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Philosophical Transactions of the Royal Society B: Biological Sciences

The Royal Society

Preprints posted in the last 30 days, ranked by how well they match Philosophical Transactions of the Royal Society B: Biological Sciences's content profile, based on 53 papers previously published here. The average preprint has a 0.05% match score for this journal, so anything above that is already an above-average fit.

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Global epistasis in ecosystems arises from resource constraints

Kuehn, S.

2026-05-15 ecology 10.64898/2026.05.12.724736 medRxiv
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Global epistasis refers to the observation that the effect of a mutation or modification depends on the state of a biological system, not its detailed composition. Such patterns have been reported across biological scales, from proteins to organisms and ecosystems. In its simplest form, global epistasis appears as a linear relationship between the change in function or fitness due to a perturbation, and the background level of function or fitness. The mechanistic basis of global epistasis, particularly in ecological systems, remains unresolved. Here, we propose that in microbial communities, global epistasis describing the impact of adding a species to a community on function arises generically from constraints imposed by shared resource pools. We illustrate this mechanism in a single-species system growing on multiple substitutable resources, where global epistasis follows directly from nutrient limitation by an essential non-substitutable resource. We then extend this framework to multi-species communities competing for a single resource and show that the marginal effect of adding a species depends linearly on background community function, with a slope determined by the fraction of the resource claimed by the added species. We show that global epistasis persists in trophic cascades, but that facilitation and niche partitioning qualitatively break the linear dependence. This study provides a simple explanation for the appearance of global epistasis in ecosystems, and suggests that global epistasis should be a null expectation in ecosystems governed by competition. Our results propose that coupling between perturbations and shared resource pools might also help explain global epistasis at the organismal level.

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Activity budgets, social behavior, and fitness outcomes associated with a baboon group fusion

Lerch, B. A.; Creighton, M. J. A.; Warutere, J. K.; Tung, J.; Archie, E. A.; Alberts, S. C.

2026-05-05 animal behavior and cognition 10.64898/2026.04.30.721977 medRxiv
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Many primates exhibit female philopatry and live in stable, female-bonded social groups. Permanent group fusions are rarely documented in these populations. We present a case study on a fusion of two social groups from a hybrid population of baboons (Papio cynocephalus x P. anubis) living in the Amboseli basin of Kenya. The fusion occurred following a period of increased human-induced mortality in one of the two social groups. After the fusion, females from the smaller group became the lowest ranking. We compared female behavior in the months following the fusion to the behavior of females in groups that had not fused and also compared pre- and post-fusion fitness outcomes. Following the fusion, the groups activity budget and patterns of agonistic interactions were typical for the study population. Females preferred familiar grooming partners for a short period following the fusion; however, after three months, patterns in female grooming were comparable to other groups, indicating rapid social integration. With the caveat that our sample size was limited, we observed no detectable fitness-related costs of group fusion in terms of birth rates or offspring survival, and adult female mortality was low following the fusion. These results demonstrate the flexibility of female baboons in navigating exposure to novel same-sex conspecifics despite a species-typic pattern of female philopatry. Based on this and previous examples of group fusions, we propose that group fusions may be most likely to occur when groups are too small to retain adult males, defend against predators, or compete with other groups.

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Activity Patterns Structure Food Web Interactions Through Time

Scott, A. M.; Studd, E. K.; Bieg, C.; Studden, B.; McCann, K.; McMeans, B.

2026-05-22 animal behavior and cognition 10.64898/2026.05.20.726571 medRxiv
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Many mobile animals move to locate and consume resources, making energy gain and growth dependent on activity. Yet the role of activity in shaping predator-prey interactions in food webs has not been broadly considered. Here, we synthesize empirical examples to examine how three activity traits (mean, variance, and timing) vary among taxa (fish, mammals, birds) and between predators and prey across temporal scales. We then use predator-prey models to explore how these diverse activity patterns influence stability. Motivated by emerging activity patterns, our theory shows that fluctuating activity rates can drive predator-prey interaction strengths with major consequences for stability. Future research is needed on activity trait patterning, links between activity and attack rates, and the consequences of activity for predator-prey interactions to whole food webs. This is especially critical as human-driven changes to abiotic cues increasingly alter animal activity rates and may rewire food webs.

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Unpredictable Motion Shapes Sensing Behaviors Across Timescales

Cadigan, S. C.; Smith, N. A.; Jones, T.; Wohlgemuth, M.

2026-05-21 animal behavior and cognition 10.64898/2026.05.18.726036 medRxiv
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Locating, tracking, and intercepting objects is a fundamental behavior for many organisms. For instance, predators must track and capture erratically moving prey for their survival. Using the echolocating bat as a model species, we investigate how short-term changes in target motion predictability affect longer-term motor plans when tracking a prey item. We used a paradigm where prey motion is under experimental control, and then applied computational methods to characterize how target motion predictability influences short- and long-term behavioral control. We find that target motion predictability during the tracking phase of insect capture influences both short-term changes in sonar call control, as well as longer-term behavioral control for transitioning between hunting phases. For changes in immediate behavioral control, bats produce more bursts of calls at a higher rate when tracking unpredictable moving prey, an indication that the bat is collecting more information about the targets motion for unpredictable than predictable trials. In terms of longer-term behavioral control, target motion unpredictability delays the transition from tracking to capture phase behaviors. We suggest that the bat does this to collect more information about target motion to time the transition from tracking to capture behaviors for hunting success. Additionally, we find the effects of target motion unpredictability are first seen as changes in the vocal motor plan and then the auditory motor plan (ear motion), hinting at a sequencing of motor changes that warrant further investigation. SummaryWhen presented with a more challenging hunting task, bats will increase their production of bursts of calls at a higher rate and delay their transition into capture behaviors.

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Brain-tuning near criticality in newborns by prenatal experience with language

Encinas, J.; Mariani, B.; Guevara, R.; Ortiz-Barajas, M.; Gervain, J.; Suweis, S.; Lombardi, F.

2026-05-22 neuroscience 10.64898/2026.05.21.726940 medRxiv
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Language development starts early, possibly even in the womb. Recent results suggest that newborns neural responses to speech in the prenatally heard language are already different from those to unfamiliar languages. However, the neural dynamics of how these differential responses emerge remains little understood. Here, we hypothesize that they are supported by a functional tuning to criticality--a state that maximizes information transmission, dynamic range, and flexibility--, induced in newborns by the prenatally experienced language. To test this hypothesis, we study resting-state brain activity before and after stimulation with naturally spoken sentences in the prenatal language, French, in a rhythmically similar unfamiliar language, Spanish, as well as in a rhythmically different unfamiliar language, English. We show that the native language elicits brain tuning near criticality, balancing network activity and enhancing temporal correlations. Importantly, we find that the network state is not sensitive to the rhythmically different language, and only partially responds to the rhythmically similar language. These results indicate a stimulus-driven tuning to criticality in newborns, a potential foundation for early neuroplasticity, which relies on prenatal experience and may respond to early functional and developmental needs.

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Social control, not service quality, explains fast growth in the cleaner wrasse Labroides dimidiatus.

Pessina, L.; Bshary, R.

2026-05-19 animal behavior and cognition 10.64898/2026.05.16.725469 medRxiv
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Interactions between cleaner fish Labroides dimidiatus and client fish, from which cleaners remove ectoparasites and mucus, represent a textbook example of mutualism involving sophisticated strategic decision-making. However, cleaners must also face intraspecific social challenges within a size-based hierarchy, where the largest females may eventually change sex and become males with higher reproductive rates. Following 540 individuals over 11 months, we found that, contrary to expectations, slow-growing females spent more time cleaning and cheated more frequently, without causing more negative client responses than fast-growing females did. Instead, variation in growth was best explained by social factors: fast-growing individuals experienced reduced social control, while slow growers spent more time in proximity to dominant individuals. As there was no evidence that spawning activity affected growth patterns, it appears that fast growth as a viable strategy for becoming a male largely depends on the lack of control by dominants.

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Referential and attentional accounts of dog point-following in an asymmetric multi-cup design

Mugleston, J. D.; Huang, S.-M.; Dahl, C. D.

2026-05-08 animal behavior and cognition 10.64898/2026.05.05.722884 medRxiv
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Human pointing is often used to test whether dogs extract object-specific information from human communicative cues. However, above-chance responses in standard object-choice tasks do not by themselves distinguish between a referential interpretation, in which the gesture identifies a specific target, and an attentional interpretation, in which it primarily biases behaviour toward a broader spatial region. We addressed this issue using an asymmetric six-cup arrangement designed to separate coarse side guidance from exact cup localisation more clearly than a symmetric multi-cup design. Performance in domestic dogs was analysed using three measures: the probability of reaching the correct side, the probability of choosing the correct cup overall, and the probability of choosing the correct cup conditional on having first reached the correct side. The principal comparison involved three matched trial classes: the symmetric 3-vs-3 condition, 2-vs-4 trials with the baited cup on the 2-cup side, and 2-vs-4 trials with the baited cup on the 4-cup side. Descriptively, pointing trials exceeded matched no-point control trials more clearly for side selection than for overall cup choice. The clearest condition effect was observed at the level of side guidance. Dogs were most likely to reach the correct side when the baited cup was located on the 4-cup side of the unequal arrangement. Mixed-effects models confirmed a reliable group effect for side accuracy, whereas overall cup accuracy showed only a weaker and less robust condition effect, and within-side localisation revealed no reliable group difference once condition-specific chance baselines were taken into account. A complementary generative model comparison converged on the same conclusion: a referential-only model fit poorly, an attention-only model captured most of the grouped outcome structure, and a combined model yielded only a modest improvement. Dog point-following is therefore best understood as a layered process dominated by attentional guidance, with only limited additional target-specific localisation.

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Minding the gap: collective determinants of multiscale structure across interacting bacterial colonies

Moran, J.; Hinczewski, M.; Shankar, S.; Wood, K. B.; Woods, R. J.; Zaman, L.

2026-05-04 ecology 10.64898/2026.04.30.721914 medRxiv
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A bacterial colony rarely exists in isolation - in natural habitats, colonies interact to form spatially structured communities across length and time scales. Eco-evolutionary feedbacks link these scales, such that structure at one level can influence another, yet the interplay between single- and multi-colony organization remains poorly understood. As a step toward addressing this, we develop a high-throughput platform to track population dynamics across spatially extended networks of colonies. A common structural feature observed at the multi-colony scale is the formation of a stable gap region between colonies, even when they are isogenic. Numerous studies observe similar patterns of behavior across species, with few resolving the underlying mechanism. Here, we ask: what are the minimal ingredients shaping this multi-colony structure? We focus on colonies of the opportunistic pathogen Enterococcus faecalis, a model organism for which this behavior has yet to be reported. By combining modeling and experiments, we show that both nutrient competition and direct growth inhibition control colony morphology and expansion of interacting colonies. We identify distinct regimes of gap formation, relating intra- and inter-colony spatial patterns to ecological interactions mediated at the cellular scale. Together, our results suggest that antagonism, even between isogenic populations through self-inhibition, is likely a common behavior of bacterial species in general.

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A competition-protection balance explains the evolution of resistance within simple microbial communities

Amicone, M.; Espinosa-Cantu, A.; Petrungaro, G.; Bollenbach, T.; Mitri, S.

2026-05-21 microbiology 10.64898/2026.05.20.726537 medRxiv
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Stressful environments can pose a threat to microbial populations, but resistant individuals can emerge and avoid extinction. Adaptation to stress is classically studied in isolated microbial species, ignoring ecological interactions, a key component of natural ecosystems. A growing body of experimental work has shown that community context can affect resistance evolution due to a large variety of mechanisms. Here we set out to identify the minimal components needed to predict the likelihood of acquiring resistance in a focal species embedded within a simple community. To achieve this, we developed a mathematical model based on evolutionary rescue theory and validated it with two experimental systems: Escherichia coli evolving on exposure to the antibiotic nitrofurantoin alone or with one of 14 bacterial isolates from urinary tract infections, and Microbacterium liquefaciens evolving in ampicillin alone or with ampicillin-degrading Comamonas testosteroni. One key factor that emerged from our analyses - the relative strength of competition versus protection - could explain whether a focal species is more or less likely to evolve resistance in the presence of a partner species. While competition always hinders the emergence of resistance, protection can rescue the focal species in two ways: (i) ecological rescue, when the partner species completely removes the antibiotic and favors the survival of the susceptible population, or (ii) evolutionary rescue, when the partner only lowers antibiotic concentrations and favors the emergence of resistant variants, a previously overlooked evolutionary consequence of detoxification. Overall, by integrating theory and experiments, we propose a framework that clarifies how ecological interactions favor or hinder the evolution of resistance to antibiotics or potentially other stressors. SignificanceBacteria can rapidly adapt to resist stressors, such as antibiotics. While resistance evolution in single populations or species is well understood, it remains unclear how ecological interactions with other species influence this process. We develop a mathematical framework to predict what interactions should favor resistance evolution and validate it with two sets of experiments where bacteria adapt to antibiotics in small communities. Our work demonstrates that interactions with other species shape the probability of evolving resistance in a predictable way, determined by the balance between competition and protection against the stressor. By identifying the key factors that drive these dynamics, our work helps explain how bacteria adapt to environmental challenges within species-rich ecosystems.

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Associations of Power Distance and Psychological Safety With Medical Researcher Well-being

Choi, J.; Kim, Y. J.; Luan, Y. L.

2026-05-19 medical education 10.64898/2026.05.15.26353300 medRxiv
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ABSTRACT OBJECTIVES To examine whether psychological safety and power distance are associated with medical researchers' well-being, and whether these associations operate through team inclusiveness and conflict. DESIGN Cross-sectional survey study. SETTING A biomedical research institute at a major UK university. PARTICIPANTS 133 medical researchers from 17 teams, including 20 principal investigators and 113 team members. MAIN OUTCOME MEASURES Job satisfaction, life satisfaction, intrinsic motivation, and psychological detachment. Mediators were dimensions of team inclusiveness and team conflict. RESULTS Psychological safety had no significant direct associations with job satisfaction, life satisfaction, intrinsic motivation, or psychological detachment, but showed several indirect associations through researchers' team experiences. It was indirectly associated with higher job satisfaction, life satisfaction, and intrinsic motivation primarily through greater integration of differences, inclusion in decision making, or more constructive forms of conflict (bs=.23-.38, ps=.032-<.001).For psychological detachment, psychological safety showed conflicting indirect associations: it had the potential to support detachment through greater integration of differences and lower avoidant conflict (bs=.21-.56, ps=.054-.002), but to undermine detachment through greater inclusion in decision-making (b=-.26, p=.082). Power distance showed a different pattern. Most notably, it was positively associated with psychological detachment (b=.54, p=.062). However, power distance was indirectly associated with lower job satisfaction, life satisfaction, and intrinsic motivation, primarily through reduced integration of differences and greater dominating conflict (bs=-.14 to -.19, ps=.068-.020). CONCLUSIONS Common assumptions about psychological safety and power distance should be revisited. Psychological safety did not show strong direct benefits for researcher well-being, whereas power distance was not uniformly harmful and was positively associated with psychological detachment. A more nuanced understanding of both cultural dimensions is needed in medical research teams.

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A standardized, surgically relevant map of organ-spesific branch emergence in the human vagus nerve

Bahadir, S.; Chen, F. L.; Tamas, I. P.; McGonagle, E. R.; Nassrallah, Z.; Pelcher, I.; Sun, J.; Xing, T.; Titunick, M.; Knutson, S. M.; Levy, T. J.; Chang, E. H.; Hill, R. V.; Zanos, T.; Barbe, M. F.; Zanos, S.

2026-05-12 neuroscience 10.64898/2026.05.08.723047 medRxiv
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IntroductionVagus nerve stimulation modulates laryngeal, cardiac, pulmonary, and gastrointestinal functions. Knowledge of where along the vagal trunk organ-specific branches emerge may support alternative surgical placements of stimulation devices to engage targeted functions while avoiding off-target effects. However, no quantified map of how vagal branches emerge and how they relate to surgically relevant anatomical landmarks exists in humans. MethodsFifty-eight vagus nerves (29 left, 29 right) from 29 embalmed donor bodies (15 females) were dissected from the jugular foramen through the thoracic cavity. Branches were traced to end organs and allocated to seven groups -- sympathetic, muscular, vascular, cardiac, pulmonary, esophageal, and multiple targets -- and several sub-groups. Distances between branch emergence and the jugular foramen (JF) were normalized to three anatomical landmarks: carotid bifurcation, laryngeal prominence, and superior border of clavicle. ResultsBranch emergence follows a proximal-to-distal order: sympathetic (5.28 cm from JF), muscular (9.59 cm), vascular (10.70 cm), cardiac (19.65 cm), pulmonary (25.36 cm), and esophageal (26.57 cm). Vagal branches emerge into two embryological domains separated near the clavicle: pharyngeal arch-targeting branches cluster proximally (9.34 cm) and primitive mediastinum-targeting branches cluster distally (23.74 cm), with sympathetic, muscular, and vascular sub-groups occupying distinct zones within the proximal domain. The largest branch-free intervals occur above the left clavicle (2.33 {+/-} 2.80 cm) and below the left carotid bifurcation (2.58 {+/-} 3.17 cm). Alternate placement regions separating targeted organs from off-targets: sympathetic vs. cervical visceral at 6/8 cm (L/R), cardiac vs. carotid sinus/bifurcation at 14/10 cm, and recurrent laryngeal vs. other cervical visceral at 18/13 cm from JF. Overall, no differences were found between male and female donors. ConclusionsThis study provides a quantified, landmark-registered map of cervical and thoracic vagal branch emergence, offering a standardized anatomical template that may inform strategies for more function-selective vagal neuromodulation.

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Species diversity increases information flow about predation in bird communities

Kumar, A.; Wu, J.; Ding, P.; Bro-Jorgensen, J.; Dutour, M.; E. Martinez, A.; Si, X.; Zhang, Q.; Goodale, E.

2026-05-11 ecology 10.64898/2026.05.05.722896 medRxiv
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The Biodiversity-Ecosystem Functioning (BEF) literature has shown species diversity to be essential for ecosystem functioning and services. Yet although acquiring information through interspecific networks can impact ecosystem functioning, it is unclear how it is modulated by species diversity. Eliciting vocal responses using predator models across a latitudinal gradient, we first show that the species diversity of birds increases public information about predation both in the low-cost system of mobbing and in the higher-cost system of alarm calls. A similar result was also found across a fragment area gradient for mobbing; this system was then used to test how species diversity affects interspecific information flow in mobbing communities. We set up two BEF playback experiments, manipulating the species richness level of the playback sound files by varying the number of species producing mobbing calls (one, two, four, eight species). In an experiment in which the call rate across treatments was held constant, and only heterospecific responses were counted, increasing species richness of the sound files increased the number of species and individuals responding, the number of calls produced and their frequency range, and decreased latency to call. An experiment in which call rate increased with the addition of species in each treatment showed a similar, but stronger pattern. There was little evidence that the signals of one particular species changed responses. This supports the hypothesis that the species diversity of a community is a key component influencing the quantity and quality of information flow inside it.

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Environmental microbial communities and host selection shape larval microbiomes

Hendricks, S. F.; Tan, A. L.; Williams, A. G.; Buckley, K. M.; Strader, M. E.

2026-05-15 ecology 10.64898/2026.05.14.725214 medRxiv
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Ocean warming is altering abiotic environments and biotic interactions experienced by marine organisms, where sensitive early developmental windows occur in biologically complex seawater communities. The impact of these interactions on developmental processes and fitness in hosts is not well understood, but likely contingent on the establishment of a host-associated microbiome. Here, we hypothesize that temperature and microbial exposure during embryogenesis influence larval microbiome assembly and host morphology. Strongylocentrotus purpuratus embryos were raised in low microbial richness (LMR) or high microbial richness (HMR) seawater at ambient (14 {degrees}C) or elevated (18 {degrees}C) temperature, then collected at 2, 4, and 6 days post-fertilization (dpf) following multiple feedings. Higher microbial diversity was observed in larvae that developed in HMR seawater when compared to LMR. Differences in relative abundances of dominant microbial families between seawater and larvae suggest some degree of host selectivity in microbiome assembly. Temperature did not strongly alter microbiome composition, but both temperature and microbial condition led to differences in larval morphology by 6 dpf, potentially due to enrichment of microbes with chemoheterotrophic functions. By linking how temperature and microbial communities interact with host development, we contribute novel insights into how early-life environmental conditions impact holobiont formation and morphology. One sentence summaryEarly developmental temperature and microbial conditions shape larval microbiome establishment and morphology.

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Demographic changes and behavioural responses shape vulnerability to infectious disease outbreaks

Evans, A.; Hart, W. S.; Jung, E.; Nah, K.; Bonic-Babic, K.; Jung, S.-m.; Thompson, R. N.

2026-05-14 ecology 10.64898/2026.05.11.724461 medRxiv
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Demographic shifts are reshaping population age structures worldwide, with implications for infectious disease dynamics. Since contact patterns, susceptibility and infectiousness often vary by age, the risk that pathogen introductions initiate a substantial outbreak depends on the populations age distribution and associated behavioural characteristics. We develop an age-structured mathematical model to estimate the risk that a single pathogen introduction leads to sustained transmission (the probability of a major outbreak) under long-term demographic transitions, incorporating changes in age-specific contact patterns and behavioural adaptation. Using the Republic of Korea (projected to become the worlds oldest population by 2050) as a case study, we show that population ageing generally reduces the probability of a major outbreak due to older individuals lower contact rates. However, this effect is attenuated for pathogens with increasing susceptibility or infectiousness with age, and if future older cohorts have higher contact levels than at present (e.g. through extended workforce participation in an ageing society). These findings demonstrate that, while outbreak risks are affected by demographic changes, they are further modified by associated behavioural responses, highlighting the importance of accounting for demographic and socio-behavioural context when assessing future infectious disease outbreak risks. Author SummaryIn the early stages of an infectious disease outbreak, the risk that initial cases lead to a substantial outbreak is shaped by a range of factors including the characteristics of the host population. Demographic changes, such as population ageing, are transforming societies worldwide, yet their implications for infectious disease emergence remain unclear. Here, we show that ageing populations reduce the likelihood that imported infections trigger major infectious disease outbreaks due to lower contact rates between individuals of older ages. However, this effect depends on how susceptibility, infectiousness and host behaviour vary with age. For example, increased social and economic activity among future older adults (due to a higher retirement age) could offset the decrease in the outbreak risk. These findings underscore the need to account for demographic and socio-behavioural factors, in addition to biological factors, when assessing future outbreak risks and designing robust public health strategies, particularly in societies undergoing rapid demographic change.

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The dispersal of released pheasants and the risk of their intrusion into English protected areas

Madden, J. R.; Sage, R. B.; Wilde, J. A.

2026-05-07 ecology 10.64898/2026.05.04.722670 medRxiv
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Large-scale annual releases of pheasants Phasianus colchicus and their subsequent management for recreational shooting create various ecological impacts in the UK. While effects at release sites are fairly well understood, dispersing birds may influence areas farther away. If they enter ecologically important but sensitive protected areas (PAs), any negative impacts could be especially harmful. Using tracking data, from 766 birds across 10 sites, we estimated survival and dispersal of released pheasants and applied these patterns to gamebird release records near English PAs to gauge intrusion risk. Of 2,885 registered release sites, just over half lay within 2 km of a PA. A large number of shoots release relatively few birds while a small number release many birds. Thus, numbers expected to enter a particular PA likely depend both on the size of releases and proximity to the PA. We estimate that, at a national level, a maximum of between 525,000 and 784,000 pheasants might be found within PAs very soon after release, representing around 1.7% of all the pheasants released annually. This number declines over the months after release until in February, we estimate that there are between 131,000 and 196,000 pheasants (0.4% of the total release) might be found within PAs. The critical metric by which ecological damage might occur is their density within PAs. Mean densities soon after release averaged 12.0 birds/ha in PAs within 250 m of release sites. This density declined markedly both in time (as birds died) and space (as they moved further from the pen as potential areas increased). By November, densities in PAs 500-1000m from release sites peaked at 0.5 birds/ha, falling to 0.16 birds/ha in February. These estimated densities are around two orders of magnitude lower than those known to cause strong, lasting impacts within release pens. The results are subject to assumptions about movement behaviour, game management and bias in registration. Despite these constraints, considerable local variation exists, with a minority of high-volume release sites very near PAs posing the greatest potential ecological risk.

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Real-time brain-state-coupled cortico-cortical paired associative stimulation of cognitive networks

Jovellar, D. B.; Turrini, S.; Belardinelli, P.; Roy, O.; Santarnecchi, E.; Ziemann, U.

2026-05-06 neuroscience 10.64898/2026.05.01.722353 medRxiv
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Brain networks coordinate distributed neuronal assemblies to support cognition. Spike-timing-dependent plasticity (STDP) and neuronal oscillations are key substrates for state-gated learning rules that shape network coupling and cognitive operations; nonetheless, how STDP mechanisms interact with neuronal oscillations is largely unexplored in humans. Cortico-cortical paired associative stimulation (ccPAS) provides a non-invasive system-level model of associative timing rules by pairing dual-site transcranial magnetic stimulation (TMS) across axonally connected regions with an inter-stimulus interval matched to pathway conduction. Here we: 1) synthesize ccPAS applications and barriers to brain-state-coupled implementation in cognitive networks; 2) provide an actionable roadmap for real-time state estimation, targeting, and dual-site parameter selection; and 3) demonstrate a novel implementation of theta-phase-locked fronto-parietal (FP) ccPAS with concurrent EEG in adult human participants. We tested whether ccPAS delivered at the positive phase of ongoing theta (POS) induces distinct changes in evoked EEG activity and FP connectivity compared to phase-uncoupled ccPAS (RAND) and phase-locked single-site prefrontal (PREF) controls. At the evoked level, POS produced a fronto-central polarity reversal of the canonical N45 component and a right parieto-temporal negativity relative to both controls. At the network level, POS induced frequency-specific reconfigurations in post-intervention connectivity beyond either control ingredient alone. Together, these changes in evoked activity and rapid network reconfiguration provide the first empirical evidence consistent with phase-gated STDP in humans--whereby oscillatory phase gates cortical excitability and modulates STDP efficacy--emerging as short-term network-level expression. Future work will assess long-term plasticity by tracking connectivity at later time points and testing for concomitant behavioral effects. SignificanceThe real-time brain state critically shapes how plasticity mechanisms are expressed in response to brain stimulation. This article provides a forward-looking synthesis of the scientific and technical challenges associated with ccPAS--an STDP induction model in the human cortex--and outlines the steps required to advance it toward real-time brain-state-coupled implementation. To our knowledge, this is the first application of brain-state-coupled ccPAS within a cognitive network. By personalizing stimulation to the individuals ongoing neural state, this approach may reduce variability, limit off-target effects, and enhance plasticity induction. Ultimately--by modulating network-level function in a brain-state-dependent manner--this technique could augment therapeutic outcomes in disorders marked by network dysfunction such as ADHD, Alzheimers disease, and major depressive disorder, potentially maximizing efficacy in patients unresponsive to existing treatments.

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Optimal release of gene drives in population connectivity networks

Halperin, J.; Perlman, S.; Shemesh, S.; Harris, K. D.; Greenbaum, G.

2026-05-13 ecology 10.64898/2026.05.11.724203 medRxiv
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Gene drives, genetic constructs that can spread deleterious alleles in wild populations, have the potential to address some of the major pressing challenges of the Anthropocene such as invasive species, spread of disease vectors, and agricultural pests. However, responsible and effective deployment of gene drive requires taking into account the complex nature of real-world population connectivity networks. In particular, it is unclear how the topological position of the deployment site affects the spread process and its final outcome. Here we develop a framework for modeling gene drive spread in population connectivity networks, and study the eco-evolutionary dynamics of gene drive spread under complex population structures. We investigated the relationship between the position of the deployment site in the topology of the network and whether the gene drive is eventually lost, fixed, or maintained at an intermediate frequency. We identified network centrality measures of deployment sites that are highly correlated with the outcome of deployment for different gene drive designs and across diverse network topologies. We also show that there is a trade-off between the time-to-fixation and the final outcome, implying that multiple centrality measures of the deployment site would need to be considered when aiming to achieve rapid and successful population control using gene drives.

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Cortical and spinal contributions to remote interlimb facilitation in humans

Sasaki, A.; Kato, T.; Kaneko, N.; Masugi, Y.; Milosevic, M.; Nakazawa, K.

2026-05-06 neuroscience 10.64898/2026.05.02.722378 medRxiv
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Voluntary contraction in one limb can facilitate motor output in a distant limb, a phenomenon commonly referred to as the remote effect. However, the neural mechanisms underlying this remote interlimb facilitation remain unclear. This study investigated cortical and spinal contributions to the remote effect in able-bodied participants. Transcranial magnetic stimulation (TMS) was applied over the hand area of the primary motor cortex using posterior-anterior (PA) and anterior-posterior (AP) current directions, which are sensitive to different cortical inputs. Cortical excitability was assessed using single- and paired-pulse paradigms to measure short-interval intracortical inhibition (SICI), short-interval intracortical facilitation (SICF), and short-latency afferent inhibition (SAI). Spinal motoneuron excitability was assessed from F-waves elicited by peripheral nerve stimulation. During voluntary lower-limb contractions, single-pulse TMS elicited larger motor evoked potentials in hand muscles across current directions, indicating a broad increase in net corticospinal output. However, only AP-sensitive paired-pulse measures showed reduced SICI and enhanced SICF during contraction, whereas PA-sensitive SICI and SICF were not significantly altered, suggesting that cortical modulation during the remote effect is expressed more clearly in AP-sensitive measures. SAI with PA stimulation was less consistently expressed during contraction, suggesting that afferent-related inhibitory modulation may also be influenced during the remote effect. In parallel, F-wave amplitude and persistence increased, consistent with enhanced spinal motoneuron excitability. Together, these results provide converging evidence that the remote effect in humans involves broad corticospinal and spinal facilitation, accompanied by current direction-dependent modulation of cortical excitability measures. KEY POINTS SUMMARYO_LIVoluntary contraction in one limb can facilitate motor output in a distant limb, but the mechanisms underlying this remote interlimb facilitation remain unclear. C_LIO_LIWe tested whether remote lower-limb contraction modulates corticospinal output, intracortical excitability, and spinal motoneuron excitability in a resting hand muscle. C_LIO_LISingle-pulse transcranial magnetic stimulation showed that motor evoked potentials in the hand were facilitated during remote lower-limb contraction across multiple current directions, indicating a broad increase in net corticospinal output. C_LIO_LIPaired-pulse measures were modulated preferentially with anterior-posterior stimulation, with reduced short-interval intracortical inhibition and increased short-interval intracortical facilitation, suggesting current direction-dependent modulation of cortical excitability measures. C_LIO_LIF-wave amplitude and persistence were also enhanced during remote lower-limb contraction, indicating increased spinal motoneuron excitability. These findings provide converging evidence that the remote effect involves both cortical and spinal contributions. C_LI

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Of Brobdingnag and Lilliput, or how the area of an island may determine the size of the bodies and genomes that inhabit it, along with their mutation rates

Rivas-Santisteban, J.

2026-05-13 evolutionary biology 10.64898/2026.05.11.724217 medRxiv
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There are some disputed hypotheses for the recurrent observations of insular gigantism and dwarfism, like the island rule: small organisms would become larger on islands, while large organisms would become smaller. But, why is the latter? In addition, not all the observations fit this rule. Here I propose a causal model. Following the Island Biogeography Theory (IBT), insular aspects influence the census N. Observations suggest that variation in N is associated with variation in effective population size (Ne). The body size of insular colonisers might change, following Damuths law, as Ne can decrease at a differential rate from the island area A, resulting in a distinctive effective density [Formula]. Interestingly, a prediction of the drift-barrier hypothesis is that Ne is affecting mutation rates. Consequently, body mass, genome size and {micro} may be predicted to some extent by island area, as they are influenced by De and Ne. Falsification of the latter hypothesis is feasible by determining changes in genomic features of insular species. We now have the opportunity to interrogate the extensive data available. Here I ask: (i) How is decreasing island area predicting average body sizes? (ii) To which levels does this prediction apply (species, cells, genomes)? (iii) How well does the model fare on predicting {micro} over paradigmatic case studies? The resolution of these questions may provide a more reliable diagnosis of the evolutionary causes for somatic size variation. Significance statementNaturalists have long reported that insular species tend to become unusually large or small compared to their mainland relatives. Despite the familiarity of this "island rule", there is still no broad mechanistic explanation for why these changes occur so consistently across different groups of organisms. This work proposes that an important neutral factor can be the change in effective density of isolated populations. By combining the expectations of Damuths law, the IBT model, and the nearly-neutral theory it offers unified predictions on how sudden constraints in island area can influence not only the evolution of body size, but also the direction of changes in genome size and evolutionary rates.

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A Deep Dive into the Cognitive Soundscape of Flow: Finding Your Groove

Bartling, B. A.

2026-05-18 animal behavior and cognition 10.64898/2026.05.13.724953 medRxiv
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Flow state, characterized by optimal engagement and performance, represents a key concept in understanding human performance and cognitive resource allocation. Grounded in Csikszentmihalyis and Sherrys flow theory and the Limited Capacity Model of Motivated Mediated Message Processing (LC4MP), this study investigated physiological and neural correlates of flow state during a simulated driving task under different music conditions and difficulty levels. Using a 2 x 3 factorial design with 20 participants, this study examined self-selected versus non-self-selected music across three difficulty levels, testing the relationship between task switching, cognitive resource allocation, and flow state. Physiological measures included heart rate and EEG (alpha/theta power) using a 4-channel Muse 2 headband, alongside a self-report measure of flow experience. Hierarchical linear modeling revealed significant physiological changes during self-selected music: heart rate decreased ({beta} = -5.15, p < .001), while alpha ({beta} = 5829.77, p < .001) and theta power ({beta} = 7637.24, p < .001) increased. Task difficulty also showed significant effects, with heart rate decreasing during hard ({beta} = -6.70, p < .001) and moderate ({beta} = -3.40, p = .001) conditions. In particular, while physiological measures showed robust changes, the self-reported flow state did not reach significance. Task switching rates showed significant decreases during self-selected music ({beta} = -0.86, p < .001) and hard difficulty ({beta} = -0.61, p < .001), supporting the LC4MP frameworks predictions regarding cognitive resource allocation. These findings demonstrate how task switching and cognitive resource allocation relate to flow state induction. The results highlight the importance of multimodal measurement approaches and demonstrate that personal relevance through music selection and task difficulty significantly influence physiological and neural responses during performance. Future research should employ more comprehensive measurement approaches to better capture the complexity of flow-related neural activity and its relationship to task switching and cognitive resource allocation.