Nutrition, Hormones, Transcriptional Regulatory Networks and Division of Labor in Honey Bee Colonies

Phenotypic plasticity – one genotype producing alternative phenotypes – is increasingly understood to be an important force in phenotypic evolution, but its mechanistic basis remains poorly understood. This thesis describes research into the molecular mechanisms underlying age-related behavioral and physiological plasticity in worker honey bees. Many animals are able to alter their behavior and physiology in response to changes in the environment. At times, these changes in behavior and physiology are stable for long periods, a phenomenon known as phenotypic plasticity [1]. For instance, short periods of food deprivation stimulate feeding and the mobilization of stored nutrients to meet an individual’s immediate energetic needs. But prolonged food deprivation can also lead to much longer-term effects, causing individuals to enter extended periods of inactivity, alter their reproductive strategy, or lose their position in a dominance hierarchy. In humans, chronic food deprivation early in life may lead to a propensity toward obesity and diabetes in later life (for an expanded and fully-referenced discussion of nutritionally-mediated phenotypic plasticity see Chapter 4). The mechanisms that enable and constrain plasticity in behavior and physiology are not well understood, but it is clear that they often involve coordinated and long-lasting changes in gene expression, brain circuitry, brain chemistry, and endocrine signaling [2]. My doctoral research has focused on understanding the molecular basis for nutritionally- and hormonally-mediated plasticity in the behavior and physiology of worker honey bees. Honey bees are social insects, living together in colonies containing tens of thousands of individuals [3]. Colony life is organized by a complex and sophisticated division of labor. Each colony contains a single queen, who is specialized for reproduction and spends most of her time laying eggs. Males, called drones, are relatively rare, and their sole role is to mate. The vast majority of the individuals in the hive are sterile worker bees that are responsible for all of the other tasks performed by the colony. The tasks performed by worker bees are further divided up among individuals via a process of behavioral maturation that is the focus of this thesis. For the first 2-3 weeks of adult life, worker bees specialize on broodcare (“nursing”). They then switch for a few days to any of a number of more specialized tasks such as building honeycomb cells, storing food in honeycomb cells, or guarding the hive entrance against intruders. Finally, for the remaining 1-2 weeks of their life, worker bees forage outside the hive for nectar and pollen, the colony’s sole sources of food. The work presented in this thesis builds on previous findings demonstrating links between worker honey bee division of labor and nutrition (reviewed in Chapter 4). Behavioral maturation in worker bees is coupled to changes in nutritional physiology, including a dramatic and stable loss of abdominal lipid that occurs prior to the onset of foraging. Moreover, previous studies had demonstrated that nutritional status can have causal influences on the timing of behavioral maturation and manipulations of a few feeding- or nutritionally-related genes accelerates or delays the age at onset of foraging. In the work described here, I first test the hypothesis that worker bee behavioral maturation, a highly derived trait, is regulated, in part, by conserved nutritionally-related hormones (Chapter 1). I demonstrate that genes related to insulin signaling are differentially expressed in the brains and fat bodies of nurses and foragers. Furthermore, I show that manipulation of the insulin-related TOR pathway influences the age at which bees initiate foraging. These results suggest that the evolution of honey bee social behavior involved new roles for ancient nutritionally-related pathways. However, my subsequent work shows that not all nutritionally-related pathways have been coopted in the same way. I describe a more complex, and less resolved, relationship between behavioral state, nutrition and brain gene expression for a second nutritionally-related hormone, Neuropeptide Y (Chapter 2). Next, using transcriptomic experiments, I demonstrate that maturation, as well as age-related stable lipid loss, involve massive changes in gene expression in the fat bodies (Chapter 3). I show that these changes in gene expression involve age-related changes in the responsiveness of hormonally and metabolically related pathways to nutrition, and roles for two evolutionarily novel, non-dietary factors: the storage protein vitellogenin and Queen Mandibular Pheromone, each of which influenced many maturationally-related genes in the fat bodies. These results also suggest the involvement in the responses to all these factors of a single nutritionally-related hormone, juvenile hormone (JH), which had previously been shown to pace behavioral maturation. In Chapter 4, I review my findings from chapters 1-2 of this thesis, and previous studies, and propose a molecular systems biology approach to understanding division of labor. Specifically, I propose that phenotypic plasticity in worker honey bees involves nutritionally- and hormonally-driven changes in transcriptional regulatory networks in the fat bodies (as well in the brain), and I suggest methodologies for their elucidation. Finally, in Chapter 5, I utilize the molecular systems biology approach outlined in Chapter 4 to show that a transcriptional regulatory network in the fat bodies underlies division of labor. I show that a juvenile hormone-related transcription factor, Ultraspiracle (USP), influences the age at onset of foraging. I then use a combination of chromatin immunoprecipitation—genomic tiling microarrays, RNAi and deep mRNA sequencing to develop a model of the USP transcriptional regulatory network in fat cells. My results suggest that JH and USP function together to induce and maintain alternative states of a transcriptional regulatory network. These alternative states may well underlie the two basic phases of worker bee life, the in-hive and foraging phases. Together, the studies presented in this thesis provide insights into the relationship between nutrition, hormones, transcriptional regulation, and phenotypic plasticity. References 1. West-Eberhard, MJ. Developmental Plasticity and Evolution. 2003. Oxford University Press, New York, NY. 794 pp. 2. Robinson, GE, Fernald, RD, Clayton, DF. Genes and social behavior. Science. 2008 Nov 7; 322(5903):896-900. doi:10.1126/science.1159277 3. Winston, ML. The Biology of the Honey Bee. 1987. Harvard University Press, Cambridge, MA. 294 pp

Program Evaluation Aspects of Atlanta Streets Alive

INTRODUCTION: Physical Activity (PA) is one of the few ways to significantly reduce the risk of early death, by reducing the risk of diabetes, obesity, and cardiovascular disease. One emerging community program that promotes PA is commonly called Ciclovía in Latin America and Open Streets in North America. This program closes a stretch of road to motor traffic for several hours on a particular day and opens the road to active transportation, such as cycling or walking. Atlanta Streets Alive (ASA) is an Open Streets program developed in Atlanta, Georgia by the Atlanta Bicycle Coalition (ABC) in 2010. Although there have been several studies to evaluate Ciclovías programs, including ASA, a thorough evaluation of the effectiveness and public health impact is often not performed. AIM: The purpose of this paper is to review the data collection and evaluation methods used by Open Streets and Ciclovías, to compare to data gathering methodologies used in Atlanta Streets Alive events, to analyze the quality and relevance of ASA data gathered, and to make recommendations to evaluate the effectiveness of the ASA program better. METHODS: The Atlanta Bicycle Coalition provided the data, including survey responses from five events and participant counts from 23 events between 2010 and 2017. The survey responses were analyzed, and demographic variables were isolated to describe participants. ASA program objectives were obtained from ABC and examined for program evaluability. RESULTS: Based on participant surveys, over 35% of respondents reported an income between 51k and 99k, over 70% were white, and over 40% had at least a Bachelor\u27s degree. ABC\u27s participant count estimates were found to be potentially overestimated, and program objectives are not measurable. DISCUSSION: As a community program that promotes physical activity, it is essential to learn more about Atlanta Streets Alive’s public health impact. It is recommended that quantifiable goals be identified, survey sample size is increased, and automated participant count methods are adapted to improve ASA\u27s reception to program evaluation

Cost-of-illness of rheumatoid arthritis and ankylosing spondylitis

OBJECTIVES:\ud To assess, quantify and summarise the cost of illness of rheumatoid arthritis (RA) and ankylosing spondylitis (AS) from the societal perspective.\ud \ud METHODS:\ud Original studies reporting costs of RA or AS were searched systematically. Both cost-of-illness studies and economic evaluations of therapies were included. Studies were appraised for patient and study characteristics, type of costs and actual costs. Reported costs were aggregated by cost categories and overall mean costs were summarised by cost domain (healthcare, patient and family, and productivity costs).\ud \ud RESULTS:\ud Overall mean costs of RA (€14,906 per year) were above that of AS (€9,374 per year), while the relative distribution of costs over cost domains was approximately similar. For both diseases, productivity costs based on the human cost approach were 3 to 10 times higher than the friction costs and accounted for more than half the total costs of both diseases.\ud \ud CONCLUSIONS:\ud Productivity costs constitute the largest part of the total cost-off-illness of RA and AS reflecting the high burden of the disease on work participation. Although total and direct costs of illness in RA were higher than in AS, the average age of AS patients was 10 years lower and therefore, lifetime costs associated with AS may actually be equal or higher

Two adaptive radiative transfer schemes for numerical weather prediction models

Radiative transfer calculations in atmospheric models are computationally expensive, even if based on simplifications such as the δ-two-stream approximation. In most weather prediction models these parameterisation schemes are therefore called infrequently, accepting additional model error due to the persistence assumption between calls. This paper presents two so-called adaptive parameterisation schemes for radiative transfer in a limited area model: A perturbation scheme that exploits temporal correlations and a local-search scheme that mainly takes advantage of spatial correlations. Utilising these correlations and with similar computational resources, the schemes are able to predict the surface net radiative fluxes more accurately than a scheme based on the persistence assumption. An important property of these adaptive schemes is that their accuracy does not decrease much in case of strong reductions in the number of calls to the δ-two-stream scheme. It is hypothesised that the core idea can also be employed in parameterisation schemes for other processes and in other dynamical models

Making a Task Difficult: Evidence That Device-Oriented Steps Are Effortful and Error-Prone

Errors in the execution of procedural tasks can have severe consequences. Attempts to ameliorate these slip errors through increased training and motivation have been shown to be ineffective. Instead, we identified the steps in a task procedure on which errors are most likely to occur, so that these might be designed out of the task procedure in the first place. Specifically, we considered whether device-oriented steps (i.e., steps in the task procedure that do not directly contribute to the achievement of the task goal) are more error-prone than task-oriented steps (i.e., steps that do directly contribute to the task goal). Two experiments are reported in which participants were trained to perform a novel procedural task. Across conditions, we manipulated the extent to which each step in the task procedure appeared to contribute to the achievement of the task goal (i.e., alternating the assignment of a task step between device- and task-oriented), while keeping the interface and underlying task procedure the same. Results show that participants made more errors and took longer to complete a task step when it played a device-oriented role rather than a task-orientated role. These effects were exacerbated by the introduction of a secondary task designed to increase working memory load, suggesting that when a task step plays a device-oriented role it is more weakly represented in memory. We conclude that device-oriented task steps are inherently problematic and should be avoided where possible in the design of task procedures