Multiple Levels Of Organization Research Articles

The application of natural language processing for the extraction of mechanistic information in toxicology

To study the ways in which compounds can induce adverse effects, toxicologists have been constructing Adverse Outcome Pathways (AOPs). An AOP can be considered as a pragmatic tool to capture and visualize mechanisms underlying different types of toxicity inflicted by any kind of stressor, and describes the interactions between key entities that lead to the adverse outcome on multiple biological levels of organization. The construction or optimization of an AOP is a labor intensive process, which currently depends on the manual search, collection, reviewing and synthesis of available scientific literature. This process could however be largely facilitated using Natural Language Processing (NLP) to extract information contained in scientific literature in a systematic, objective, and rapid manner that would lead to greater accuracy and reproducibility. This would support researchers to invest their expertise in the substantive assessment of the AOPs by replacing the time spent on evidence gathering by a critical review of the data extracted by NLP. As case examples, we selected two frequent adversities observed in the liver: namely, cholestasis and steatosis denoting accumulation of bile and lipid, respectively. We used deep learning language models to recognize entities of interest in text and establish causal relationships between them. We demonstrate how an NLP pipeline combining Named Entity Recognition and a simple rules-based relationship extraction model helps screen compounds related to liver adversities in the literature, but also extract mechanistic information for how such adversities develop, from the molecular to the organismal level. Finally, we provide some perspectives opened by the recent progress in Large Language Models and how these could be used in the future. We propose this work brings two main contributions: 1) a proof-of-concept that NLP can support the extraction of information from text for modern toxicology and 2) a template open-source model for recognition of toxicological entities and extraction of their relationships. All resources are openly accessible via GitHub (https://github.com/ontox-project/en-tox).

Induced Chirality in Canthaxanthin Aggregates Reveals Multiple Levels of Supramolecular Organization

AbstractCarotenoids tend to form supramolecular aggregates via non‐covalent interactions where the chirality of individual molecules is amplified to the macroscopic level. We show that this can also be achieved for non‐chiral carotenoid monomers interacting with polysaccharides. The chirality induction in canthaxanthin (CAX), caused by heparin (HP) and hyaluronic acid (HA), was monitored by chiroptical spectroscopy. Electronic circular dichroism (ECD) and Raman optical activity (ROA) spectra indicated the presence of multiple carotenoid formations, such as H‐ and J‐type aggregates. This is consistent with molecular dynamics (MD) and density functional theory (DFT) simulations of the supramolecular structures and their spectroscopic response.

Induced Chirality in Canthaxanthin Aggregates Reveals Multiple Levels of Supramolecular Organization.

Carotenoids tend to form supramolecular aggregates via non-covalent interactions where the chirality of individual molecules is amplified to the macroscopic level. We show that this can also be achieved for non-chiral carotenoid monomers interacting with polysaccharides. The chirality induction in canthaxanthin (CAX), caused by heparin (HP) and hyaluronic acid (HA), was monitored by chiroptical spectroscopy. Electronic circular dichroism (ECD) and Raman optical activity (ROA) spectra indicated the presence of multiple carotenoid formations, such as H- and J-type aggregates. This is consistent with molecular dynamics (MD) and density functional theory (DFT) simulations of the supramolecular structures and their spectroscopic response.

The Effects of Wastewater Reuse on Smallmouth Bass (Micropterus dolomieu) Relative Abundance in the Shenandoah River Watershed, USA.

Municipal and industrial wastewater effluent is an important source of water for lotic systems, especially during periods of low flow. The accumulated wastewater effluent flows-expressed as a percentage of total streamflow (ACCWW%)-contain chemical mixtures that pose a risk to aquatic life; fish may be particularly vulnerable when chronically exposed. Although there has been considerable focus on individual-level effects of exposure to chemical mixtures found in wastewater effluent, scaling up to population-level effects remains a challenging component needed to better understand the potential consequences of exposure in wild populations. This may be particularly important under a changing climate in which wastewater reuse could be essential to maintain river flows. We evaluated the effects of chronic exposure to wastewater effluent, as measured by ACCWW%, on the relative abundance of young-of-year (YOY), juvenile, and adult smallmouth bass (Micropterus dolomieu) populations in the Shenandoah River Watershed (USA). We found that increases in ACCWW% in the previous year and during the prespawn period were negatively correlated with the relative abundance of YOY, resulting in an average 41% predicted decrease in abundance (range = 0.5%-94% predicted decrease in abundance). This lagged effect suggests that adult fish reproductive performance may be compromised by chemical exposure during periods of high ACCWW%. No relationships between ACCWW% and juvenile or adult relative abundance were found, suggesting that negative effects of ACCWW% on YOY abundance may be offset due to compensatory mechanisms following higher ACCWW% exposure. Understanding the effects of wastewater effluent exposure at multiple levels of biological organization will help in the development of management strategies aimed at protecting aquatic life. Environ Toxicol Chem 2024;43:1138-1148. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Freshwater systems in the Anthropocene: why we need to evaluate microplastics in the context of multiple stressors

Microplastics are a diverse contaminant with complex physical and chemical properties. While microplastics have varying effects, most studies to date have focused on evaluating microplastics as a single stressor under stable environmental conditions. In reality, organisms are exposed to more than microplastics, and thus, it will be increasingly important to evaluate the effects of microplastics in the context of multiple anthropogenic stressors. Here, we highlight the need to assess the physical and chemical effects of microplastics, as well as their interactions with other anthropogenic stressors, at multiple levels of biological organization (i.e., sub-organismal, individual, population, community, ecosystem). We also outline research priorities and recommendations that will facilitate ecotoxicological assessments to better encompass the multidimensionality of microplastics as environmental conditions continue to change. By taking a multi-stressor ecotoxicological approach, we can work toward a better understanding of microplastic and other stressor effects at multiple levels of biological organization to help inform robust, evidenced-based policy and management decisions.

Imprints of indirect interactions on a resource-mediated ant-plant network across different levels of network organization.

Indirect interactions are pivotal in the evolution of interacting species and the assembly of populations and communities. Nevertheless, despite recently being investigated in plant-animal mutualism at the community level, indirect interactions have not been studied in resource-mediated mutualisms involving plant individuals that share different animal species as partners within a population (i.e., individual-based networks). Here, we analyzed an individual-based ant-plant network to evaluate how resource properties affect indirect interaction patterns and how changes in indirect links leave imprints in the network across multiple levels of network organization. Using complementary analytical approaches, we described the patterns of indirect interactions at the micro-, meso-, and macro-scale. We predicted that plants offering intermediate levels of nectar quantity and quality interact with more diverse ant assemblages. The increased number of ant species would cause a higher potential for indirect interactions in all scales evaluated. We found that nectar properties modified patterns of indirect interactions of plant individuals that share mutualistic partners, leaving imprints across different network scales. To our knowledge, this is the first study tracking indirect interactions in multiple scales within an individual-based network. We show that functional traits of interacting species, such as nectar properties, may lead to changes in indirect interactions, which could be tracked across different levels of the network organization evaluated.

Does Behavior Evolve First? Correlated Responses to Selection for Voluntary Wheel-Running Behavior in House Mice.

AbstractHow traits at multiple levels of biological organization evolve in a correlated fashion in response to directional selection is poorly understood, but two popular models are the very general "behavior evolves first" (BEF) hypothesis and the more specific "morphology-performance-behavior-fitness" (MPBF) paradigm. Both acknowledge that selection often acts relatively directly on behavior and that when behavior evolves, other traits will as well but most with some lag. However, this proposition is exceedingly difficult to test in nature. Therefore, we studied correlated responses in the high-runner (HR) mouse selection experiment, in which four replicate lines have been bred for voluntary wheel-running behavior and compared with four nonselected control (C) lines. We analyzed a wide range of traits measured at generations 20-24 (with a focus on new data from generation 22), coinciding with the point at which all HR lines were reaching selection limits (plateaus). Significance levels (226 P values) were compared across trait types by ANOVA, and we used the positive false discovery rate to control for multiple comparisons. This meta-analysis showed that, surprisingly, the measures of performance (including maximal oxygen consumption during forced exercise) showed no evidence of having diverged between the HR and C lines, nor did any of the life history traits (e.g., litter size), whereas body mass had responded (decreased) at least as strongly as wheel running. Overall, results suggest that the HR lines of mice had evolved primarily by changes in motivation rather than performance ability at the time they were reaching selection limits. In addition, neither the BEF model nor the MPBF model of hierarchical evolution provides a particularly good fit to the HR mouse selection experiment.

Metamicrobiome diversity promotes the evolution of host-microbial mutualisms.

Ecological theory suggests that a host organism's internal spatial structure can promote the persistence of mutualistic microbes by allowing for the turnover of tissue occupied by non-beneficial or cheating microbes. This type of regulation, whereby a host preferentially rewards tissue occupied by beneficial members of its microbiome but sanctions tissue occupied by non-beneficial cheaters, is expected to generate a competition-extinction trade-off by allowing beneficial microbes to experience a lower extinction rate than competitively dominant cheaters. Using an adaptive dynamics approach, we demonstrate that although ecologically stable, microbial regulation via sanctioning is not stable in any evolutionary sense, as each individual host will be under pressure to reduce the costs incurred from cheater suppression in order to maximize its own fitness at the expense of the rest of the host population. However, increasing the diversity of non-beneficial cheaters in the host population metamicrobiome can lead to an increase in the relative fitness of hosts that actively sanction non-performing tissue, thus facilitating the evolutionary emergence and persistence of such strategies in host-microbial systems. These counter-intuitive results demonstrate how diversity at multiple levels of biological organization and spatiotemporal scales can interact to facilitate the establishment and maintenance of mutualistic relationships.

Linking intrinsic scales of ecological processes to characteristic scales of biodiversity and functioning patterns

Ecology is a science of scale, which guides our description of both ecological processes and patterns, but we lack a systematic understanding of how process scale and pattern scale are connected. Recent calls for synthesis between population ecology, community ecology, and ecosystem ecology motivate the integration of phenomena at multiple organizational levels. Furthermore, many studies leave out the scaling of a critical process: species interactions, which may be non‐local through movement or foraging and must be distinguished from dispersal scales. Here, we use simulations to explore the consequences of three different process scales (species interactions, dispersal, and the environment) on emergent patterns of biodiversity, ecosystem functioning, and their relationship, in a spatially‐explicit landscape and stable equilibrium setting. A major result of our study is that the spatial scales of dispersal and species interactions have opposite effects: a larger dispersal scale homogenizes spatial biomass patterns, while a larger interaction scale amplifies their heterogeneity. Interestingly, the specific scale at which dispersal and interaction scales begin to influence landscape patterns depends on the scale of environmental heterogeneity – in other words, the scale of one process allows important scales to emerge in other processes. This interplay between process scales, i.e. a situation where no single process dominates, can only occur when the environment is heterogeneous and the scale of dispersal small. Finally, contrary to our expectations, we observe that the spatial scale of ecological processes is more clearly reflected in landscape patterns (i.e. distribution of local outcomes) than in global patterns such as species–area relationships (SARs) or large‐scale biodiversity–functioning relationships. Overall we conclude that long‐range interactions often act differently and even in opposite ways to dispersal, and that the landscape patterns that emerge from the interplay of long‐ranged interactions, dispersal and environmental heterogeneity are not well captured by often‐used metrics like the SAR.

Cell-based homologous expression system for in-vitro characterization of environmental effects on transmembrane peptide transport in fish

All organisms encounter environmental changes that lead to physiological adjustments that could drive evolutionary adaptations. The ability to adjust performance in order to cope with environmental changes depends on the organism's physiological plasticity. These adjustments can be reflected in behavioral, physiological, and molecular changes, which interact and affect each other. Deciphering the role of molecular adjustments in physiological changes will help to understand how multiple levels of biological organization are synchronized during adaptations. Transmembrane transporters, which facilitate a cell's interaction with its surroundings, are prime targets for molecular studies of the environmental effects on an organism's physiology. Fish are subjected to environmental fluctuations and exhibit different coping mechanisms. To study the molecular adjustments of fish transporters to their external surrounding, suitable experimental systems must be established. The Mozambique tilapia (Oreochromis mossambicus) is an excellent model for environmental stress studies, due to its extreme salinity tolerance. We established a homologous cellular-based expression system and uptake assay that allowed us to study the effects of environmental conditions on transmembrane transport. We applied our expression system to investigate the effects of environmental conditions on the activity of PepT2, a transmembrane transporter critical in the absorption of dietary peptides and drugs. We created a stable, modified fish cell-line, in which we exogenously expressed the tilapia PepT2, and tested the effects of water temperature and salinity on the uptake of a fluorescent di-peptide, β-Ala-Lys-AMCA. While temperature affected only Vmax, medium salinity had a bi-directional effect, with significantly reduced Vmax in hyposaline conditions and significantly increased Km in hypersaline conditions. These assays demonstrate the importance of suitable experimental systems for fish ecophysiology studies. Furthermore, our in-vitro results show how the effect of hypersaline conditions on the transporter activity can explain expression shifts seen in the intestine of saltwater-acclimated fish, emphasizing the importance of complimentary studies in better understanding environmental physiology. This research highlights the advantages of using homologous expression systems to study environmental effects encountered by fish, in a relevant cellular context. The presented tools and methods can be adapted to study other transporters in-vitro.

INTRINSIC HEALTH: TOWARD A FRAMEWORK FOR THE OBJECTIVE STUDY OF THE BIOLOGY OF HEALTH

Abstract Many definitions of health have been proposed over the years, but all share the characteristic of being subjective and therefore hard to tie to objective measures of biology. While there are undoubtedly subjective aspects of health, here we propose the notion of “intrinsic health” as the capacity of an organism to maintain its internal, biological dynamic equilibrium. Building on first principles, Cohen and Picard show how intrinsic health emerges from the dynamic interplay of energy, communication, and structure at multiple levels of biological organization. The following three talks then propose novel ways to measure intrinsic health. Khan and Wei show how quantile aberrance – modeling when biomarker values are extreme based on the joint distributions of many biomarkers – can be used to quantify intrinsic health. Liu, Xu, Honfo, and Cohen show how metrics of proteome dynamics reflect communication within the organism and can be extracted to quantify health. Finally, Wang and Pei show how transfer entropy – the synchronization between multiple time series – can be extracted to measure health. While these three metrics are still in preliminary stages of development, they show the potential to measure health based on the multivariate dynamics of our internal systems. Going forward, these and other approaches may be integrated to derive robust, objective metrics of intrinsic health, and could serve as the basis for a novel understanding of how aging emerges from declines in intrinsic health over time.

Adoption of Electronic Health Record Among Substance Use Disorder Treatment Programs: Nationwide Cross-Sectional Survey Study.

Electronic health record (EHR) systems have been shown to be associated with improvements in care processes, quality of care, and patient outcomes. EHR also has a crucial role in the delivery of substance use disorder (SUD) treatment and is considered important for addressing SUD crises, including the opioid epidemic. However, little is known about the adoption of EHR in SUD treatment programs or the organizational-level factors associated with the adoption of EHR in SUD treatment. We examined the adoption of EHR in SUD programs, with a focus on changes in adoption from 2014 to 2017, and identified organizational-level factors associated with EHR adoption. We used data from the 2014 and 2017 National Drug Abuse Treatment System Surveys. Our analysis included 1027 SUD programs (531 in 2014 and 496 in 2017). We used chi-square and Mann-Whitney U tests for categorical and continuous variables, respectively, to assess changes in EHR adoption, technology use, program, and client characteristics. We also investigated differences in characteristics and barriers to adoption by EHR adoption status (adopted EHR vs had not adopted or were planning to adopt EHR). We then conducted multivariate logistic regressions to examine internal and external factors associated with EHR adoption. The adoption of EHR increased significantly from 57.6% (306/531) in 2014 to 69.2% (343/496) in 2017 (P<.001), showing that nearly one-third (153/496, 30.8%) of SUD programs had not yet adopted an EHR system by 2017. We identified a significant increase in technology use and ownership by a parent company (P=.01 and P<.001) and a decrease in the percentage of uninsured patients in 2017 (P<.001), compared to 2014. Our analysis further showed significant differences by adoption status for three major barriers to adoption: (1) start-up costs, (2) ongoing financial costs, and (3) privacy or security concerns (P<.001). Programs that used computerized scheduling (adjusted odds ratio [AOR] 3.02, 95% CI 2.23-4.09) and billing systems (AOR 2.29, 95% CI 1.62-3.25) were more likely to adopt EHR. Similarly, ownership type, such as private nonprofit (AOR 1.86, 95% CI 1.31-2.65) and public (AOR 2.14, 95% CI 1.27-3.67), or interest in participating in a patient-centered medical home (AOR 1.93, 95% CI 1.29-2.92), were associated with an increased likelihood to adopt EHR. Overall, SUD programs were more likely to adopt an EHR system in 2017 compared to 2014 (AOR 1.44, 95% CI 1.07-1.94). Our findings highlighted that SUD programs may be on track to achieve widespread EHR adoption. However, there is a need for focused strategies, resources, and policies explicitly designed to systematically address barriers and tackle obstacles to expanding the adoption of EHR systems. These efforts must be holistic and address factors at multiple organizational levels.

From leaves to the whole tree: Mistletoe effects on the productivity, water relations, and demography of a Neotropical savanna tree

AbstractTrees' responses to mistletoes occur at multiple organization levels (e.g., leaf, individual, population), yet integrating these multi‐scale responses is still challenging. Here, we compared the traits of infected versus uninfected trees over multiple scales, from leaf anatomy and physiology to canopy allometries and individual growth rate and survivorship. We tested the hypotheses that mistletoes lead in the host (1) the production of leaves with a conservative resource‐use strategy, (2) more mechanically stable canopies and (3) reductions in growth and survival probability in the trees they infect. We addressed these hypotheses in the widespread savanna tree Vochysia thyrsoidea and xylem‐tapping mistletoe Psittacanthus robustus in the Brazilian Cerrado, a global biodiversity hotspot. We found that (1) mistletoe infection did not affect key traits associated with resource conservativeness, such as leaf mass per area (LMA) and carbon assimilation rates (A). Likewise, (2) hosts did not increase the mechanical safety of their trunks in response to mistletoe infection since infected and uninfected trees had a similar allometric scaling between height and crown volume against stem diameter. (3) At the population level, both the relative growth rate and survival probability decreased as the number of parasites increased. However, zero growth and a 50% chance of mortality were estimated to occur in a minority of heavily infected trees (&gt;7 and 14 parasites, respectively). Our results challenge the idea that mistletoes have a ubiquitous negative impact on their hosts. We highlight, therefore, the need for clarifying the mechanisms that allow trees to maintain their functioning even in the face of mistletoe parasitism.

Homeostasis, injury, and recovery dynamics at multiple scales in a self-organizing mouse intestinal crypt.

The maintenance of the functional integrity of the intestinal epithelium requires a tight coordination between cell production, migration, and shedding along the crypt-villus axis. Dysregulation of these processes may result in loss of the intestinal barrier and disease. With the aim of generating a more complete and integrated understanding of how the epithelium maintains homeostasis and recovers after injury, we have built a multi-scale agent-based model (ABM) of the mouse intestinal epithelium. We demonstrate that stable, self-organizing behaviour in the crypt emerges from the dynamic interaction of multiple signalling pathways, such as Wnt, Notch, BMP, ZNRF3/RNF43, and YAP-Hippo pathways, which regulate proliferation and differentiation, respond to environmental mechanical cues, form feedback mechanisms, and modulate the dynamics of the cell cycle protein network. The model recapitulates the crypt phenotype reported after persistent stem cell ablation and after the inhibition of the CDK1 cycle protein. Moreover, we simulated 5-fluorouracil (5-FU)-induced toxicity at multiple scales starting from DNA and RNA damage, which disrupts the cell cycle, cell signalling, proliferation, differentiation, and migration and leads to loss of barrier integrity. During recovery, our in silico crypt regenerates its structure in a self-organizing, dynamic fashion driven by dedifferentiation and enhanced by negative feedback loops. Thus, the model enables the simulation of xenobiotic-, in particular chemotherapy-, induced mechanisms of intestinal toxicity and epithelial recovery. Overall, we present a systems model able to simulate the disruption of molecular events and its impact across multiple levels of epithelial organization and demonstrate its application to epithelial research and drug development.

Transcriptomic profiling of prefrontal cortex reveals shared mechanisms underlying Alzheimer’s and Parkinson’s Diseases

AbstractBackgroundAlzheimer’s disease (AD) and Parkinson’s disease (PD) have overlapping characteristics in terms of symptoms and brain pathology. Understanding the similarities in these diseases could lead to more effective treatments. While there is only limited evidence for genetic overlap between the two, enrichment of heritability in genetic regions that are related to microglia has been found in both diseases. However, most of the transcriptomics studies published on AD and PD employed postmortem brains, which obscures the identification of alteration of gene expression within individual cell types.MethodHere we used single‐nucleus transcriptomics to examine over eight million nuclei generated from prefrontal cortex samples of over a thousand postmortem donors with AD, PD, both diseases and controls. Then, we built gene regulatory networks (GRNs) to detect the shared gene expression alterations in all major cell types and detected key drivers within each module.ResultExamining multiple levels of transcriptomic organization, such as gene expression and GRNs for both protein‐coding and noncoding genes, provided a comprehensive understanding of the molecular pathology of AD and PD. Our analysis revealed cell‐specific modules linked to shared and distinct mechanisms of both diseases. Network‐derived signatures showed cell‐type specificity, implicating regulatory regions within AD and PD genetic risk loci that participate in a variety of biological pathways as well as changes in TF regulation.ConclusionThe integration of transcriptomic and genetic data from AD and PD provides a quantitative, genome‐wide resource for mechanistic insight and potential therapeutic development. Funding: U01NS125580, R01AG067025, AARF‐21‐722200

Special Issue: Experiencing Well-BeingPlayfulness andthe meaningful life: an active inference perspective.

Our paper takes as its starting point the recent proposal, at the core of this special issue, to use the active inference framework (AIF) to computationally model what it is for a person to live a meaningful life. In broad brushstrokes, the AIF takes experiences of human flourishing to be the result of predictions and uncertainty estimations along many dimensions at multiple levels of neurobiological organization. Our aim in this paper is to explain how AIF models predict that uncertainty can sometimes, under the right conditions, be conducive to the experiences of flourishing. Our focus is on playfulness, because playful individuals have learned a high-level prior that in certain safe contexts, uncertainty and error should be tolerated and explored. They have expanded the phenotypic bound on the amount of surprise they are prepared to tolerate in their lives. The positive embracing of uncertainty has a number of positive knock-on effects for the kind of lives playful individuals are able to lead. First, a playful individual attends to the world in a way that is open and expansive, a mode of attending that is effortless and therefore conducive to being in the present. This openness to the present moment allows for deep engagement and participation in experience that can furnish a renewed appreciation for life. Second, playful individuals will actively seek out spaces at the edge of their own abilities and will therefore be more likely to grow and develop in their skills and relationships in ways that contribute to their living a good life. Finally, playful agents seek out situations in which they can monitor, observe, and learn from their own affective responses to uncertainty. Thus, uncertainty becomes something familiar to them that they not only learn to tolerate but also enjoy positively exploring, in ways that provide them opportunities to grow. For these three reasons, we will argue that playfulness and openness to experiences of uncertainty and the unknown may be important ingredients in human flourishing.

Perspective: “Current understanding of NADs dynamics and mechanisms of Disease”

Chromatin architecture is essential for gene regulation, and multiple levels of the 3D chromatin organization exhibit dynamic changes during organismal development and cell differentiation. Heterochromatin, termed compartment B in Hi-C datasets, is a phase-separating gene-silencing form of chromatin, preferentially located at the two nuclear sites, nuclear (lamina-associate chromatin domains, LADs) and nucleoli (nucleoli-associated chromatin domains, NADs) peripheries. LADs and NADs contain both interchangeable and location-specific chromatin domains. Recent studies suggest striking dynamics in LADs and NADs during the differentiation of embryonic stem cells into neural progenitors and neurons. Here we discuss recent advances in understanding NADs changes during neuronal differentiation and future questions on how NADs integrity can contribute to healthy neurodevelopment and neurodevelopment diseases.

Higher-order dialectic variation and syntactic convergence in the complex warble song of budgerigars.

Dialectic signatures in animal acoustic signals are key in the identification of and association with group members. Complex vocal sequences may also convey information about behavioral state, and may thus vary according to social environment. Some bird species, such as psittaciforms, learn and modify their complex acoustic signals throughout their lives. However, the structure and function of vocal sequences in open-ended vocal learners remains understudied. Here, we examined vocal sequence variation in the warble song of budgerigars, and how these change upon contact between social groups. Budgerigars are open-ended vocal learners which exhibit fission-fusion flock dynamics in the wild. We found that two captive colonies of budgerigars exhibited colony-specific differences in the syntactic structure of their vocal sequences. Individuals from the two colonies differed in the propensity to repeat certain note types, forming repetitive motifs which served as higher-order signatures of colony identity. When the two groups were brought into contact, their vocal sequences converged, and these colony-specific repetitive patterns disappeared, with males from both erstwhile colonies now producing similar sequences with similar syntactic structure. We present data suggesting that the higher-order temporal arrangement of notes/vocal units is modified throughout life by social learning as groups of birds continually associate and dissociate. Our study sheds light on the importance of examining signal structure at multiple levels of organization, and the potential for psittaciform birds as model systems to examine the influence of learning and social environment on acoustic signals.

Developing and Planning a Protocol for Implementing Health Promoting Animal Assisted Interventions (AAI) in a Tertiary Health Setting.

The Ottawa Charter identifies that multiple levels of government, non-government, community, and other organizations should work together to facilitate health promotion, including in acute settings such as hospitals. We outline a method and protocol to achieve this, namely an Action Research (AR) framework for an Animal Assisted Intervention (AAI) in a tertiary health setting. Dogs Offering Support after Stroke (DOgSS) is an AR study at a major tertiary referral hospital. AAI has been reported to improve mood and quality of life for patients in hospitals. Our project objectives included applying for funding, developing a hospital dog visiting Action Research project, and, subsequent to ethics and governance approvals and finance, undertaking and reporting on the Action Research findings. The Action Research project aimed to investigate whether AAI (dog-visiting) makes a difference to the expressed mood of stroke patients and their informal supports (visiting carers/family/friends), and also the impact these visits have on hospital staff and volunteers, as well as the dog handler and dog involved. We provide our protocol for project management and operations, setting out how the project is conducted from conception to assess human and animal wellbeing and assist subsequent decision-making about introducing dog-visiting to the Stroke Unit. The protocol can be used or adapted by other organizations to try to avoid pitfalls and support health promotion in one of the five important action areas of the Ottawa Charter, namely that of reorienting health services.

Multiomic interpretation of fungus-infected ant metabolomes during manipulated summit disease

Camponotus floridanus ants show altered behaviors followed by a fatal summiting phenotype when infected with manipulating Ophiocordyceps camponoti-floridani fungi. Host summiting as a strategy to increase transmission is also observed with parasite taxa beyond fungi, including aquatic and terrestrial helminths and baculoviruses. The drastic phenotypic changes can sometimes reflect significant molecular changes in gene expression and metabolite concentrations measured in manipulated hosts. Nevertheless, the underlying mechanisms still need to be fully characterized. To investigate the small molecules producing summiting behavior, we infected C. floridanus ants with O. camponoti-floridani and sampled their heads for LC–MS/MS when we observed the characteristic summiting phenotype. We link this metabolomic data with our previous genomic and transcriptomic data to propose mechanisms that underlie manipulated summiting behavior in “zombie ants.” This “multiomic” evidence points toward the dysregulation of neurotransmitter levels and neuronal signaling. We propose that these processes are altered during infection and manipulation based on (1) differential expression of neurotransmitter synthesis and receptor genes, (2) altered abundance of metabolites and neurotransmitters (or their precursors) with known behavioral effects in ants and other insects, and (3) possible suppression of a connected immunity pathway. We additionally report signals for metabolic activity during manipulation related to primary metabolism, detoxification, and anti-stress protectants. Taken together, these findings suggest that host manipulation is likely a multi-faceted phenomenon, with key processes changing at multiple levels of molecular organization.