PLoS Biol. [JOURNAL]
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200 papers
Does adaption require a complex symphony or just "three chords and the truth?".
Udekwu KI, Marx CJ
PLoS Biol · 2026 Mar · PMID 41894319 · Full text
How predictable are the collateral effects of adaptation? A new study of evolved yeast strains published in PLOS Biology suggests that growth across environments is fairly predictable because the selected mutations only...
How predictable are the collateral effects of adaptation? A new study of evolved yeast strains published in PLOS Biology suggests that growth across environments is fairly predictable because the selected mutations only affected a few latent fitness-impacting phenotypes.
Prenatal and early postnatal periods differentially shape the maturation of human cortical microstructure and myelin.
Tsigaras T, Dukart J, Oldham S … +2 more , Eickhoff SB, Paquola C
PLoS Biol · 2026 Mar · PMID 41886498 · Full text
During late gestation and early postnatal development a combination of intrinsic and extrinsic factors drive the maturation of the human cortex. This process is regionally heterogeneous, with cortical areas developing at...
During late gestation and early postnatal development a combination of intrinsic and extrinsic factors drive the maturation of the human cortex. This process is regionally heterogeneous, with cortical areas developing at different paces and trajectories. Leveraging submillimetre T1-weighted/T2w-weighted (T1w/T2w) magnetic resonance imaging (MRI) from pre- and full-term neonates (n = 599, 26-44 weeks), we sampled intracortical profiles across the cortex and characterized the profiles' shapes according to their central moments. We found that gestational age at birth dominated the effects on early cortical development, with significant, global increases in intracortical homogeneity and a bimodal change in the balance of myelin-sensitive signal between superficial and deeper cortical layers. On the other hand, weeks since birth (i.e., postnatal age) exhibited different effects on myelin, with increasing intracortical heterogeneity and intracortical balance only shifting towards deeper layers in posterior temporal, occipital, medial parietal areas and some prefrontal areas. These effects align with low spatial-frequency geometric eigenmodes of the human cortex, specifically the anterior-posterior and superior-inferior axes. Our findings demonstrate that separating prenatal from postnatal influences, and analyzing intracortical profiles rather than macroscale features, provides finer-grained insights into how human cortical myelin changes during perinatal development and lays the groundwork for investigating the biological underpinnings that govern normative cortical maturation.
A responsible authorship culture is needed and it is a collective responsibility.
Kiermer V, Bibbins-Domingo K, Skipper M
PLoS Biol · 2026 Mar · PMID 41886481 · Full text
In this Formal Comment, representatives from PLOS, Nature and JAMA call for action on adopting a principle-based approach for a responsible authorship culture.
In this Formal Comment, representatives from PLOS, Nature and JAMA call for action on adopting a principle-based approach for a responsible authorship culture.
Cell cycle dynamics regulate H3K27 and H3K9 histone modifications in Drosophila.
Nogay L, Vijayakumar Maya A, Heckmann L … +7 more , Cardamone F, Grass I, Singh A, Frey A, Ernst L, Iovino N, Classen AK
PLoS Biol · 2026 Mar · PMID 41886469 · Full text
Cell cycle progression presents a fundamental challenge to epigenome integrity, particularly due to the need to reestablish post-translational histone modifications (PTMs) following DNA replication. Although proliferativ...
Cell cycle progression presents a fundamental challenge to epigenome integrity, particularly due to the need to reestablish post-translational histone modifications (PTMs) following DNA replication. Although proliferative and differentiating tissues exhibit markedly different cell cycle dynamics, how these differences shape the histone modification landscape in vivo remains largely unexplored. Here, we show that levels of H3K27ac, H3K27me3, and H3K9me3 are tightly linked to cell cycle dynamics in the Drosophila wing imaginal disc. We demonstrate that both physiological and pathological elongation of the cell cycle led to an accumulation of H3K9me3 and H3K27me3, whereas cell cycle acceleration reduces their levels. In contrast, H3K27ac exhibits the opposite pattern: levels decrease in arrested cells and increase with faster cycling. Genome-wide CUT&Tag analysis reveals that these changes predominantly affect genomic loci already modified in normally proliferating tissue. Importantly, the regulation of methylation levels at H3K9 and H3K27 is not solely mediated by the cell cycle machinery but reflects a metabolically guided process in which the rate of methylation is coupled to the rate of cell proliferation through metabolic activity, including signaling via the Insulin/PI3K/Akt pathway. Our study thus reveals key principles for understanding histone methylation in proliferating, senescent, and differentiating cells. In contrast, H3K27 acetylation is regulated through a distinct, cell cycle-coupled mechanism. We find that CBP/Nejire-mediated acetylation of H3K27 peaks during early and late S-phase and is reversed by HDAC1, as cells exit replication. Together, our findings establish a robust link between cell cycle progression and histone modification dynamics, highlighting the necessity of maintaining balanced PTM levels under varying proliferative states. These insights have broad implications for our understanding of development, aging, and tumor growth.
Neuronal populations across the cortex underlie discrete, categorical, and subjective representations of visual durations.
Centanino V, Fortunato G, Bueti D
PLoS Biol · 2026 Mar · PMID 41886464 · Full text
The neural processing of subsecond durations recruits a wide network of areas. Although unimodal tuning has been shown in many of these regions, its role and link to perception remain unclear. Here, we used 7T functional...
The neural processing of subsecond durations recruits a wide network of areas. Although unimodal tuning has been shown in many of these regions, its role and link to perception remain unclear. Here, we used 7T functional MRI while participants performed a visual duration categorization task to characterize unimodal responses along the cortical hierarchy. We found topographically organized neuronal populations tuned to all presented durations in parietal and premotor cortices, and in the caudal supplementary motor area (SMA). In contrast, rostral SMA, inferior frontal cortex, and anterior insula showed neuronal preferences centered around the mean duration, which correlated with the boundary duration participants employed in the task. These differences suggest specialized roles of duration tuning across cortical regions -from discrete to categorical and subjective duration representations. Finally, correlations of neuronal preferences across areas highlighted a hierarchical organization of duration tuning. Together, our findings provide a mechanistic framework for duration perception in vision.
Self-allocation bias in performance-based cooperative decisions is driven by self-interest rather than distorted performance encoding.
Zhang S, Yong X, Ma Y … +1 more , Korn CW
PLoS Biol · 2026 Mar · PMID 41886463 · Full text
Human cooperation often involves performing joint tasks, where success relies on how collective rewards are allocated among cooperating parties based on their individual performance and contribution to task outcomes. How...
Human cooperation often involves performing joint tasks, where success relies on how collective rewards are allocated among cooperating parties based on their individual performance and contribution to task outcomes. However, it remains unclear whether and how individual performance and contribution give rise to self-related biases in such allocation decisions. Here, we developed a novel performance-based social allocation task that manipulated how individual performance contributed to joint outcomes. Across two experiments, participants exhibited a robust self-allocation bias: they allocated more rewards to themselves and disproportionately disregarded their own performance, particularly when their performance did not causally contribute to the joint outcome. This self-allocation bias was amplified in individuals with stronger individualistic social preferences, as measured by social value orientation. At the neural level, self-relevant (versus self-irrelevant) allocation decisions were associated with increased activity in the medial prefrontal cortex extending into the anterior cingulate cortex, insula, and temporoparietal junction (TPJ). Moreover, the dorsomedial prefrontal cortex, lateral orbitofrontal cortex, and TPJ tracked trial-by-trial variations in relative performance as a function of contribution structure, independent of self-relevance. Together, these findings suggest that self-allocation bias in performance-based decisions is unlikely to arise from distorted neural encodings of performance. Instead, self-interest may shape how contribution-structured performance information is used in social-allocation choices, providing a more precise account of how self-serving behavior emerges in cooperative contexts.
Genotype-fitness mapping of adaptive mutants reveals shifting low-dimensional structure across divergent environments.
Ghosh OM, Kinsler G, Good BH … +1 more , Petrov DA
PLoS Biol · 2026 Mar · PMID 41886417 · Full text
A central goal in evolutionary biology is to predict the effect of a genetic mutation on fitness. This is a major challenge because it requires knowledge of both the phenotypic effects of a mutation and their importance...
A central goal in evolutionary biology is to predict the effect of a genetic mutation on fitness. This is a major challenge because it requires knowledge of both the phenotypic effects of a mutation and their importance in an arbitrary environment, which are high-dimensional quantities and difficult to guess a priori. Here, we address this problem by taking a top-down, data-driven approach to infer the mapping between genotypes, latent phenotypes, and fitness. We measure the fitness effects of a large collection of adaptive yeast mutants in many lab environments, from which we build low-dimensional, linear fitness landscapes. We find that these models are highly predictive of fitness variation for thousands of adaptive mutants, both in environments similar to where they evolved and also in divergent environments. This implies that the underlying genotype-phenotype-fitness maps for these adaptive mutants tend to be broadly low-dimensional. We further demonstrate that these maps only partially overlap across divergent environments, suggesting that the phenotypic determinants of fitness shift with the environment but remain low-dimensional. These results combine to emphasize the importance of environmental context in evolution, and suggest that top-down, low-dimensional fitness landscapes pave the way for evolutionary prediction.
Oligomeric lactic acid nanoplastics induce intrauterine growth restriction in mice by disrupting GATA2-mediated placental vascular development.
Lv J, Wang M, Shi C … +11 more , Wang Y, Zhang Y, Gao C, Bi TQ, Yang J, Xu Y, Wang Q, Wang H, Xu DX, Fang M, Huang Y
PLoS Biol · 2026 Mar · PMID 41886399 · Full text
Humans are increasingly exposed to "eco-friendly" biodegradable microplastic pollution, whose usage in packaging and medical applications is growing exponentially. The bioplastic polylactic acid (PLA) has recently been d...
Humans are increasingly exposed to "eco-friendly" biodegradable microplastic pollution, whose usage in packaging and medical applications is growing exponentially. The bioplastic polylactic acid (PLA) has recently been demonstrated to release large quantities of oligomeric lactic acid (OLA) nanoplastics causing adverse health effects. No research has reported on intrauterine biodistribution of OLA, and how gestational exposure may impact on early development of the fetus. Here, we reveal that OLA plastics can readily breach the placental barrier and accumulate in various fetal organs in a mouse model. Gestational exposure to environmentally relevant dose of OLA impairs vasculature development, causing intrauterine growth restriction in the pups. Mechanistically, OLA causes blockage of the vascular endothelial growth factor pathway and abnormal physiological development of placenta, which is mediated by the obstruction of transcription factor GATA2 translocation into the nucleus. This study highlights the potential developmental health effect of oligomer nanoparticles released from biodegradable PLA plastic.
Plug-and-play evolution of the Klebsiella pneumoniae capsule locus enables serotype exchange across genetic backgrounds.
Le Bris J, Varet H, Rocha EPC … +1 more , Rendueles O
PLoS Biol · 2026 Mar · PMID 41880352 · Full text
Understanding how complex, multi-gene systems evolve and function across genetic backgrounds is a central question in molecular evolution. While such systems often impose costs through epistatic interactions, some may be...
Understanding how complex, multi-gene systems evolve and function across genetic backgrounds is a central question in molecular evolution. While such systems often impose costs through epistatic interactions, some may behave as modular, "plug-and-play" units that retain function with minimal disruption. Here, we tested this using the polysaccharide capsule locus of Klebsiella pneumoniae, a highly exchangeable and fast-evolving locus, as a model. We genetically engineered capsule exchanges (swaps) across diverse genetic backgrounds and combined transcriptomics, fitness assays, and evolution experiments to show that capsule exchange has negligible effects on global expression and only marginal fitness costs, regardless of capsule type (or K type). Adaptation to capsule-costly environments consistently reduced capsule production regardless of K type, revealing shared adaptive trajectories rather than K type-specific pathways. Moreover, K type-specific traits involved in bacterial virulence, such as biofilm formation and hypermucoviscosity, were conserved across genetic backgrounds. This reveals that capsule swapping can directly shape host-pathogen interactions and influence within-patient evolution. Our findings provide strong evidence that capsule loci display plug-and-play dynamics: they are transferable, functional across contexts, and minimally disruptive to the host genome. This allows capsules to be seamlessly swapped, and help explain the evolutionary success, ecological versatility, and pervasive exchangeability of capsules in K. pneumoniae.
Three-dimensional scene boundary representations for wall orientation and distance are represented distinctly in the human visual cortex.
Wu Y, Li S
PLoS Biol · 2026 Mar · PMID 41880342 · Full text
Human spatial navigation relies on the brain's ability to visually represent the 3D layout of the environment. To understand how the brain encodes the layout information, it is crucial to identify the key features of env...
Human spatial navigation relies on the brain's ability to visually represent the 3D layout of the environment. To understand how the brain encodes the layout information, it is crucial to identify the key features of environmental layout and how they are processed in the human brain. The vector coding principle, which highlight the role of boundary distance and orientation, provides a theoretical framework supported by physiological evidence from rodents. In this study, we developed a reconstruction approach to quantitatively estimate 3D layout information from natural indoor scene images. This approach enabled analyses of fMRI data from the large-scale Natural Scenes Dataset (NSD) using vector-based models of 3D layout. To validate the NSD-based results and examine task-related dynamics, we further conducted fMRI and MEG experiments with navigation-related and non-navigational tasks. Controlling for low-, mid-, and high-level visual and semantic features of natural indoor scenes, we found a spatiotemporal dissociation between boundary distance and orientation representations in the human brain. Relative distance was encoded in the early visual cortex during early processing in a task-invariant manner, whereas orientation was represented in scene-selective higher visual areas during later processing and was modulated by navigation-related tasks. Importantly, task modulation manifested as enhanced orientation coding in early visual cortex, potentially reflecting top-down feedback and short-term maintenance mechanisms. Together, these findings provide a novel perspective on how the human brain represents navigation-relevant information about the immediate surrounding environment, advancing our understanding of the neural mechanisms that link perception to action in spatial navigation.
Frontotemporal network interactions causally support rapid concreteness judgments during reading.
Murphy E, Woolnough O, Morse CW … +2 more , Scherschligt X, Tandon N
PLoS Biol · 2026 Mar · PMID 41880289 · Full text
Neurobiological models of conceptual processing have been limited in spatiotemporal resolution, and uncertainty remains about the causal role of specific regions in concept representation. We utilized intracranial record...
Neurobiological models of conceptual processing have been limited in spatiotemporal resolution, and uncertainty remains about the causal role of specific regions in concept representation. We utilized intracranial recordings in human neurosurgical patients with epilepsy (n = 19) during a concreteness judgement paradigm of single word reading. Concrete concepts showed greater high-frequency activation across a frontal and ventrotemporal network, while greater activation for abstract words was found in lateral posterior middle temporal cortex. Intercortical communications, measured by high-frequency partial direct coherence, revealed bidirectional frontal and ventral plus lateral temporal interactions. Words occupying the middle range of the concreteness scale (e.g., "profit") activated similar regions, but high-frequency signatures were not modulated by the participants' semantic decisions about these words. Cortical stimulation of ventrotemporal cortex and inferior frontal cortex disrupted the ability to make concreteness judgements. These results suggest that semantic information is encoded via a causally directed system of bidirectional cortical cascades: early visual-linguistic integration in ventrotemporal cortex initiates directed information flow to frontal hubs, and later processing shows reciprocal flow back to ventral and lateral temporal regions integrating distinct conceptual features, with these convergence zones differing based on semantic type. Our results provide a systems-level account for how the human brain transforms word forms into grounded conceptual meaning that is invariant of subjective judgment.
TDP-43 is coming to the cottage: A new tool to study neurodegenerative diseases.
Rayner SL, Gitler AD
PLoS Biol · 2026 Mar · PMID 41880238 · Full text
In some neurodegenerative diseases, the protein TDP-43 is both lost from the nucleus and forms clumps in the cytoplasm. These two pathologies can be challenging to model, but a study in PLOS Biology presents a new system...
In some neurodegenerative diseases, the protein TDP-43 is both lost from the nucleus and forms clumps in the cytoplasm. These two pathologies can be challenging to model, but a study in PLOS Biology presents a new system that captures both features.
Disrupting CD22-cis-ligand interactions ameliorates type 1 diabetes and graft rejection by expanding regulatory B cells.
Long W, Endo A, Walakulu Gamage HN … +7 more , Yang T, Suzuki T, Nitta T, Takematsu H, Honda K, Asano M, Tsubata T
PLoS Biol · 2026 Mar · PMID 41875099 · Full text
CD22 is an inhibitory receptor expressed in B cells and is constitutively associated with α2,6-sialylated membrane proteins expressed on the same cell (cis-ligands). However, interaction with cis-ligands is required for...
CD22 is an inhibitory receptor expressed in B cells and is constitutively associated with α2,6-sialylated membrane proteins expressed on the same cell (cis-ligands). However, interaction with cis-ligands is required for the function of CD22 only in part. To address the role of ligand interaction of CD22 in immune responses, here we generated anti-CD22 antibody 1C5 that specifically inhibits ligand binding of CD22. Both Cd22-/- mice and mice treated with 1C5 show expansion of regulatory B (Breg) cells in follicular (FO) B cells, suggesting a crucial role of ligand interaction of CD22 in inhibiting the expansion of FO Breg cells. CD22 appears to recognize BCR and TLRs thereby directly or indirectly suppressing TLR signaling essential for expansion of Breg cells. Treatment of mice with 1C5 ameliorates skin graft rejection and type 1 diabetes with expansion of regulatory γδ T cells probably through expansion of Breg cells, suggesting ligand interaction of CD22 as a novel target of therapy for autoimmune diseases and graft rejection.
Immersive NREM2 dreaming preserves subjective sleep depth against declining sleep pressure.
Michalak A, Marzoli D, Pietrogiacomi F … +9 more , Bergamo D, Elce V, Pedreschi B, Mosca G, Navari A, Emdin M, Ricciardi E, Handjaras G, Bernardi G
PLoS Biol · 2026 Mar · PMID 41875080 · Full text
Perceived sleep depth is a key determinant of subjective sleep quality, traditionally thought to reflect unconsciousness and reduced cortical activation. Here, we combined high-density EEG with a serial awakening paradig...
Perceived sleep depth is a key determinant of subjective sleep quality, traditionally thought to reflect unconsciousness and reduced cortical activation. Here, we combined high-density EEG with a serial awakening paradigm during NREM2 (N2) sleep in healthy human participants to examine its neural and experiential correlates. As expected, deeper sleep was associated with reduced cortical activation, reflected in a lower high-to-low frequency power ratio. Yet, this relationship weakened in the presence of dreaming, indicating that immersive conscious experiences may counteract the impact of cortical activation on perceived depth. Indeed, perceived sleep depth was lowest during minimal forms of awareness characterized by a mere sense of presence, and highest during immersive dreaming or deep unconsciousness. Across the night, physiological sleep pressure and subjective sleepiness declined, but perceived sleep depth rose alongside increasing dream immersiveness. These findings challenge the view that the feeling of deep sleep arises solely from reduced brain activity and suggest instead that immersive dreaming may help sustain the subjective experience of deep sleep as homeostatic pressure wanes.
A quantitative cell-based reporter links TDP-43 aggregation and dysfunction to define pathogenic mechanisms.
Mamede LD, Hu M, Vaquer-Alicea J … +8 more , Titus AR, Passos PM, Lantelme E, French RL, Kirschner PA, Diamond MI, Miller TM, Ayala YM
PLoS Biol · 2026 Mar · PMID 41875078 · Full text
TDP-43 pathology is a hallmark of fatal neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and limbic-predominant age-related TDP-43-encephalopathy (LATE). In affec...
TDP-43 pathology is a hallmark of fatal neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and limbic-predominant age-related TDP-43-encephalopathy (LATE). In affected patients, cytoplasmic TDP-43 aggregates are accompanied by disruption of its normal nuclear localization and function. Because TDP-43 is an RNA binding protein that controls transcript processing, including repression of cryptic exon splicing, its loss leads to dysregulation of gene expression. Despite its central significance in disease, the connection between TDP-43 aggregation and dysfunction remains poorly understood, and models to study the underlying mechanisms are limited. Here, we characterize a robust and quantitative cell-based reporter that captures both aggregation and the resulting loss of function. Using this human biosensor cell line, we show that aggregation initiated by prion-like seeding drives progressive depletion of nuclear TDP-43 and induces signature features of diminished TDP-43 activity, such as increased DNA damage and activation of cryptic exon splicing. We find that aggregate seeding also induces cryptic exon splicing in human neurons implying that this pathological link extends to disease-relevant models. The seeding model provides a platform for dissecting mechanisms that underlie TDP-43 pathology and for identifying factors that modulate the aggregation-to-dysfunction transition. Our data shows that aggregate seeding impacts TDP-43 autoregulation, initiating a toxic feed-forward mechanism that disrupts TDP-43 homeostasis. Furthermore, reducing ataxin-2 levels decreases aggregation and restores TDP-43 activity. Together, these findings reveal a molecularly guided strategy to directly impact TDP-43 activity by decreasing its misfolding and aggregation, highlighting approaches to prevent TDP-43 dysfunction and mitigate toxicity under pathological conditions.
How does the cerebellum contribute to cognitive functions?
Diedrichsen J, McDougle SD
PLoS Biol · 2026 Mar · PMID 41871032 · Full text
Over the past 70 years, neuroscience has gained a deep understanding of how the cerebellum supports basic motor functions. Anatomical, clinical, and neuroimaging studies, however, have also firmly established that the ce...
Over the past 70 years, neuroscience has gained a deep understanding of how the cerebellum supports basic motor functions. Anatomical, clinical, and neuroimaging studies, however, have also firmly established that the cerebellum holds an important role in cognition. Even though this topic has received considerable attention, we still do not know the exact nature of this contribution. This Unsolved Mystery reviews known facts about how the cerebellum contributes to cognition and identifies roadblocks that have prevented the development of a unified theory. Addressing these key questions should help the field develop the testable, falsifiable hypotheses that are needed to solve this intriguing question.
Curvature of the Drosophila corneal lens depends on localized chitin secretion.
Ghosh N, Rojo-Iost E, Treisman JE
PLoS Biol · 2026 Mar · PMID 41860940 · Full text
The Drosophila corneal lens is an apical extracellular matrix structure with a biconvex shape that enables it to focus light onto the underlying photoreceptors. Here, we investigated how this shape is influenced by the s...
The Drosophila corneal lens is an apical extracellular matrix structure with a biconvex shape that enables it to focus light onto the underlying photoreceptors. Here, we investigated how this shape is influenced by the source of one of its major components, the polysaccharide chitin. Knocking down the chitin synthase Krotzkopf verkehrt strongly reduced the thickness and curvature of the corneal lens. Conversely, enhancing chitin export by overexpressing Rebuf expanded and distorted the corneal lens. We found that the cone and primary pigment cells in the center of each ommatidium produce most of the chitin, and preventing chitin synthesis by these central cells reduced corneal lens curvature. Increasing chitin export from central cells increased the thickness of the central corneal lens, while increasing export from peripheral lattice cells made the edges thicker. The wild-type biconvex shape thus results from high levels of chitin production by central cells relative to peripheral cells, indicating that localized chitin secretion is critical for normal corneal lens curvature.
Host jumps need not be common just because spillover is.
Yuksel M, Mideo N
PLoS Biol · 2026 Mar · PMID 41860900 · Full text
Can we predict which pathogen will be responsible for the next pandemic? Emergence risk is a hotly debated topic and a new study in PLOS Biology challenges the idea that pathogens that frequently spill over are more like...
Can we predict which pathogen will be responsible for the next pandemic? Emergence risk is a hotly debated topic and a new study in PLOS Biology challenges the idea that pathogens that frequently spill over are more likely to emerge.
Pathogen host jump risk is not predicted by spillover rate, but rather by novelty.
Simony BJ, Kennedy DA
PLoS Biol · 2026 Mar · PMID 41855227 · Full text
Host jumps-defined as the process by which a pathogen establishes sustained transmission in novel hosts-are threats to human and animal welfare, but anticipating which pathogen will be the next to successfully host jump...
Host jumps-defined as the process by which a pathogen establishes sustained transmission in novel hosts-are threats to human and animal welfare, but anticipating which pathogen will be the next to successfully host jump remains elusive. A spillover event must precede a host jump, and so spillover rate is thought to be related to risk. However, nonendemic pathogens that spill over frequently have demonstrated a poor ability to host jump from any given spillover. So which is riskier, pathogens that spill over rarely or commonly? Applying a Bayesian framework to a general model of host jump risk, we show that 1) the riskiest pathogens can be those that spill over at low, intermediate, or high rates, and 2) as the rate of spillover gets large, the information gained from past spillovers is exactly counterbalanced by the increased number of future spillovers. Taken together, this means that spillover rate has little to no value in explaining host jump risk. Rather, we show that novel pathogens (i.e., pathogens with a relatively short history of spilling over in their current form) are substantially more likely to result in host jumps than pathogens that have had long-associated opportunities for spillover into the novel host. Notably, a pathogen might be thought of as novel if spillover only recently became possible, or if it recently underwent substantial evolutionary change. We therefore propose that the length of historical association, but not spillover rate, will be an important predictor of host jump risk.
Pharmacological and non-pharmacological methods of inducing wakefulness activate distinct neural populations in the mouse brain.
Maciel R, Malcey J, Gautier K … +6 more , Chancel A, Duval B, Brunel T, Fort P, Queiroz CM, Luppi PH
PLoS Biol · 2026 Mar · PMID 41855181 · Full text
A large body of data indicate that the aminergic, cholinergic and hypocretin/orexin neurons are responsible for inducing wakefulness. However, recent data showed that other systems might also play a key role. Further, wa...
A large body of data indicate that the aminergic, cholinergic and hypocretin/orexin neurons are responsible for inducing wakefulness. However, recent data showed that other systems might also play a key role. Further, wakefulness induced by different drugs versus non-pharmacological means could be generated by different populations of neurons. To address these questions, we evaluated at the whole brain level in the same mice using TRAP2 model whether the same neurons were activated by the wake-inducing drugs modafinil and solriamfetol versus non-pharmacological wake. Our results show that nine subcortical structures namely the oval part of the bed nucleus of the stria terminalis, lateral part of the central amygdalar nucleus, paraventricular hypothalamic and thalamic and supraoptic nuclei, external part of the lateral parabrachial nucleus, caudal part of the nucleus of the solitary tract and the area postrema are significantly more activated by solriamfetol than modafinil and non-pharmacological wakefulness. In contrast, a second category of structures including the orexin neurons, the parasubthalamic and laterodorsal tegmental nucleus are strongly activated in all types of induced wake. Further, some classical wake systems like the dopaminergic neurons of the ventral tegmental area or the dorsal raphe nucleus and the noradrenergic neurons of the locus coeruleus are either very poorly or not strongly activated. These results reveal that many structures not previously involved in wakefulness might play a key role in regulating the state and that some structures might be more recruited by solriamfetol than modafinil or non-pharmacological wakefulness. Our results are particularly relevant for pathologies such as hypersomnia. They open a new era in the study of the mechanisms responsible for inducing wakefulness.
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