6 resultados para Pilgrimage of Grace, 1536-1537.
em CORA - Cork Open Research Archive - University College Cork - Ireland
Resumo:
Despite studies demonstrating that inhibition of cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) has significant chemotherapeutic benefits in vitro and in vivo, inhibition of COX enzymes is associated with serious gastrointestinal and cardiovascular side effects, limiting the clinical utility of these drugs. PGE2 signals through four different receptors (EP1–EP4) and targeting individual receptor(s) may avoid these side effects, while retaining significant anticancer benefits. Here, we show that targeted inhibition of the EP1 receptor in the tumor cells and the tumor microenvironment resulted in the significant inhibition of tumor growth in vivo. Both dietary administration and direct injection of the EP1 receptor-specific antagonist, ONO-8713, effectively reduced the growth of established CT26 tumors in BALB/c mice, with suppression of the EP1 receptor in the tumor cells alone less effective in reducing tumor growth. This antitumor effect was associated with reduced Fas ligand expression and attenuated tumor-induced immune suppression. In particular, tumor infiltration by CD4+CD25+Foxp3+ regulatory T cells was decreased, whereas the cytotoxic activity of isolated splenocytes against CT26 cells was increased. F4/80+ macrophage infiltration was also decreased; however, there was no change in macrophage phenotype. These findings suggest that the EP1 receptor represents a potential target for the treatment of colon cancer.
Resumo:
Background and Aim: During carcinogenesis, tumours develop multiple mechanisms to evade the immune system and suppress the anti-tumour immune response. Upregulation of Fas Ligand (FasL/CD95L) expression may represent one such mechanism. FasL is a member of the tumour necrosis factor superfamily that triggers apoptotic cell death following ligation to its receptor Fas. Numerous studies have demonstrated upregulated FasL expression in tumor cells, with FasL expression associated with numerous pro-tumorigenic effects. However, little is known about the mechanisms that regulate FasL expression in tumours. The cyclooxgenase (COX) signalling pathway may play an important role in colon carcinogenesis, via the production of prostaglandins, in particular PGE2. PGE2 signals through four different receptor subtypes, EP1 – EP4. Thus, the aim of this study was to investigate the effect of targeting the PGE2-FasL signaling pathway. Results: (i) PGE2 induces FasL expression via the EP1 receptor in colon cancer cells. (ii) Suppression of FasL expression in colon tumour cells in vivo significantly delays and reduces tumour growth. (iii) Blocking EP1 receptor signaling, or suppression of the EP1 receptor in colon tumour cells, reduces tumour growth in vivo. Suppression of tumour growth correlates in part with suppression of FasL expression. (iv) The reduction in tumour growth is associated with an improved anti-tumour immune response. Tumour infiltration by Treg cells and macrophages was reduced, and the cytotoxic activity of CTL generated from splenocytes isolated from these mice increased. Conclusion: 1) Targeting FasL expression by blocking PGE2-EP1 receptor signalling reduces tumour development in vivo. 2) The mechanism is indirect but is associated with an increased anti-tumour immune response. Thus, unraveling the mechanisms regulating FasL expression and the pro-tumorigenic effects of the EP1 receptor may aid in the search for new therapeutic targets against colon cancer.
Resumo:
The parasite Bonamia ostreae has decimated Ostrea edulis stocks throughout Europe. The complete life cycle and means of transmission of the parasite remains unknown. The methods used to diagnose B. ostreae were examined to determine sensitivity and reproducibility. Two methods, with fixed protocols, should be used for the accurate detection of infection within a sample. A 13-month study of two stocks of O. edulis with varying periods of exposure to B. ostreae, was undertaken to determine if varying lengths of exposure would translate into observations of differing susceptibility. Oyster stocks can maintain themselves over extended periods of time in B. ostreae endemic areas. To identify a well performing spat stock, which could be used to repopulate beds within the region, hatchery bred spat from three stocks found in the North sea were placed on a B. ostreae infected bed and screened for growth, mortality and prevalence of infection. Local environmental factors may influence oyster performance, with local stocks better adapted to these conditions. Sediment and macroinvertebrate species were screened to investigate mechanisms by which B. ostreae may be maintaining itself on oyster beds. Mytilus edulis was positive, indicating that B. ostreae may use incidental carriers as a method of maintaining itself. The ability of oyster larvae to pick up infection from the surrounding environment was investigated by collecting larvae from brooding oysters from different areas. Larvae may acquire the pathogen from the water column during the process of filter feeding by the brooding adult, even when the parents themselves are uninfected. A study was undertaken to elucidate the activity of the parasite during the initial stage of infection, when it cannot be detected within the host. A naïve stock screened negative for infection throughout the trial, using heart imprints and PCR yet B. ostreae was detected by in-situ hybridisation.
The Celtic dragon slayer - a literary analysis of Tochmarc Emire in connection with Tristan et Iseut
Resumo:
As Celtic scholars have long noted, the medieval Irish tale Tochmarc Emire “The Courtship of Emer” is heavily indebted to other medieval Irish texts. In this tale of courtship and otherworldly quests, the Irish hero Cú Chulainn must prove himself worthy of the hand of the noblewoman Emer. Among his overseas adventures, Cú Chulainn rescues a princess from three attackers of the Fomoire. This episode may represent the only medieval Irish example of AT300 “The Dragon Slayer”, a story pattern known from classical models such as the stories of Perseus and Andromeda; and Hercules and Hesione. Moreover, in the company of Cú Chulainn we find a character otherwise unknown to Irish tradition by the name of Drust mac Seirb. This has led scholars to argue that Tochmarc Emire may preserve a Celtic precursor of the Continental Tristan legend, seeing in Drust the Pictish origin of the character Tristan, himself a famous dragon slayer. In this interdisciplinary dissertation, a number of questions are addressed. If the redactor of Tochmarc Emire drew on material from outside Irish tradition, what does this tell us about medieval Irish concepts of literature and genre? Further, what evidence do we have for tracing the origin of the Continental Tristan legend back to Pictland, and what explanation might we offer for a putative Pictish prince featuring in an Irish Dragon Slayer story? Finally, what place does the Dragon Slayer episode occupy within Tochmarc Emire and can we find other narratives, Celtic or classical or other, fitting the pattern of AT300, which may strengthen the link between Tochmarc Emire and Tristan?
Resumo:
In moments of rapid social changes, as has been witnessed in Ireland in the last decade, the conditions through which people engage with their localities though memory, individually and collectively, remains an important cultural issue with key implications for questions of heritage, preservation and civic identity. In recent decades, cultural geographers have argued that landscape is more than just a view or a static text of something symbolic. The emphasis seems to be on landscape as a dynamic cultural process – an ever-evolving process being constructed and re-constructed. Hence, landscape seems to be a highly complex term that carries many different meanings. Material, form, relationships or actions have different meanings in different settings. Drawing upon recent and continuing scholarly debates in cultural landscapes and collective memory, this thesis sets out to examine the generation of collective memory and how it is employed as a cultural tool in the production of memory in the landscape. More specifically, the research considers the relationships between landscape and memory, investigating the ways in which places are produced, appropriated, experienced, sensed, acknowledged, imagined, yearned for, appropriated, re-appropriated, contested and identified with. A polyvocal-bricoleur approach aims to get below the surface of a cultural landscape, inject historical research and temporal depth into cultural landscape studies and instil a genuine sense of inclusivity of a wide variety of voices (role of monuments and rituals and voices of people) from the past and present. The polyvocal-bricoleur approach inspires a mixed method methodology approach to fieldsites through archival research, fieldwork and filmed interviews. Using a mixture of mini-vignettes of place narratives in the River Lee valley in the south of Ireland, the thesis explores a number of questions on the fluid nature of narrative in representing the story and role of the landscape in memory-making. The case studies in the Lee Valley are harnessed to investigate the role of the above questions/ themes/ debates in the act of memory making at sites ranging from an Irish War of Independence memorial to the River Lee’s hydroelectric scheme to the valley’s key religious pilgrimage site. The thesis investigates the idea that that the process of landscape extends not only across space but also across time – that the concept of historical continuity and the individual and collective human engagement and experience of this continuity are central to the processes of remembering on the landscape. In addition the thesis debates the idea that the production of landscape is conditioned by several social frames of memory – that individuals remember according to several social frames that give emphasis to different aspects of the reality of human experience. The thesis also reflects on how the process of landscape is represented by those who re-produce its narratives in various media.
Resumo:
Using the lenses of contemporary cultural geography, this research develops an understanding of pilgrimage as a relational and reciprocal process that co-produces self and world. Drawing on the phenomenology of Merleau-Ponty, I argue that through the performances and experiences of contemporary pilgrimage in Ireland, participants and locations emerge as pilgrims and pilgrimage places. This approach unites different strands of cultural geography, including the mobilities field, more-than representational concerns, discussions of embodiment and practice, emotional and affective geographies, and religious and spiritual geographies. I explore how pilgrimage is an active process in which self and world, belief and practice, and the numinous and material entwine and merge. An autoethnographic methodology is enacted as an embodied, intersubjective, and reflexive research approach that incorporates the motivations, experiences, and beliefs of research participants, alongside my own descriptions and reflections. The methodology is focused on encountering and documenting pilgrimage practices as they occur in place and relating these embodied spatial practices to the accounts of pilgrims. The insights generated by engagements with research participants and through my own pilgrimages, offer new appreciations of the enduring appeal of pilgrimage in Ireland as a religious-spiritual and cultural activity that allows people to express personal intentions, to develop their faith, and to seek numinous encounters. Through the pilgrimages at Lough Derg, Croagh Patrick, and three holy wells, I produce a layered account of the empirical circumstances of the practices. The presentation of these places and events is enhanced by the use of evocative images and audiovisual recordings. By centring my study on the practices and experiences of different pilgrimages in present-day Ireland, and critically deploying strands of cultural geography and pilgrimage studies, this research produces new qualitative understandings of pilgrimage and contributes to discussions concerned with the relationships between self and world.