This thesis examines the development ofnatural history in the Spanish Empire (1750-1850). I explore why the Spanish Crown promoted scientific institutions and expeditions in the second halfofthe eighteenth century, and I situate Spanish engagement with natural history within an imperial context. One Spanish commentator, scrutinising the contents ofthe Real Gabinete de Historia Natural in 1788, gloried that 'we have seen form this immense collection of singularities ofnature, brought at considerable expense, not only from all regions ofEurope, but also from Asia, Africa and America; so that all parts ofthe world may contribute to forming the most complete treasure ofNatural History that exists in the Universe'. I suggest that Spain's capacity to procure and exhibit exotic natural treasures reflected the potency ofher imperial structures. I also address the social, religious and economic benefits associated with the classification, collection and cultivation of natural objects. I am especially interested in the part that Spanish Americans played in this process, and the ways in which the development ofthe natural sciences on the imperial periphery intersected with the evolution of creole patriotism in the late colonial period. I consider how the creation, legitimisation and dissemination of scientific knowledge reflected broader questions of imperial power and national identity. I examine the ambiguous position ofcreole naturalists, who were simultaneously anxious to secure European recognition for their work, to celebrate the natural wealth oftheir homelands and, in some cases, to vindicate local forms of knowledge against purportedly universal European systems such as Linnaean botany, and I extend this analysis beyond independence, asking whether political freedom fomented or compromised the pursuit of natural history in the former colonies.

D-serine is a co-agonist at NMDA receptors in the brain but the study of this amino acid is restricted by current techniques. I have designed highly sensitive D-serine biosensors that permit accurate real-time recordings of D-serine in the brain in a selective manner. I demonstrate that these tools are ideal for investigating factors involved in the regulation of this amino acid and the role that D-serine plays in excitotoxic cell death mediated via NMDA receptors. I have established that the extracellular basal concentrations of D-serine in the rat brain are heterogeneous and vary even within brain structures. This suggests that Dserine is an important regulatory constraint for NMDA receptor activation, as receptor response can only be potentiated in regions with low D-serine content. Additionally, I show that these microelectrode biosensors have the potential to be used in vivo to detected extracellular D-serine levels. In addition I have observed real-time activity dependent regulation (both loss and release) of D-serine by ionotropic glutamate receptor agonists AMPA, NMDA and kainate, PAR1-agonist TFFLLRNH2 and high frequency stimulation in vitro in a number of brain areas. A decrease in D-serine concentration is potentially neuroprotective as it suggests a reduction in NMDA receptor activation. However, D-serine release can be observed in regions where the co-agonist site of the NMDA receptor is likely to be already saturated implying an alternative function of D-serine in the brain. These findings indicate multifaceted regulation of this amino acid that is brain-region specific. Finally, I have investigated the role of D-serine release during models of stroke (hypoxia and ischemia) and found that D-serine levels are reduced in brain regions deprived of oxygen. This is ultimately neuroprotective as it will reduce over - excitation at the NMDA receptor during these insults. In the more profound model of stroke, oxygen-glucose deprivation, D-serine is eventually released. This release precedes anoxic depolarisation and could therefore contribute to its initiation via enhanced activation of the NMDA receptor.

Theoretical modelling of the microtubule-Dam1-ring force generation mechanism and the pulling of tubes from surface-supported lipid bilayers are presented and discussed. Atomic force microscopy (AFM) force data of tube pulling experiments is analysed and compared with theoretical predictions. Featurescommonto recent computational models are simplified and examined independently where possible. In particular, the steric confinement of the Dam1 ring on a microtubule (MT) by protofilaments (PFs), the powerstroke produced by curling PFs, the depolymerisation of the MT, and the binding attraction between Dam1 and the MT are modelled. Model parameters are fitted to data. Functional force generation is equally demonstrated when attachment is maintained by steric confinement alone (protofilament model) or by a binding attraction alone (binding model). Moreover, parameters amenable to experimental modification are shown to induce differences between the protofilament model and the binding model. Changing the depolymerisation rate of MTs, the diffusion coefficient of the Dam1 ring, or applying an oscillating load force will allow discrimination of these two different mechanisms of force generation and kinetochore attachment. A previously described theoretical model of pulling lipid bilayer tubes from vesicles is modified for the case of pulling tubes from surface-supported lipid bilayers. A shape equation for axisymmetric membranes is derived variationally and solved numerically for zero pressure. Free energy profiles and force curves are calculated for various AFM probe sizes and compared to experimental data where a ground flat AFM probe is used to pull tubes from surface-supported lipid bilayers. The predicted force curves partially fit the experimental data, although not at short distances, and estimates of the bilayer surface tension are given. Pressure and volume profiles are calculated for the extension of the model to the nonzero pressure case.

In the absence of telomerase, Saccharomyces cerevisiae telomeres erode leading to senescence. Rare cells can survive after this stage as they can elongate their telomeres utilizing homologous recombination. Two different types of survivors can be easily distinguished by Southern blot. Type I survivor cells, elongate the telomere by amplifying Y elements and require RAD51, RAD54, RAD55 and RAD57 for establishment. Type II survivors elongate their telomere by amplifying TG1-3 repeats, however, they require the following genes to be established: RAD50, MRE11 and XRS2, RAD59, SGS1 and KU80 in some cases. Both types require the gene RAD52. In this study several candidate genes were deleted individually in diploid type II survivor strains. The main aim of this work was to see if these genes were required for type II telomere maintenance. Most of these genes are not required for type II telomere maintenance at least until ~150 generations after deleting these genes. The exceptions were KU80 and RPB9. Ku80Δ strains switched to a new survivor type that is similar to type I and continued for the long term. RPB9 was required for two independent type II survivor strains to survive, whereas the third type II strain did not require this gene at ~150 generations after deleting the gene. After many generations (~ 350), this strain switched to type I. At long term propagation (~500 generations) after deletion of the candidate genes, all type II strains displayed telomere shortening until the propagation was stopped. However, Rad50Δ strains switched to type I after long term. Finally, the absence of the candidate genes did not affect the sensitivity of type II survivor strains to temperature. On the other hand, type II survivor strains with some genes deleted displayed sensitivity to UV.

A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) are a family of proteins that are closely related to the matrix metalloproteinases (MMPs). It has been suggested that the proteins have a critical role in the breakdown of articular cartilage during osteoarthritis (OA). More recently it has been suggested that their actions could potentially regulate atherosclerotic plaque stability. Atherosclerosis is a chronic, inflammatory disorder characterised by lipid and cholesterol accumulation and the development of fibrotic plaques within the walls of large and medium arteries. The stability of the plaques is very important because clinical symptoms are only presented after rupture of the unstable plaques, leading to thrombosis and ischemia. During the current study, immunohistochemical analysis confirmed that ADAMTS-­1, -­4 and -­5 were being expressed within human carotid atherosclerotic lesions; macrophages were identified as major contributors to their expressions. Following on from this THP-­1 macrophages were stimulated with transforming growth factor-­β (TGF-­β), interferon-­γ (IFN-­γ), TNF-­like protein 1A (TL1A), interleukin (IL)-­17A and IL-­33. The regulation of ADAMTS-­1, -­4 and -­5 expressions were analysed using quantitative polymerase chain reactions (QPCR) and western blots. It was shown that TGF-­β increased the expressions of ADAMTS-­1 and -­5 and decreased the expression of ADAMTS-­4. IL-­33 decreased the expressions of ADAMTS-­1, -­4 and -­5 and IFN-­γ also decreased the expression of ADAMTS-­1. TL1A and IL-­17A stimulation of macrophages had no regulatory actions over ADAMTS-­1, -­4 or -­5 expressions. Looking at evidence from previous studies, TL1A and IL-­17A were identified as agents that could potentially act in synergy to amplify pro­inflammatory cytokine responses. To investigate this further, THP-­1 macrophages were stimulated with TL1A and IL-­17A, TL1A and IFN-­γ and also IL-­17A combined with IFN-­γ. TL1A and IL-­17A were shown to act in synergy to increase the expressions of ADAMTS-­1, -­4 and -­5 in macrophages. The regulation of ADAMTS-­1, -­4 and -­5 expressions in macrophages by IL-­33 was studied further. The mechanism of signal transduction was studied using RNA interference (RNAi) targeting extracellular signal-­‐regulated kinases (ERK)-­1, ERK-­2, p38, c-­Jun N-­terminal kinases(JNK)-­1/2, c-­Jun, phosphoinositide 3-­kinase(PI3K)-­γ, PI3K-­δ, p50, p65 and Janus kinase(JAK)-­1/2. It was determined that the attenuation of ADAMTS-­1, -­4 and -­5 expressions occurred through transcriptional regulation that was dependent on the ST2 receptor. ERK-­1, ERK-­2, JNK-­1/2, c-­Jun, PI3K-­γ and PI3K-­δ were also involved in the signal transduction of the response. The cellular roles of ADAMTS activity within atherosclerotic disease progression remain poorly understood. During the current study adenoviral vectors were created that delivered shRNA-­targeting ADAMTS-­1, -­4 and -­5. The adenoviral vectors were utilised in studies designed to investigate the roles of ADAMTS-­1, -­4 and -­5 during macrophage migration and foam cell formation. The studies showed that knockdown of ADAMTS-­1, -­4 and -­5 had no effect on macrophage migration or foam cell formation. More research is required into the cellular roles that ADAMTS proteases play during atherosclerotic disease progression. The field of research is now growing and could potentially provide some exciting opportunities for novel therapeutics of the future.

Oxbow lakes are of high ecological importance due to the number and the diversity of habitats they provide. They are created after the abandonment of meanders and subsequent sediment infilling leads to their progressive terrestrialisation, taking from a few months up to several centuries. Nonetheless, little is known about oxbow lake terrestrialisation processes, sediment composition, or why such a disparity exists in lakes’ longevity. To understand the controls on oxbow lakes alluviation, field observations, remotely sensed data and GIS analyses were combined. Sediment transfers in oxbow lakes were documented by topographic and sampling surveys of sites in France and Wales. Aerial photographs and maps were used to date cutoff events, analyse oxbow lakes geometry, and understand the controls on oxbow lake terrestrialisation for eight rivers of different characteristics. Findings from this study illustrate that the specific mechanism by which an oxbow lake is formed is critical to its persistence as a lake and to the sedimentary processes experienced. Chute cutoff oxbow lakes filled in 10 times faster than neck cutoffs and showed significantly different sediment deposits. Results also highlighted that oxbow lakes are not only fine-grained sediment stores, as often referred to, but can be significant bed material sinks since a site on the Ain River sequestered up to 34% of the bed material supply. However, the volume of sediment mobilised in the main channel during cutoff appeared to be larger than the bed-load stored in the former channel within the first decade after abandonment (40%). Sedimentary evidence showed that the terrestrialisation of oxbow lakes is driven by several processes: a flow separation zone at the entrance of the channel creating a sediment plug, sediment sorting by flow gradients and decantation in ponded areas. These results have important implications for the management of meandering rivers by providing a comprehensive analysis of depositional processes which also helps to predict oxbow lake longevity.

1. Rivers are highly structured ecosystems in which habitat complexity and heterogeneity are postulated to affect species diversity and abundance. However, the exact links between habitat structure and organisms such as macro-invertebrates remain poorly understood. 2. Field surveys at the patch and reach scale were combined with a field experiment in the Rivers Wye and Usk, Wales, to: i) quantify variations in habitat complexity and heterogeneity among habitats and river sections, ii) assess their influence on macro-invertebrates, iii) separate the ecological effects of confounding physical factors and iv) determine whether habitat type and heterogeneity promote nestedness of assemblages. 3. At the patch scale, surface complexity but not habitat heterogeneity increased macro-invertebrate diversity, richness and abundance independently of surface area, but only when habitat type was ignored. Surface complexity and heterogeneity were minor determinants of variations in macro-invertebrates among habitat types. 4. A field experiment involving baskets containing cobbles, pebbles, gravel or 50:50 mixtures revealed that flow type explained significant variations in macro-invertebrate richness, abundance and composition, and appeared to filter organisms based on their body size. Surface complexity and interstitial volume had no ecological effect, implying that differences in assemblages among mineral habitats may result from flow-related effects. 5. Macro-invertebrate assemblages occurring in some mineral habitats, typically with lower macro-invertebrate diversity, richness, abundance and trait diversity, appeared to be nested sub-sets of those occurring in some organic habitats. Nested assemblages had reduced trait diversity and altered trait representation. River sections containing fewer habitats supported assemblages of lower abundance, which appeared to be weakly nested sub-sets of those in heterogeneous sections. 6. Habitat complexity and heterogeneity are concluded to have consistently weak effects on macro-invertebrates at the scales studied. In contrast, habitat type and flow type affected macro-invertebrate assemblage composition, structure, and traits, with important implications for river management and conservation.

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This thesis offers an immanent critique and reconstruction of green moral and political theory. In chapter 1, the critical-reconstructive approach and spirit of the thesis is outlined in terms of contributing to the process of developing a green political theory that is different from 'ecologism' or ideological accounts of green politics. In chapter 2, deep ecology is critically interrogated in terms of its metaphysical (2.3) and psychological claims (2.4). Its view of the 'ecological crisis' as a 'crisis' of western culture is criticised as is its a priori defence of environmental preservation over the human productive use of nature. While its ecocentrism is rejected as the normative basis for green politics, its concern with virtue ethics is held to be an important contribution. In chapter 3, a self-reflexive version of anthropocentrism is developed as the most appropriate moral basis for green politics. Some naturalistic arguments are presented in order to support 'speciesism', and defend it from claims of arbitrariness and as being akin to sexism or racism. Arguments centring on demonstrating the tenuous character of the differences between humans and nonhumans are argued to neglect the fundamental moral significance of the difference between 'human' and 'nonhuman'. I argue that an ethic of use, understood as a reflexive mode of interaction with the nonhuman world, is a defensible form of anthropocentrism for green political purposes. The basis of this reflexive anthropocentrism turns on the claim that while human interests are a necessary condition for justifying a particular human use of nature, it is not a satisfactory one. Issues pertaining to the 'seriousness' of the human interest which is fulfilled are held to be important in distinguishing 'use' from 'abuse'.