Current evidence suggests that thyroid hormones (THs) may impact development of the immune system. However, studies that explore the role of THs in immune development are limited, and the mechanisms leading to alterations in immune function are poorly understood. It is important to elucidate the role of THs in immune development given that many environmental contaminants have been shown to disrupt TH homeostasis and may also have negative impacts on the immune system. As such, the main goal of this study was to determine the long-term consequences of early life stage (ELS) hypothyroidism on immune function. To achieve this goal, it was first necessary to further characterize basic immune function in the selected model species, the fathead minnow (FHM, Pimephales promelas). Preliminary studies were conducted to describe the transcriptomic response to Yersinia ruckeri and adapt assays for the assessment of respiratory burst and phagocytic cell activity. To determine the long-term effects of ELS hypothyroidism, FHMs were exposed to the model thyroid suppressant propylthiouracil (PTU) from <1 to 30 days post hatch and reared under normal conditions. Upon reaching adulthood, ex vivo immune cell function and the in vivo immune response to Y. ruckeri were assessed. Fish exposed to PTU experienced significant alterations in gene networks associated with immune cell function as well as significant decreases in phagocytic cell activity. However, immune-related alterations at the molecular and cellular levels did not manifest themselves at higher levels of organization as ELS hypothyroidism did not affect any other immune-related endpoints, including pathogen resistance. To our knowledge, this is the first study to provide evidence that ELS hypothyroidism causes long-term effects on the immune system in fish.

To minimize the damage caused by oil spills, responders may chemically disperse floating oil into the underlying water before it contacts shorelines and wildlife. Quantifying this strategy’s net ecological and commercial benefits requires an analysis of its effects on subsurface ecosystems and biota. Unfortunately, spill-responders have little empirical data on which to base such an analysis. Herein I report the effects of dispersed oil to early life stages of Atlantic herring (Clupea harengus). Medium South American crude oil (MESA) dispersed with Corexit 9500 caused blue sac disease (BSD) in embryos, but not in free-swimming embryos. The ages of embryos were negatively correlated with their sensitivity to oil, making those that were freshly fertilized the most sensitive. However, sensitivity was also high after hatch. Free-swimming embryos displayed signs of narcosis following brief exposure to dispersed oil. Gametes were also tested; dispersed oil dramatically impaired fertilization success. Toxicity was a function of concentration and duration of exposure, as well as of the life stage exposed. When the duration of exposure was < 24 h, gametes and free-swimming embryos were the most sensitive life stages (i.e. responded to the lowest concentrations). For durations > 24 h, young embryos (< 1 day old) were most sensitive. The results are presented as toxicity models that incorporate developmental stage, oil concentration, and exposure duration. Current effects-forecasting models for oil dispersion are based on published chronic toxicity data, which do not account for the effects of exposure duration and developmental events on toxicity. Thus, the results will better-enable modelers to estimate the effects of realistic exposures to dispersed oil in various locations, including spawning shoals. / Thesis (Master, Biology) -- Queen's University, 2009-04-26 12:55:12.266

Despite the plethora of research on migration, little is known about behaviours and experiences of older working age migrants. This thesis focuses on Polish migrants aged 45-65, who have arrived in the UK since 2004 looking for work and better opportunities. The purpose of the study is to explore links between age and migration by investigating older migrants who are still economically active. Thirty five interviews were carried out across the UK using an oral history qualitative approach. These migrants were particularly affected by redundancy during the transitional period from socialism to capitalism in Poland; they then found it almost impossible to find other work because of their age. The decision to migrate may have been influenced by an early exposure to Western influences; however, it was the impact of unemployment and debt that led to a re-evaluation of their lives. Although they may be at different family stages, these older migrants' shared background and perception of their lack of value has shaped their migration experience. They represent parents, grandparents, sons, daughters, married couples, widows and single persons; this age group gives a more complete and nuanced picture of family life and relationships. The emotional costs are high when families are separated through migration, especially when elderly parents are involved. Despite the wide age range, family experiences are often very similar, with preferences for staying at home and watching Polish television. However, the opportunity of employment in the UK has given them an economic and social value no longer available to them in their homeland. As so much of their life course has been invested in Poland, many see no need to learn English; it is not a priority as they have virtual social interactions with family and friends in Poland and continue to inhabit a Polish-speaking world. This age group are also more likely to be pioneer migrants, accessing new destinations.

Cryptosporidiosis is a common diarrheal disease caused by intestinal infection with the apicomplexan parasite Cryptosporidium, in humans usually either with C. hominis or C. parvum. Unfortunately, given a large burden of disease in children and immunocompromised people like AIDS patients, the only currently approved treatment, nitazoxanide, is unreliable for these patient populations. To address the urgent need for new drugs for the most vulnerable populations, large phenotypic screening efforts have been established to identify anti-Cryptosporidium growth inhibitors in vitro (hits). However, in the absence of a gold standard drug, the in vitro and in vivo characteristics that should be used to prioritize screening hits are not known. This thesis is focused on identifying promising anti-Cryptosporidium hits and drug leads, and using them to establish validated methods to guide hit-to-lead studies for anti-Cryptosporidium drug development. A re-analysis of our phenotypic screen of the Medicines for Malaria Venture Open Access Malaria Box identified a promising C. parvum growth inhibitor, MMV665917. It had similar in vitro activity against C. hominis, C. parvum Iowa, and C. parvum field strains, and it was amenable to preliminary structural activity relationship studies using commercially available variants, with one variant demonstrating nanomolar potency. Furthermore, MMV665917 was effective in vivo in an acute interferon-γ mouse model of cryptosporidiosis; and it appeared to cure an established infection in the chronic NOD SCID gamma (NSG) mouse model, unlike nitazoxanide, paromomycin, and clofazimine. We hypothesized that anti-Cryptosporidium activity in the highly immunocompromised chronic NSG mouse model might relate to compounds being capable of killing and eliminating parasites (cidal), rather than only preventing growth (static). To test this, we developed a novel in vitro parasite persistence assay that showed that MMV665917 was potentially cidal, whereas nitazoxanide, paromomycin and clofazimine appeared static. This pharmacodynamic assay also provided the concentration of compound required to maximize rate of parasite elimination, which could help design in vivo experiments. To further characterize compounds based on mechanism of action, we developed a range of in vitro medium-throughput life-stage assays. To validate and gain value from the assays, a “learner set” of compounds from our in-house screens and collaborations were tested in all of the in vitro assays and in the in vivo NSG mouse model. Using these assays, it was possible to group molecules based on chemical class/mechanism of action. Because compounds from distinct groups showed activity in the NSG mouse model, these methods could be used to obtain a diverse set of early-stage Cryptosporidium inhibitors for prioritization. Furthermore, compounds that appeared static in the in vitro parasite persistence assay did not have activity in the NSG mouse model. In summary, we report the identification and development of a highly promising initial lead, MMV665917, and report a range of in vitro assays that can be used to prioritize anti-Cryptosporidium hits and leads.

<p>The study of work motivation has yielded many applicable theories. This thesis investigated how older employees viewed factors that have been linked to the advancement of age and believed to affect work motivation. Three different conceptualisations of age were included in the study; organisational age, chronological age and life stage. By using a qualitative approach, participants were allowed to shed light on this complex area and give their own views on possible age effects. More specifically, changes in needs and values, the effects on goal setting and the development of skills were investigated. Chronologically younger employees placed greater value in their careers and reported that they would continue to work even if they became financially independent. Older employees attributed less importance to their careers and said that they would choose early retirement in order to have more time if they had money to enjoy it.</p>

The study of work motivation has yielded many applicable theories. This thesis investigated how older employees viewed factors that have been linked to the advancement of age and believed to affect work motivation. Three different conceptualisations of age were included in the study; organisational age, chronological age and life stage. By using a qualitative approach, participants were allowed to shed light on this complex area and give their own views on possible age effects. More specifically, changes in needs and values, the effects on goal setting and the development of skills were investigated. Chronologically younger employees placed greater value in their careers and reported that they would continue to work even if they became financially independent. Older employees attributed less importance to their careers and said that they would choose early retirement in order to have more time if they had money to enjoy it.

D’après le dernier rapport du groupe d'experts intergouvernemental sur l'évolution du climat (GIEC), le réchauffement climatique devrait se poursuivre au cours du siècle prochain. La température atmosphérique moyenne pourrait augmenter de 0,3°C à 4,8°C avec des valeurs extrêmes allant de 1°C à 6°C en 2100. Ces changements de température auront des conséquences directes et indirectes sur l’ensemble de la biodiversité et plus particulièrement sur les poissons qui sont des animaux poïkilothermes. Dans cette étude, trois espèces ont été choisies en prenant en compte leur stratégie de reproduction et leur différence de tolérance thermique : la truite commune (Salmo trutta), le brochet (Esox lucius) et la carpe commune (Cyprinus carpio). Nous avons, pour chacune des trois espèces, appliqué les mêmes différences de température par rapport à leur température de référence (-4, -2, Tref, +2, +4°C) et étudié les effets sur la survie et le développement des embryons et des larves au cours de l’ensemble de la période d’alimentation endogène. Ce travail a confirmé la loi générale de l’impact de la température sur la période d’incubation (Q10 ~3). La truite commune montre une forte diminution de sa survie lors d’une augmentation de quatre degrés, néanmoins les larves survivantes sont plus grandes et ont un contenu énergétique plus important. La survie des larves de brochet augmente avec la température, ces larves sont les plus grandes et leur contenu énergétique est plus important à la température la plus élevée. La survie de la carpe n’est pas affectée par la température ; néanmoins les larves élevées à basse température sont les plus petites et présentent un faible contenu énergétique. Les résultats de survie pour les premiers stades de vie sont en concordance avec les modélisations des aires de répartition actuelle. Dans le futur, la prise en compte de la niche thermique théorique des premiers stades de vie pourrait permettre d’affiner les prévisions des aires de répartition / According to the latest report of the Intergovernmental Panel on Climate Change (IPCC), global warming is expected to continue over the next century, the average temperature could increase by 0.3 ° C to 4.8 ° C with extreme values ranging from 1 ° C to 6 ° C by 2100. These temperature changes will have direct and indirect consequences on the overall biodiversity and specifically fish which are poikilotherms. In this study three species were selected taking into account their reproductive strategy and their thermal tolerance: brown trout (Salmo trutta), pike (Esox lucius) and common carp (Cyprinus carpio). We have applied for all three species the same temperature range of from their referential temperature (-4, -2, Tref °C, +2, + 4 ° C). To carry out this study, we investigated biological traits related to survival and development during the endogenous feeding period. This work confirmed the general law of the impact of temperature during incubation phase (Q10 ~ 3). For brown trout, the results show a collapse of its population with an increase of four degrees; nevertheless surviving larvae were the longest and had a more energetic content. The survival rate of pike larvae increased when temperature increased, these larvae were the longest and the had more energetic content. The survival of the carp was not affected by temperature; nevertheless, at the lowest temperature (16°C), the larvae were smaller and had a lower energetic content. The survival results for the early stages of life are an agreement with the current distribution models. In view of this study the theoretical thermal niche species of early live stage should be undertaken to continue to refine prediction models from range

Traditional wastewater treatment is known not to be specifically designed to eliminate the new generation of chemical residues that ends up in the sewage system. Polluted wastewatereffluent therefore reaches the aquatic environment possibly causing adverse effects in aquatic wildlife. The effects of effluent water from five Swedish sewage treatment plants sampled on 6 occasions 2017, were studied in developing zebrafish (Danio rerio). The study included morphological, physiological and behavioural endpoints. Overall there were few effectswhere deviations from control animals could be seen in the exposed zebrafish. The overall outcome of this assessment was that the wastewater effluent had no consistent effects on the early development of zebrafish. The consequences of continuous low-level exposure duringthe whole life-cycle of wild fish are presently unknown and further studies are needed to evaluate potential risks.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第22048号 / 工博第4629号 / 新制||工||1722(附属図書館) / 京都大学大学院工学研究科社会基盤工学専攻 / (主査)教授 中北 英一, 准教授 山口 弘誠, 准教授 田中 賢治 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

The purpose of this study was to investigate how people in Skellefteå municipality transport behavior looks like. Skellefteå municipality is working on developing the traffic planning, but are the improvement opportunities similar to that the people in this study put forward. To investigate what limitations and other underlying factors there are that can influence these people's choice of means of transport. To see if these people could consider switching to using more environmentally friendly means of transport during their daily commute. Since Skellefteå municipality's goal is that car use within the municipality should not continue to relatively increase. To investigate and analyze this, seven respondents from the municipality of Skellefteå were interviewed, what their daily commutes look like and their experiences and opinions within the various transport options. The results show that depending on the stage of life the respondents are in, there are more or fewer restrictions on their daily commute. The people in the study also faced limitations in their daily commute that could be explained by restrictions in time geography that affected their movement between their home and work. With all aspects in mind, changing means of transport within the daily commute is seen as complex. Currently, the people in this study do not see public transport in Skellefteå as an alternative that would replace the car within their daily commute, as public transport does not meet their needs. But to use a bicycle within its daily commute as more likely, as the measures presented by the municipality and the improvement opportunities presented by the respondents in this study agreed to some extent. The development that the municipality of Skellefteå is carrying out in pedestrian and bicycle traffic could lead to these respondents switching to a certain extent using bicycles as an alternative means of transport within their daily commute. Nudging is used to see how the municipality of Skellefteå works with measures that could promote traffic behavior among the municipality's residents, which could result in more environmentally friendly passenger traffic.