Expression and function of the neurotrophic factors GDF5 and GDNF in the nigrostriatal system during development and in rat models of Parkinson's disease

Growth/differentiation factor 5 (GDF5) and glial cell line-derived neurotrophic factor (GDNF) are neurotrophic factors that promote the survival of midbrain dopaminergic neurons in vitro and in vivo. Both factors have potent neurotrophic and neuroprotective effects in rat models of Parkinson's disease (PD), and may represent promising new therapies for PD. The aim of the present study was to investigate the endogenous expression and function of GDF5 and GDNF in the nigrostriatal dopaminergic system during development and in rat models of PD. Examination of the temporal expression patterns of endogenous GDF5, GDNF, and their respective receptors, in the developing and adult nigrostriatal dopaminergic system suggest that these factors play important roles in promoting the survival and maturation of midbrain dopaminergic neurons during the period of postnatal programmed cell death. The relative levels of GDF5 and GDNF mRNAs in the midbrain and striatum, and their individual temporal expression patterns during development, suggest that their modes of actions are quite distinct in vivo. Furthermore, the sustained expression of GDF5, GDNF, and their receptors into adulthood suggest roles for these factors in the continued support and maintenance of mature nigrostriatal dopaminergic neurons. The present study found that endogenous GDF5, GDNF, and their receptors are differentially expressed in two 6-hydroxydopamine-induced lesion adult rat models of PD. In both terminal and axonal lesion models of PD, GDF5 mRNA levels in the striatum increased at 10 days post-lesion, while GDNF mRNA levels in the nigrostriatal system decreased at 10 and 28 days post-lesion. Thus, despite the fact that exogenous GDF5 and GDNF have similar effects on midbrain dopaminergic neurons in vitro and in vivo, their endogenous responses to a neurotoxic injury are quite distinct. These results highlight the importance of studying the temporal dynamic changes in neurotrophic factor expression during development and in animal models of PD.

History, revolution and the British popular novel: historical fiction in the romantic age

“History, Revolution and the British Popular Novel” takes as its focus the significant role which historical fiction played within the French Revolution debate and its aftermath. Examining the complex intersection of the genre with the political and historical dialogue generated by the French Revolution crisis, the thesis contends that contemporary fascination with the historical episode of the Revolution, and the fundamental importance of history to the disputes which raged about questions of tradition and change, and the meaning of the British national past, led to the emergence of increasingly complex forms of fictional historical narrative during the “war of ideas.” Considering the varying ways in which novelists such as Charlotte Smith, William Godwin, Mary Robinson, Helen Craik, Clara Reeve, John Moore, Edward Sayer, Mary Charlton, Ann Thomas, George Walker and Jane West engaged with the historical contexts of the Revolution debate, my discussion juxtaposes the manner in which English Jacobin novelists inserted the radical critique of the Jacobin novel into the wider arena of history with anti-Jacobin deployments of the historical to combat the revolutionary threat and internal moves for socio-political restructuring. I argue that the use of imaginative historical narrative to contribute to the ongoing dialogue surrounding the Revolution, and offer political and historical guidance to readers, represented a significant element within the literature of the Revolution crisis. The thesis also identifies the diverse body of historical fiction which materialised amidst the Revolution controversy as a key context within which to understand the emergence of Scott’s national historical novel in 1814, and the broader field of historical fiction in the era of Waterloo. Tracing the continued engagement with revolutionary and political concerns evident in the early Waverley novels, Frances Burney’s The Wanderer (1814), William Godwin’s Mandeville (1816), and Mary Shelley’s Valperga (1823), my discussion concludes by arguing that Godwin’s and Shelley’s extension of the mode of historical fiction initially envisioned by Godwin in the revolutionary decade, and their shared endeavour to retrieve the possibility enshrined within the republican past, appeared as a significant counter to the model of history and fiction developed by Walter Scott in the post-revolutionary epoch.

Investigation of the function of the LNX family of E3 ubiquitin ligases in the nervous system

The Lnx1 (Ligand of Numb protein X 1) and Lnx2 genes belong to a family of PDZ domain-containing RING finger domain E3 ubiquitin ligases. mRNA expression for both genes have been reported in early murine central nervous system. However, there have been limited reports with regards to the expression patterns for both the proteins in vivo. Hence, we have attempted to characterize the significance of these proteins in the context of morphology and physiology of the central nervous system. Through our studies, we have attempted to examine closely the expression of these two genes in the murine central nervous system. We have also looked at novel interacting ligands for both proteins. Interacting partners have been examined with particular relevance to possible roles of their interactions with LNX1 and LNX2 in the functioning of the nervous system. Moreover, we have performed loss-of-function studies by way of creation and characterization of knockout mice.

The politics of hazard: imminent critique and deconstruction of ecological modernisation in Ireland

This dissertation sets out to provide immanent critique and deconstruction of ecological modernisation or ecomodernism.It does so, from a critical social theory approach, in order to correctly address the essential issues at the heart of the environmental crisis that ecomodernism purports to address. This critical approach argues that the solution to the environmental crisis can only be concretely achieved by recognising its root cause as being foremost the issue of material interaction between classes in society, and not simply between society and nature in any structurally meaningful way. Based on a metaphysic of false dualism, ecological modernisation attributes a materiality of exchange value relations to issues of society, while simultaneously offering a non- material ontology to issues of nature. Thus ecomodernism serves asymmetrical relations of power whereby, as a polysemic policy discourse, it serves the material interests of those who have the power to impose abstract interpretations on the materiality of actual phenomena. The research of this dissertation is conducted by the critical evaluation of the empirical data from two exemplary Irish case studies. Discovery of the causal processes of the various public issues in the case studies and thereafter the revelation of the meaning structures under- pinning such causal processes, is a theoretically- driven task requiring analysis of those social practices found in the cognitive, cultural and structural constitutions respectively of actors, mediations and systems.Therefore, the imminent critique of the case study paradigms serves as a research strategy for comprehending Ireland’s nature- society relations as influenced essentially by a systems (techno- corporatist) ecomodernist discourse. Moreover, the deconstruction of this systems ideological discourse serves not only to demonstrate how weak ecomodernism practically undermines its declared ecological objectives, but also indicates how such objectives intervene as systemic contradictions at the cultural heart of Ireland’s late modernisation.

The role of metabolism in the pathogenesis of adherent invasive Escherichia coli (AIEC)

Crohn’s disease (CD) is a chronic, relapsing inflammatory condition affecting the gastrointestinal tract of humans, of which there is currently no cure. The precise etiology of CD is unknown, although it has become widely accepted that it is a multifactorial disease which occurs as a result of an abnormal immune response to commensal enteric bacteria in a genetically susceptible host. Recent studies have shown that a new group of Escherichia coli, called Adherent Invasive Escherichia coli (AIEC) are present in the guts of CD patients at a higher frequency than in healthy subjects, suggesting that they may play a role in the initiation and/or maintenance of the inflammation associated with CD. Two phenotypes define an AIEC and differentiate them from other groups of E. coli. Firstly, AIEC can adhere to and invade epithelial cells; and secondly, they can replicate in macrophages. In this study, we use a strain of AIEC which has been isolated from the colonic mucosa of a CD patient, called HM605, to examine the relationship between AIEC and the macrophage. We show, using a systematic mutational approach, that while the Tricarboxylic acid (TCA) cycle, the glyoxylate pathway, the Entner-Doudoroff (ED) pathway, the Pentose Phosphate (PP) pathway and gluconeogenesis are dispensable for the intramacrophagic growth of HM605, glycolysis is an absolute requirement for the ability of this organism to replicate intracellularly. We also show that HM605 activates the inflammasome, a major driver of inflammation in mammals. Specifically, we show that macrophages infected with HM605 produce significantly higher levels of the pro-inflammatory cytokine IL-1β than macrophages infected with a non-AIEC strain, and we show by immunoblotting that this is due to cleavage of caspase-1. We also show that macrophages infected with HM605 exhibit significantly higher levels of pyroptosis, a form of inflammatory cell death, than macrophages infected with a non-AIEC strain. Therefore, AIEC strains are more pro-inflammatory than non-AIEC strains and this may have important consequences in terms of CD pathology. Moreover, we show that while inflammasome activation by HM605 is independent of intracellular bacterial replication, it is dependent on an active bacterial metabolism. Through the establishment of a genetic screen aimed at identifying mutants which activate the inflammasome to lower levels than the wild-type, we confirm our observation that bacterial metabolism is essential for successful inflammasome activation by HM605 and we also uncover new systems/structures that may be important for inflammasome activation, such as the BasS/BasR two-component system, a type VI secretion system and a K1 capsule. Finally, in this study, we also identify a putative small RNA in AIEC strain LF82, which may be involved in modulating the motility of this strain. Overall this works shows that, in the absence of specialised virulence factors, the ability of AIEC to metabolise within the host cell may be a key determinant of its pathogenesis.

Evanescent field sensing: optical nanofibres, whispering-gallery-mode microspherical and microbubble resonators

In this thesis, the evanescent field sensing techniques of tapered optical nanofibres and microspherical resonators are investigated. This includes evanescent field spectroscopy of a silica nanofibre in a rubidium vapour; thermo-optical tuning of Er:Yb co-doped phosphate glass microspheres; optomechanical properties of microspherical pendulums; and the fabrication and characterisation of borosilicate microbubble resonators. Doppler-broadened and sub-Doppler absorption spectroscopic techniques are performed around the D2 transition (780.24 nm) of rubidium using the evanescent field produced at the waist of a tapered nanofibre with input probe powers as low as 55 nW. Doppler-broadened Zeeman shifts and a preliminary dichroic atomic vapour laser lock (DAVLL) line shape are also observed via the nanofibre waist with an applied magnetic field of 60 G. This device has the potential for laser frequency stabilisation while also studying the effects of atom-surface interactions. A non-invasive thermo-optical tuning technique of Er:Yb co-doped microspheres to specific arbitrary wavelengths is demonstrated particularly to 1294 nm and the 5S1/2F=3 to 5P3/2Fʹ=4 laser cooling transition of 85Rb. Reversible tuning ranges of up to 474 GHz and on resonance cavity timescales on the order of 100 s are reported. This procedure has prospective applications for sensing a variety of atomic or molecular species in a cavity quantum electrodynamics (QED) experiments. The mechanical characteristics of a silica microsphere pendulum with a relatively low spring constant of 10-4 Nm-1 are explored. A novel method of frequency sweeping the motion of the pendulum to determine its natural resonance frequencies while overriding its sensitivity to environmental noise is proposed. An estimated force of 0.25 N is required to actuate the pendulum by a displacement of (1-2) μm. It is suggested that this is of sufficient magnitude to be experienced between two evanescently coupled microspheres (photonic molecule) and enable spatial trapping of the micropendulum. Finally, single-input borosilicate microbubble resonators with diameters <100 μm are fabricated using a CO2 laser. Optical whispering gallery mode spectra are observed via evanescent coupling with a tapered fibre. A red-shift of (4-22) GHz of the resonance modes is detected when the hollow cavity was filled with nano-filtered water. A polarisation conversion effect, with an efficiency of 10%, is observed when the diameter of the coupling tapered fibre waist is varied. This effect is also achieved by simply varying the polarisation of the input light in the tapered fibre where the efficiency is optimised to 92%. Thus, the microbubble device acts as a reversible band-pass to band-stop optical filter for cavity-QED, integrated solid-state and semiconductor circuit applications.

An dátheangachas agus an t-aitheantas: déagóirí Éireannacha sa 21ú haois

Tugann an staidéar taighde aghaidh ar an dátheangachas i bPoblacht na hÉireann agus go háirithe ar thuairimí dhaoine óga dátheangacha sa 21ú haois. Is é cuspóir an staidéir ná iniúchadh a dhéanamh ar mheonta déagóirí Éireannacha dátheangacha i leith na Gaeilge agus a gcuid aitheantais mar dhéagóirí dátheangacha. Déanann an staidéar anailís ar mheonta daltaí a fhreastalaíonn ar iar-bhunscoileanna lán-Ghaeilge. Féachtar ar thuairimí tuismitheoirí, múinteoirí agus iar-scoláirí freisin. Is í príomhcheist an staidéir seo ná: Cad iad meonta déagóirí Éireannacha dátheangacha i leith teanga na Gaeilge agus cad iad a n-aitheantais mar Éireannaigh óga dátheangacha? Baineadh úsáid as modhanna cáilíochtúla idir agallaimh, agallamh grúpa, scríbhneoireacht phearsanta agus ríomhphoist chun eolas a bhailiú i scoil an staidéir cháis. Roghnaíodh modh cainníochtúil an cheistneora náisiúnta chun cur leis an eolas. Tugann an taighde le tuiscint go mothaíonn déagóirí Éireannacha dearfach faoi theanga na Gaeilge agus faoin a gcuid aitheantais mar dhaoine dátheangacha. Léiríonn torthaí an taighde gurb ionann teanga na Gaeilge dóibh agus seoid luachmhar a sholáthraíonn buntáistí, deiseanna agus féidearthachtaí dóibh. Maidir le cruthú aitheantais, chuaigh formhór na ndéagóirí i scoil an staidéir cháis i dtreo a ndá ghrúpa teangeolaíochta agus chruthaigh siad “linguistic brokerage” (Shenk, 2008) a tharraing a taobh Gaelach is Béarla le chéile. Mothaíonn formhór na ndéagóirí dátheangacha seo go bhfuil aitheantas amháin acu ach go bhfuil an dá theanga, an dá chultúr agus an dá pháirt dá saoil mar pháirt den gcomhaitheantas sin. Ach ba léir go raibh éagsúlachtaí i measc na rannpháirtithe freisin. Tacaíonn torthaí an taighde le gnéithe den litríocht ar a rinneadh athbhreithniú chun ról lárnach na teanga i gcruthú aitheantais an déagóra a léiriú. Cuireann an taighde seo leis an réimse toisc go soláthraíonn sé eolas luachmhar agus fiúntach faoin dátheangachas agus aitheantas i bPoblacht na hÉireann sa 21ú haois.

Synthesis & characterisation of group IV semiconducting nanowires

Semiconductor nanowires, particularly group 14 semiconductor nanowires, have been the subject of intensive research in the recent past. They have been demonstrated to provide an effective, versatile route towards the continued miniaturisation and improvement of microelectronics. This thesis aims to highlight some novel ways of fabricating and controlling various aspects of the growth of Si and Ge nanowires. Chapter 1 highlights the primary technique used for the growth of nanowires in this study, namely, supercritical fluid (SCF) growth reactions. The advantages (and disadvantages) of this technique for the growth of Si and Ge nanowires are highlighted, citing numerous examples from the past ten years. The many variables involved in this technique are discussed along with the resultant characteristics of nanowires produced (diameter, doping, orientation etc.). Chapter 2 outlines the experimental methodologies used in this thesis. The analytical techniques used for the structural characterisation of nanowires produced are also described as well as the techniques used for the chemical analysis of various surface terminations. Chapter 3 describes the controlled self-seeded growth of highly crystalline Ge nanowires, in the absence of conventional metal seed catalysts, using a variety of oligosilylgermane precursors and mixtures of germane and silane compounds. A model is presented which describes the main stages of self-seeded Ge nanowire growth (nucleation, coalescence and Ostwald ripening) from the oligosilylgermane precursors and in conjunction with TEM analysis, a mechanism of growth is proposed. Chapter 4 introduces the metal assisted etching (MAE) of Si substrates to produce Si nanowires. A single step metal-assisted etch (MAE) process, utilising metal ion-containing HF solutions in the absence of an external oxidant, was developed to generate heterostructured Si nanowires with controllable porous (isotropically etched) and non-porous (anisotropically etched) segments. In Chapter 5 the bottom-up growth of Ge nanowires, similar to that described in Chapter 3, and the top down etching of Si, described in Chapter 4, are combined. The introduction of a MAE processing step in order to “sink” the Ag seeds into the growth substrate, prior to nanowire growth, is shown to dramatically decrease the mean nanowire diameters and to narrow the diameter distributions. Finally, in Chapter 6, the biotin – streptavidin interaction was explored for the purposes of developing a novel Si junctionless nanowire transistor (JNT) sensor.

The Viking age glass beads of Ireland and their North Atlantic context

Hitherto, the majority of studies which have included the discussion of Viking glass beads have mainly focused on the assemblages from individual sites, with limited use of known parallels. Exceptions to this include recent publications regarding the Icelandic material and Callmer’s 1977 catalogue of the finds from mainland Scandinavia, now over thirty years old. Analysis of these finds from Ireland was, for the most part, non-existent. The aim of this research is to address this lack of analysis within Ireland, while incorporating the wider context of the beads within the Viking North Atlantic. The research thus examines the use of glass beads of diagnostically Scandinavian manufacture and import found in Ireland, particularly in relation to their context and distribution. The history of research from Ireland as well as from across the Viking world is considered and explored throughout the thesis, with critique of methods and discussions used. Focussed analysis of both published and unpublished material detailing artefacts from Scandinavia (especially Vestfold), Britain, Iceland, the Faroe Islands and L’Anse aux Meadows is presented within the thesis in order to provide the greater picture for the core section of the thesis, the glass beads found in Ireland. Three appendices are included within Volume 2, databases of the glass beads under discussion from Ireland, the Vestfold region graves in Norway and the topsoil finds from the Kaupang trading place, also located within Vestfold. These appendices therefore represent the first-hand analysis of glass beads by the author. In total, this research represents the most up-to-date analysis of Viking glass beads from Ireland and presents a new look at the patterns of use, trade and interpersonal contact that affected the everyday lives of individuals living within Viking Age Ireland.

A study of the Zhiqing identity

More than seventeen million Chinese urban youth (Zhiqing in Chinese) went to the countryside, lived and engaged in agricultural work there during the Up to the Mountains and Down to the Countryside (UMDC) Movement (1967-1981). Although this movement was officially terminated in 1981, it has left an imprint on these people – the Zhiqing identity by which they are still characterized as a unique group in Chinese society and a special generation in Chinese history. Historical and sociological perspectives are combined in this study. By applying Glen H. Elder’s life course approach, the study reveals how Zhiqing’s life trajectories are embedded in the social history and identifies a series of interrelated factors that made Zhiqing into a unique generation. With the guidance of Henri Tajfel’s social identity theory, the study uncovers the emergence of the Zhiqing group and the Zhiqing identity, explains individuals’ acquisitions of the Zhiqing identity and analyzes how it has kept influencing individuals’ lives during and after the UMDC Movement. Using Zhiqing’s life stories allowed the researcher to combine the historical and sociological aspects in her examination of Zhiqing’s identity issues. In each life story, the narrator reviewed his/her life experience, reflected on socio-historical changes and expressed his/her emotions and ideas about identity issues. Utilizing methods of in-depth interview and thematic analysis, the researcher completed the study and presents this thesis as one interpretation on the Zhiqing identity, which, as according the researcher’s hermeneutic stance, is open to further discussion and future research.

Initial losses, corporate governance and earnings management

This thesis examines the relationship between initial loss events and the corporate governance and earnings management behaviour of these firms. This is done using four years of corporate governance information spanning the report of an initial loss for companies listed on the UK Stock Exchange. An industry- and sizematched control sample is used in a difference-in-difference analysis to isolate the impact of the initial loss event during the period. It is reported that, in general, an initial loss motivates an improvement in corporate governance in those loss firms where a relative weakness existed prior to the loss and that these changes mainly occur before the initial loss is announced. Firms with stronger (i.e. better quality) corporate governance have less need to alter it in response to the loss. It is also reported that initial loss firms use positive abnormal accruals in the year before the loss in an attempt to defer/avoid the loss — the weaker corporate governance the more likely is it that loss firms manage earnings in this manner. Abnormal accruals are also found to be predictive of an initial loss and when used as a conditioning variable, the quality of corporate governance is an important mitigating factor in this regard. Once the loss is reported, loss firms unwind these abnormal accruals although no evidence of big-bath behaviour is found. The extent to which these abnormal accruals are subsequently unwound are also found to be a function of both the quality of corporate governance as well as the severity of the initial loss.

Student voice in Irish post-primary schools: a drama of voices

This research is an exploration of the expression of student voice in Irish post-primary schools and how its affordance could impact on students’ and teachers’ experiences in the classroom, and at whole-school level through a student council. Student voice refers to the inclusion of students in decisions that shape their experiences in classrooms and schools, and is fundamental to a rights-based perspective that facilitates students to have a voice and a say in their education. Student voice is essential to the development of democratic principles, active citizenship, and learning and pedagogy. This qualitative research, based in three post-primary case-study schools, concerns teachers in eighteen classrooms engaging in dialogic consultation with their students over one school year. Teachers considered the students’ commentary and then adjusted their practice. The operation of student councils was also examined through the voices of council members, liaison teachers and school principals. Theorised within socio-cultural (social constructivist), social constructionist and poststructural frames, the complexity of student voice emerges from its conceptualisation and enactment. Affording students a voice in their classroom presented positive findings in the context of relationships, pedagogical change and students’ engagement, participation and achievement. The power and authority of the teacher and discordant student voices, particularly relating to examinations, presented challenges affecting teachers’ practice and students’ expectations. The functional redundancy of the student council as a construct for student voice at whole-school level, and its partial redundancy as a construct to reflect prefigurative democracy and active citizenship also emerge from the research. Current policy initiatives in Irish education situate student voice in pedagogy and as dialogic consultation at classroom and whole-school level. This work endorses the necessity for and benefit of such a positioning with the author further arguing that it should not become the instrumental student voice of data source, accountability and performativity.

The intra-Traveller debate on ‘Traveller ethnicity’ in the Republic of Ireland. A critical discourse analysis

This dissertation assesses from an under-explored angle the enduring contention over Travellers’ ethnic recognition in the Republic of Ireland, particularly over the last decade. The novelty of this study concerns not only its specific focus on and engagement with the debate on ‘Traveller ethnicity’ among Traveller activists. It also pertains to the examination of Travellers’ arguments for and against ethnicity in light of critical theorisations as well as insights from identity politics. Furthermore, the adoption of a Critical Discourse Analytical framework offers new perspectives to this controversy and its potential implications. Finally, this thesis’ relevance extends beyond the contention on ‘Traveller ethnicity’ in itself. It also draws attention to the complex dynamics of colonisation and appropriation between the global and the local. Particularly, it points to the interplay between international human rights discourses and the local ones, formulated by NGOs struggling for equality. In this way it sheds light on more general issues such as the dialectical potential of human rights discourses: the benefits and pitfalls of framing recognition claims in the legalistic terms of human rights. In this study it is argued that the contention on ‘Traveller ethnicity’ defies a simplistic polarisation between Irish Travellers and the Irish State since it has been simultaneously played out within the Travelling community. Specifically, this study explores how ‘Traveller ethnicity’ has been introduced, embraced, promoted and contested within Traveller politics to the point of becoming a hotly debated and divisive issue among Traveller activists and at the heart of the community itself. Putting Traveller activists centre-stage, their discourses for and against ‘Traveller ethnicity’ are examined and assessed against one another and their potential implications for Traveller politics, policies and identities are pointed out. Contending discourses are historically contextualised as the product of specific structural, material and discursive configurations of power and socio-economic relations within Irish society. Discourses for and against ‘Traveller ethnicity’ are assessed as being significant beyond the representational level. They are regarded as contributing to dialectically constitute Travellers’ ways of being, representing and acting. Furthermore these discourses are considered as sites and means of power struggles, whose stakes are not only words, but relate to issues of power and leadership within the Travelling community; adjudications over material resources; the adoption of certain policy approaches over others; and, finally, the consolidation of certain subject positions over others for Travellers to draw upon and relate to mainstream society. This study highlights an ongoing ideological struggle for the naturalisation of ‘Traveller ethnicity’ as a self-evident ‘fact’, which involves no active choice by Travellers themselves. Overall, ‘Traveller ethnicity’ appears to constitute an enduring source of dilemmas for the Travelling community. These revolve around the contradictory potential of ethnicity claims-making —both its perils and advantages— and its status as a potent political strategic resource that can both challenge and reinforce existing power relations, policies and identities.

Mícheál Coimín agus a shaothar

Is é a chuirim romham a dhéanamh sa tráchtas seo ná eagar a chur ar shaothar liteartha Mhíchíl Coimín; file agus údar próis a bhí ag saothrú na litríochta i gCill Chorcoráin, Contae an Chláir san ochtú haois déag. D’éag sé sa bhliain 1760 nuair a bhí sé beagnach 90 bliain d’aois. Is féidir a rá go bhfuil an Coimíneach, ó thaobh chanóin litríocht na Gaeilge de i measc na mionscríbhneoirí, agus níl aon dabht faoi ach go bhfuil an-chuid de léitheoirí na Gaeilge sa lá atá inniu ann dall ar a chuid scríbhneoireachta. Tá cáil air mar údar ‘Laoi Oisín i dTír na n-Óg’ ach mar a léireofar sa tráchtas seo, tá gach cuma ar an scéal nárbh é a scríobh. Tá againn óna pheann dornán beag dánta agus dhá scéal rómánsaíochta (‘Eachtra Thoroilbh Mhic Stairn’ agus ‘Eachtra a Thriúr Mac’) a scríobh sé nuair a bhí an traidisiún sin próis ar an dé deiridh. Níl aon chuid dá shaothar ar fáil in eagráin a shásódh léitheoirí an lae inniu ná na critéir scolártha atá i bhfeidhm anois. Níor tháinig aon lámhscríbhinn, i lámh an Choimínigh, anuas chugainn agus dá bhrí sin bhí dúshlán áirithe ag baint leis an bpróiseas eagarthóireachta. Sa tráchtas rinne mé an suirbhé is iomláine go dtí seo ar a shaothar i dtraidisiún na lámhscríbhinní agus ar na scríobhaithe a rinne é a sheachadadh. Bhí sé mar aidhm agam teacht ar na lámhscríbhinní is údarásaí sa traidisiún d’fhonn eagráin a réiteach a bheadh dílis dá bhunshaothar. Chomh maith leis sin tabharfar cuntas ar a bheatha agus ar a chúlra liteartha, agus déanfar iniúchadh criticiúil ar a shaothar próis agus fileata.

Functional genomics of motile commensal intestinal bacteria

Flagella confer upon bacteria the ability to move and are therefore organelles of significant bacteriological importance. The innate immune system has evolved to recognise flagellin, (the major protein component of the bacterial flagellar filament). Flagellate microbes can potentially stimulate the immune systems of mammals, and thus have significant immunomodulatory potential. The flagellum-biogenesis genotype and phenotype of Lactobacillus ruminis, an autochthonous intestinal commensal, was studied. The flagellum-biogenesis genotypes of motile enteric Eubacterium and Roseburia species were also investigated. Flagellin proteins were recovered from these commensal species, their amino-termini were sequenced and the proteins were found to be pro-inflammatory, as assessed by measurement of interleukin-8 (IL-8) secretion from human intestinal epithelial cell lines. For L. ruminis, this IL-8 secretion required signalling through Toll Like Receptor 5. A model for the regulation of flagellum-biogenesis in L. ruminis was inferred from transcriptomics data and bioinformatics analyses. Motility gene expression in this species may be under the control of a novel regulator, LRC_15730. Potential promoters for genes encoding flagellin proteins in the Eubacterium and Roseburia genomes analysed were inferred in silico. Relative abundances of the target Eubacterium and Roseburia species in the intestinal microbiota of 25 elderly individuals were determined. These species were found to be variably abundant in these individuals. Motility genes from these species were variably detected in the shotgun metagenome databases generated by the ELDERMET project. This suggested that a greater depth of sequencing, or improved evenness of sequencing, would be required to capture the full diversity of microbial functions for specific target or low abundance species in microbial communities by metagenomics. In summary, this thesis used a functional genomics approach to describe flagellum-mediated motility in selected Gram-positive commensal bacteria. The regulation of flagellum biosynthesis in these species, and the consequences of flagella expression from a host-interaction perspective were also considered.