, the genetic variants most strongly associated with convergent color pattern switches are located in similar noncoding regions near the genes ivory and optix. In the more distantly related moth species, color pattern variation is associated with a ~1 Mb inversion which also contains ivory, closely mirroring the supergene architecture of the co-mimetic butterfly Heliconius numata. In contrast to previous studies on Heliconius butterflies, we find limited evidence that convergence among closely related Ithomiini species results from alleles shared by hybridization. Repeated parallel evolution of regulatory switches via reuse of the same two genes suggests that convergent color pattern evolution is highly constrained and predictable even across large evolutionary timescales. Such constraints may have facilitated diverse taxa joining this species-rich mimicry ring.
There is extensive evidence that the spread of innovation via social learning can facilitate uptake of new foraging behaviours in populations. In comparison, social learning about novel food types has received comparativ...There is extensive evidence that the spread of innovation via social learning can facilitate uptake of new foraging behaviours in populations. In comparison, social learning about novel food types has received comparatively little attention. Yet the adoption of novel food is vital to persistence in, or colonisation of, novel environments. Here, we present a novel food (almonds in the shell, coloured either blue or red) in a two-option and control cultural diffusion experiment to five neighbouring roosts of 705 individually-marked sulphur-crested cockatoos (Cacatua galerita) living in a highly urbanised environment. From 4 initially trained individuals, a total of 349 individuals across all roosts learned to feed on the novel food within 10 days of first exposure. Using network-based diffusion-analysis (N = 214 learners out of 322 individuals with available social information), we demonstrated that this spread occurred almost exclusively through social learning, with information spreading through social network ties. Second, using experience-weighted attraction models, we described age-differences in social learning strategies, with juveniles, but not adults, exhibiting a conformist bias to prefer the most frequently chosen food colour. Third, when analysing 539 opening techniques of the novel food by 147 individuals across the five roosts, we found that opening techniques were more similar between roost communities when the distance between sites was small, or the degree of movement between sites was high. In addition, when focusing on a subset for which social association data were available (273 openings by 78 individuals), techniques tended to be more similar between close associates. Taken together, our study suggests that the adoption of novel food in urban-living sulphur-crested cockatoos is facilitated by social transmission of knowledge through networks, with food choice further influenced in juveniles by a conformist learning bias. Social networks influenced both food choice and acquisition of foraging techniques within and between roosting communities, leading to differences at surprisingly local scales. The utilisation of new food resources is a fundamental component of adaptive behavioural responses to novel environments. Our study demonstrates how cognitive and social influences can be vital determinants of this adaptive flexibility.
Arboviruses induce acute lytic infection in human cells but establish persistent infection in their mosquito vectors, a viral strategy that is essential for sustained viral transmission. How mosquito cells maintain conti...Arboviruses induce acute lytic infection in human cells but establish persistent infection in their mosquito vectors, a viral strategy that is essential for sustained viral transmission. How mosquito cells maintain continuous production of viral progeny without compromising host cell viability remains a fundamental unresolved question. Because arbovirus replication in human cells relies on viral takeover of the host translational machinery, we investigated how translation is regulated during persistent infection in mosquito cells using chikungunya virus (CHIKV) as a model. A temporal analysis of viral RNA translation in RNAi-competent and RNAi-deficient Aedes albopictus cells revealed that persistence was associated with reduced viral protein production resulting from translation repression of viral RNAs. Subcellular localization analyses of the viral protein nsP2 and LC-MS/MS analyses of host tRNAs showed that, in contrast to human cells, CHIKV infection in mosquito cells neither induced nuclear relocalization of viral nsP2 to induce global host mRNA depletion, nor reshaped the tRNA modification landscape to compensate for the suboptimal codon usage of viral RNAs. Together, our results indicate that persistent infection in mosquito cells is characterized by a balanced host-virus translational state, in which limited viral translation is maintained while viral takeover of the host translational machinery is avoided. Notably, translation repression of viral RNAs was also observed during Zika virus (ZIKV) infection, suggesting that this mechanism may represent a general RNAi-independent feature of arbovirus persistence in mosquito cells.
Virulent bacteriophages infecting Klebsiella pneumoniae often show capsule-driven host tropism due to the presence of capsule-specific depolymerases. Yet for temperate phages the genetic and functional basis of such caps...Virulent bacteriophages infecting Klebsiella pneumoniae often show capsule-driven host tropism due to the presence of capsule-specific depolymerases. Yet for temperate phages the genetic and functional basis of such capsular specificity remains less well understood. Depolymerases appear unexpectedly rare in prophage genomes, raising unresolved questions about which prophage genes mediate capsular specificity, whether this apparent scarcity reflects biological or ecological differences versus annotation limitation, and whether prophage-encoded receptor-binding proteins (RBPs) are functionally active. To address these questions, we analysed 3,900 Klebsiella genomes from diverse ecological niches to identify prophage-encoded proteins mediating capsular specificity. We conducted a genome-wide association study (GWAS) correlating prophage protein clusters (from 8,105 prophages) with confidently assigned bacterial K-loci. GWAS revealed statistically supported predictors of capsular specificity for 16 of the 35 most diverse K-loci analysed. These predictors were dominated by diverse RBPs, including classical [Formula: see text]-helix depolymerases (6 predictors), SGNH-domain hydrolases predicted to deacetylate polysaccharides (6 predictors), and structurally novel RBPs lacking known depolymerase folds (2 predictors). Nearly one-third of K-loci yielded no statistically significant predictors. A targeted experimental screen of 50 candidate prophage depolymerases showed that 34 failed to yield detectable recombinant expression, and neither sequence similarity, structural prediction, nor prophage genomic context reliably predicted activity. Of the 14 active enzymes, 5 targeted a K-type different from that predicted of their bacterial host, and enzyme specificity was not consistently explained by sequence or structural homology. Comparison with GWAS predictions revealed that 10 of the 12 strongest GWAS predictors were experimentally validated, while 2 remained inconclusive. Together, these results highlight the intrinsic difficulty of predicting activity and capsular specificity of prophage-encoded RBPs from genomic information alone. Finally, analysis of 4,598 high-completeness prophages revealed that SGNH-domain hydrolases are among the most prevalent enzymatic domains in prophage RBPs. Two SGNH-domain RBPs identified by GWAS were experimentally confirmed as active esterases, supporting capsule deacetylation as a widespread alternative to polysaccharide depolymerisation in temperate phages. Our findings reveal that Klebsiella prophages encode structurally diverse RBPs, suggesting temperate phages may rely not only on depolymerisation but also on capsule modification-such as deacetylation-for infection. This also suggests that capsule modification may contribute to phage-host interactions in ways not fully captured by current K-locus assignments, with potential implications for phage specificity, competition and vaccine design.
Uncovering what drives select biomolecules to form phase-separated condensates in vivo and identifying their physiological significance are topics of fundamental importance. Here, we show that nitrogen-starved Escherichi...Uncovering what drives select biomolecules to form phase-separated condensates in vivo and identifying their physiological significance are topics of fundamental importance. Here, we show that nitrogen-starved Escherichia coli produces long-chain polyphosphates, which scaffold the RNA chaperone Hfq into high molecular weight complexes, which eventually phase separate together with components of the RNA translation and processing machinery. The presence of polyphosphate within these condensates controls Hfq function by selectively stabilizing polyadenylated RNAs involved in transcription and protein translation and by promoting interactions with translation- and RNA-metabolism-associated proteins involved in de novo protein synthesis. Lack of polyphosphate significantly impairs condensate formation, increases cell death, and hinders recovery from N-starvation. In functional analogy, we demonstrate that polyP contributes specifically to the formation of Processing (P)-bodies in mammalian cell lines, revealing that a single, highly conserved and ancestral polyanion serves as a modulator for functional phase-separated condensate formation across the tree of life.
Humans exhibit a striking and near-universal population-level right-hand preference, an evolutionary singularity unmatched among primates. Despite its pervasiveness, the origins of this lateralization remain poorly under...Humans exhibit a striking and near-universal population-level right-hand preference, an evolutionary singularity unmatched among primates. Despite its pervasiveness, the origins of this lateralization remain poorly understood. Here, we combine phylogenetic comparative methods with meta-analysis to investigate manual lateralization across 41 anthropoid species (n = 2,025), testing longstanding eco-evolutionary hypotheses for handedness direction (mean handedness index, MHI) and strength (mean absolute handedness index, MABSHI). Our models reveal significant phylogenetic signal for both traits and identify Homo sapiens as an evolutionary outlier, exhibiting exceptional rightward bias and strength relative to phylogenetic expectations. However, this outlier status disappears when brain size (endocranial volume) and intermembral index are included, suggesting these factors are central to the emergence of human handedness. We also show that high MABSHI evolved early in hominin evolution, while MHI increased to unparalleled levels with the appearance of the genus Homo. Our findings identify bipedalism and neuroanatomical expansion as likely key drivers of uniquely human lateralization, while also revealing broader ecological patterns shaping handedness across primates. This work provides a framework for disentangling human-specific adaptations from general primate trends in the evolution of behavioral asymmetries.
Termites produce the most diverse array of terpenoids among terrestrial metazoans, comprising over 200 structures. However, their biosynthesis has not yet been elucidated. Here, we identify a gene family which arose thro...Termites produce the most diverse array of terpenoids among terrestrial metazoans, comprising over 200 structures. However, their biosynthesis has not yet been elucidated. Here, we identify a gene family which arose through a series of duplications of geranylgeranyl pyrophosphate synthase in the common ancestor of Neoisoptera, the terpene-producing termite lineage. We functionally characterized several proteins from this rich GGPPS-like family as terpene synthases generating biologically relevant sesqui- and diterpenes. These include the queen pheromone (3R,6E)-nerolidol in Embiratermes neotenicus and the presumed precursor of polycyclic defensive diterpenes (E,E,E)-neocembrene in Nasutitermes takasagoensis. We report significant enrichment of transposable elements in the GGPPS-like genomic loci, study the selection pressures acting in the evolution of the GGPPS-like family, and highlight an amino acid site crucial for cyclization capacity and enantiospecificity of the characterized enzymes. We conclude that we have identified an enzyme family that facilitated the emergence of the remarkable richness of termite terpenoids.
Response inhibition is an important cognitive control mechanism that enables flexible behavior by stopping inappropriate actions. Intracranial recordings across species have identified a neural circuit that implements re...Response inhibition is an important cognitive control mechanism that enables flexible behavior by stopping inappropriate actions. Intracranial recordings across species have identified a neural circuit that implements response inhibition via the subthalamic nucleus of the basal ganglia. However, this work has been limited to simple tasks, in which unequivocal, salient "stop"-signals require the inhibition of all ongoing responses. Notably, response inhibition in the real world is substantially different. Real-world response inhibition is selective: it occurs only after specific salient signals ('stimulus-selectivity') and stops only specific movements while others continue ('response-selectivity'). If and how the fronto-subthalamic system implements selective inhibition is largely unknown. Here, we recorded subthalamic local field potentials and scalp-EEG in humans performing a novel, selective inhibition task. Salient signals either required stopping all initiated responses (global inhibition), stopping only some responses (response-selective inhibition), or continuing all responses-i.e., ignoring the signal (which ensures stimulus-selectivity). All three signals initially triggered a common fronto-subthalamic inhibitory process, signified by a rapid increase in β-burst activity. During global inhibition, subthalamic β-bursting subsequently increased above baseline, persisting for over a second. During response-selective inhibition, this activity was delayed, which enabled a second bout of disinhibition and allowed appropriate responses to continue. Throughout this period, frontal cortical and subthalamic β-band activity were tightly coupled. This shows that selective inhibition is accompanied by rapid, context-dependent engagement and release of fronto-subthalamic inhibition. Moreover, subthalamic activity lasted substantially longer than assumed by classic behavioral-computational models. This supports recent theoretical models that assume protracted response inhibition during action-stopping.
Spatial structure can functionally determine ecological interactions and evolution of microbial communities. The gut microbiota is known to be spatially structured longitudinally along the gastrointestinal tract, but mic...Spatial structure can functionally determine ecological interactions and evolution of microbial communities. The gut microbiota is known to be spatially structured longitudinally along the gastrointestinal tract, but micro-scale structure in the gut lumen has not been extensively explored. Here, we show that bacteria cluster within species in the cecum of gnotobiotic mice. We find that clustering is not driven by active swimming, antibody-mediated aggregation, or factors exclusive to the host, but likely due to bacterial growth in the matrix of gut content. In samples from mice and humans, we show that upper large-intestinal content behaves as a nonNewtonian fluid that changes its viscoelastic properties under the force of gut contractions. We argue that microbial growth in the gel-like structure of cecum content can lead to micro-scale bacterial clustering, which is periodically disrupted by peristalsis-driven shear thinning and clearance. Our study shows mechanistically how spatial structure in the gut emerges through the interplay between microbial and host physiology and highlights the possibility of host control over gut microbiota distribution through gut contractions.
Eggs released in the environment are at risk from many threats. A recent study in PLOS Biology reveals that plastid-derived carotenoid crystals in sea urchin eggs benefit larval survival and trans-oceanic dispersal.Eggs released in the environment are at risk from many threats. A recent study in PLOS Biology reveals that plastid-derived carotenoid crystals in sea urchin eggs benefit larval survival and trans-oceanic dispersal.
Carrier TJ, Rufino-Navarro A, Knoop T
… +10 more, Repnik U, Caraballo-Rodríguez AM, Needham DM, Bang C, Franzenburg S, Bramkamp M, Rath W, Biastoch A, Hernández JC, Hentschel U
Development in the sea has long been thought to be a nutritional gamble that disproportionately ends in starvation. Here, we support the premise that components of plastids appear to be incorporated into sea urchin eggs...Development in the sea has long been thought to be a nutritional gamble that disproportionately ends in starvation. Here, we support the premise that components of plastids appear to be incorporated into sea urchin eggs and that these, in turn, benefit development. We find chromoplast-derived carotenoid crystals and chromoplast-specific metabolites inside the eggs of the sea urchin Arbacia lixula. We find evidence of plastid DNA in the eggs of 11 other sea urchins, with diatoms being the primary source and taxonomic richness of these plastid taxa directly related to egg size. The light-dependent activity of these chromoplast components influences phytohormone and lipid metabolism as well as offspring development, morphological plasticity, and survival. Offspring that benefit from these chromoplast components are predicted to disperse further, over larger geographic areas, and use a wider range of currents, including those that cross ocean basins. Data presented here challenge the long-held belief that components of non-metazoan organelles are unable to enter the germline and be passed between generations. We hypothesize that sea urchins manipulate plastids solely for their self-interest with the result of this process being a novel and adaptive form of maternal provisioning.
Cilia dysfunction is implicated in a range of disorders. Here, we present CiliaKB, a manually curated knowledge base that serves as a one-stop platform for researchers to rapidly access mechanistic data and mine for tran...Cilia dysfunction is implicated in a range of disorders. Here, we present CiliaKB, a manually curated knowledge base that serves as a one-stop platform for researchers to rapidly access mechanistic data and mine for translational clues about cilia.
P2X receptors are ATP-gated cation channels, and the P2X3 subtype plays crucial roles in peripheral sensory neurons, including in chronic pain and chronic cough. Accordingly, P2X3 receptors have attracted substantial int...P2X receptors are ATP-gated cation channels, and the P2X3 subtype plays crucial roles in peripheral sensory neurons, including in chronic pain and chronic cough. Accordingly, P2X3 receptors have attracted substantial interest as a therapeutic target. Gefapixant, a negative allosteric modulator (NAM) of P2X3 receptors, has been approved in some countries for the treatment of chronic cough; however, its limited selectivity for P2X3 homomers over P2X2/P2X3 heteromers is associated with taste disturbance as a prominent adverse effect. These limitations have motivated the development of next-generation NAMs with improved subtype selectivity, but their subtype-specific allosteric inhibition mechanisms are unclear. Here, we report the cryo-EM structure of the human P2X3 receptor in complex with ATP and the P2X3-selective next-generation NAM sivopixant, an investigational drug. Sivopixant binds to an allosteric site at the portal of the central pocket in the extracellular domain, and structure-based mutational analysis by electrophysiology identifies key residues required for sivopixant-dependent inhibition of human P2X3 receptors. Structural comparisons across P2X subtypes, together with patch-clamp analyses of gain-of-function mutants that confer sensitivity to two investigational drugs, sivopixant and camlipixant, provided a broadly applicable structural framework for subtype selectivity. Furthermore, structural comparisons with apo and ATP-bound open states of P2X3 receptors, together with molecular dynamics simulations, revealed that sivopixant expands the upper-body domain to suppress the lower-body movements required for channel activation, thereby preventing channel opening even in the presence of ATP.
Bats are asymptomatic reservoirs of several zoonotic viruses. This may result from long-term co-evolution between viruses and bats, that have led to host adaptations contributing to an effective balance between strong an...Bats are asymptomatic reservoirs of several zoonotic viruses. This may result from long-term co-evolution between viruses and bats, that have led to host adaptations contributing to an effective balance between strong antiviral responses with innate immune tolerance. To better understand these virus-host interactions, we combined comparative transcriptomics, phylogenomics and functional assays to characterize the evolution of bat innate immune antiviral factors. First, we stimulated the type I interferon immune pathway in Myotis yumanensis primary cells and identified guanylate-binding protein 5 (GBP5) as the most differentially expressed interferon-stimulated gene (ISG). Phylogenomic analyses showed that bat GBP5 has been under strong episodic positive selection, with numerous rapidly evolving sites and species-specific gene duplications, suggesting past evolutionary arms races. Functional tests on GBP5 orthologs from 10 bat species covering the >60 million years of Chiroptera evolution revealed species- and virus-specific restrictions against RNA viruses (retrovirus HIV, and rhabdoviruses European bat lyssavirus and VSV), which are typical signatures of adaptations to past viral epidemics. Interestingly, we also observed a lineage-specific loss of the GBP5 prenylation motif in the common ancestor of Pipistrellus and Eptesicus bats. Importantly, resurrection of the prenylation motif in Eptesicus fuscus GBP5 in corresponding bat cells was associated with different GBP5 subcellular localization and loss of anti-rhabdoviral functions, suggesting specific adaptation to ancient viral epidemics ~22 million years ago. Altogether, our results highlight adaptations that contribute to bat specific immunity and provide insights into the functional evolution of antiviral effector GBP5.
The ribosome is responsible for protein synthesis in all cells, and is the cell's largest energy consumer. We propose that the ribosome originated as a mutualistic symbiont of an RNA-dependent RNA polymerase ribozyme, su...The ribosome is responsible for protein synthesis in all cells, and is the cell's largest energy consumer. We propose that the ribosome originated as a mutualistic symbiont of an RNA-dependent RNA polymerase ribozyme, supplying peptides that enhanced replication. As life transitioned from the RNA to the RNA-protein world, autonomous replicators became irreversibly addicted to the ribosome for producing replication proteins. Subsequent evolution is construed as a ribosomal takeover, whereby the ribosome evolved to consume most of the cell's resources, while other cellular componentry ensured the propagation of the ribosome, while being fully dependent on it. Under this perspective, the ribosome is a complex symbiont of the cell with pronounced selfish properties.
As team science grows, so do 'equal contribution' designations, yet this information is routinely hidden or lost, creating inequity in recognition and crediting. We must fix this problem, now.As team science grows, so do 'equal contribution' designations, yet this information is routinely hidden or lost, creating inequity in recognition and crediting. We must fix this problem, now.