Dissertations / Theses on the topic 'Degeneration'
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1
Axell, Tim. "Degeneration av varumärken." Thesis, Örebro universitet, Institutionen för juridik, psykologi och socialt arbete, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-92939.
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Rooney, Timothy M. "Genes Required for Wallerian Degeneration Also Govern Dendrite Degeneration: A Dissertation." eScholarship@UMMS, 2015. https://escholarship.umassmed.edu/gsbs_diss/775.
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Neurons comprise the main information processing cells of the nervous system. To integrate and transmit information, neurons elaborate dendritic structures to receive input and axons to relay that information to other cells. Due to their intricate structures, dendrites and axons are susceptible to damage whether by physical means or via disease mechanisms. Studying responses to axon injury, called Wallerian degeneration, in the neuronal processes of Drosophila melanogaster has allowed the identification of genes that are required for injury responses. Screens in Drosophila have identified dsarm and highwire as two genes required for axon degeneration; when these genes are mutated axons fail to degenerate after injury, even when completely cut off from the neuronal cell body. We found that these genes are also required for dendrite degeneration after injury in vivo. Further, we reveal differences between axon and dendrite injury responses using in vivo timelapse recordings and GCaMP indicators of intracellular and mitochondrial calcium transients. These data provide insights into the neuronal responses to injury, and better define novel targets for the treatment of neurodegenerative diseases.
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Rooney, Timothy M. "Genes Required for Wallerian Degeneration Also Govern Dendrite Degeneration: A Dissertation." eScholarship@UMMS, 2004. http://escholarship.umassmed.edu/gsbs_diss/775.
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Neurons comprise the main information processing cells of the nervous system. To integrate and transmit information, neurons elaborate dendritic structures to receive input and axons to relay that information to other cells. Due to their intricate structures, dendrites and axons are susceptible to damage whether by physical means or via disease mechanisms. Studying responses to axon injury, called Wallerian degeneration, in the neuronal processes of Drosophila melanogaster has allowed the identification of genes that are required for injury responses. Screens in Drosophila have identified dsarm and highwire as two genes required for axon degeneration; when these genes are mutated axons fail to degenerate after injury, even when completely cut off from the neuronal cell body. We found that these genes are also required for dendrite degeneration after injury in vivo. Further, we reveal differences between axon and dendrite injury responses using in vivo timelapse recordings and GCaMP indicators of intracellular and mitochondrial calcium transients. These data provide insights into the neuronal responses to injury, and better define novel targets for the treatment of neurodegenerative diseases.
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Goldsmith, P. "Zebrafish models of retinal degeneration." Thesis, University of Cambridge, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.599478.
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This project has explored whether zebrafish can model human neurological disease, using retinal degeneration as the prototype. The retinal degenerations are a major cause of morbidity, being the commonest cause of blindness in the Western world. Age-related macular degeneration, the commonest retinal degeneration, affects 1 in 20 of the population, and is not treatable. The project began with an F2 mutagenesis screen for candidate blind fish, using an optokinetic assay. Blind fish were characterised using a variety of histological techniques and transplantation studies. Two strains of fish were then selected for more detailed genetic analysis, as they appeared to have a photoreceptor degeneration resembling human retinal degenerations. This involved further mapping of the genes responsible for the phenotype in these two mutants and candidate gene selection.
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Hetherington, Leonard. "Reparative strategies for retinal degeneration." Thesis, University of Sheffield, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.425592.
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Chong, Ngai Hang Victor. "Retinal degeneration : model and therapies." Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268911.
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Treppo, Steven. "Physical diagnostics of cartilage degeneration." Thesis, Massachusetts Institute of Technology, 1999. http://hdl.handle.net/1721.1/85263.
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Thesis (Ph.D.)--Harvard--Massachusetts Institute of Technology Division of Health Sciences and Technology, February 1999."January 1999."
Includes bibliographical references (leaves 219-239).
by Steven Treppo.
Ph.D.
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Hughes, Edward Howard. "Microglial behaviour during photoreceptor degeneration." Thesis, University College London (University of London), 2004. http://discovery.ucl.ac.uk/1446879/.
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Inherited photoreceptor dystrophies are a leading cause of blindness and have no effective treatment. Despite advances in our understanding of the genetic mechanisms underlying this diverse group of conditions, the sequence of events leading from genetic miscoding to photoreceptor death by apoptosis are still unknown, although influences from other cells within the retina have been implicated. Microglia, the macrophages of the central nervous system, have previously been shown to increase in number and migrate to the photoreceptor layer to phagocytose apoptotic cell debris. However increasing awareness of the cytotoxic potential of microglia, has led me to undertake this work with the primary remit of investigating the possible involvement of microglia in photoreceptor apoptosis using the rds mouse model of inherited photoreceptor degeneration. Using immunohistochemical and immunofluorescent methods I have demonstrated increased microglial numbers in the degenerating rds retina, resulting from both in situ proliferation and recruitment from the blood, with migration to the outer retinal layers and sub-retinal space. However, by closely scrutinising the period of greatest disease activity we have demonstrated that the peak rate of photoreceptor apoptosis precedes the peak in microglial numbers by approximately five days, suggesting that microglia respond to, rather than cause photoreceptor death. In addition, evidence of oxidative damage (a major mechanism of microglial cytotoxicity) is absent and depletion of retinal microglia using macrophage-depleting clodronate liposomes did not lead to a reduction in the rate of photoreceptor death, providing further evidence that microglia are not involved in causing photoreceptor apoptosis. Additional studies with the neuroprotective tetracycline antibiotic, minocycline showed that this drug was able to delay the onset of photoreceptor apoptosis in the rds mouse, possibly through a direct inhibitory effect on apoptosis and the caspase cascade. Delayed apoptosis was associated with a corresponding delay in microglial migration to the outer retina.
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Schindler, Emily Isaak. "Genetics of inherited retinal degeneration." Diss., University of Iowa, 2011. https://ir.uiowa.edu/etd/1075.
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Heritable retinal degenerations dramatically affect individuals across the lifespan. Heritable degenerations with onset in childhood or young adulthood, such as the ABCA4- associated maculopathies, generally obey Mendelian segregation and are attributable to mutations within a single gene. Retinal degenerations with onset in late adulthood, such as age-related macular degeneration, are usually influenced by a complex constellation of genetic and environmental factors. This thesis applies several complementary, high-throughput genotyping platforms to identify relationships between specific heritable retinal phenotypes and genetic variation. This findings of this thesis will aid in the development of guidelines for inclusion in retinal gene therapy trials and help physicians refine their prognoses based on genetic information.
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Fornasin, Nelvis [Verfasser], Sebastian [Akademischer Betreuer] Goette, and Katrin [Akademischer Betreuer] Wendland. "[eta] invariants under degeneration to cone-edge singularities = η invariants under degeneration to cone-edge singularities." Freiburg : Universität, 2019. http://d-nb.info/1203804326/34.
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González, Guitiérrez Ramiro Arturo. "Biomechanical study of intervertebral disc degeneration." Doctoral thesis, Universitat Politècnica de Catalunya, 2012. http://hdl.handle.net/10803/76781.
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Degeneration and age affect the biomechanics of the intervertebral disc, by reducing its stiffness, flexibility and shock absorption capacities against daily movement and spinal load. The biomechanical characterization of intervertebral discs is achieved by conducting mechanical testing to vertebra-disc-vertebra segments and applying axial, shear, bend and torsion loads, statically or dynamically, with load magnitudes corresponding to the physiological range. However, traditional testing does not give a view of the load and deformation states of the disc components: nucleus pulposus, annulus fibrosus and endplate. Thus, the internal state of stress and strains of the disc can only be predicted by numerical methods, one of which is the finite element method. The objective of this thesis was, to study the biomechanics of degenerated intervertebral discs to load conditions in compression, bending and torsion, by using mechanical testing and a finite element model of disc degeneration, based on magnetic resonance imaging (MRI). Therefore, lumbar discs obtained from cadavers corresponding to spinal levels L2-L3 and L4-L5 with mild to severe degeneration were used. Intervertebral osteochondrosis and spondylosis deformans were identified, being the disc space collapse, the most striking feature. Next, all discs were tested to static and dynamic load conditions, the results gained corresponded to the disc stiffness (in compression, bending and torsion), stress relaxation and dynamic response. Of these, the stiffness response was used to validate the disc model. The testing results suggest that discs with advanced degeneration over discs with mild degeneration are, less rigid in compression, less stiffer under bending and torsion, showed less radial bulge, and reduce their viscoelastic and damping properties. This study shows that degeneration has an impact on the disc biomechanical properties which can jeopardize normal functionality. Development of one finite element model of disc degeneration started by choosing a MRI of a L2-L3 disc. Segmentation of vertebra bone and disc materials followed, and were based on pixel brightness and radiology fundamentals, then a finite element mesh was created to account for the disc irregular shape. The disc materials were modeled as hyperelastic and the bone materials were modeled as orthotropic and isotropic. Adjustment of material properties was based on integrity of the annulus fibrosus, giving a stiffness value matching that of a mild degeneration disc. Then, validation of the model was performed, and included a study of the distributions of stress and strain under loads of compression, bending and torsion. The results from all load simulations show that the disc undergoes large deformations. In contrast, the vertebrae are subjected to higher stress but with negligible deformations. In compression, the model predicted formation of symmetrical disc bulge which agree with the testing behavior. The nucleus pulposus showed to be the principal load carrier with negative principal stresses and strains. In bending and torsion, the annulus fibrosus showed to be the principal load carrier with large symmetrical principal strains and stresses for the former loading and large shearing for the latter. The study showed the importance of soft tissue deformation, mostly noticed in advanced degeneration. In contrast, the higher stresses in the vertebra over those of the intervertebral disc showed the relevance of bone predisposition to fracture. Such kind of studies, should contribute to the understanding of the biomechanics of the intervertebral disc.La degeneración y edad afectan la biomecánica del disco intervertebral, reduciendo la capacidad de rigidez, flexibilidad y atenuación de impactos, contra el movimiento y carga del raquis. La caracterización biomecánica del disco se realiza con ensayos mecánicos a segmentos de vértebra-disco-vértebra y aplicando cargas axiales, cortantes, flexión y torsión, estáticas ó dinámicas, con magnitudes de carga según el intervalo fisiológico. Sin embargo, las pruebas tradicionales no dan una visión de los estados de carga y deformación de los componentes del disco: núcleo pulposo, anillo fibroso y placa terminal. Por lo tanto, el estado interno de esfuerzos y deformaciones del disco, solo puede ser predicho con métodos numéricos, uno de los cuales es el método de elemento finito. El objetivo de esta tesis fue, estudiar la biomecánica de discos intervertebrales degenerados a las condiciones de carga en compresión, flexión y torsión, mediante el uso de ensayos mecánicos y de un modelo de elementos finitos de la degeneración de disco, basado en imágenes con resonancia magnética (MRI). Por lo tanto, se usaron discos lumbares L2-L3 y L4-L5 obtenidos de cadáveres, con degeneración leve a severa. Se identificó osteocondrosis intervertebral y espondilosis deformante, siendo el colapso del espacio intervertebral el aspecto más relevante. Luego, todos los discos fueron ensayados a condiciones de carga estática y dinámica, y los resultados correspondieron a la rigidez del disco (a compresión, flexión y torsión), a la relajación de tensiones y a la respuesta dinámica. De éstos, la rigidez fue usada para validar el modelo de disco. Los resultados de los ensayos sugieren que los discos con degeneración avanzada sobre aquellos con degeneración leve son, menos rigidos a compresión, menos rigidos a flexión y torsión, presentan menor protuberancia radial, y reducen sus propiedades viscoelásticas y de amortiguamiento. El estudio muestra que la degeneración impacta las propiedades biomecánicas del disco, poniendo en riesgo la funcionalidad normal. El desarollo de un modelo de elementos finitos de la degeneración de disco inició eligiendo una secuencia de resonancia magnética de un disco L2-L3. La segmentación de los materiales del disco y de las vértebras se realizó basado en intensidad de brillo del pixel y en fundamentos de radiología, y se creó una malla de elementos finitos correspondiente a la forma irregular del disco. Los materiales del disco se modelaron como hiperelásticos y los tejidos óseos se modelaron como materiales ortotrópicos e isotrópicos. El ajuste de propiedades de los materiales fue basado en la integridad del anillo fibroso, y dio una rigidez correspondiente a la de un disco con degeneración leve. Luego, se realizó la validación del modelo, e incluyó un estudio de las distribuciones de esfuerzo y deformación a las condiciones de carga en compresión, flexión y torsión. Los resultados de todas las simulaciones de carga mostraron que el disco es sometido a grandes deformaciones. En contraste, las vértebras fueron sometidas a mayores esfuerzos pero con deformaciones insignificantes. En compresión, el modelo predijo la formación de una protuberancia radial simétrica, en concordancia con la experimentación. El núcleo pulposo mostró ser el portador principal de carga, con tensiones y deformaciones principales negativas. En flexión y torsión, el anillo fibroso mostró ser el portador principal de carga, con grandes deformaciones y tensiones principales simétricas para la primera carga, y con grandes tensiones cortantes para la segunda carga. El estudio mostró la importancia de las deformaciones de los tejidos blandos, principalmente notados en la degeneración avanzada. Por el contrario, las tensiones mayores en los cuerpos vertebrales sobre aquellas del disco intervertebral mostraron la relevancia de la predisposición a las fracturas óseas. Este tipo de estudio debe contribuir a la comprensión de la biomecánica del disco intervertebral.
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Skoglund, Lena. "Molecular Mechanisms of Frontotemporal Lobar Degeneration." Doctoral thesis, Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9550.
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The aim of this thesis was to identify genetic factors involved in frontotemporal lobar degeneration (FTLD), a neurodegenerative disorder clinically characterised by a progressive change in personality, behaviour and language. FTLD is a genetically complex disorder and a positive family history is found in up to 40% of the cases. In 10-20% of the familial cases the disease can be explained by mutations in the gene encoding the microtubule associated protein tau (MAPT). In the first study we describe the clinical and neuropathological features of a Finnish family with FTLD caused by a mutation in MAPT. We also provide evidence that the pathogenic mechanism of this mutation is through altered splicing of MAPT transcripts. Recently, mutations in the gene encoding progranulin (PGRN) were identified as a major cause of FTLD. In the second study we describe a Swedish family with FTLD caused by a frameshift mutation in PGRN. We provide a clinical and neuropathological description of the family, as well as evidence that the pathogenicity of this mutation is through nonsense-mediated decay of the mutant mRNA transcripts and PGRN haploinsufficiency. In the third study we describe a novel PGRN splice site mutation and a previously described PGRN frameshift mutation, found in a mutation screen of 51 FTLD patients. We describe the clinical and neuropathological characteristics of the mutation carriers and demonstrate that haploinsufficiency is the pathogenic mechanism of the two mutations. In the fourth study we investigate the prevalence of PGRN and MAPT gene dosage alterations in 39 patients with FTLD. No gene dosage alterations were identified, indicating that variations in copy number of the PGRN and MAPT genes are not a common cause of disease, at least not in this FTLD patient collection.
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Chan, Alex Dart Ming. "Neurogenic modulation of articular cartilage degeneration." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ41123.pdf.
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Osti, Orso L. "Annular tears and intervertebral disc degeneration /." Title page, contents and abstract only, 1990. http://web4.library.adelaide.edu.au/theses/09PH/09pho85.pdf.
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Ho, Wai-hung Daniel, and 何偉雄. "Genetic study of lumber disc degeneration." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B42841215.
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Omar, R. "Nonverbal processing in frontotemporal lobar degeneration." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1381829/.
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Frontotemporal lobar degeneration (FTLD) refers to a group of diseases characterised by focal frontal and temporal lobe atrophy that collectively constitute a substantial source of clinical and social disability. Patients exhibit clinical syndromes that are dominated by a variety of nonverbal cognitive and behavioural features such as agnosias, altered emotional and social responses, impaired regulation of physiological drives, altered chemical sense, somatosensory and interoceptive processing. Brain mechanisms for processing nonverbal information are currently attracting much interest in the basic neurosciences and deficits of nonverbal processing are a major cause of clinical symptoms and disability in FTLD, yet these clinical deficits remain poorly understood and accurate diagnosis is often difficult to achieve. Moreover, the cognitive and neuroanatomical correlates of behavioural and nonverbal cognitive syndromes in FTLD remain largely undefined. The experiments described in this thesis aim to address the issues of improving our understanding of the social and behavioural symptoms in FTLD through the integration of detailed neuro-behavioural, neuropsychological and neuroanatomical analyses of a range of nonverbal functions (including emotions, sounds, odours and flavours) with high-resolution structural magnetic resonance imaging (MRI). A prospective study of emotion recognition in various domains including music, faces and voices shows that music is especially vulnerable to the effects of damage in FTLD. A profile of brain atrophy associated with impaired emotion recognition in music is identified, comprising a distributed bilateral cerebral network involving areas previously implicated in representing and evaluating the emotional content of stimuli including mesial temporal structures, insula and their connections in the mesolimbic system. Prospective studies of face and chemosensory processing provide further insights into the neuroanatomical framework and structural neuroanatomy for face, odour and flavour processing deficits in FTLD. A profile of cognitive deficits in different components of face processing is shown which correlate with distinct but partly overlapping brain networks. Deficits in flavor and odour identification are shown in FTLD with neuroanatomical correlates involving temporal and limbic areas which include entorhinal cortex, hippocampus and parahipocampal gyrus. A detailed systematic study of music knowledge in two expert musicians with different dementia diseases, sematic dementia (SemD) and dementia with Lewy bodies (DLB), involving a series of novel neuropsychological experiments probing various dimensions of music knowledge, yields new insights into the cognitive architecture of music knowledge and the brain organization of nonverbal knowledge systems. This thesis therefore provides neuropsychological and imaging data in relation to various nonverbal cognitive processes in FTLD that can offer greater insights into our understanding of behavioural symptoms in this group of diseases as well as the cognitive architecture of hitherto relatively poorly understood nonverbal cognitive modalities such as music knowledge, emotion and chemosensory processing.
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Rohrer, J. D. "Language impairment in frontotemporal lobar degeneration." Thesis, University College London (University of London), 2010. http://discovery.ucl.ac.uk/516148/.
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The term frontotemporal lobar degeneration (FTLD) describes a heterogeneous group of neurodegenerative disorders associated with frontal and temporal lobe atrophy. Within this spectrum, two progressive aphasia syndromes, progressive nonfluent aphasia (PNFA) and semantic dementia (SD), are well described. FTLD is commonly a genetic disorder and mutations in two genes, microtubule-associated protein tau (MAPT) and progranulin (GRN) account for a large proportion of familial cases. A retrospective imaging study using cortical thickness measures shows involvement of the anteroinferior temporal lobes in SD and the left inferior frontal lobe/insula in PNFA. Studies of disease severity and of longitudinal imaging reveal spread through the left hemisphere and into the right hemisphere in both groups. A genetics and heritability study shows that PNFA can be familial, although much less than the behavioural variant of FTLD, and that this is often due to mutations in GRN. Differing patterns of atrophy are shown between different genetic mutations and also between different pathologies with the same clinical syndrome. Evidence from the neurological, neuropsychological, neuroanatomical, genetic and pathological features of the nonfluent aphasias suggests that there are at least three nonfluent aphasia syndromes: a disorder with motor speech impairment with or without agrammatism, a disorder with agrammatism but no apraxia of speech (found in patients with progranulin mutations) and a disorder without agrammatism or apraxia of speech but with word-finding pauses (consistent with descriptions of logopenic/phonological aphasia and pathologically associated with Alzheimer’s disease). Studies of specific deficits (single word processing, prosody, neologistic jargon, apraxia and behavioural symptoms) in the progressive aphasias provide further insight into the disease. This thesis therefore provides neurological, neuropsychological and imaging data with related genetic and pathological information that can provide greater insights into the natural history and classification, and therefore pathophysiological basis of the neurodegenerative disorders that cause primary progressive language impairment.
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Shan, Haidong. "Neuroprotection gene therapy in retinal degeneration." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:30f9b5c3-b9a6-4ad0-a952-6840bd73bbc3.
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Retinal degenerative disease, which includes age-related macular degeneration and retinitis pigmentosa, is the main cause of blindness in developed countries. Degeneration of the retinal pigment epithelium (RPE) and photoreceptor cells through apoptosis is believed to be the main mechanism of cell death. X-linked inhibitor of apoptosis (XIAP) is an endogenous anti-apoptotic protein that mediates its effects through the inhibition of caspases - the proteins regulating the final stages of apoptosis. The neuroprotection of XIAP has been demonstrated in various neurodegenerative models. Retinal gene therapy based on adeno-associated virus (AAV) has recently been proven safe and effective in clinical trials of Leber's congenital amaurosis. However, studies are very limited so far about AAV-mediated XIAP effect on degeneration of the RPE and photoreceptor cells. In this thesis, a comprehensive study of AAV-mediated XIAP was performed in the RPE and photoreceptor degenerative models. First, an oxidative stress model was investigated using H2O2 in a human RPE cell line. Second, AAV2-mediated XIAP conferred marked protection on the RPE cells against H2O2 induced apoptosis. Third, an in vivo analysis using confocal scanning laser ophthalmoscope was applied to the NaIO3 induced retinopathy in two transgenic mice (NRL-GFP and B6TGOPN1LW-EGFP). However, subretinal injection of AAV2-XIAP did not rescue photoreceptor cells in the NaIO3-treated animals. Finally, AAV8-XIAP was tested in a rhodopsin mutant mouse line with retinal degeneration (the Rho-/- B6TGOPN1LW-EGFP mouse) but did not reveal any protection on cone photoreceptors. Overall the work in this thesis indicates a limited protection of AAV-mediated XIAP on the RPE and photoreceptor cells in the degenerative models used. XIAP based gene therapy may be helpful for RPE preservation in atrophic AMD, but it needs further research.
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Gillett-Cooper, Anita M. "Development and degeneration in visual pathways." Thesis, University of Oxford, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.670398.
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Gu, Jiayin. "Biomarkers for Age-Related Macular Degeneration." Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1225388164.
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Ho, Wai-hung Daniel. "Genetic study of lumber disc degeneration." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B42841215.
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Devarajan, Gayathri. "Activation of microglia in ageing retina and in age-related macular degeneration and their role in RPE degeneration." Thesis, University of Aberdeen, 2012. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=192261.
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Ponjavic, Vesna. "Phenotypes and genotypes in families with hereditary tapetoretinal degenerations." Lund : Dept. of Ophthalmology, Lund University, 1997. http://books.google.com/books?id=PLpsAAAAMAAJ.
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Lennerfors, Thomas Taro. "The Vicissitudes of Corruption : Degeneration - transgression - jouissance." Doctoral thesis, KTH, Industriell ekonomi och organisation (Inst.), 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4601.
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In a time when corruption is receiving increasing media coverage and when many claim to wage a war on corruption, this book brings up the need for a problematisation and an increased understanding of the different manifestations – the vicissitudes – of corruption and also what measures are taken against it. The book advances the claim that corruption is tightly related to modernity and particularly to a transgression of the public / private dichotomy. It furthermore explores ancient, postmodern and psychoanalytic critiques of the modern understanding of corruption. The ancient perspective stems from theorists arguing that there is an ancient core meaning of corruption, i.e. degeneration. This perspective is also informed by a discussion about virtues based on Alasdair MacIntyre. The postmodern perspective is based on Zygmunt Bauman. It is held that corruption is the remnant of the classification of the world into the public and the private, caused by the inherent ambiguity of reality. The psychoanalytic perspective, based on Jacques Lacan and Slavoj Žižek, deepens the analysis and relates corruption to stolen enjoyment – jouissance. These different understandings of corruption are used to analyse primarily bribery in Swedish public sector procurement. In interviews, project managers responsible for public procurement give their account not only of bribes and gifts, but also about partiality and objectivity in supplier evaluations. Using these interviews and theoretical perspectives, the book problematises corruption and investigates how it is addressed and externalised with clear rules, virtues and rituals separating the public role from the private .QC 20100512
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Kelempisioti, A. (Anthi). "Genetic risk factors for intervertebral disc degeneration." Doctoral thesis, Oulun yliopisto, 2016. http://urn.fi/urn:isbn:9789526211350.
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Abstract Low back pain (LBP) is the leading cause of years lived with disabilities worldwide. Intervertebral disc (IVD) degeneration is a strong contributing factor to LBP. Recent studies have shown that genetic determinants contribute markedly to IVD degeneration but knowledge about the actual genes involved as well as their roles is still limited. The aim of this thesis work was to study genetic factors that may predispose to IVD degeneration. Using both family and case-control association study designs, variants in five genes showed association with IVD degeneration on magnetic resonance imaging (MRI) in a population-based sample and among patients with sciatica due to lumbar disc herniation (LDH). We performed a candidate gene association study of the known variants implicated in IVD degeneration in a Finnish cohort of 538 young individuals with a moderate degree of lumbar IVD degeneration on MRI. We were able to confirm the associations of variants in the IL6, SKT, and CILP genes, which provides further evidence for true associations. Based on our earlier linkage study in Finnish sciatica families, we performed a candidate gene analysis and identified IL17F as a potential candidate gene. To the best of our knowledge this is the first study to observe an association between this gene and discogenic sciatica. Both IL-6 and IL-17 are pro-inflammatory cytokines with elevated expression levels in herniated tissues, which suggest a role in IVD degeneration. Study of the role of genes coding for inflammatory mediators is of interest as it may contribute to the understanding of the overall inflammatory response of the disc. In addition, we reported on the involvement of SKT in the etiology of lumbar disc herniation (LDH) both in Japanese and Finnish case-control samples. Experimental studies in mice have shown that Skt homozygous mutants exhibit disc abnormalities resulting in a kinky tale phenotype. We hypothesized that the human homolog SKT could have long-term importance in the onset of IVD degeneration by making the discs more vulnerable. Finally, through linkage studies and in the subsequent association analyses, the role of CHST3 as a novel risk factor for IVD degeneration was identified. CHST3 encodes an enzyme that catalyzes the sulfation of chondroitin, and mutations in this gene are associated with spondylepiphyseal dysplasia and humerospinal dysostosis. In our study, we identified this gene using genome –wide linkage based on data from a Southern Chinese family and speculated that mild CHST3 reduction caused by the reported susceptibility SNP could result in disc degeneration in adults in conjunction with other risk factors. This thesis provides new information about the genetic background of IVD degeneration and new insights into the etiology of the disease. The specific roles of these genes in the IVD function and pathogenesis of sciatica are not clear however, and need to be elucidatedTiivistelmä Alaselkäkipu on yksi yleisimmistä sairauksista ja johtava syy työkyvyttömyyteen. Välilevyrappeuma myötävaikuttaa merkittävästi alaselän kipuun. Vaikka aiemmat tutkimukset ovat osoittaneet, että perintötekijöillä on vahva osuus välilevyrappeumaan, altistavat geenit ja niiden rooli tunnetaan huonosti. Tämän tutkimuksen tavoitteena oli arvioida tiettyjen perintötekijöiden osuutta välilevyrappeumassa ja tunnistaa taudille altistava geeni perheaineistossa aiemmin havaitulta kromosomialueelta. Aineistoina tutkimuksessa olivat perheaineistot sekä laajat potilas-kontrolliaineistot suomalaisesta ja aasialaisista väestöistä. Tutkimuksessa osoitimme, että perimän vaihtelut viidessä tutkitussa geenissä altistivat erilaisille välilevyrappeuman taudin muodoille. Tutkimus, jossa analysoimme aiemmin tunnistettuja alttiusgeenejä, vahvisti IL6, SKT ja CILP geenien vaihteluiden osuuden taudin alttiustekijöinä. Tutkimusaineistona oli pohjoissuomalainen syntymäkohortti, jossa välilevyrappeuma oli määritetty magneettikuvauksella (MRI). Suomalaisessa perheaineistossa tehdyn kokogenomin laajuisen kartoituksen pohjalta analysoimme IL17F geenin mahdollisena uutena alttiusgeeninä oireiselle välilevytaudille. Kahdesta geenin variantista koostuva haplotyyppi assosioitui tautiin merkitsevästi. Lisäksi osoitimme, että SKT-geenin tietty muutos altistaa välilevyn pullistumille sekä japanilaisessa että suomalaisessa potilasaineistossa. Hiirikokeissa on havainnoitu, että SKT-geenin homotsygootti mutaatio johtaa välilevy-poikkeamaan, joka edelleen aiheuttaa hiiren poikkeavan häntäilmiasun-. Hypoteesimme oli, että ihmisen SKT -geeni voi myötävaikuttaa välilevypullistuman kehittymiseen altistamalla välilevyt rappeumalle. Edelleen, laajassa usean populaation aineiston käsittävässä tutkimuksessa osoitimme CHST3-geenin muutoksen altistavan välilevyrappeumalle. Peittyvästi periytyvät muutokset tässä geenissä aiheuttavat perinnöllisiä harvinaisia luusairauksia. Tämä väitöstutkimus tarjoaa uutta tietoa välilevyrappeuman geneettisestä taustasta ja auttaa taudin syiden tutkintaa. Geenien rooli välilevyn toiminnassa ja muutosten vaikutus taudin kulkuun vaativat kuitenkin vielä lisätutkimuksia
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Tribble, James R. "Retinal degeneration and remodelling in experimental glaucoma." Thesis, Cardiff University, 2016. http://orca.cf.ac.uk/93668/.
Full textAbstract:
Glaucoma is an optic neuropathy characterised by the loss of retinal ganglion cells (RGC). Dendritic atrophy occurs early in the disease, prior to soma and axonal degeneration. RGCs exhibit reduced branching density and dendritic field size. This thesis seeks to further characterise dendritic atrophy in glaucoma in the context of two external factors that may contribute to the disease pathology – immune system effects mediated via complement and the influence of the perineuronal net (PNN), a specialised extracellular matrix that surrounds RGCs. RGC morphology was investigated in a rat bead model of experimental glaucoma using ballistic labelling techniques; morphological changes were related to synaptic loss and PNN composition using immunohistochemistry. A model was derived for the classification of diseased RGCs in order to prevent labelling bias in subsequent investigations. The immune system was modulated using a complement inhibitor (using a transgenic mouse and pharmacological agent in rats) and PNNs disrupted using the bacterial enzyme Chondroitinase ABC. Experimental glaucoma caused significant dendritic loss, with partial protection conferred by both complement inhibition and PNN digestion. Analysis of retinal sections also revealed partial protection of synapses. PNNs did not show any changes in their composition in the rat in experimental glaucoma but human glaucoma eyes showed increased glycosaminoglycan sulphation in the RGC layer which was correlated with visual deficit. Manipulation of the RGC external environment therefore proved successful in protecting from dendritic atrophy.
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Yap, Cheng-Hon. "Factors influencing cryopreserved allograft heart valve degeneration." Connect to thesis, 2006. http://repository.unimelb.edu.au/10187/2120.
Full textAbstract:
Heart valve replacement is becoming more commonplace in developed nations. Despite this the ideal valve prosthesis has not been found. The allograft valve has been used for over 40 years and remains an important prosthesis with many advantages. However, like other biological valve prosthesis, they have a finite durability. The causes of allograft valve degeneration are still unknown. The study aims to identify factors associated with cryopreserved allograft valve degeneration. Knowledge of such factors will improve our understanding of the potential causes and mechanisms of allograft heart valve degeneration. (For complete abstract open document)
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Renganathan, Kutralanathan. "Oxidative stress and age related macular degeneration." online version, 2008. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1193002743.
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Gangaeva, Anna Evgenyevna. "Genome degeneration in obligate parasites and endosymbionts." Thesis, University of British Columbia, 2008. http://hdl.handle.net/2429/4086.
Full textAbstract:
Microorganisms are a goidmine for evolutionary genetics as their genomes can
evolve at an extraordinary rate which results in some of the most extravagant adaptations
in terms of genome structure and function as well as survival in the most unusual
environments. One trend observed in several evolutionary scenarios is genome
degeneration. It is most prominent in endosymbionts and obligate intracellular parasites
and is a consequence of many constraints encountered in the intracellular environment.
The process involves loss of many protein-coding genes, resulting in greater dependence
on the host, and loss of non-coding DNA such as intergenic regions, which has a direct
impact on regulation of genome function. I have chosen two evolutionarily distinct
systems to analyze the stages and functional consequences of genome degeneration,
namely the impact of genome compression on transcription in an obligate parasite
Antonospora locustae (genus Microsporidia), and gene content in the mitochondrion of a
diatom endosymbiont found in the dinoflagellate Durinskia baltica. I have successfully
mapped transcriptional start and termination sites from 14 loci in Antonospora locustae,
and cloned fragments of two genes that are part of the electron transport chain from the
mitochondrion of the diatom endosymbiont in Durinskia baltica. My analysis reveals
that transcription in A. locustae is always initiated immediately upstream of the open
reading frame at a single point for every locus, whereas transcriptional termination can
occur at several points for a single gene and, in some instances overlaps with a
downstream reading frame. The identification ofNADH5 and ATPase9 from the
mitochondrion of the endosymbiont in D. baltica is further evidence for the preservation
of function in this enigmatic organelle.
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Dyachenko, Evgueniya, and Nikolai Tarkhanov. "Degeneration of boundary layer at singular points." Universität Potsdam, 2012. http://opus.kobv.de/ubp/volltexte/2012/6013/.
Full textAbstract:
We study the Dirichlet problem in a bounded plane domain for the heat
equation with small parameter multiplying the derivative in t. The behaviour of solution at characteristic points of the boundary is of special interest.
The behaviour is well understood if a characteristic line is tangent to the boundary with contact degree at least 2. We allow the boundary to not only have contact of degree less than 2 with a characteristic line but also a cuspidal singularity at a characteristic point. We construct an asymptotic solution of the problem near the characteristic point to describe how the boundary layer degenerates.
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Hristova, Gergana. "Calcification in Intervertebral Disc Degeneration and Scoliosis." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=86948.
Full textAbstract:
In degenerative and scoliotic intervertebral discs (IVD), calcification is a pathological process that may lead to impairment of the nutrient supply and a disturbance in disc metabolism. However, the process of calcification in disc degeneration and scoliosis is not well understood. The purpose of this study was to assess the calcification markers in IVD of patients with degenerative disc disease and adolescent idiopathic scoliosis. For this purpose, 34 IVDs from 16 adult patients with degenerative disc disease and 25 IVDs from 9 adolescent patients with adolescent idiopathic scoliosis were obtained after surgery or autopsy. The concave and the convex parts of the scoliotic discs were analyzed separately. Von Kossa staining was performed to visualize calcium deposits, while type X collagen expression, which is associated with endochondral ossification, was measured by immunohistochemistry and Western blot. Alkaline phosphatase (ALP) activity and calcium and inorganic phosphate (Pi) concentrations were used as markers of the calcification process. Results showed the presence of calcium deposits and type X collagen only in degenerative and scoliotic intervertebral discs, but not in control discs. Results also demonstrated a large individual variability in ALP activity and calcium and Pi concentrations in degenerative and scoliotic discs. Moreover, the level of the calcification markers was consistently higher in degenerative and scoliotic discs than in control discs. The results suggest that disc degeneration in adults involves mineral deposition and that mineralization in adolescent idiopathic scoliosis discs might reflect an ongoing premature degenerative process.Dans les disques intervertébraux (DIV) dégénérés et de scoliose, la calcification est un processus pathologique qui peut mener à une diminution de l'apport nutritif et à un débalancement du métabolisme. Cependant, le processus de calcification de ces disques est très peu connu. Le but de la présente étude était d'évaluer le potentiel de calcification des DIVs de patients avec une maladie dégénérative des disques (MDD) ou avec une scoliose idiopathique chez l'adolescent (SIA). Pour ce faire 34 DIVs provenant de 16 adultes avec MDD et 25 DIVs de 9 patients avec SIA ont été obtenus après chirurgie ou autopsie. Les côtés convexe et concaves des disques scoliotiques on été analysés séparément. Une coloration de Von Kossa a été faite afin de visualiser les dépôts de calcium alors que l'expression du collagène de type X, associé à l'ossification endochondrale, a été mesurée par immunohistochimie et par buvardage de type Western. L'activité de la phosphatase alcaline (PA) ainsi que les concentrations de calcium et de phosphate inorganique (Pi) ont servi d'indicateurs du potentiel de calcification. Les résultats montrent la présence de dépôts de calcium et de collagène de type X uniquement dans les DIVs des patients ayant une MDD ou une SIA, mais non dans les disques témoins. Les résultats montrent également une grande variabilité individuelle de l'activité de la PA ainsi que des concentrations de calcium et de Pi. De plus, les niveaux de ces marqueurs du potentiel de calcification était plus élevés dans les disques dégénérés et scoliotiques que dans les disques témoins. Les résultats suggèrent que la dégénération du disque intervertébral adulte est associée à une déposition de minéraux et que la minéralisation du disque scoliotique pourrait refléter un processus de dégénération prématurée.
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Binns, Alison Mary. "Electrophysiological investigation of age-related macular degeneration." Thesis, Cardiff University, 2005. http://orca.cf.ac.uk/55964/.
Full textAbstract:
Age-related macular degeneration (AMD) affects 12.7 million people in Europe and North America (Klein et al., 1995 Klein et al. 1999). As a combination of decreasing birth rate and increasing longevity alter the demographic of the population, the impact of this disease can only increase. This places an immense burden, not only on the individuals afflicted by the condition, but on the financial resources of society as a whole. Unfortunately, treatment for AMD is still very restricted, and even our understanding of the pathogenesis of the disease is far from complete One concern in tackling the growing problem of AMD is that methods used in the assessment of the condition are limited, usually based on fundus appearance and visual acuity. The aim of this study was to develop a battery of electrophysiological tests which would be sensitive to the most subtle changes in retinal function in AMD. Such tests may aid diagnosis, provide a more sensitive measure of disease progression, and allow an early identification of phenotypic subtypes. Protocols were included for the recording of the focal rod ERG, the focal cone ERG, the S-cone ERG and the dynamic focal cone ERG, along with psychophysical tests of colour vision and dark adaptation. These tests were then applied to 31 subjects with ARM (12 with bilateral ARM, 11 with unilateral wet AMD and 8 with unilateral dry AMD), and 28 controls. In the analysis of ERG amplitudes a ratio of focal to full-field amplitude was introduced as a novel means of reducing intersubject variability in response. This was found to increase the accuracy of all tests in distinguishing between subject groups. The greatest separation between ARM and control groups was provided by the dynamic tests of visual function i.e. rod-cone break time of the dark adaptation function, and time constant of recovery of the dynamic focal cone ERG. The time to rod-cone break also showed potential in identifying subjects at increased risk of exudative retinal changes. Subjects were assigned to groups in this study on the basis of fundus appearance. However, individuals within each subject group showed a range of retinal function which belied the homogeneity of retinal signs. This raises the question of whether 'form' or 'function' should form the basis of classification and assessment of individuals with ARM and AMD.
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Beirowski, Bogdan Karl. "Mechanisms of axon degeneration and its blockade." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608571.
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Kamal, Barishna. "Central auditory decline: degeneration or negative plasticity?" Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=121582.
Full textAbstract:
Perceptual decline is an almost universal aspect of natural aging that remains poorly understood. In auditory pathways, these perpetual deficits most often result in difficulties identifying minute spectral and temporal details of stimuli, as well as a reduced ability to understand speech in noisy environments. Several processing abnormalities have been described at the level of the primary auditory cortex (A1), the main conduit of auditory information between the brainstem and cerebral cortical fields. Many of these impairments have been identified in the aging rat, a model gaining popularity to study age-related auditory decline. These include poor frequency tuning selectivity, neural desynchronization, and a reduced ability to increase the contrast of low-probability sounds in the presence of distractors. Since many of these age-related auditory processing deficits can be partially reversed with auditory training, it appears that these changes are not be purely degenerative but rather represent “negative” plastic adjustments in response to some sort of change in external or internal brain conditions. Based on indirect evidence from previous studies, I speculate that a driver for these changes could be a reduction in the clarity of auditory pattern reaching the brain due to degenerating peripheral sensory organs. To test this hypothesis, I exposed young adult rats (5-6 m.o) to low-grade continuous broadband noise for 8 weeks, a paradigm previously shown to produce auditory cortex profiles similar to those seen in aged rats. Several aspects of A1 function, structure and connectivity were compared to aged rats (21-26 m.o). I found the impact of noise exposure on A1 spectral and temporal properties to be almost indistinguishable from the effect of natural aging on A1. In addition, I found that these functional changes were paralleled by a reduction in inhibitory interneuron population and of intra-cortical myelin, which are both negatively affected by normal aging. However, most of these changes were recovered after I returned the rats to a noise-free environment. Finally, aged rats (21 m.o) placed in an enriched environment containing highly patterned auditory stimuli for two weeks showed improvements in many aspects of temporal, and spectral processing. These results suggest that age-related changes in A1 have a strong activity-dependent component and indicate that the presence or absence of clear auditory input patterns reaching the cortex appear to play an important role in the maintenance of normal adult A1 function. Changes in connectivity between A1 and the rest of the brain could play an important role in the emergence of age-related auditory processing deficits. Most A1 processes require continuous integration of "bottom- up" and "top-down" influences. The ability to selectively suppress distracting auditory inputs, one of the most commonly reported auditory impairment in healthy older adults is highly dependent on this integration. In the second part of this thesis, I examined the role of sensory input statistics, more specifically the impact of auditory noise on the connectivity between A1 and a number of "high-order" cortical field involved in auditory processing. This was done using a combination of simultaneous electrophysiological recordings and tracer studies in young adult rats previously exposed to low-grade noise as in part one of the thesis and aged naive rats for comparison. Noise exposure was found to reduce the anatomical and functional connectivity of A1 to downstream cortical fields, as was evident by a decrease in the amplitude and an increase in latency of the responses following electrical stimulation in A1. Furthermore, I found a decrease in synaptic bouton density of A1 afferents reaching the frontal cortical fields. These results suggest that "bottom-up" processes (noise exposure) might have the capacity to induce changes in cortical fields involved in "top-down" modulation.Le déclin des capacités perceptuelles est un aspect presqu'universel du vieillissement naturel qui reste en grande partie à élucider. Dans les voies auditives, ces déclins perceptuels se traduisent le plus souvent par des difficultés à identifier les détails temporels et spectraux subtils d'un son, de même que par une réduction de la capacité à comprendre le langage dans un environnement bruyant. Plusieurs anomalies du traitement de l'information auditive ont été décrites au niveau du cortex auditif primaire (A1) qui sert de canal principal à l'information auditive entre le tronc cérébral et les régions corticales cérébrales. Nombre de ces déficits ont été identifiés chez le rat âgé, un modèle qui gagne en popularité dans les études du déclin auditif lié à l'âge. Ils incluent une faible sélectivité de la mise au point par fréquence, une désynchronisation neurale et une diminution de la capacité à contraster les sons peu probables en présence de distracteurs. Puisque beaucoup de ces déficits du traitement auditif liés à l'âge apparaissant avec l'âge peuvent être partiellement inversés par l'entraînement auditif, il apparaît que ces changements ne sont pas entièrement dégénératifs mais représentent plutôt des ajustements plastiques « négatifs » en réponse à un changement des conditions cérébrales internes ou externes. Sur la base d'évidences indirectes obtenues lors d'études précédentes, nous avons émis l'hypothèse qu'une réduction de la clarté des motifs auditifs parvenant au cerveau causée par la dégénération des organes sensoriels périphériques pourrait entraîner ces changements. Pour tester cette hypothèse, j'ai exposé de jeunes rats adultes (5-6 mois) à du bruit continu peu défini à haut débit pendant 8 semaines utilisant un paradigme expérimental connu pour produire des profils du cortex auditif similaires à ceux rencontrés chez des rats âgés. J'ai comparé plusieurs aspects de la fonction, structure et connectivité d'A1 à ceux de rats âgés (21-26 mois). Il en est ressorti que l'effet de l'exposition au bruit sur les propriétés temporales et spectrales de A1 était presqu'identique à celui du vieillissement naturel sur A1. De plus, mes résultats montrent que ces changements fonctionnels ont eu lieu parallèlement à une réduction de la population d'interneurones inhibiteurs et de la myéline intra-corticale, toutes les deux amoindries par le vieillissement normal. Toutefois, la plupart de ces changements ont été inversés après avoir replacé les rats dans un environnement sans bruit. Finalement, des rats âgés (21 mois) placés dans un environnement enrichi de stimuli auditifs aux motifs complexes pendant deux semaines ont montrés de nombreuses améliorations dans le traitement des aspects temporel et spectral. Ces résultats suggèrent que les changements liés à l'âge dans A1 ont une composante fortement dépendante de l'activité et indiquent que la présence ou l'absence de motifs auditifs entrant clairs parvenant au cortex semblent jouer un rôle important dans le maintient des fonctions normales d'A1 chez l'adulte.Des changements de la connectivité entre A1 et le reste du cerveau pourraient jouer un rôle important dans l'émergence des déficits du traitement auditif liés à l'âge. La plupart des procédés d'A1 nécessitent l'intégration continuelle d'influences « ascendantes » et « descendantes ». La capacité à supprimer de façon sélective les données auditives distrayantes, l'une des faiblesses auditives les plus couramment rapportées par des adultes âgés, dépend fortement de cette intégration. Dans la deuxième partie de cette thèse, j'ai examiné le rôle de la statistique des données sensorielles, et en particulier l'impact de la présence du bruit auditif sur la connectivité entre A1 et plusieurs régions corticales « de haut niveau » impliquées dans le traitement auditif.
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Chermenina, Maria. "GDNF and alpha-synuclein in nigrostriatal degeneration." Doctoral thesis, Umeå universitet, Histologi med cellbiologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-91811.
Full textAbstract:
Parkinson’s disease is a common neurological disorder with a complex etiology. The disease is characterized by a progressive loss of dopaminergic cells in the substantia nigra, which leads to motor function and sometimes cognitive function disabilities. One of the pathological hallmarks in Parkinson’s disease is the cytoplasmic inclusions called Lewy bodies found in the dopamine neurons. The aggregated protein α-synuclein is a main component of Lewy bodies. In view of severe symptoms and the upcoming of problematic side effects that are developed by the current most commonly used treatment in Parkinson’s disease, new treatment strategies need to be elucidated. One such strategy is replacing the lost dopamine neurons with new dopamine-rich tissue. To improve survival of the implanted neurons, neurotrophic factors have been used. Glial cell line-derived neurotrophic factor (GDNF), which was discovered in 1993, improves survival of ventral mesencephalic dopamine neurons and enhances dopamine nerve fiber formation according to several studies. Thus, GDNF can be used to improve dopamine-rich graft outgrowth into the host brain as well as inducing sprouting from endogenous remaining nerve fibers. This study was performed on Gdnf gene-deleted mice to investigate the role of GDNF on the nigrostriatal dopamine system. The transplantation technique was used to create a nigrostriatal microcircuit from ventral mesencephalon (VM) and the lateral ganglionic eminence (LGE) from different Gdnf gene-deleted mice. The tissue was grafted into the lateral ventricle of wildtype mice. The results revealed that reduced concentrations of GDNF, as a consequence from the Gdnf gene deletion, had effects on survival of dopamine neurons and the dopamine innervation of the nigrostriatal microcircuit. All transplants had survived at 3 months independently of Gdnf genotype, however, the grafts derived from Gdnf gene-deleted tissue had died at 6 months. Transplants with partial Gdnf gene deletion survived up to 12 months after transplantation. Moreover, the dopaminergic innervation of striatal co-grafts was impaired in Gdnf gene-deleted tissue. These results highlight the role of GDNF for long-term maintenance of the nigrostriatal dopamine system. To further investigate the role of GDNF expression on survival and organization of the nigrostriatal dopamine system, VM and LGE as single or combined to double co-grafts created from mismatches in Gdnf genotypes were transplanted into the lateral ventricle of wildtype mice. Survival of the single grafts was monitored over one year using a 9.4T MR scanner. The size of single LGE transplants was significantly reduced by the lack of GDNF already at 2 weeks postgrafting while the size of single VM was maintained over time, independently of GDNF expression. The double grafts were evaluated at 2 months, and the results revealed that lack of GDNF in LGE reduced the dopamine cell survival, while no loss of dopamine neurons was found in VM single grafts. The dopaminergic innervation of LGE was affected by absence of GDNF, which also caused a disorganization of the striatal portion of the co-grafts. Small, cytoplasmic inclusions were frequently found in the dopamine neurons in grafts lacking GDNF expression. These inclusions were not possible to classify as Lewy bodies by immunohistochemistry and the presence of phospho-α-synuclein and ubiquitin; however, mitochondrial dysfunction could not be excluded. To further study the death of the dopamine neurons by the deprivation of GDNF, the attention was turned to how Lewy bodies are developed. With respect to the high levels of α-synuclein that was found in the striatum, this area was selected as a target to inject the small molecule – FN075, which stimulates α-synuclein aggregation, to further investigate the role of α-synuclein in the formation of cytoplasmic inclusions. The results revealed that cytoplasmic inclusions, similar to those found in the grafts, was present at 1 month after the injection, while impairment in sensorimotor function was exhibited, the number of dopamine neurons was not changed at 6 months after the injection. Injecting the templator to the substantia nigra, however, significantly reduced the number of TH-positive neurons at 3 months after injection. In conclusion, these studies elucidate the role of GDNF for maintenance and survival of the nigrostriatal dopamine system and mechanisms of dopamine cell death using small molecules that template the α-synuclein aggregation.
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Evans, Jennifer Rosemary. "Age-related macular degeneration in the UK." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2003. http://researchonline.lshtm.ac.uk/682315/.
Full textAbstract:
The aim of this thesis was to investigate the prevalence and impact of age-related macular degeneration (AMD) causing visual impairment in people aged 75 years and above in the UK. A secondary objective was to investigate a small number of potential risk factors for AMD. This was an add-on study to the MRC Trial of the Assessment and Management of Older People in the Community. The prevalence of AMD causing visual impairment was estimated at 3.7% (95% confidence interval 3.2% to 4.2%) in people aged 75 years and above. This prevalence increased sharply with age. There was a higher risk of AMD causing visual impairment in women. There were estimated to be approximately 192,000 people aged 75 years and above in the UK living in the community with visual impairment due to AMD (95% confidence interval 144,000 to 239,000) of whom 60,000 are aged 90 years or above. The prevalence of AMD causing visual impairment did not vary by socio-economic group or region. After controlling for appropriate confounding factors, compared to people not visually impaired, people visually impaired due to AMD were more likely to have functional difficulties, report poor health and be depressed. They were more likely to be in the worst quintile for the home management and mobility dimensions of the Sickness Impact Profile (SIP). After controlling for appropriate confounding factors including binocular acuity score, compared to people visually impaired due to other causes, people visually impaired due to AMD were more likely to have functional difficulties and report poor health and less likely to be in the worst quintile for SIP body care and movement dimension or die. There was an association between smoking status and risk of being visually impaired due to AMD. This effect was particularly strong in people aged 75-79 years of age. In these people there was a dose-response relationship between pack years of smoking and risk of AMD causing visual impairment. There were no statistically significant associations between alcohol consumption, cardiovascular disease and reproductive factors (in women) and AMD causing visual impairment.
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Clark, C. N. "Social signal decoding in frontotemporal lobar degeneration." Thesis, University College London (University of London), 2016. http://discovery.ucl.ac.uk/1508105/.
Full textAbstract:
Frontotemporal lobar degeneration (FTLD) is associated with progressive social cognitive impairment. Currently a comprehensive pathophysiological model allowing disease effects to be understood and anticipated at the level of the whole brain is lacking. In this thesis I explored candidate cognitive operations underpinning complex behaviours in patients with the canonical syndromes of FTLD; behavioural variant frontotemporal dementia (bvFTD) and semantic dementia (SD). I correlated behavioural deficits with brain network disintegration using the structural magnetic resonance imaging (MRI) technique, voxel based morphometry (VBM). I created synthetic scenes to manipulate congruity across semantic and emotional domains (Chapter 3) and showed deficits across both patient groups. The deficits have grey matter correlates in prefronto-parieto-temporo-insular network and a temporo-insulo-striatal network. I used music as a non-verbal syntactic probe to investigate reward anticipation and valuation (Chapter 4) and demonstrated dissociable deficits across dementias. Performance was associated with grey matter in a distributed network including anterior temporal cortex and orbitofrontal cortex (OFC), previously implicated in computing diverse rewards. I created a novel neuropsychological test of humorous intent (Chapter 5) to model incongruity processing. bvFTD demonstrates a particular difficulty decoding novel humorous situations while SD produces a more general deficit of humour detection. Humour detection accuracy was associated with temporoparietal junction (TPJ) and anterior superior temporal cortical volume which are hubs for processing incongruity and semantic associations. To assess the relevance of these findings (Chapter 5) to daily life behaviour I explored humour preferences across dementias (Chapter 6). Altered sense of humour is particularly salient in bvFTD and SD, but also frequent in AD and may predate more typical symptoms. In conclusion, impairment in incongruity processing and reward allocation was shown across paradigms. The neuroanatomical networks underpinning these processes overlapped with areas known to be targeted by FTLD. These processes have implications for our understanding of the social dysfunction that defines bvFTD.
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Goverdhan, Srinivas. "Immunogenetic pathways in age related macular degeneration." Thesis, University of Southampton, 2008. https://eprints.soton.ac.uk/66006/.
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Renganathan, Kutralanathan. "Oxidative Damage and Age Related Macular Degeneration." Case Western Reserve University School of Graduate Studies / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1193002743.
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Wang, Yang. "Gene Discovery for Age-related Macular Degeneration." Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1228364622.
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NI, JIAQIAN. "Plasma Biomarkers for Age-Related Macular Degeneration." Cleveland State University / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=csu1236700270.
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Godzik, Katharina. "The NAD salvage pathway and Wallerian degeneration." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.707906.
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Wu, Juan. "Dietary Determinants of Age-Related Macular Degeneration." Thesis, Harvard University, 2016. http://nrs.harvard.edu/urn-3:HUL.InstRepos:27201715.
Full textAbstract:
Age-related macular degeneration (AMD) is the most common cause of irreversible blindness in older Americans. There has been a long standing interest in the role of diet in the development of AMD. As early as the first National Health and Nutrition Examination Survey in the 1970s, higher intakes of fruits and vegetables were inversely correlated with the prevalence of AMD. Carotenoids and omega3 fatty acids are the most studied dietary factors due to strong biological plausibility. However, evidence from epidemiologic studies and clinical trials on the relations has been inconsistent.
Chapter I prospectively examined the intakes of lutein/zeaxanthin and other common carotenoids in relation to the risk of AMD over more than two decades of follow-up among two large US cohorts, the Nurses’ Health Study and Health Professionals Follow-Up Study. We assessed nutrient intakes by repeated food frequency questionnaires. We also computed bioavailable plasma carotenoid scores directly from food intake using validated regression models. Cox proportional hazards models were used to compute the associations. Higher intakes of bioavailable carotenoids (except lycopene) were inversely associated with advanced AMD but not intermediate AMD. Analyses based on bioavailable intakes resulted in stronger associations than conventional nutrient intakes.
Chapter II prospectively evaluated the marine long-chain omega3 fatty acids. We found that long-chain omega3 fatty acids were inversely associated with visually significant intermediate AMD. There was no association with advanced AMD; however, the totality of current evidence for advanced AMD is also discordant.
Chapter III further investigated the plant-derived omega3 fatty acids, α-linolenic acid (ALA). We found that higher intake of ALA was associated with intermediate AMD before 2002 but not after. This coincides with the same time period when trans ALA was found in our participants’ blood and in mayonnaise, a primary food source of ALA. Whether trans ALA mediates this positive association warrants further studies.
Although randomized trials are usually believed as the “gold standard”, dietary factors are hard to be adequately studied by randomized trials due to the complexities of diet and disease relations. Thus, findings in this thesis from large long-term prospective cohort studies provide the next best form of evidence.
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Wu, Baosen. "A degeneration formula of Donaldson-Thomas invariants /." May be available electronically:, 2007. http://proquest.umi.com/login?COPT=REJTPTU1MTUmSU5UPTAmVkVSPTI=&clientId=12498.
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Wang, Yang. "Gene discovery of age-related macular degeneration." Cleveland, Ohio : Case Western Reserve University, 2008. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1228364622.
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Brandauer, Barbara. "Feinmotorische Kraftkontrolle bei Patienten mit zerebellärer Degeneration." Tönning Lübeck Marburg Der Andere Verl, 2009. http://d-nb.info/994297653/04.
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Schobesberger, Martina. "Oligodendroglial degeneration in distemper : apoptosis or necrosis? /." [S.l.] : [s.n.], 1998. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Yu, Yang. "Degeneration of Period Matrices of Stable Curves." 京都大学 (Kyoto University), 2017. http://hdl.handle.net/2433/225385.
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Hemphill, Mandy. "Vitamin D and Age-Related Macular Degeneration." ScholarWorks, 2017. https://scholarworks.waldenu.edu/dissertations/3448.
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Age-related macular degeneration (AMD) is the leading cause of vision loss in individuals aged 50 years and older and is estimated to affect as many as 11 million individuals in the United States. The purpose of this study was to examine the association between vitamin D and AMD disease progression. The life course epidemiology framework model was used to explore how vitamin D level as a risk factor may have an association to AMD disease through time. Data in the 2005-2008 National Health and Nutrition Examination Survey (NHANES) database were collected on vitamin D levels and identified stages of AMD level based on graded fundus eye exams from an available sample size of 5,604 participants. A quantitative cross-sectional study approach was used to address this gap in knowledge. A bivariate analysis was used to examine each independent variable (age, race/ethnicity, smoking status, and diabetes) to the dependent variable AMD from the 2005-2008 NHANES dataset. A multivariate logistic regression analysis was performed with AMD including each independent variable found to be significant. The findings from this study failed to suggest an association between vitamin D levels to AMD, with or without the covariates included in the model. There was not an association found between vitamin D level and presence of AMD. An association was found between age, smoking, and race to presence of AMD in each of the bivariate models. The findings from this study could be used for positive social change by encouraging medical and public health agencies to target screening programs at high-risk age, smoking, and race groups. There remains to be conflicting data in the literature. This study adds to the body of literature suggesting that higher levels of vitamin D are not necessarily beneficial as they pertains to AMD.
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Whitmore, Steven Scott. "Molecular investigations of age-related macular degeneration." Diss., University of Iowa, 2015. https://ir.uiowa.edu/etd/1798.
Full textAbstract:
An estimated 170.38 million elderly adults suffer from some stage of age-related macular degeneration (AMD) worldwide, a vision defect that damages the macula, the central region of the retina required for sharp vision, such as reading, driving, and recognizing faces. Genetic factors strongly modify one's risk for developing AMD, and most of these genetic changes are found in genes of the alternative complement cascade, a component of the immune system. The lack of effective AMD prevention calls for the identification of druggable molecules and pathways.
In my research, I use microarrays and RNA sequencing to investigate the events occurring in early AMD, the reasons for macular susceptibility to AMD, and the events triggering aberrant blood vessel growth in late AMD. First, I found that genes associated with endothelial cells tend to be expressed at lower levels in human donors eyes affected by early AMD than in control eyes, concordant with previous studies indicating loss of choriocapillaris in early AMD. Second, I found that molecular signals across regions of the retina, retinal pigment epithelium, and choroid generally mirror the distribution of cell types in these regions. Third, I found that damage to cultured primate chorioretinal endothelial cells by the end product of complement activation, membrane attack complex, produces an environment conducive to choroidal neovascularization, a symptom of late-stage AMD. I propose a model that bridges genetic variants in the complement cascade genes with blood vessel loss in early AMD and the pathological growth of blood vessels in late AMD.