The human immune-regulatory protein, complement receptor type 1 (CR1, CD35), occurs on erythrocytes where it serves as the immune adherence receptor. It interacts with C3b, C4b, C1q and mannan-binding lectin (MBL). It additionally binds the Plasmodium falciparum protein, Rh4, in the non-sialic acid-dependent erythrocye-invasion pathway, and is also important for rosetting, via an interaction with P. falciparum erythrocyte membrane protein 1 (PfEMP1). A C3b/C4b, and PfEMP1 binding site lies in CCP modules 15-17 (out of 30 in CR1), while polymorphisms that afford advantage to some populations in dealing with severe malaria occur in CCPs 24-25, begging the question central to this thesis – do these polymorphism modulate function, and if so how? We hypothesized that the CR1 architecture apposes CCPs 15-17 and CCPs 24-25 using the exceptionally long linker between CCPs 21 and 22 as a hinge, thus polymorphic variants in CCPs 24-25 modulate functionality in CCPs 15-17. To test this, a panel of recombinant CR1 protein fragments (CCPs 21, 21-22, 20-23, 15-17, 17, 10-11, 17-25, 15-25 and 24-25) were produced in Pichia pastoris along with polymorphic forms of the relevant constructs. After purification, biophysical and biological methods were used to assess whether the linker does indeed act as a hinge, and the comparative abilities of the CCPs 15-25 variants (along with soluble CR1 (sCR1), CCPs 1-3 and the panel of CR1 fragments) to interact with a range of ligands were measured. We found no evidence from NMR for face-to-face contacts between CCPs 21 and 22 that would be consistent with the long linker permitting a 180-degree bend between them. Indeed, based on scattering and analytical ultracentrifugation data, CCPs 20-23 form an extended rather than a bent-back structure. All of the four Knops blood-group variants of the CCPs 15-25 proteins produced similar results according to dynamic light scattering and AUC indicating no structural difference or change in self-association state between variants. In addition, based on the data collected from surface plasmon resonance (SPR), ELISA and fluid-phase cofactor (for factor I) assays, there were no evidence of any difference between the polymorphic forms with respect to their interactions with C3b, C4b, C1q and MBL. Only weak interaction was observed for sCR1, and all CCPs 15-25 variants, with the relevant part of PfEMP1, and there was no measurable difference amongst the variants in disrupting rosettes. The sCR1-Rh4.9 interaction was confirmed by SPR; affinities measured between the binding domain of Rh4 and the panel of CR1 fragments identified CCPs 1-3 (site 1) as the main interaction site. It seemed unlikely therefore that CCPs 24 and 25 could modulate Rh4 binding; indeed none of the four CR1 15-25 variants bound Rh4.9 appreciably. Thus we concluded that allotypic variations in CCPs 24-25 have no measurable effect on the architecture as well as binding of CR1 to its host or parasite ligands The inferred selective pressure acting on these variants likely arise from some other (i.e. besides malaria) geographically localised infectious diseases.

Understanding and predicting the way in which species interactions may change under the uncertain climatic future is imperative if the management of important resources is to be successful. Consumer – resource interactions underlie population dynamics and distribution, yet there is little known about how these interactions will respond to increasing temperature. Temperature increase can facilitate the movement and settlement of alien species into new ranges. Introduced species can often be ecologically damaging and unpredictable due to novel predator-prey interactions. Comparative functional response analysis has been used to gain insight into resource dependent behaviour and population dynamics. This study is an assessment of the way in which predicted temperature changes can affect resource consumption in three predators. The red lionfish Pterois volitans (Linnaeus, 1758) is a successful and hugely damaging invader in the Western Atlantic and sources point to an ongoing Mediterranean invasion. Through a series of laboratory experiments I assessed how temperature, habitat complexity, and light wavelength affect the functional response of lionfish towards a crustacean prey. I establish that lionfish have a persistent Type II functional response and that lower temperature decreased the magnitude of the functional response, suggesting that movement into the comparatively colder waters of the Mediterranean and British Isles could reduce the per capita response. Further, I found that red light reduced the maximum feeding rate of lionfish, compared to blue and white light, by dampening the attack rate. I assessed how temperature increase affects the proportional consumption of an amphipod prey by an intertidal predator, the bleniid, Lipophrys pholis (Linnaeus, 1758). Functional response analysis revealed that the shanny has a hump shaped relationship with increasing temperature wherein maximum feeding rate decreased at the highest temperature. Two prey supply models, where prey density was allowed to deplete, and where prey were replaced after consumption were compared and found to have differential results due to model choice. I used gut content data to assess the abundance, prey selection, degree of dietary overlap, in a commercial predator, cod (Gadhus morhua; Linnaeus, 1758) and a non-commercial predator, dogfish (Sycliorhinus canicula; Linnaeus, 1758) with regards to substrate type. While there were no significant conclusions to be made about habitat use, I found significantly larger populations of S. canicula and higher consumption of commercial invertebrates by S. canicula. I vi used this field data to inform further experiments, having highlighted S. canicula as a potential threat to commercial fisheries. A two-by-two experimental design was used to understand how differential acclimation of predator (S. canicula) and amphipod prey species (Echinogammarus marinus; Leach, 1815) affects the functional response of the predator. Increasing temperature concomitantly increased the magnitude functional response of S. canicula, however raised temperature caused a shift in functional response type, from Type II to Type III, conferring low prey density protection. Handling time was shorter when both predator and prey were acclimated to the raised temperature and as a result there was a significant interaction effect where maximum feeding rate was significantly higher when both predator and prey were acclimated. This increase in predation impact by S. canicula has the potential to affect valuable fisheries stocks due to the increasing populations of Scyliorhinus canicula and the additive effects of acclimation to raised temperature. Having highlighted the differential ways in which temperature can affect the per capita response of consumers I postulate a new metric wherein “Relative Impact Potential” of a consumer can be predicted under a set of environmental variables. This metric takes into account the per capita response, numerical response, and the potential change in predator and prey populations under the proposed conditions. I suggest the use of this metric as a rapid way of assessing and predicting potential threats to sustainability of fisheries under predicted climatic change. Overall, this thesis identifies species and scenarios wherein sustainability of important fisheries could be threatened. While this work focuses mainly on thermal responses, it demonstrates: (i) the utility of functional response analysis in assessing relative change in ecological impact under climate change scenarios; (ii) the species specificity of thermal responses and provides empiricle evidence of a hump shaped thermal response; (iii) the importance of considering both predator and prey when assessing ecological change, with reference to acclimation and population dynamics; and (iv) a metric with which to assess potential threats and ecological impact in a way that is standardized and easily accessible by managers and stakeholders alike.

Anêmonas-do-mar do gênero Diadumene Stephenson, 1920 foram encontradas em grande abundância fixadas sobre substratos naturais e estruturas artificiais na Baía de Paranaguá. Em 1989, em trabalho realizado no mesmo local, a quantidade de anêmonas deste gênero, não identificadas em nível de espécie, era baixa. Sua grande abundância atual pode ser explicada por sua alta taxa de reprodução assexuada, por fissão longitudinal, um dos fatores que poderiam caracterizar essas anêmonas como sendo uma espécie exótica e invasora. A elucidação dos aspectos sistemáticos dessas anêmonas e a compreensão de alguns de suas características biológicas são essenciais para definir o status da espécie na costa brasileira. Para isso, foram realizadas cinco (5) coletas no Iate Clube de Paranaguá, entre agosto de 2009 e agosto de 2010. Em cada coleta, aproximadamente 200 espécimes foram coletados e levados ao laboratório para serem submetidos aos estudos taxonômicos ou aos experimentos de resposta a parâmetros ambientais. A definição da espécie foi realizada com base em ferramentas taxonômicas comumente utilizadas para a ordem Actiniaria (morfologia externa, interna, elementos musculares e cnidoma) e através do seqüenciamento do gene mitocondrial 16s rRNA. Além disso, foi testada a tolerância da espécie a diferentes salinidades, à dessecação e a preferência por locais iluminados, sendo que os dois primeiros testes revelam se existe uma adaptabilidade característica de espécies invasoras, e o último sua capacidade de colonizar um local de águas calmas, mas onde há grande interferência humana por ser um porto movimentado A análise morfológica mostrou que a espécie de Paranaguá apresentava diferenças, segundo a literatura, em relação a todas as demais espécies do gênero Diadumene, sendo os caracteres responsáveis pela diferença: presença de cínclides na coluna dispostas em fileiras longitudinais, presença de nematocistos do tipo macrobásico p-amastigóforo nos tentáculos e nematocistos do tipo microbásico p-amastigóforo nos acôncios. No entanto, a análise molecular mostrou que a população da Baía de Paranaguá provavelmente é oriunda de uma população da espécie Diadumene cincta Stephenson, 1925. Nos experimentos, notou-se uma grande tolerância da espécie aos diversos fatores ambientais, mostrando que a espécie pode apresentar a plasticidade fenotípica característica de espécies invasoras. D. cincta já apresenta registros na literatura que a caracterizam como espécie invasora nos mares europeus e na costa atlântica européia, e acredita-se que a sua introdução na Baía de Paranaguá tenha se dado através de incrustação em cascos de navios, já que a região onde a anêmona foi encontrada é próxima ao Porto de Paranaguá. O monitoramento das espécies exóticas encontradas na costa brasileira é de grande importância, já que estas podem vir a causar impactos no ambiente ou nas atividades socioeconômicas que afetam o ser humano. Além disso, é imprescindível que sejam realizados mais estudos sobre as características das populações das espécies marinhas introduzidas no local, inclusive D. cincta / A great number of sea anemones of the genus Diadumene Stephenson, 1920 were found fixated on natural and artificial substrates at the Paranaguá Bay. In 1989, in a study conducted at the same location, the number of anemones of this genus, not identified to a specific level, was much lower. The great abundance of anemones that has currently been observed may be explained by the population\'s high rate of asexual reproduction, by longitudinal fission, one of the factors that may characterize these anemones as an exotic and invasive species. The elucidation of the systematic aspects of these anemones and the understanding of some of their biological characteristics are essential for defining the status of this species along the Brazilian coast. For this purpose, approximately 200 specimens were collected in five different dates, between August 2009 and August 2010, at the Iate Club of Paranaguá. The specimens were taken to the laboratory and submitted to taxonomical studies and experiments of response to environmental parameters. The definition of the species was based on the taxonomical features usually used for the order Actiniaria (external and internal morphology, muscle elements and cnidoma) and on the sequencing of the mitochondrial 16S rRNA gene. The species\' tolerance to different salinities and to air exposure was tested, as was it\'s preference for illuminated places. The first two tests would reveal if the sea anemone has an adaptability that is characteristic of invasive species, while the latter would test its ability to colonize calm waters with great human interference (due to the proximity to the Paranaguá Port). The morphological analysis revealed that the species from Paranaguá differed from the other species of the genus, because of the presence of the following characteristics: cinclids on the capitulum in longitudinal rows, macrobasic p-amastigophores in the tentacles and microbasic amastigophores in the acontia. However, molecular analysis showed that population of Paranaguá was probably originated from a population of the species Diadumene cincta Stephenson, 1925. The experiments showed that the species has a high tolerance to the tested environmental factors, showing that it may present the phenotypic plasticity that is characteristic of invasive species. D. cincta is already registered as an invasive species in European seas and the Atlantic coast of Europe, and it is believed that its introduction in the Paranaguá Bay was by fouling on shiphulls, as the species was found in a location near the Port of Paranaguá. The monitoring of alien species found along the Brazilian coast is very important, since these species may cause impacts on the environment or on human socio-economic activities. Moreover, it is necessary to conduct more studies on the characteristics of populations of marine species introduced in the Paranaguá Bay, including D. cincta

Worker. Trade Agent. Serf. Etain Ixtii detests the labels others give her, but there are some things she must accept. She was genetically designed to do specific tasks. Her breeding instincts interrupt her life every forty-five days. But workers like Etain are taught not to question so when she returns from training questioning her home world Gno's profit-based caste system, she risks her life. She doesn't want to be an agent and doesn't want to cross through the wormhole to never return. Why does she have to go? Can't someone else? Usurer Serria, the owner of Etain's birth and training debt, quickly tires of her problem worker and launches Etain through a collapsing wormhole so she can collect the insurance payout. Very bad business indeed, but Etain manages to survive the attempt, arriving on the other side plagued by debilitating headaches and hounded by a dangerous insectoid enemy that no one, including Physician Leigheas Sternbow, the Takla royal physician, and Mercine Feney, the Empire's powerful female leader, can make disappear. / https://dc.etsu.edu/alumni_books/1028/thumbnail.jpg

The objective of this study was to retrospectively evaluate the prevalence of perineural invasion in cases of mucoepidermoid carcinoma (MEC). The study will determine if previously assessed perineural invasion by original pathology reports would be increased by re-review of the originally hematoxylin-eosin-(H &E) stained slides as well as review of slides reacted immunohistochemically with S100 to enhance visualization of nerves. The study will also assess whether perineural invasion or its absence in MEC is associated with clinical outcome. Thirty-one cases of major and minor salivary gland MEC were reviewed for perineural invasion and compared to the perineural invasion status stated on the original pathology report when available (13/31). All H & E-stained slides were reviewed as well as S100-reacted sections of each case’s tissue blocks that contained tumor. Patient demographics and clinical outcome were collected from electronic medical records. Perineural invasion was identified in 23% (3/13) of tumors in the original reports, 13% (4/31) of the authors' re-review of the same slides, and 29% (9/31) when cases were reacted with S100. A positive relationship was seen between the discovery of perineural invasion on H & E-stained slides and a greater number of foci of perineural invasion. Perineural invasion and larger-diameter nerve involvement was significantly associated with death at 5-year follow-up. In conclusion, immunohistochemical enhancement improves the accuracy, ease and speed of perineural invasion determination. Perineural invasion is a significant factor in the decreased survival outcome of cases of MEC. These findings support continued inclusion of the presence or absence of perineural invasion as a grading parameter in MEC.

Brown trout (Salmo trutta), one of the world’s most successful introduced species, negatively impacts native aquatic communities through predation, competition, and ecosystemlevel effects. Thus, there is a need to understand factors controlling the distribution of exotic brown trout in river systems, in order to prioritize and develop conservation and management strategies. Within the context of invasion success, I investigated how the physical template of the Logan River influences the distribution of brown trout along a longitudinal gradient, and the potential for brown trout predation on the native mottled sculpin (Cottus bairdi). The Logan River, Utah USA, is a high-elevation, mountain river exhibiting a wide range of physical habitat characteristics along the altitudinal (or elevational) gradient. In chapter 1, I evaluated whether longitudinal trends in geomorphology contribute to higher potential mortality of brown trout fry at high elevations due to flood-caused streambed scour. High-elevation spawning gravels did not exhibit higher scour compared to low elevations, because brown trout locally chose low-scour areas for spawning. In chapter 2, I investigated the importance of gravel availability, versus other habitat factors, in controlling the spatial distribution of brown trout redd densities. Using a Bayesian hierarchical modeling approach, I demonstrated that anchor ice, distance from high-quality backwater habitat, and to a lesser-extent gravel availability, best explained redd densities. Finally, in chapter 3, I evaluated the potential predatory effects of exotic brown trout on native mottled sculpin (Cottus bairdi). High rates of sculpin consumption contrasted to previously documented low rates of predation by native Bonneville cutthroat (Oncorhynchus clarkii) and depended on abiotic factors controlling the distribution of both species. Collectively, my research suggests that both abiotic factors and source-population dynamics structure brown trout distributions on the Logan River, and ultimately the potential impacts of this invasive fish. Specifically, the distribution of anchor ice and distance from dam backwaters are important drivers of the brown trout distribution, which may extend to other systems. These drivers, including how they may be influenced by future climate change and habitat alteration, should be considered in management efforts to control brown trout expansion and to limit the predatory impacts of brown trout.

The interactions between neighboring cells and between cells and their attached substrate have long been studied in tissue culture. These in vitro studies may provide information regarding cell behavior in vivo including cell movement, cell proliferation, tissue development and wound healing. Transcellular resistance (or impedance) measurements, using various dc or ac techniques have been used to study the barrier function of epithelial and endothelial cell layers. With an appropriate equivalent circuit used for data analysis, junctional resistance between cells and other cellular properties, including cell membrane capacitance, can be determined. However, these techniques have seldom been applied to fibroblastic cell layers because the transcellular resistance is so small that it is difficult to measure it accurately. This research is based on detecting the invasive activities of metastatic cells in vitro using electric cell-impedance sensing (ECIS). The metastatic cells where added over the established endothelial cells and were observed to attach and invade the cell layer. Human umbilical vein endothelial cells (HUVECs) were first grown and then loaded on eight well gold electrodes. The impedance of these electrodes was followed after the suspension of different sublines of cancer cells (SKOV3, OVCA429). For highly metastatic sublines, within an hour after being challenged, the impedance of confluent HUVECs layer was substantially reduced. In addition the conditioned cancer media and heat-killed cancer cells was also suspended which had no substantial effect on the impedance. This result suggests that ECIS based assay might be used with primary human cultures to establish the metastatic abilities of cells.

Les invasions biologiques ont des conséquences écologiques et économiques considérables. Si leurs mécanismes démographiques, écologiques et génétiques sont maintenant connus, elles restent cependant difficiles à prédire. Les approches fondées sur la recherche des caractéristiques écologiques des espèces envahissantes ou des écosystèmes envahis n'ont pas encore abouti. Nous encourageons une approche évolutive pour mieux appréhender les mécanismes d'invasion, approche qui s'attache à la résolution de deux paradoxes. (1) Pourquoi une espèce "étrangère" réussit-elle à s'établir et à envahir un écosystème auquel elle n'est pas adaptée, surpassant parfois certaines espèces locales ? (2) Pourquoi les populations envahissantes réussissent-elles à s'adapter si rapidement à leur nouvel environnement malgré les effets de fondation ? L'ambroisie commune, envahissante dans la vallée du Rhône, est une Asteraceae d'origine nordaméricaine. Cet adventice des cultures pose d'importants problèmes de santé publique, son pollen étant très allergène. Pour tenter de résoudre les deux paradoxes évolutifs, nous avons mené plusieurs études comparant des populations envahissantes françaises à des populations nord-américaines de l'aire d'origine. Nous avons ainsi détecté un relâchement de la pression des herbivores qui pourrait avantager l'ambroisie dans l'aire d'invasion. En revanche, nous n'avons décelé aucune adaptation consécutive à cette diminution de pression d'herbivorie. Par ailleurs, après avoir développé des marqueurs microsatellites spécifiques, nous avons mis en évidence une diversité génétique plus élevée dans les populations françaises que dans les populations nord-américaines. Les effets de fondation furent probablement limités par l'introduction en France d'individus provenant de plusieurs populations sources. Enfin, nous proposons un cadre théorique évolutif où nous distinguons trois types d'invasion: celles ne nécessitant aucun changement de l'environnement ou de l'espèce, celles qui sont la conséquence d'un changement de l'environnement et celles qui résultent de l'adaptation de l'espèce.

Malgré les procédures de quarantaine, de nombreuses invasions par des mouches des fruits polyphages (famille des Tephritidae) ont été observées dans différentes parties du monde. Dans cette étude les paramètres démographiques, des co-infestations expérimentales dans un même fruit et l'interférence entre femelles adultes sont comparés entre quatre espèces de Tephritidae : trois espèces invasives qui se sont installées successivement à La Réunion et une espèce endémique de cette île. Les résultats suggèrent un trade-off interspécifique entre les traits K et r. La compétition larvaire a un effet négatif sur le poids pupal et la survie larvaire. Chez les femelles adultes, des comportements d'expulsion loin du fruit par d'autres femelles ont été observés. L'asymétrie de la compétition larvaire et des interactions directes entre femelles semble corrélée au rang d'établissement sur l'île, l'espèce arrivée la plus récemment ayant de bonnesperformances dans la compétition larvaire comme dans l'aptitude à déplacer d'autres femelles d'un fruit. La coexistence entre espèces est cependant permise par la variabilité de la tolérance aux conditions climatiques (température et humidité) et par celle de la gamme d'hôtes. L'espèceendémique a non seulement de plus faibles paramètres de survie et de fécondité que les autres espèces mais voit également les axes climatiques et de ressource de sa niche inclus dans celles de ses compétiteurs. Une coexistence stable devrait s'installer entre les trois espèces invasives alors que l'extinction de l'espèce endémique est considérée comme possible.

The establishment of exotic species in novel environments is a major environmental concern, however, few long-term studies have examined the effects of these species on their host environment and community, especially in forest ecosystems. The arrival and subsequent spread of the greater European pine shoot beetle, Tomicus piniperda (L.) (Coleoptera: Curculionidae, Scolytinae), into southern Ontario pine forests provided a natural experiment to assess biotic interactions between an exotic species and its new community over several years. Reproductive success of Tomicus piniperda colonies of various ages was studied between 2001 and 2004. The size and composition of competitor and natural enemy complexes present in these communities were also quantified over time. The impact of the natural enemy complexes on T. piniperda reproduction was assessed, Brood production (no. eggs and galleries/female) by T. piniperda populations rapidly approached those reported from its native range in Europe, with lower densities of parental adults. Thus, reproduction remained consistently above the replacement level for this beetle over all four years of study suggesting that these recently-introduced populations were growing rapidly and at a greater rate than in their country of origin. Tomicus piniperda successfully integrated into a large bark beetle community, and appeared to be capable of displacing native beetles to more marginal bark habitats, however, these competitors were not eliminated during the course of the study. The long-term effect of this marginalization on populations of native beetles is uncertain. Tomicus piniperda rapidly acquired natural enemies in the introduced areas, however, natural enemy-caused mortality did not show a regulating effect on its populations. It seems that intraspecific competition, rather than predation, regulates T. piniperda populations following introduction. The implications of these findings for the establishment and spread of exotic species in forest systems are examined, especially with reference to a prominent theory for success, the Enemy Release Hypothesis. In short, the Enemy Release Hypothesis is not applicable to an exotic species that is not regulated by natural enemies in its native range, and assessments of the Enemy Release Hypothesis should always include a determination of enemy regulation of the exotic in its native range.