Synecology in soft sediment bivalves: the influence of parasites, physiological processes, and environmental stressors on health and disease

Ecosystem goods and services provided by estuarine and near coastal regions are being increasingly recognised for their immense value, as is the biodiversity in these areas and these near coastal communities have been identified as sentinels of climate change also. Population structure and reproductive biology of two bivalve molluscs, Cerastoderma edule and, Mytilus edulis were assessed at two study sites over a 16-month study period. Following an anomalously harsh winter, advancement of spawning time was observed in both species. Throughout Ireland and Europe the cockle has experienced mass surfacings in geographically distinct regions, and a concurrent study of cockles was undertaken to explore this phenomenon. Surfaced and buried cockles were collected on a monthly basis and their health compared. Age was highlighted as a source of variation between dying and healthy animals with a parasite threshold being reached possibly around age three. Local factors dominated when looking at the cause of surfacing at each site. The health of mussels was explored too on a temporal and seasonal basis in an attempt to assess what constitutes a healthy organism. In essence external drivers can tip the balance between “acceptable” levels of infection where the mussel can still function physiologically and “unacceptable” where prevalence and intensity of infection can result in physiological impairment at the individual and population level. Synecological studies of intertidal ecosystems are lacking, so all bivalves encountered during the sampling were assessed in terms of population structure, reproduction, and health. It became clear, that some parasites might specialize on one host species while others are not so specific in host choice. Furthermore the population genetics of the cockle, its parasite Meiogymnophallus minutus, and its hyperparasite Unikaryon legeri were examined too. A small nucleotide polymorphism was detected upon comparison of Ireland and Morocco.

Synthesis and evaluation of novel azaindolocarbazole derivatives as cancer chemotherapeutics

This thesis details the design and implementation of novel chemical routes towards a series of highly propitious 7-azaindolyl derivatives of the indolocarbazole (ICZ) and bisindolylmaleimide (BIM) families, with subsequent evaluation for use as cancer chemotherapeutic agents. A robust synthetic strategy was devised to allow the introduction of a 7-azaindolyl moiety into our molecular template. This approach allowed access to a wide range of β-keto ester and β-keto nitrile intermediates. Critical analysis identified F-ring modulation as a major theme towards the advancement of ICZ and BIM derivatives in drug therapy. Thus, the employment of cyclocondensation methodology furnished a number of novel aminopyrazole, isoxazolone, pyrazolone and pyrimidinone analogues, considerably widening the scope of the prevalent maleimide functionality. Photochemical cyclisation provided for the first reported aza ICZ containing a six-membered F-ring. Another method towards achieving the aza ICZ core involved use of a Perkin-type condensation approach, with chemical elaboration of the headgroup instigated post-aromatisation. Subsequent use of a modified Lossen rearrangement allowed access to further analogues containing a six-membered F-ring. Extensive screening of the novel aza ICZ and BIM derivatives was carried out against the NCI-60 cancer cell array, with nine prospective candidates selected for continued biological evaluation. From these assays, a number of compounds were shown to inhibit cancer cell growth at concentrations of below 10 nM. Indeed, the most active aza ICZ tested is currently under assessment by the Biological Evaluation Committee of the NCI due to excellent antiproliferative activity demonstrated across the panel of cell lines, with a mean GI50 of 34 nM, a mean total growth inhibition (TGI) of 4.6 μM and a mean cytotoxicity (LC50) of 63.1 μM. Correlation to known topoisomerase I (topo I) inhibitors was revealed by COMPARE analysis, and subsequent topo I-mediated DNA cleavage assays showed inhibitory activity below 1 μM for several derivatives.

Biodiversity change in the Irish uplands - the effects of grazing management

As a prominent form of land use across much of upland Europe, extensive livestock grazing may hold the key to the sustainable management of these landscapes. Recent agricultural policy reform, however, has resulted in a decline in upland sheep numbers, prompting concern for the biodiversity value of these areas. This study quantifies the effects of varying levels of grazing management on plant, ground beetle and breeding bird diversity and assemblage in the uplands and lowlands of hill sheep farms in County Kerry, Ireland. Farms represent a continuum of light to heavy grazing, measured using a series of field indicators across several habitats, such as the internationally important blanket bog, home to the ground beetle, Carabus clatratus. Linear mixed effects modelling and non-metric multidimensional scaling are employed to disentangle the most influential management and environmental factors. Grazing state may be determined by the presence of Molinia caerulea or Nardus stricta, and variables such as % traditional ewes, % vegetation litter and % scrub prove valuable indicators of diversity. Measures of ecosystem functioning, e.g. plant biomass (nutrient cycling) and % vegetation cover (erosion rates) are influenced by plant diversity, which is influenced by grazing management. Levels of the ecosystem service, soil organic carbon, vary with ground beetle abundance and diversity, potentially influencing carbon sequestration and thereby climate change. The majority of species from all three taxa are found in the lowlands, with the exception of birds such as meadow pipit and skylark. The scale of measurement should be determined by the size and mobility of the species in question. The challenge is to manage these high nature value landscapes using agri-environment schemes which enhance biodiversity by maintaining structural heterogeneity across a range of scales, altitudes and habitats whilst integrating the decisions of people living and working in these marginal areas.

From respect for nature to agency as realisation in response to the ecological emergency

'The ecological emergency’ describes both our emergence into, and the way we relate within, a set of globally urgent circumstances, brought about through anthropogenic impact. I identify two phases to this emergency. Firstly, there is the anthropogenic impact itself, interpreted through various conceptual models. Secondly, however, is the increasingly entrenched commitment to divergent conceptual positions, that leads to a growing disparateness in attitudes, and a concurrent difficulty with finding any grounds for convergence in response. I begin by reviewing the environmental ethics literature in order to clarify which components of the implicit narratives and beliefs of different positions create the foundations for such disparateness of views. I identify the conceptual frameworks through which moral agency and human responsibility are viewed, and that justify an ethical response to the ecological emergency. In particular, I focus on Paul Taylor's thesis of 'respect for nature' as a framework for revising both the idea that we are ‘moral’ and the idea that we are ‘agents’ in this unique way, and I open to question the idea that any response to the ecological emergency need be couched in ethical terms. This revision leads me to formulate an alternative conceptual model that makes use of Timothy Morton’s idea of enmeshment. I propose that we dramatically revise our idea of moral agency using the idea of enmeshment as a starting point. I develop an alternative framework that locates our capacity for responsibility within our capacity for realisation, both in the sense of understanding, and of making real, sets of conditions within our enmeshment. I draw parallels between this idea of ‘realisation as agency’ and the work of Dōgen and other non-dualists. I then propose a revised understanding of ‘the good’ of systems from a biophysical perspective, and compare this with certain features of Asian traditions of thought. I consider the practical implications of these revisions, and I conclude that the act of paying close attention, or realising, contains our agency, as does the attitude, or manner, with which we focus. This gives us the basis for a convergent response to the ecological emergency: the way of our engagement that is the key to responding to the ecological emergency

An túrscéal iar-nua-aoiseach sa Ghaeilge

Is éard atá curtha romham agam sa tráchtas seo ná an t-úrscéal iar-nua-aoiseach sa Ghaeilge a phlé; chun aitheantas a thabhairt don seánra mar rud ar leith; chun a fhréamhacha a aimsiú agus a thréithe sainiúla a léiriú. Féachaim anseo lena léiriú go bhfuil baint shainiúil ag an úrscéal iar-nua-aoiseach sa Ghaeilge le stair shochteangeolaíoch agus liteartha na hÉireann. Chruthaigh scríbhneoirí Béarla na hÉireann, ar nós Joyce, Beckett agus Flann O’Brien (Brian Ó Nualláin), cur chuige liteartha a raibh toradh ollmhór aige ar chúrsaí liteartha an domhain – go háirithe sa chomhthéacs (iar)-nua-aoiseach. Léireoidh mé gur tháinig an cur chuige seo chun cinn de bharr an choibhnis shainiúil atá ag muintir na hÉireann le teanga – coibhneas atá ginte i nguagacht faoin rud is teanga féin ann. Áitím gur eascair an ghuagacht seo as an athrú stádais – ó phríomhtheanga go mionteanga – a tharla don Ghaeilge. Áitím gur cruthaíodh feasacht ar fholús i bhféiniúlacht na tíre nuair a tharla an t-athrú sin agus go raibh tionchar ag an bhfeasacht seo ar litríocht na hÉireann – idir Ghaeilge agus Bhéarla. Is minic a fhéachann an túrscéal iar-nua-aoiseach, i ngach teanga ina gcleachtar a leithéid, le staidéar a dhéanamh ar na slite ina gcruthaítear brí sa saol trí theanga agus trí reacaireacht. Murab ionann is a mbíonn i gceist san úrscéal ‘traidisiúnta’ – an t-úrscéal ‘réadach’ mar a tuigtear leis – glacann iar-nua-aoiseachas leis go bhfuil solúbthacht agus saorgacht i ngach léiriú ar an mbrí seo. Léiríonn na húrscéalta atá faoi chaibidil sa tráchtas seo an-doimhneacht liteartha. Is saothair fhéinchomhfhiosacha agus mheitificseanúla iad a thaispeánann éiginnteacht i leith brí absalóidigh. Oibríonn siad mar léiriú ar fheidhm na teanga sa saol agus ar na slite ina gcruthaíonn gach reacaireacht a fírinne féin. Cé gur tréithe iar-nua-aoiseacha iad siúd, is tréithe iad chomh maith a bhaineann le stádas na mionteanga.