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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.

Posttranslational modifications of human M3 muscarinic acetylcholine receptor: zooming in its functional implications

Romero Fernández, Wilber 20 May 2011 (has links)
The human M3 muscarinic acetylcholine receptor (M3R) regulates many important physiological roles in the central and peripheral nervous systems, and it is involved in the pathophysiology of several neurodegenerative and autoimmune diseases, representing attractive potential pharmacological target for intervention. However, the lack of structural information on this receptor hampered the development of new potent antagonist with increased selectivity and lower side effects. Such structural information can be only achieved by means of experimental biophysical techniques, which require large quantities of pure receptor. Considering that under physiological conditions the expression of G-protein coupled receptors (GPCRs) is relatively low, optimization of the receptor overexpression is a pre-requisite for structural studies efforts to be performed. In addition, although is has well established that GPCR undergo post-translational and increase evidences support that these are tight links to receptor roles, little progress has been made in the post-translational modifications field in some GPCRs, such as the case of M3R. In this study, we provide some strategies to improve muscarinic receptor heterologous expression in mammalian cells guaranteeing proper post-translational modifications. In addition, we have been able to extract high levels of functional receptor from COS-7 cells using a detergent combination tested, and to purify the receptor to near homogeneity-keeping the full wild type receptor properties- by means of different affinity purification methods. Regarding the post-translational modifications studied, our findings provide the first evidence of the critical role that N-glycan chains play in determining muscarinic receptor distribution and localization, as well as in cell integrity. Furthermore, our data reveal a role for palmitoylation in determining M3R residence within lipid raft, as well as in receptor internalization and down-regulation / El receptor muscarínico de acetilcolina subtipo M3 humano (M3R) regula importantes funciones en el sistema nervioso central y periférico, y está implicado en la fisiopatología de varias enfermedades neurodegenerativas y autoinmunes, lo que representa una atractiva diana terapéutica para la intervención farmacológica. Sin embargo, la falta de la información estructural sobre este receptor obstaculizado el desarrollo de nuevos y potente fármacos de gran selectividad y bajo efecto secundario. Tal información estructural, puede lograrse por medio de la experimentación con técnicas biofísicas que requieren grandes cantidades de receptor puro. Teniendo en cuenta que en condiciones fisiológicas la expresión de receptores acoplados a proteínas G (GPCR) es baja, la sobreproducción del receptor es un pre-requisito para que los estudios estructurales puedan ser realizados. Además, aunque se ha establecido que los GPCR sufren modificaciones post-translationales y que en los últimos años un significante número de reportes sugieren que estas modificaciones están estrechamente vinculadas a las funciones del receptor, poco se ha avanzado en el estudio de estas modificaciones en el campo de algunos GPCRs, como es el caso de M3R. En este estudio, nosotros describimos algunas estrategias para mejorar la expresión de los receptores muscarínicos en células de mamíferos garantizando unas correctas modificaciones post-translacionales. Además, hemos sido capaces de extraer altos niveles de receptor funcional a partir de células COS-7 con una combinación de detergentes, purificamos el receptor M3R cerca de la homogeneidad, mantenimiento de la totalidad de las propiedades biológicas encontradas en el receptor silvestre. En relación a las modificaciones post-translationales estudiadas, nuestros resultados proporcionan la primera evidencia del papel crítico de las cadenas de N-glicanos en la determinación de la localización de estos receptores, así como en la integridad celular. Además, nuestros datos revelan un importante papel de las modificaciones lipídicas de M3R en relación a la distribución del receptor en microdominios resistente a detergentes, así como en la regulación del receptor. En resumen, las estrategias utilizadas pueden contribuir al incremento de la expresión M3R. De esta forma los esfuerzos para la purificación del receptor a gran escala pueden ser iniciados. Para ellos, nosotros revelamos una posible estrategia. Además, proponemos los posibles sitios de N-glicosilación y S-acilación en el M3R expresado en células COS-7, y proporcionamos evidencias experimentales que avalan la implicación funcional de estas modificaciones en el papel del receptor.

Ecological studies on Sargassum muticum (Yendo) Fensholt

Critchley, A. T. January 1981 (has links)
No description available.

Distribution modelling, macroecology and conservation : cacti of the Chihuahuan Desert Region

Cabello, Barbara Karen Lucfa Goettsch January 2007 (has links)
The literature has seen an astounding increase in the use of formal statistical/mathematical models to predict the potential distributions of species. In part this is because the possible applications of such models are diverse, from theoretical ecology to the future implications of global climate change. In particular, they have become important tools in conservation planning (e.g. establishment of protected areas), filling gaps in the known distributions of species. This said, many gaps remain in understanding of how well different kinds of models predict the distributions of species in many higher taxa and regions, and what some of the consequences of those predictions might be. In this thesis, I explore such issues using as a study group the Cactaceae from the Chihuahuan Desert Region (CDR), which is highly endangered and in need of conservation. Models were constructed for a number of species representing a range of biologies and distributions, and te'sted using common statistical methodologies (e.g. data partitioning to apply X2 tests, ROC curves), expert opinion, and directly in the field. Field testing was done not only considering the presence-absence of species but their densities at sites. Important macroecological patterns of cacti that have implications for conservation strategies were also studied; i) density distributions, ii) density-area of occupancy relationship, iii) environmental variables related with distributions, and iv) patterns of species richness. Finally, I couple predictive models and an advanced method of landscape prioritisation to find areas of conservation importance for cacti in the CDR. The study demonstrates the potential of predictive models to aid conservation planning and their usefulness in the selection of prospective areas for sampling. The importance of careful interpretation of such predictions when they are to be applied to solving practical problems (e.g. reserve selection programs) is discussed.

Home range and territorial behaviour of the feral mink (Mustela vision schreber) in Devon

Birks, J. D. S. January 1981 (has links)
No description available.

Ecological complexity : a conceptual analysis of dynamics and organisation in contrasting environments

Dyer, Jacqueline Ruth January 2004 (has links)
No description available.

A study of the ecology of leptophyes punctatissima

Deura, K. January 1980 (has links)
No description available.

Iodine in sea ice and the polar atmosphere

Atkinson, Helen January 2011 (has links)
The volatilisation of iodine from the ocean and release to the atmosphere in the ice-covered polar regions has been studied. Laboratory experiments involving sea ice- and ice associated- diatoms have shown how the extreme conditions experienced in sea ice brine channels may lead to an increase in production of organic forms of iodine. Trends were observed in production by different classes of enzymes, active in the oxidative metabolism of the cell. An enhancement in trace gas concentrations due to the concentration effect of solvent volume reduction has also been demonstrated. Field campaigns have been undertaken in both the Arctic and Antarctic. Ship-based measurements in the Weddell Sea have implicated I2 as a key species in the mechanism of enhancement of atmospheric iodine in this region. Organic and inorganic forms of iodine were measured in seawater, sea ice and the atmosphere. On the Brunt ice shelf, enhanced concentrations of CH3I and C2H5I were measured in the snow firn air, with a diurnal profile, suggesting the snow may be a source of these compounds. These measurements have implications for atmospheric mixing ratios of IO, measured from the ship and validated by satellite data, and new particle formation. This is the first combined in situ study in Antarctica of organic and inorganic iodine compounds in sea water, ice and air. On the Western Antarctic Peninsula, IO was detected in the atmosphere, and seawater measurements of iodocarbons have demonstrated how organic compounds of iodine are enhanced during the phytoplankton bloom; these measurements are also a first. Iodine emissions in the sea ice zone were also quantified in two campaigns in the Arctic environment. High concentrations of halocarbons were measured in the brine of sea ice, with respect to the water below, in the Arctic Ocean. High atmospheric halocarbon mixing ratios and flux calculations have demonstrated the effect on the atmosphere above. In the Canadian sub-Arctic, where the ice had quite different physical properties, halocarbon concentrations were the highest ever recorded for some compounds, due to extreme concentration in very cold ice. The enhancement of organic forms of iodine in sea ice has therefore been demonstrated. I2 has been implicated as a key species in iodine emissions. Therefore, understanding has been furthered on the chemistry of iodine in sea ice and polar atmosphere.

Polar föhn winds and warming over the Larsen C Ice Shelf, Antarctica

Elvidge, Andrew January 2013 (has links)
Recent hypotheses that the foehn effect is partly responsible for warming to the east of the Antarctic Peninsula (AP) and enhanced melt rates on the Larsen C Ice Shelf are supported in a study combining the analysis of observational and high resolution model data. Leeside warming and drying during foehn events is observed in new aircraft, radiosonde and automatic weather station data and simulated by the UK Met Office Unified Model at ~1.5 km grid spacing (MetUM 1.5 km). Three contrasting cases are investigated. In Case A relatively weak southwesterly flow induces a nonlinear foehn event. Strongly accelerated flow above and a hydraulic jump immediately downwind of the lee slopes lead to high amplitude warming in the immediate lee of the AP, downwind of which the warming effect diminishes rapidly due to the upward ‘rebound’ of the foehn flow. Case C defines a relatively linear case associated with strong northwesterly winds. The lack of a hydraulic jump enables foehn flow to flood across the entire ice shelf at low levels. Melt rates are high due to a combination of large radiative heat flux, due to dry, clear leeside conditions, and sensible heat flux downward from the warm, well-mixed foehn flow. Climatological work suggests that such strong northwesterly cases are often responsible for high Larsen C melt rates. Case B describes a weak, relatively non-linear foehn event associated with insignificant daytime melt rates. Previously unknown jets – named polar foehn jets – emanating from the mouths of leeside inlets are identified as a type of gap flow. They are cool and moist relative to adjacent calmer regions, due to lower-altitude upwind source regions, and are characterised by larger turbulent heat fluxes both within the air column and at the surface. The relative importance of the three mechanisms deemed to induce leeside foehn warming (isentropic drawdown, latent heating and sensible heating) are quantified using a novel method analysing back trajectories and MetUM 1.5 km model output. It is shown that, depending on the linearity of the flow regime and the humidity of the air mass, each mechanism can dominate. This implies that there is no dominant foehn warming mechanism, contrary to the conclusions of previous work.

Organising science policy : participation, learning & experimentation in British democracy

Pallett, Helen January 2014 (has links)
The incorporation of public participation into science policy processes has been an important feature of policy practice and the academic literature for more than two decades, yet it has failed to realise its democratising potential or to engender broader changes in organisational and political cultures. To understand this apparent paradox this thesis focuses on organisational changes and practices around public participation, thus transcending the conventional focus on individual participation processes which characterises much academic work on the topic. Given the apparent lack of learning from and about public participation in key science policy organisations, this thesis explores diverse processes and facets of organisational learning, reflection and reflexivity in and around Sciencewise, a UK Government-funded body, which is emblematic of emerging professionalised organisations of participation. Drawing upon ethnographic and qualitative methods within a co-productionist idiom (Jasanoff 2004a), the thesis tells a number of stories about Sciencewise’s organisational learning processes during 2013; some are localised and specific, others identify more coherent shifts, and others draw connections between Sciencewise and broader political events. Diverse facets of organisational learning are explored from themes of spatiality, formal organisational mechanisms and organisational memory to non-knowledge, future imaginaries and processes of experimentation. It is argued that organisational learning cannot be understood without attention to the minutiae of everyday meetings and communications systems, or to broader political shifts like civil service reform. Despite the apparent rigidity of Sciencewise practices and discourses, there were significant instances of learning and change observed, resulting in shifting organisational categories, understandings and practices. These represent examples of more reflective and reflexive capacities within the programme. The thesis makes significant conceptual contributions to understandings of organisational learning, contributes empirical insights into the institutionalisation of participation in UK policy practice, and offers practical insights into the challenge of conducting engaged research and encouraging organisational reflexivity.

Föhn winds on South Georgia and their impact on regional climate

Bannister, Daniel January 2015 (has links)
South Georgia is a small and mountainous island, located in the remote Southern Ocean. The island’s subantarctic climate is controlled by its location and steep orography; with 19 peaks over 2000m and situated within a belt of strong westerly winds South Georgia acts as an effective barrier to the winds that impinge upon it. Since the 1920s, average summer temperatures have risen by ~1oC on South Georgia. Coupled with this has been an increase in the rate of glacial retreat throughout the last century, with glaciers on the northeast leeside of the island retreating at a faster rate than those on the southwest side. These asymmetrical changes are thought to be linked with the strengthening of the westerlies. If the strength of the westerlies is sufficient, downslope winds can develop on the leeside of the island causing significant temperature increases as the descending air warms adiabatically; this is known as the föhn effect. Therefore, the aim of this thesis is to investigate whether the observed asymmetric pattern of regional warming and glacier retreat are caused by the föhn warming process. To explore the link between the föhn effect and its impact on the regional climate of South Georgia, a 10 year climatology (2003 – 2012) of föhn events is created. Using automatic weather station observations to identify abrupt changes in temperature, humidity and wind speed, it is found that föhn events are frequently observed (874 events are identified in total) with one event occurring every four days. Following this, sensitivity simulations with the Weather Research and Forecasting model for four föhn cases studies are presented, with the aim of deducing the optimal model setup for South Georgia. The model analysis is largely supported by observations, and föhn flow is well captured at high (< 3.3km) horizontal resolution. With the model optimised for South Georgia, a 21 month model run (at 0.9km resolution) produces the first ever detailed regional climatology of South Georgia. The results from this simulation illustrate the asymmetrical impact of föhn on the island’s climate. During September 2011 – August 2012, modelled föhn events produced +2oC air temperature anomalies and up to 3m water equivalent ablation at the termini of South Georgia’s north-eastern glaciers. This supports the view that föhn is partly responsible for the asymmetrical retreat of glaciers, via enhanced leeside surface warming and melting. These results support the original hypothesis that an enhancement of the föhn warming process could have implications on future asymmetrical warming and melt.

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