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Chen, Lina. "Structural and functional studies of the cell cycle regulator RGC-32." Thesis, University of Sussex, 2017. http://sro.sussex.ac.uk/id/eprint/68451/.
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Wilkinson, Craig. "Understanding the catalytic cycle of membrane pyrophosphatases through structural and functional studies." Thesis, University of Leeds, 2017. http://etheses.whiterose.ac.uk/19131/.
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Membrane pyrophosphatases (M-PPases) couple pyrophosphate hydrolysis to the translocation of sodium ions/protons, using the resulting ion gradients to drive abiotic stress resistance and in the infectivity of protozoan parasites. I have solved two M-PPase structures in different catalytic states, combining these with previous structures to update the model of the catalytic cycle of M-PPases. These new structures confirm previous findings that substrate binding breaks interactions between K12.50 and D6.43 due to motion of helix 12, leading to a rearrangement of helix 6 and priming the enzyme for hydrolysis. Previously this information was only visible between the structures of two-distinct M-PPases, a H+-PPase and Na+-PPase. The current structures allow for comparisons to be made between structures of the same type of M-PPase. Electrometric data was acquired using the Nanion SURFE2R technique, which showed a proton-pumping signal was generated by the non-hydrolysable inhibitor, imidodiphosphate. This provided sufficient information to update the model of the complete catalytic cycle, favouring the hypothesised Binding change mechanism, in which substrate binding induces a series of conformational changes during which ion pumping occurs first, followed by substrate hydrolysis. Additionally, crystal optimisation techniques improved the resolution of the Pyrobaculum aerophilum M-PPase structure to 3.8, providing an overview of the K+-independent M-PPase. The hydrolytic centre and ion gate regions showed similar coordination to previous structures, with differences seen in the conformation of several outer ring helices, potentially linked to K+-independence. I also carried out mutational studies investigating K12.46 and T12.49, both involved in K+-independence and found that both mutations were required to generate a K+-dependent variant of PaPPase. Overall, this information has improved our understanding of the structure and function of the membrane pyrophosphatases, providing a basis for drug-design programmes targeting protozoan parasites, to which the membrane pyrophosphatases are a vital part of growth and infectivity.
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Cheung, Ngai. "Structural and functional characterization of EEN/EndophilinA2, a fusion partner in acute leukemia /." View the Table of Contents & Abstract, 2005. http://sunzi.lib.hku.hk/hkuto/record/B31540284.
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Cheung, Ngai, and 張毅. "Structural and functional characterization of EEN/EndophilinA2, a fusion partner in acute leukemia." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B45014760.
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Sontheimer, Jana. "Functional characterization of proteins involved in cell cycle by structure-based computational methods." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2012. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-86778.
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In the recent years, a rapidly increasing amount of experimental data has been generated by high-throughput technologies. Despite of these large quantities of protein-related data and the development of computational prediction methods, the function of many proteins is still unknown. In the human proteome, at least 20% of the annotated proteins are not characterized. Thus, the question, how to predict protein function from its amino acid sequence, remains to be answered for many proteins. Classical bioinformatics approaches for function prediction are based on inferring function from well-characterized homologs, which are identified based on sequence similarity. However, these methods fail to identify distant homologs with low sequence similarity. As protein structure is more conserved than sequence in protein families, structure-based methods (e.g. fold recognition) may recognize possible structural similarities even at low sequence similarity and therefore provide information for function inference. These fold recognition methods have already been proven to be successful for individual proteins, but their automation for high-throughput application is difficult due to intrinsic challenges of these techniques, mainly caused by a high false positive rate. Automated identification of remote homologs based on fold recognition methods would allow a signi cant improvement in functional annotation of proteins. My approach was to combine structure-based computational prediction methods with experimental data from genome-wide RNAi screens to support the establishment of functional hypotheses by improving the analysis of protein structure prediction results.
In the first part of my thesis, I characterized proteins from the Ska complex by computational methods. I showed the benefit of including experimental information to identify remote homologs: Integration of functional data helped to reduce the number of false positives in fold recognition results and made it possible to establish interesting functional hypotheses based on high con dence structural predictions. Based on the structural hypothesis of a GLEBS motif in c13orf3 (Ska3), I could derive a potential molecular mechanism that could explain the observed phenotype.
In the second part of my thesis, my goal was to develop computational tools and automated analysis techniques to be able to perform structure-based functional annotation in a high-throughput way. I designed and implemented key tools that were successfully integrated into a computational platform, called StrAnno, which I set up together with my colleagues. These novel computational modules include a domain prediction algorithm and a graphical overview that facilitates and accelerates the analysis of results.
StrAnno can be seen as a first step towards automatic functional annotation of proteins by structure-based methods. First, the analysis of long hit lists to identify promising candidates for further analysis is substantially facilitated by integration and combination of various sequence-based computational tools and data from functional databases. Second, the developed post-processing tools accelerate the evaluation of structural and functional hypotheses. False positives from the threading result lists are removed by various filters, and analysis of the possible true positives is greatly enhanced by the graphical overview. With these two essential benefits, fold recognition techniques are applicable to large-scale approaches. By applying this developed methodology to hits from a genome-wide cell cycle RNAi screen and evaluating structural hypotheses by molecular modeling techniques, I aimed to associate biological functions to human proteins and link the RNAi phenotype to a molecular function. For two selected human proteins, c20orf43 and HJURP, I could establish interesting structural and functional hypotheses. These predictions were based on templates with low sequence identity (10-20%). The uncharacterized human protein c20orf43 might be a E3 SUMO-ligase that could be involved either in DNA repair or rRNA regulatory processes. Based on the structural hypotheses of two domains of HJURP, I predicted a potential link to ubiquitylation processes and direct DNA binding. In addition, I substantiated the cell cycle arrest phenotype of these two genes upon RNAi knockdown.
Fold recognition methods are a promising alternative for functional annotation of proteins that escape sequence-based annotation due to their low sequence identity to well-characterized protein families. The structural and functional hypotheses I established in my thesis open the door to investigate the molecular mechanisms of previously uncharacterized proteins, which may provide new insights into cellular mechanisms.
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Dunlop, Allan John. "Structural and functional studies of the DSC1 cell cycle transcription factor complex in fission yeast." Thesis, University of Glasgow, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.404284.
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Leon, Ronald P. "Structural and functional analysis of MCM helicases in eukaryotic DNA replication /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.
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Thesis (Ph.D. in Biophysics & Genetics, Program in Molecular Biology) -- University of Colorado Denver, 2007.Typescript. Includes bibliographical references (leaves 90-98). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;
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Liaci, Antonio Manuel [Verfasser], and Thilo [Akademischer Betreuer] Stehle. "Structural and Functional Studies on the Early Steps of Polyomavirus and Adenovirus Life Cycles / Antonio Manuel Liaci ; Betreuer: Thilo Stehle." Tübingen : Universitätsbibliothek Tübingen, 2019. http://d-nb.info/1199545732/34.
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Sontheimer, Jana [Verfasser], M. Teresa [Akademischer Betreuer] Pisabarro, Francis [Akademischer Betreuer] Stewart, and Frank [Akademischer Betreuer] Buchholz. "Functional characterization of proteins involved in cell cycle by structure-based computational methods / Jana Sontheimer. Gutachter: Francis Stewart ; Frank Buchholz. Betreuer: M. Teresa Pisabarro." Dresden : Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2012. http://d-nb.info/1068443146/34.
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Lavergne, Céline. "Rôle (structure et fonction) des communautés procaryotes (bactéries et archées) dans le cycle de l’azote d’une vasière littorale du Pertuis Charentais : influence des facteurs biotiques et abiotiques par une approche multi-échelle." Thesis, La Rochelle, 2014. http://www.theses.fr/2014LAROS034/document.
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Dans les vasières intertidales dominées par les diatomées, la production primaire est particulièrement forte à marée basse. Ce microphytobenthos peut être limité par les nutriments azotés en lien avec les communautés de procaryotes impliquées dans le cycle de l’azote. Ainsi, ce travail de thèse cherche, via une approche écologique, à décrire le rôle des communautés de procaryotes benthiques notamment liées au cycle de l’azote et ce, suivant différentes échelles temporelles liées aux cycles du microphytobenthos. Des échantillons de sédiment ont été prélevés dans la baie de Marennes-Oléron (Côte Atlantique, France) entre 0 et 10 cm de profondeur suivant 5 couches (0-0,5 cm, 0,5-1 cm, 1-2 cm, 2-5 cm, 5-10 cm). Différents facteurs biotiques et abiotiques ont été mesurés et mis en relation avec la production bactérienne, les activités enzymatiques et les gènes fonctionnels liés au cycle de l’azote (impliqués dans la nitrification, la dénitrification et l’anammox). De plus, la diversité bactérienne et archéenne a été évaluée par pyroséquençage 454 afin de caractériser les communautés et leurs dynamiques en lien avec les facteurs forçants biotiques et abiotiques. Dans le but d’évaluer l’influence des paramètres abiotiques et de la production du microphytobenthos, des mesures in situ ont été couplées avec des mesures en conditions semi-contrôléesIn diatoms-dominated intertidal mudflats, at low tide the primary production is particularly high and microphytobenthos that can be limited by nitrogen-related nutrients is linked with N-related prokaryotic communities. Thus, this PhD thesis aim at describing by ecological approach, the role of benthic prokaryotic communities especially N-related ones, at various temporal scales linked to microphytobenthos life cycles. Sediment samples from Marennes-Oleron mudflat (Atlantic coast, France) were collected according to 5 layers : 0-0.5 cm, 0.5-1 cm, 1-2 cm, 2-5 cm and 5 to 10 cm below sediment surface (bsf). Various biotic (i.e. chlorophyll a) and abiotic parameters (i.e. nutrients, exopolymeric substances, water content, salinity, pH, temperature…) were recorded and linked with benthic bacterial production, enzymatic activities and N-related functional genes (i.e. implied in nitrification, denitrification, and anammox). Furthermore, the bacterial and archaeal diversity was assessed by 454 pyrosequencing in order to characterize the communities and shift in link with biotic and abiotic drivers. Aiming at evaluating the influence of abiotic parameters and microphytobenthic activities on the prokaryotic communities, in situ measurements were coupled to a semi-controlled approach
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Muszynski, Bartosz. "Structure Function Studies of Rotavirus NSP5." Doctoral thesis, Scuola Normale Superiore, 2008. http://hdl.handle.net/11384/85974.
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Rotaviruses, causative agents of gastroenteritis in young animals and humans, are
large icosahedral viruses with a complex architecture. The double-stranded RNA (dsRNA)
genome composed of 11 segments, that codes for 6 structural and 6 non-structural proteins, is
enclosed within three concentric capsid layers.
NSP5, a non structural protein, is encoded by segment 11. It is produced early in
infection and localizes in ‘viroplasms’, cytoplasmic inclusion bodies in which viral RNA
replication and packaging take place. NSP5 is essential for the replicative cycle of the virus
since, in its absence, viroplasms are not formed and viral RNA replication and transcription
do not occur.
NSP5 is known to undergo two different types of posttranslational modifications, a
cytoplasmic O-glycosylation and phosphorylation, which lead to the formation of proteins
differing in electrophoretic mobility. Although the hyperphosphorylation process of NSP5
seems to be very complex, its role in the replicative cycle of rotavirus is unknown.
We demonstrated that NSP5 operates as an auto-regulator of its own phosphorylation
as a consequence of two distinct activities of the protein: substrate and activator. In the first
part of the thesis we have shown, that phosphorylation of Ser-67 within the SDSAS motif
(amino acids 63-67) was required to trigger hyperphosphorylation by promoting the activation
function. The evidence coming from iv vitro experiments, including kinase assay with
recombinant casein kinase 1α from zebrafish, proved that this enzyme is responsible for a key
phosphorylation step that initiates the whole hyperphosphorylation cascade of NSP5.
In the second part of the dissertation, using MALDI TOF/TOF spectroscopy, we added
new data to the information about the posttranslational modifications of NSP5. We confirmed
that the region of the protein encompassing Ser-67 is phosphorylated in vivo. Additionally we
managed to map which parts of NSP5 sequence carries N-acetyloglucosamine and which
regions bear phosphorylated serines or threonines.
There is no evidence about structure of NSP5 so far. In the last chapter we focused on
investigating the structural organization of this crucial viral protein. To achieve this, in
addition to the full length protein, one point mutation and two different truncation mutants
were constructed, expressed, purified and refolded. The secondary structure of the different
proteins was analyzed by circular dichroism spectroscopy and general information about
protein conformation was provided. Our findings, together with an analysis of NSP5 sequence
indicate that NSP5 can be an intrinsically unfolded/disordered protein.
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Mouchet, Maud. "Structure fonctionnelle des assemblages ichtyologiques le long de gradients environnementaux (système lagunaire de Patos-Mirim, Brésil)." Thesis, Montpellier 2, 2010. http://www.theses.fr/2010MON20143.
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Les écosystèmes procurent de nombreux services essentiels aux sociétés humaines à travers les effets positifs de la biodiversité des communautés d'espèces. Par conséquent, identifier le rôle des organismes vivants et les facteurs influençant la diversité de leurs fonctions (ou diversité fonctionnelle), est indispensable pour prédire efficacement l'évolution des écosystèmes soumis aux pressions locales et globales.Cette thèse s'articule donc autour de deux axes: (i) établir un cadre méthodologique pour décrire la structure fonctionnelle locale et régionale des communautés, et (ii) améliorer la connaissance de l'impact des poissons sur la dégradation de la matière organique.Dans un premier temps, nous avons consolidé les outils méthodologiques permettant (i) d'améliorer la fiabilité des dendrogrammes fonctionnels, (ii) l'étude comparative des principaux indices de diversité fonctionnelle à l'échelle locale, et (iii) le développement d'une nouvelle décomposition de la diversité fonctionnelle en composantes locale (α), régionale (γ) et turnover (β). Appliqué aux communautés ichthyologiques échantillonnés le long d'un gradient de salinité, dans le système lagunaire de Patos-Mirim (Brésil), ce socle méthodologique nous a permis de révéler une structure fonctionnelle stable le long du gradient, en dépit d'une forte variabilité en composition d'espèces, ces communautés étant structurées majoritairement par un filtre environnemental agissant sur les capacités de locomotion des poissons.Dans un second temps, nous avons étudié l'impact des communautés ichthyologiques sur le cycle des nutriments. Plus précisément, nous avons estimé le potentiel de dégradation de la matière organique de plusieurs espèces de poissons, en étudiant la diversité fonctionnelle et génétique de leur flore bactérienne intestinale. Nous avons montré que les communautés ichthyologiques pouvaient influencer le recyclage des nutriments de façon non négligeable en raison d'un important potentiel de dégradation commun à la plupart des espèces étudiées, ce potentiel étant peu affecté par la diversité génétique ou les facteurs environnementauxEcosystems provide many services essential to Human societies through the positive effects of biodiversity exhibited by species communities. Therefore, identifying the role of living organisms and the factors influencing the diversity of their functions (i.e. functional diversity) is fundamental to accurately predict the evolution of ecosystems undergoing local and global pressures.This thesis is organized around two axes: (i) establishing a methodological framework to describe the functional structure of local and regional communities, and (ii) improving our knowledge of the impact of fish on the degradation of organic matter.First, we have consolidated the methodological tools through (i) the improvement of functional dendrograms reliability, (ii) the comparative study of the main indices estimating local functional diversity, and (iii) the development of a new decomposition of functional diversity into local (α) and regional (γ) components, and functional turnover (β). Applied to fish assemblages sampled along a salinity gradient in Patos-Mirim lagoons complex (Brazil), this methodological framework allowed us to reveal a steady functional structure, despite a high variability in species composition, these communities being primarily structured by environmental filtering acting on fish locomotion abilities. In a second step, we studied the impact of fish communities on nutrient cycling. More specifically, we estimated degradation of organic matter potential of several fish species by studying the genetic and functional diversity of their intestinal bacterial flora. We showed that the fish community could significantly influence nutrient cycling through an important degradation potential, common to most species studied, which is weakly affected by genetic diversity or environmental factors
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Samson, Samantha. "Profilage in silico de la protéine multifonctionnelle Mfd, une cible thérapeutique innovante dans la lutte contre l'antibiorésistance bactérienne." Electronic Thesis or Diss., université Paris-Saclay, 2024. http://www.theses.fr/2024UPASL125.
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Face à la montée préoccupante de la résistance aux antibiotiques, la recherche de nouveaux antimicrobiens constitue un enjeu de santé urgent. Nous avons identifié la protéine bactérienne Mutation Frequency Decline (Mfd) comme étant une cible thérapeutique innovante pour le développement de nouveaux médicaments. Un criblage in silico à haut débit a été réalisé, dans un premier temps, afin de sélectionner des molécules pouvant se lier spécifiquement au site actif de la protéine et inhiber son activité, empêchant donc la résistance bactérienne face au stress immunitaire de l'hôte. Les molécules identifiées se sont révélées efficaces in vitro et efficaces et non toxiques in vivo, dans un modèle d'infection chez l'insecte, sur au moins deux pathogènes bactériens. Ces données préliminaires ont constitué une preuve de concept du potentiel innovant de ces molécules et ont également servi de base aux travaux présentés dans cette thèse.L'objectif principal de ce travail était l'identification des interactions moléculaires critiques entre ces molécules inhibitrices et le site actif de Mfd chez E. coli, ainsi que l'élargissement de cette analyse aux pathogènes prioritaires du groupe ESKAPE. En conséquence de quoi, un modèle optimal d'inhibiteur a été déterminé et ses dérivés sont actuellement testés in vitro et in vivo en tant que potentiels agents antimicrobiens. En parallèle, l'analyse de la séquence et de la structure de Mfd, provenant de souches environnementales et cliniques, met en évidence les caractéristiques d'une corrélation moléculaire entre la séquence de Mfd et le phénotype de virulence du pathogène. La confirmation in vitro est actuellement en cours d'évaluation. Enfin, mon objectif final est de repositionner la fonction motrice de Mfd dans un cadre plus large de remodelage conformationnel et fonctionnel afin de mieux comprendre cette cible et son rôle dans la réparation par excision de nucléotides. En produisant plusieurs simulations de dynamique moléculaire sur des « linkers » clés qui relient les principaux modules fonctionnels de Mfd, l'investigation de leur flexibilité intrinsèque et de leur conservation vise à récapituler le remodelage extensif des conformations de Mfd au cours de son cycle fonctionnel, tel qu'il a été décrit précédemment par cryo-EM. Cela a pour but de documenter dans quelle mesure ces linkers, qui relient cette protéine multi-modulaire, sont plus que de simples "connecteurs" et portent, dans leur séquence et leur longueur, des propriétés internes leur permettant d'adopter des états discrets garantissant la transition boucle-hélice nécessaire au bon fonctionnement de MfdIn an alarming context of antibiotic resistance, the search for new antimicrobials is an urgent health issue. We had identified the bacterial protein Mutation Frequency Decline (Mfd) as an innovative target for the development of new drugs. A high throughput in silico screening was initially performed in order to select molecules specifically binding to the active site of the target and inhibiting its activity, thereby preventing bacterial resistance to host immune stress. The identified hits were shown to be efficient in vitro and efficient and non-toxic in vivo, in an insect model of infection on at least two bacterial pathogens. These preliminary data have constituted a proof of concept of the innovative potential of these hits and were also the basis of this thesis.The main objective of this work was the identification of the critical molecular interaction found between those hits and the active site of Mfd in E. coli and also enlarged to the priority pathogens of the ESKAPE group. As a result, an optimal inhibitor scaffold was determined and its derivatives are currently tested in vitro and in vivo as potential antimicrobial agents. In parallel, the sequence and structure analysis of Mfd, from environmental and clinical strains, showcase the basic features of a molecular correlation between Mfd sequence and virulence phenotype. The in vitro confirmation is currently being evaluated. Finally, my goal reposition this motor function of Mfd into a larger conformational and functional remodeling of Mfd in order to get a better understanding of this target and its role in the Nucleotide Excision Repair. Using molecular dynamics simulation on distinguished linkers that connect the main functional modules of Mfd, the investigation of their intrinsic flexibility and resilience to recapitulate the extensive remodeling of Mfd conformations within its functional cycle that has been previously described by cryo-EM. This aims to document to which extent the linkers that connect this multi-module protein are more than "linkers" and harbor, in their sequence and length, internal properties to adopt discrete states that guarantee disorder-to-coil transition to assure the functional machinery of Mfd
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Brown, N. R. "Structural studies of cell cycle proteins." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299526.
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Gountouna, Viktoria-Eleni. "Multicentre structural and functional MRI." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/9536.
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Neuroimaging techniques are likely to continue to improve our understanding of the brain in health and disease, but studies tend to be small, based in one imaging centre and of uncertain generalisability. Multicentre imaging studies therefore have great appeal but it is not yet clear under which circumstances data from different scanners can be combined. The successful harmonisation of multiple Magnetic Resonance Imaging (MRI) machines will increase study power, flexibility and generalisability. I have conducted a detailed study of the performance of three research MRI scanners in Scotland under the name CaliBrain, with the aims of developing reliable, valid image acquisition and analysis techniques that will facilitate multicentre MRI studies in Scotland and beyond. Fourteen healthy volunteers had two brain scans on each of three 1.5T MRI research machines in Aberdeen, Edinburgh and Glasgow. The scans usually took place 2-3 weeks apart. Each scan was performed using an identical scanning protocol consisting of a detailed structural MRI (sMRI) and a range of functional MRI (fMRI) paradigms. The quality assurance (QA) of scanner performance was monitored in all three sites over the duration of the study using a three-part protocol comprising a baseline assessment, regular measures and session specific measures. The analyses have demonstrated that the data are comparable but also that within- and between-scanner variances are evident and that harmonisation work could enhance the level of agreement. The QA data suggest that scanner performance was similar between and within machines over the course of the study. For the structural MRI scans an optimised methodology was utilised to minimise variation in brain geometry between scanners and fit all the scanned brains into a common stereotactic space, such that repeated measures analyses yielded no significant differences over time for any of the three scanners. I examined the reproducibility of the fMRI motor task within and between the three sites. Similar results were obtained in all analyses; areas consistently activated by the task include the premotor, primary motor and supplementary motor areas, the striatum and the cerebellum. Reproducibility of statistical parametric maps was evaluated within and between sites comparing the activation extent and spatial agreement of maps at both the subject and the group level. The results were within the range reported by studies examining the reproducibility of similar tasks on one scanner and reproducibility was found to be comparable within and between sites, with between site comparisons often exceeding the within site measures. A components of variance analysis showed a relatively small contribution of the factor site with subject being the main source of variation. Similar results were obtained for the working memory task. The analysis of the emotional face processing task showed poor reproducibility both within and between sites. These findings suggest that multicentre structural and functional MRI studies are feasible, at least on similar machines, when a consistent protocol is followed in all participating scanning sites, a suitable fMRI task is employed and appropriate analysis methods are used.
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Nagra, Manbir K. "Myopia : structural and functional correlates." Thesis, Aston University, 2010. http://publications.aston.ac.uk/10048/.
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Ocular dimensions are widely recognised as key variants of refractive error. Previously, accurate depiction of eye shape in vivo was largely restricted by limitations in the imaging techniques available. This thesis describes unique applications of the recently introduced 3-dimensional magnetic resonance imaging (MRI) approach to evaluate human eye shape in a group of young adult subjects (n=76) with a range of ametropia (MSE= -19.76 to +4.38D). Specific MRI derived parameters of ocular shape are then correlated with measures of visual function. Key findings include the significant homogeneity of ocular volume in the anterior eye for a range of refractive errors, whilst significant volume changes occur in the posterior eye as a function of ametropia. Anterior vs. posterior eye differences have also been shown through evaluations of equivalent spherical radius; the posterior 25% cap of the eye was shown to be relatively steeper in myopes compared to emmetropes. Further analyses showed differences in retinal quadrant profiles; assessments of the maximum distance from the retinal surface to the presumed visual axes showed exaggerated growth of the temporal quadrant in myopic eyes. Comparisons of retinal contour values derived from transformation of peripheral refraction data were made with MRI; flatter retinal curvature values were noted when using the MRI technique. A distinctive feature of this work is the evaluation of the relationship between ocular structure and visual function. Multiple aspects of visual function were evaluated through several vehicles: multifocal electroretinogram testing, visual field sensitivity testing, and the use of psychophysical methods to determine ganglion cell density. The results show that many quadrantic structural and functional variations exist. In general, the data could not demonstrate a significant correlation between visual function and associated measures of ocular conformation either within or between myopic and emmetropic groups.
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Hofmann, Lukas. "Structural Endeavors in the Retinoid (Visual) Cycle." Case Western Reserve University School of Graduate Studies / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1497045464455384.
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Kougoulis, Ioannis-Stefan. "Symmetric functional modeling in life cycle assessment." Aachen Shaker, 2008. http://d-nb.info/999723227/34.
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Boart, Patrik. "Life cycle simulation support for functional products /." Luleå, 2005. http://epubl.luth.se/1402-1757/2005/20.
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Kougoulis, Ioannis-Stefean. "Symmetric functional modeling in life cycle assessment." Aachen Shaker, 2008. http://d-nb.info/98922015X/04.
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Azeem, Muhammad. "Structure-function analysis of the key cell cycle regulator CDKB2 in Arabidopsis." Thesis, Strasbourg, 2012. http://www.theses.fr/2012STRAJ012.
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Le cycle cellulaire est fermement contrôlé par l’activité de kinases cycline dépendantes (CDKs). Les CDKs d’Arabidopsis, plante à fleur, ont été classées en six types, parmi lesquels les CDKs de type A- et B- sont les acteurs pajeurs du cycle cellulaire végétal. Les CDKs de type B sont spécifiques aux plantes, alors que les CDKs de type A sont des homologues fonctionnels des cdc2/Cdc28p de levure et contiennent un motif conservé PSTAIRE. Il a récemment été observé que, même si les plantes mutantes cdka;1-/- sont viables, elles sont naines et ne peuvent survivre en culture sur sol. La restauration de cette croissance en terre de culture peut néanmoins être obtenue par expression des CDKs de type B. Mais ce sauvetage est incomplet et n’a pu être observé que pour l’expression de CDKB1 et non CDKB2. Ce résultat soulignant le fait que les CDKA;1, CDKB1 et CDKB2 ont des fonctions différentes. Ici, nous avons réalisé une analyse de corrélation entre structure et fonction en échangeant des acides aminés clefs ou domaines entres ces différentes kinases. Les résultats obtenus ont mis en exergue le fait que la structure dans son intégralité est importante pour la fonction de chaque CDK et que les domaines ne peuvent être facilement échangés au sein des différentes CDKs. De plus, la non complémentation des plantes mutantes cdka;1-/- par l’expression des protéines cdc2/CDC28 de levure ou Cdk1 et Cdk2 humaines, démontre le rôle spécifique de la CDK1;1 de plante. Fait intéressant, des plantes qui surexpriment CDK2;2 montrent une croissance accélérée du système racinaire et aérien conduisant à une floraison précoce de 10-15 jours par rapport à une plante sauvage et à une augmentation significative du poids sec de la partie aérienne de la plante et de ses graines. Ces dernières, semées et cultivées sur un milieu contenant de la Bléomycine (composé domageant l’ADN) ont à nouveau montré une meilleure croissance racinaire que des plantes sauvages. Ce résultat indique donc que la répression de l’expression des protéines CDKB2 suivant des dommages à l’ADN n’est pas essentielle. La modulation de l’activité des protéines CDKB2 représente ainsi une nouvelle possibilité d’augmenter la croissance végétale en condition de culture rudeThe cell cycle is tightly controlled through the activities of cyclin-dependent kinases (CDKs). CDKs in the flowering plant Arabidopsis have been classified into six types, among which the A- and B-type CDKs are key players of the plant cell cycle. While B-type CDKs are plant specific, A-type CDKs are functional homologs of yeast cdc2/Cdc28p and contain a conserved PSTAIRE motif. It has been recently observed that, although cdka;1-/- mutant plants are viable, they are extremely dwarfed and cannot survive on soil.. Growth on soil of cdka;1-/- mutants can be restored by the expression of B-type CDKs. However, this rescue was incomplete and was only observed when CDKB1 and not CDKB2 was expressed. These results pointed at distinct features of the three kinases CDKA;1, CDKB1, and CDKB2. Here, exchanging key amino acids and swapping domains between these kinases performed a structure-function analysis. However, the obtained results emphasize that structural integrity of each CDK is delicate and that individual domains cannot be easily exchanged between different CDKs. Moreover, the failure of yeast cdc2/CDC28 and human Cdk1 and Cdk2 to rescue cdka;1-/- mutants stresses the plant specific role of CDKA;1. Interestingly, plants expressing CDKB2;2 showed accelerated growth of the root and the shoot leading to flowering at approximately 10-15 days earlier than the wild type with a significant increase in aboveground dry biomass and seed weight. Remarkably, the roots of CDKB2;2 overexpression lines grew even on DNA damage-inducing media faster than wild-type roots, indicating that the previously observed down-regulation of CDKB2 expression after DNA damage is not essential in the DNA damage response. Thus, modulation of CDKB2 activity represents a novel possibility to enhance plant growth even on adversary conditions
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Li, Zhuo. "Structure and function of hip, an attenuator of the Hsp70 chaperone cycle." Diss., Ludwig-Maximilians-Universität München, 2014. http://nbn-resolving.de/urn:nbn:de:bvb:19-166974.
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Badar, Muhammad, and Ansir Iqbal. "Polya's Enumeration Theorem : Number of colorings of n-gons and non isomorphic graphs." Thesis, Linnaeus University, School of Computer Science, Physics and Mathematics, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-6199.
Full textAbstract:
Polya’s theorem can be used to enumerate objects under permutation groups. Using grouptheory, combinatorics and some examples, Polya’s theorem and Burnside’s lemma arederived. The examples used are a square, pentagon, hexagon and heptagon under theirrespective dihedral groups. Generalization using more permutations and applications tograph theory.Using Polya’s Enumeration theorem, Harary and Palmer [5] give a function whichgives the number of unlabeled graphs n vertices and m edges. We present their work andthe necessary background knowledge.
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Karlsson, Anders. "Structural and functional properties of transthyretin." Doctoral thesis, Umeå universitet, Umeå centrum för molekylär patogenes (UCMP) (Teknisk-naturvetenskaplig fakultet), 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1507.
Full textAbstract:
The hereditary transthyretin (TTR) amyloidoses are rare, and in severe cases, fatal disorders caused by mutations in the TTR gene. The clinical picture is diverse, involving neuropathies and myopathies, and mainly depends on the causative mutation and the sites and rates of amyloid deposition. The ultimate aim of the field of research presented in this thesis is to prevent TTR amyloid disease. To reach this ambitious goal, a thorough understanding of the normal as well as the pathological properties of the protein is essential. Here, comparisons between TTR from humans and other species may provide valuable information. The three-dimensional structure of TTR from Gilthead sea bream (Sparus aurata) was determined at 1.75 Å resolution by X-ray crystallography, and was found to be structurally similar to human TTR. However, significant differences were observed in the area at and around β-strand D, an area believed to dissociate from the structure prior to amyloid formation, thereby allowing the β-strands A and B to participate in polymerization. During evolution, the preference of TTR for the thyroid hormones, 3,5,3’-triiodo-L-thyronine (T3) and 3,5,3’,5’-tetraiodo-L-thyronine (T4), has shifted. While human TTR has higher affinity for T4, the opposite is true in lower vertebrates, e.g. fish and reptiles, where T3 is the main ligand. We have determined two separate structures of sea bream TTR in complex with T3 and T4, both at 1.9 Å resolution, as well as the complex of human TTR with T3. A significantly wider entrance and narrower thyroid hormone binding channel suggest a structural explanation to the differences in thyroid hormone preference between human and piscine TTR. The Tyr114Cys substitution in TTR is associated with severe systemic amyloidosis. The mutation introduces a second cysteinyl group in the TTR monomer, and has been shown to inhibit the formation of fibril formation in vitro, promoting the formation of disulfide-bonded amorphous aggregates. To deduce the role of intermolecular disulfide bonds in fibril formation we characterized the TTR Cys10Ala/Tyr114Cys double mutant. Our results suggest that an intermolecular disulfide bond at position 114 enhances the exposure of Cys10, which promotes the formation of additional intermolecular disulfide-linked assemblies. Also, we were able to isolate a disulfide-linked dimeric form of this mutant that formed protofibrils in vitro, suggesting the architecture of TTR amyloid may be the result of different underlying structures rather than that of a highly stringent assembly. We have also been able to successfully adapt a method of protein pre-heating to enable crystallization, thereby succeeding in a particularly problematic protein crystallization experiment. By heating the protein solution, we succeeded in separating several forms of protein micro-heterogeneities from the properly folded protein species, thereby allowing the growth of well diffracting crystals.Ärftlig transthyretinamyloidos är en ovanlig och i allvarliga fall dödlig proteininlagringssjukdom som orsakas av mutationer i genen för transthyretin. Den kliniska bilden är huvudsakligen beroende av den bakomliggande genförändringen samt amyloidlokaliseringen och -depositionshastigheten och omfattar vanligen neuropatier och myopatier av varierande grad. Det slutgiltiga målet med forskningsfältet som presenteras i denna avhandling är att förhindra eller bota transthyretinamyloidos. En förutsättning för att lyckas med detta ambitiösa mål är en ingående förståelse för proteinets grundläggande egenskaper, såväl i normalfallet som i de patologiska processerna, bland annat genom jämförande studier av humant och icke-humant transthyretin (TTR). Den tredimensionella röntgenkristallografiska strukturen av TTR från fisken guldsparid (Sparus aurata) bestämdes till en upplösning på 1,75Å och befanns vara strukturellt snarlik humant TTR. Signifikanta skillnader observerades emellertid i och kring β-sträng D, en region som tros dissociera från huvudstrukturen innan själva bildningen av amyloid. Enligt denna hypotes leder D-strängsdissociationen till exponering av β-strängarna A och B, vilka därmed kan delta i de reaktioner som bildar amyloid. Under evolutionen har bindningspreferenserna för thyroideahormonerna T3 (3,5,3’-trijod-L-thyronin) och T4 (3,5,3’,5’-tetrajod-L-thyronin) hos TTR ändrats. Humant TTR har högre affinitet för T4 än för T3, medan det motsatta förhållandet gäller för lägre vertebrater, t ex fisk, där T3 är den huvudsakliga liganden. Strukturerna bestämdes för guldsparid i komplex med T4 och med T3 till 1,9 Å upplösning, samt för humant TTR i komplex med T3 till 1,7 Å upplösning. Jämförande analyser visade på signifikanta skillnader i thyroideahormonbindningskanalen, vilken var vidare och grundare i fisk än i människa. Dessa strukturella skillnader kan delvis förklara olikheterna i hormonbindning mellan högre och lägre vertebrater. Substitutionen Tyr114Cys i TTR är kopplad till en allvarlig form av systemisk transthyretinamyloidos. Mutationen introducerar en andra cysteinylgrupp i TTR-monomererna, vilket förhindrar fibrillbildning in vitro, men gynnar bildningen av amorfa disulfidbundna aggregat. För att närmare studera betydelsen av disulfidbindningar vid fibrillbildning av detta protein så karakteriserades dubbelmutanten TTR Cys10Ala/Tyr114Cys. Baserat på våra resultat föreslår vi att intermolekylära disulfidbindningar i position 114 ökar exponeringen av Cys10, vilket förstärker tendensen att bilda ytterligare disulfidbundna aggregat. Vi isolerade även en disulfidbunden dimerisk form av dubbelmutanten som kan bilda protofibriller in vitro. Baserat på denna observation föreslår vi att transthyretinamyloids underliggande arkitektur är sammansatt och kan nås genom sammanfogning av olika substrukturer snarare än genom en strikt ordnad uppbyggnad. Vi har också modifierat och anpassat en metod för uppvärmning av proteiner för att möjliggöra kristallisation i ett synnerligen problematiskt proteinkristallisations-experiment. Genom uppvärmning av proteinlösningen lyckades vi separera olika former av mikroheterogeniteter från det rättveckade proteinet, som sedan bildade kristaller av god röntgendiffraktiv kvalitet.
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Smith-Forrester, Jenna Rae. "Structural and functional imaging of tauopathies." Thesis, University of British Columbia, 2015. http://hdl.handle.net/2429/54109.
Full textAbstract:
Repetitive head trauma is a known cause of tau protein accumulation and the leading cause of chronic traumatic encephalopathy (CTE). Currently, no robust method for in vivo detection of CTE exists and definitive diagnosis can only be made post-mortem. This thesis aimed to address two gaps in the literature surrounding head injury and tau accumulation. First, we sought to evaluate the effects of concussion on adolescent brain structure using mathematical modeling applied to diffusion tensor imaging (DTI). In our study, 12 adolescent athletes completed DTI in the sub-acute phase of recovery from concussion. The primary outcome measures included Complex Network Analysis metrics related to efficiency, nodal clustering, and fibre tract length. These measures were applied to diffusivity output (FA, MD, and number of tracts) in subnetworks of vulnerability, with specific focus on the Default Mode Network (DMN). Here we found microstructural changes in the DMN of concussed athletes with increased clustering and shorter path lengths, indicating increased local efficiency. A corresponding decrease in global efficiency and alterations in core hubs may underlie the clinical profile, suggesting concussion results in large-scale network disconnection. Longitudinal studies with network analysis may serve as a marker of collective injury and provide early detection of pathological structural organization. Second, we established the baseline measures of a novel positron emission tomography (PET) radioligand, ¹¹C-PBB3, which is specific for hyperphosphorylated tau protein. We collected data on healthy, elderly individuals (n = 8), and tested the tracer in a probable (n = 1) and severe (n = 1) case of Progressive Supranuclear Palsy (PSP), a known tauopathy. We found that tracer circulated in the venous sinuses in our healthy controls with little to no deposition in brain tissue. We also present preliminary findings of tracer accumulation in the basal ganglia and thalamus in the PSP cases. These results suggest ¹¹C-PBB3 is a viable tracer for use in other tauopathies, including CTE. Longitudinal studies with combined DTI and PET are necessary to elucidate the potentially synergistic interactions between damage to white matter tracts, tau accumulation, inflammation, and the initiation of processes leading to CTE and other tauopathies.Medicine, Faculty of
Graduate
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Zhu, Ling. "Structural and functional study of picornaviruses." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:b589c6fd-daab-427b-b246-1ebec5431bf9.
Full textAbstract:
Picornaviruses are responsible for a variety of human and animal diseases, ranging from hepatitis A, foot and mouth disease, through polio to hand-foot-and-mouth disease and the common cold. In addition to their importance in causing diseases, they also serve as models for understanding the basic mechanisms of host-pathogen interactions, virus entry and viral genome release. Although the structure of a number of picornaviruses from the Entero, Cardio, Aphtho and Senecavirus genera have been determined at close to atomic resolution with X-ray crystallography, structural and functional studies on Parecho, Kobu and Hepatovirus are very limited. I have thus studied members of these genera: Ljungan virus, Aichi virus and hepatitis A virus to further understanding of the molecular basis of pathogenesis, viral entry, assembly and stability for these viruses in particular and for picornaviruses in general. In addition I have studied the VLPs of CVA16 as potential vaccine candidates. The atomic structure of Ljungan virus determined by cryo-EM, shows remarkable features, including an extended VP1 C-terminus, forming a major protuberance on the outer surface of the virus, and a basic motif at the N-terminus of VP3, which orders some 12% of the viral genome. This charge-driven RNA attachment suggests that this branch of the picornaviruses use a different mechanism of genome encapsidation. The cryo-EM structure of Aichi virus at 3.7 Ã
resolution is intermediate between the enteroviruses and cardioviruses. On the outer surface a polyproline helix structure, not seen previously in picornaviruses is present at the C-terminus of VP1, corresponding to the position where integrin binding motifs are found in some other picornaviruses. A peptide corresponding to this polyproline motif somewhat attenuates virus infectivity suggesting a role in attachment to a cellular receptor. The cryo-EM structure of a complex between hepatitis A virus and a potent neutralizing antibody, together with other data suggest that this antibody mimics receptor binding. 2A proteins from Ljungan virus, Sebokele virus and human parechovirus play a different role in these viruses compared to other members of the picornavirus family and the X-ray structures of these proteins reveal incredible plasticity and an H-box motif that may not be catalytically active. In summary, this thesis provides an insight into some important aspects of host-virus interactions especially the events occurring during viral assembly and receptor recognition.
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Vinson, Mary. "Structural and functional studies on sialoadhesin." Thesis, University of Oxford, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362115.
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Hansen, Soren Prag. "Structural and functional analysis of muskelin." Thesis, University College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.408222.
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Kerai, Preeti. "Structural and functional characterisation of PKCI." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325029.
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Wharton, J. T. "Structural functional surface design and manufacture." Thesis, Liverpool John Moores University, 2018. http://researchonline.ljmu.ac.uk/7782/.
Full textAbstract:
The main purpose of this investigation was to explore the potential benefits of structural functional surfaces using facilities available within the University. The potential benefits were demonstrated by applying functional surfaces to a set of particular engineering applications. The thesis mainly concentrated on improving the frictional performance of a surface structure for hydrodynamic bearing application. This thesis has also included some preliminary investigation into drag-reducing riblet structures but this chapter mainly discusses the development of a novel experimental apparatus which is needed for precise boundary layer profile measurements and also to obtain the actual surface drag for each sample. To be able to assess these surfaces experimentally, they first, have to be manufactured. So, an extensive literature review of current manufacturing technologies was carried out. Each manufacturing method was ranked in its ability to cost-effectively produce surfaces with accuracy and repeatability also being considered. It was concluded that rolling, currently, has the best ability to structure large surface areas with the lowest costs associated. Other manufacturing methods, such as laser surface texturing, provide excellent repeatability and accuracy as well as the ability to create complex surface structures but is incredibly time-consuming for large surface areas. It was suggested that a hybrid of multiple manufacturing technologies would be incredibly useful for structuring surfaces. By combining rolling with more elaborate surface texturing methods (i.e. use a method such as LST to texture the roller surface), it is possible to amplify the productivity of less efficient methods, substantially. Before any journal components were textured, it was decided to test a batch of ground components. These components were finished with an abrasive tape process. The process parameters were varied for each sample and by doing this, a set of components with different roughness characteristics should have been obtained. The components were measured for 2D roughness parameters, 3D roughness parameters and surface energy. The components were tested on a tribometer apparatus in order to obtain a coefficient of friction (COF) for each sample. Correlation coefficients were then generated for the different surface measurements against COF, so that any strong correlations or trends could be identified. The idea was to try and obtain a reliable performance indicator (PI) so that frictional losses could be identified. It was found that the roughness parameters Sc (core void voume), Ssc (mean summit curvature) and Rku/Sku (profile/surface kurtosis) showed promise in the ability to predict the performance of a surface. The next stage was to texture the surface of the journal component. This would done by the application of the type III texturing grinding process, described by Stepien (Surface Engineering, 24: 219-225), to the cylindrical grinding process. Some initial components were manufactured and the textures generated were found to be of an ellipsoidal shape. In order to guarantee the benefits of such surfaces, the configuration of the surface pattern has to be optimised. A python script was developed during this investigation in order to automate a full modelling process. The computational fluid dynamics (CFD) modelling used a full 3D Navier-Stokes approximation. This script was used in conjunction with the Taguchi optimisation technique and a best surface configuration was found, resulting in a maximum surface drag reduction of 16.6% at a 3μm clearance. Further grinding trials were performed and the input parameters of the process were designed so that surface patterns were close to the recommendations of the optimisation process. The performance of the textured samples was impressive, with a maximum reduction in COF of 18.4% seen against a non-textured component with similar average roughness (Sa) value. Again, all components were measured for the aforementioned roughness parameters and surface energy. Sku continued to predict the best-performing component, showing promise as PI for both non-textured and textured samples.
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Filippetto-Manon, Florence. "Structural and functional studies of NOD1." Université Joseph Fourier (Grenoble), 2006. http://www.theses.fr/2006GRE10101.
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NOD1 est une protéine de surveillance intracellulaire jouant un rôle crucial dans la défense immunitaire innée. Suite à la reconnaissance d'un ligand bactérien spécifique, NOD1 recrute RICK au moyen d'une interaction CARO-CARO. RICK module ensuite l'activation du facteur de transcription NF-KB et initie une cascade de signalisation pro-inflammatoire. Le but de cette thèse était de déterminer la base structurale de ce processus. Le domaine CARO de NOD1 a été cloné, exprimé et purifié à la station EMBL de Grenoble. La structure de ce domaine a été résolue par résonance magnétique nucléaire à l'IBS de Grenoble. Cette structure est généralement similaire à celle des autres domaines CARO connus, étant constituée d'un paquet compact de 6 hélices a. Cependant elle présente des caractéristiques inhabituelles concernant la conformation de certaines boucles inter-hélices ainsi que la longueur et l'orientation de la sixième hélice. Des mutations dans les domaines CARDs des protéines NOD1 et RICK entières ont été réalisées pour identifier les résidus importants pour l'interaction ou la signalisation. Des expériences de co immunoprécipitation et d'activation de NF-KB ont été effectuées à l'Université du Michigan. Trois résidus d'un patch acide de NOD1 (E53, 054 et E56) et trois résidus d'un patch basique de RICK (R444, R483 et R488) sont indispensables à l'interaction, qui serait donc de nature électrostatique. Deux autres résidus du patch acide du CARO de NOD1, L44 et 157, ont été identifiés comme importants pour la signalisation. Ils peuvent potentiellement contribuer à la formation d'une interaction CARO-CARO fonctionnelle, ou bien également interagir avec d'autres régions de RICKNOD1 is a cytosolic signaling host pattern-recognition receptor playing a crucial role in innate immunity. It regulates pro-inflammatory pathways by mediating the activation of the nuclear factor NF-KB via its downstream effector RICK following the recognition of a specific bacterial ligand. RICK is recruited by NOD1 through a CARO-CARO interaction. The goal of this thesis was to determine the structural basis of this process. NOD1 CARO was cloned, expressed and purified at the Grenoble EMBL Outstation. Its structure was determined by nuclear magnetic resonance at the IBS in Grenoble. It is generally similar to other CARDs of known structure, consisting of six tightly packed a-helices, although the conformation of sorne of the inter-helical loops and the orientation and length of the last helix are unusual. Mutations in the CARO domains of both NOD1 and RICK full-Iength proteins were made in order to define residues important for CARO-CARO interaction. Co-immunoprecipitation of cell Iysates and NF-KB activation assays were performed at the University of Michigan Medical School. The results suggest that the interaction is primarily electrostatic and dependent on a patch of three acidic residues on NOD1 CARO (E53, 054, and E56) and three basic residues on RICK CARO (R444, R483 and R488). Ln addition, two amino acids L44 and 157, located in or close to the acidic patch of NOD1 were found to affect NOD1 signaling. These could be involved in the precise formation of a functional CARO-CARO interaction, or they could interact with other regions of RICK than the CARO domain
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Zaleska, Mariola Krystyna. "Structural and functional characterisation of MS1." Thesis, King's College London (University of London), 2014. http://kclpure.kcl.ac.uk/portal/en/theses/structural-and-functional-characterisation-of-ms1(bfa94533-48b0-4c9c-ac53-5fec68e4977d).html.
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MS1 (Myocyte stress 1) is a muscle specific protein, implicated in the development of cardiac muscle hypertrophy. In rat models of induced left ventricular hypertrophy, MS1 expression is increased 3 times after applying stress signal with a peak expression before day 1. It may suggest that MS1 can act as a very important stress sensor that correlates external signals with a cellular response, however its complete mode of action needs to be further elucidated. It is has been proposed that MS1 is indirectly involved in gene expression regulation through a mechanism that involves actin dynamics and SRF. However, this work will show evidence that MS1 could be directly involved in gene expression regulation through a binding of specific DNA sequences. Based on our previous structural data it was found that MS1 contains a winged helix-turn-helix domain (WHTH), a common DNA binding domain present in transcription factors. Consequently, we hypothesised that MS1 could be a DNA binding protein itself and potentially it could act as a transcription factor. This work shows that MS1 possesses almost all characteristics of a transcription factor such as presence of a DNA binding domain, nuclear localisation and binding of a specific DNA sequence. In Chapter 3 a detailed subcellular localisation of MS1 will be characterised and it will provide evidence that MS1 cytoplasmic/nuclear localisation is more complex than anticipated and that it depends on a developmental stage as well as on environmental conditions such as presence of stress factors. In Chapter 4 DNA binding properties of MS1 will be characterised and ultimately it will be shown that MS1 binds to a defined DNA sequence in a manner typical of a winged helix-turn-helix domain. The findings of this thesis expand the present knowledge about MS1 function, where apart from its involvement in actin dynamics regulation it binds DNA opening up the possibility that it may be directly involved in gene expression regulation via acting as a transcription factor.
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Pandya, Ashka Y. "Structural and functional analysis of KLF4." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2007. https://www.mhsl.uab.edu/dt/2009r/pandya.pdf.
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Holland, Arthur Ekasatrya. "Structural and functional analysis of TREX." Thesis, University of Sheffield, 2015. http://etheses.whiterose.ac.uk/8312/.
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The TREX (Transcription-Export) complex is a well-conserved assembly of proteins, which is essential in eukaryotic gene expression. The expression of mRNA involves a number of processing events of primary transcripts to form a mature mRNA. TREX functions at the interface between transcription and export, associating with transcripts at various stages during its processing and packages it into an export-competent mRNP. Export of most mRNAs is dependent on the export receptor, Nxf1. This protein is recruited to the mRNP by directly binding to TREX components. Because the association of TREX with the mRNA is dependent on accurate processing events, it serves as a quality control signal for the recruitment of Nxf1 to promote export. Furthermore, newly identified TREX8 associated factors suggest that TREX could integrate into a wide range of cellular functions and mounting evidence indicates that TREX is essential for the maintenance of genome stability. Aberrations in TREX expression cause harmful RNA:DNA hybrid structures, which are susceptible to DNA damage. TREX therefore, represents an important target for studying the regulation of gene expression.
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Wang, Junjie. "Functional and Structural Study of Pannexin1 Channels." Scholarly Repository, 2009. http://scholarlyrepository.miami.edu/oa_dissertations/207.
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Pannexins are vertebrate proteins with limited sequence homology to the invertebrate gap junction proteins, the innexins. However, in contrast to innexins and the vertebrate connexins, pannexins do not form gap junction channels. Instead they appear to solely function as unpaired membrane channels allowing the flux of molecules, including ATP, across the plasma membrane. We provided additional evidence for their ATP release function by demonstrating that the connexin mimetic peptides, which were thought to inhibit ATP release through connexin channels, do not inhibit their host connexin channels but instead inhibit pannexin1 channels by a mechanism of steric block. Therefore, the inhibitory effects of mimetic peptides on ATP release may represent supporting evidence for a role of pannexin1 in ATP release. We also analyzed the pore structure of pannexin1 channels with the Substituted Cysteine Accessibility Method. The thiol reagents MBB and MTSET reacted with several positions in the external portion of the first transmembrane segment and the first extracellular loop. In addition, MTSET reactivity was found in the internal portion of TM3. These data suggest that portions of TM1, E1 and TM3 line the pore of pannexin1 channels. Thus, the pore structure of pannexin1 is similar to that of connexin channels.
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Celebi, Hatice. "Structural And Functional Analysis Of Henry James." Master's thesis, METU, 2003. http://etd.lib.metu.edu.tr/upload/597/index.pdf.
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The aim this thesis is to analyse the narrative structure of the novel, The Portrait
of A Lady, with the aim of revealing how meaning is made and to show how certain
elements are transferred to the film version and the consequent changes in meaning and
emphasis. The structural analysis of The Portrait will chiefly rely on Shlomith Rimmon-
Kenan&rsquos scheme she draws in her book Narrative Fiction. The functional analysis to show the consequent changes in meaning and emphasis, on the other hand, will rely on Roland Barthes&rsquo
s theory of functions he discusses in his article &ldquo
Structural Analysis of Narratives&rdquo
. In order to explore the narrative structure of The Portrait of A Lady, this thesis will examine story, characterization, time and focalization and demonstrate the techniques Henry James uses in narration. In the functional analysis of the novel, on the other hand, the functions of the units discussed in the story and the characterization will be compared to the functions of the same units that are transferred to the adaptation of the novel to reveal how the meaning and emphasis of the novel changes.
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Ribas, i. de Pouplana Lluís. "Structural and functional studies on Drosophila ADH." Thesis, University of Edinburgh, 1993. http://hdl.handle.net/1842/26877.
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The enzyme alcohol dehydrogenase of the fruit-fly Drosophila (DADH) catalyzes the same reaction as mammalian alcohol dehydrogenases, transforming alcohols into aldehydes through the reduction of nicotinamide-adenine-dinucleotide. Despite this apparently identical catalytic behaviour the enzyme has a strikingly different three-dimensional architecture to the mammalian alcohol dehydrogenases. The study of the structure-function relationships of DADH is of interest because large amounts of biochemical, evolutionary and genetical data have accumulated which require structural information on the enzyme for its proper interpretation. The aim of this project was two-fold: to set up a suitable system for protein engineering studies on DADH and to start such studies by producing and analyzing a first set of site-directed mutants. The first part of the project involved: a) creating suitable genetic vectors for the introduction of mutations, their sequencing and the expression of the mutated enzymes in yeast; b) the development of a purification method to obtain pure enzyme solutions from the expressing yeast culture; c) the development of biochemical and biophysical assays for the evaluation of the effects of the mutations and, d) the construction of a three-dimensional model for the enzyme that could offer structural explanations to such effects, given that no three-dimensional structure is as yet available. The second part consisted of the actual introduction of five different point mutations, designed to test the structure of the putative cofactor binding site, and their further evaluation using the system set up in the first place.
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Runke, Gregory S. "Functional and structural studies of mitochondrial porin." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0012/MQ53217.pdf.
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Kozlenkov, Alexey. "Structural/functional studies on human alkaline phosphatases /." Umeå : Univ, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-136.
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Robson, Catherine Ruth. "Aspects of ocular structural and functional assessment." Thesis, Cardiff University, 2006. http://orca.cf.ac.uk/55449/.
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This thesis is a continuation of previous work within the Research Group and comprises an investigation of two perimetry-related topics; firstly, the role of ocular media properties on the visual field derived by Short Wavelength Automated Perimetry (SWAP); and, secondly, the perimetric assessment of patients with epilepsy treated with vigabatrin and the potential of alternative (imaging) techniques to overcome the subjective limitations of perimetry. The influence of ocular media adsorption and intra-ocular straylight on the visual field indices Mean Sensitivity, Mean Deviation, Pattern Standard Deviation and Short-term fluctuation derived by white-on-white (W-W) perimetry and by SWAP was investigated in 35 normal individuals. Approximately 62% of the variance for W-W perimetry was explained by the assessment of logMAR visual acuity in conjunction with a low contrast chart. However, no relationship was evident for SWAP. This suggests that ocular media properties are a component of the between-individual variability in SWAP but that their contribution is masked by other sources of variability. The prevalence of visual field loss associated with vigabatrin, (VAVFL), was investigated for 80 individuals with long-term exposure to vigabatrin (Mean duration 8.6 years SD3.5 and mean cumulative dose 7.6kg SD4.4). The prevalence was 62.5%; risk factors for VAVFL were treatment duration (p=0.001) and male gender (p=0.04). The ability of Optical Coherence Tomography (OCT) and confocal Scanning Laser Ophthalmoscopy (cSLO) to detect retinal damage in 21 patients exposed to VGB and 43 control patients (16 exposed to carbamazepine monotherapy, 7 exposed to sodium valproate monotherapy and 20 normals) was investigated. In patients with VAVFL, RNFL was attenuated but macular thickness was normal compared to the remaining individuals in the cohort.
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Taylor, Alexander Iain. "Structural and functional characterisation of avian IgY." Thesis, King's College London (University of London), 2007. https://kclpure.kcl.ac.uk/portal/en/theses/structural-and-functional-characterisation-of-avian-igy(243a793c-be0b-47bf-a48a-cfae4edea9e4).html.
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Gill, D. J. "Structural and functional organisation of ESCRT complexes." Thesis, University of Cambridge, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.599420.
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My structure of the highly conserved heterotrimeric ESCRT-I core provides a blueprint for the assembly of ESCRT-I. The structure shows a fan-like arrangement of three helical hairpins, each corresponding to a different subunit. Vps23/TSG101 is the central hairpin sandwiched between the other subunits, explaining the critical role of its “steadiness box” in the stability of ESCRT-I. Subsequently, Mvb12, a fourth subunit of ESCRT-I was identified in yeast. I find that Mvb12 engages ESCRT-I directly, with nanomolar affinity to form a 1:1:1:1 heterotetramer. Mvb12 plays a critical role in maintaining structural stability of the ESCRT-I complex, through extensive interactions with both the fan-shaped structural core and another region within ESCRT-I built from upstream sequences present in the Vps23 and Vps37 subunits. Yeast ESCRT-I and ESCRT-II interact directly in vitro, however, this association is not detected in yeast cytosol. To gain understanding of the molecular mechanisms of this link, I have characterised the ESCRT-I/-II super-complex and determined the crystal structure of its interface. The link is formed by the Vps28 C-terminus (ESCRT-I) binding with nanomolar affinity to the Vps36-NZF-N zinc-finger domain (ESCRT-II). A hydrophobic patch on the Vps28-CT four-helix bundle contacts the hydrophobic knuckles of the Vps36-NZF-N. Mutation of the ESCRT-I/-II link results in a cargo-sorting defect in yeast, apparently due to the failure to generate ILVs on the maturing endosome. Interestingly, the two Vps36 NZF domains, NZF-N and NZF-C, despite having the same core fold, use distinct surfaces to bind ESCRT-I or ubiquitinated cargo. Mvb12 does not affect the affinity of ESCRT-I for ESCRT-II in vitro. In contrast, deletion of Mvb12 results in formation of a constitutive ESCRT-I/II association in vivo. These data suggest a complex regulatory mechanism for the ESCRT-I/-II link in yeast.
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Swain, Gemma V. "Structural and Functional Studies of Clostridial Phospholipases." Thesis, Imperial College London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.503819.
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Ioannidou, Sofia. "Structural and functional analysis of vascular permeability." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1444750/.
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Vascular permeability and its regulation are indispensable for normal circulatory function and tissue homeostasis. When unregulated, vascular permeability contributes significantly to blood vessel related pathologies, such as cancer and diabetic retinopathy. Interposed between blood and tissues, endothelial cells become structurally and functionally differentiated, to mediate controlled permeability. The aim of this thesis work was to develop suitable systems to study two different aspects of vascular permeability, endothelial fenestrae formation and tyrosine phophatase-based regulation of paracellular permeability. Transcellular permeability describes the passage of water and macromolecules across endothelial cells. A route for transcellular permeability is provided by fenestrae, the 60 nm circular pores that span the entire thickness of highly attenuated endothelia encountered in endocrine or filtrating organs. In an attempt to gain insight into the structure and biogenesis of fenestrae I helped set up an in vitro culture system where fenestrae could be rapidly induced in cell biological and biochemical quantities. To understand the molecular composition of fenestrae I established a biochemical method for their enrichment. Subtractive proteomic analysis performed on a subcellular fraction enriched in plasma membranes revealed proteins with roles in actin filament disassembly, plasma membrane remodeling, endocytosis, and membrane to cytoskeleton linkage. One particular candidate, the membrane-cytoskeleton linker moesin, was validated as a component of fenestrae by immunocytochemical means. Paracellular permeability occurs through tight or adherens junctions that join endothelial cells. In order to understand the regulation of paracellular permeability through adherens junctions I focused on Vascular Endothelial Protein Tyrosine Phosphatase (VE-PTP), a demonstrated phosphatase modulator of the junctional protein VE-cadherin. To this end I established transgenic mice with inducible expression of wildtype or mutant VE-PTP in endothelial cells. A correlation between VE-PTP expression at the RNA level and embryonic defects suggests the potential utility of the mice as models of adherens junction dysfunction.
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Lim, Eun Jeong. "STRUCTURAL AND FUNCTIONAL STUDIES OF SYNAPTIC ENZYMES." UKnowledge, 2006. http://uknowledge.uky.edu/gradschool_diss/259.
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Thimet oligopeptidase (TOP, EC 3.4.24.15) and neurolysin (EC 3.4.24.16) are zincdependent metallopeptidases that metabolize small bioactive peptides. The two enzymes share60 % sequence identity and their crystal structures demonstrate that they adopt nearly identicalfolds. They generally cleave at the same sites, but they recognize different positions on somepeptides, including neurotensin, a 13-residue peptide involved in modulation of dopaminergiccircuits, pain perception, and thermoregulation.On the basis of crystal structures and previous mapping studies, four residues(E469/R470, M490/R491, H495/N496, and R498/T499, TOP residues listed first) in thesubstrate-binding channel appear positioned to account for differences in specificity. TOPmutated to the neurolysin residues at all four position cleaves neurotensin at the neurolysin siteand neurolysin mutated to the TOP residues at all four sites cleaves at the TOP position. Using aseries of constructs mutated at only three sites, it was determined that only two of the mutations,E469/R470 and R498/T499, are required to swap the specificity of TOP and neurolysin. Theseresults were confirmed by testing the two mutation constructs, and either single mutant of TOPshown an intermediate specificity, cleaving at both sites.Crystal structures of the two mutation constructs of TOP and neurolysin unligandedforms, the mutations do not perturb local structure, but side chain conformations at theR498/T499 position differ from those of the mimicked enzyme. A model for differentialrecognition of neurotensin based on differences in surface charge distribution in the substratebinding sites is proposed. The model is supported by finding that reducing the positive charge onthe peptide results in cleavage at both hydrolysis sites.This dissertation also includes a description of the production and crystallization trials ofhuman neprilysin (E.C. 3.4.24.11), which will be used as another model system for studyingspecificity in metallopeptidases. In addition, the production and crystallization, and crystalcharacterization of human choline acetyltransferase (EC 2.3.1.6) is described.
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Wu, QiongLi. "Sensitivity Analysis for Functional Structural Plant Modelling." Phd thesis, Ecole Centrale Paris, 2012. http://tel.archives-ouvertes.fr/tel-00719935.
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Global sensitivity analysis has a key role to play in the design and parameterization of functional-structural plant growth models (FSPM) which combine the description of plant structural development (organogenesis and geometry) and functional growth (biomass accumulation and allocation). Models of this type generally describe many interacting processes, count a large number of parameters, and their computational cost can be important. The general objective of this thesis is to develop a proper methodology for the sensitivity analysis of functional structural plant models and to investigate how sensitivity analysis can help for the design and parameterization of such models as well as providing insights for the understanding of underlying biological processes. Our contribution can be summarized in two parts: from the methodology point of view, we first improved the performance of the existing Sobol's method to compute sensitivity indices in terms of computational efficiency, with a better control of the estimation error for Monte Carlo simulation, and we also designed a proper strategy of analysis for complex biophysical systems; from the application point of view, we implemented our strategy for 3 FSPMs with different levels of complexity, and analyzed the results from different perspectives (model parameterization, model diagnosis).
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Moffett, C. L. "Structural and functional characterization of nematode neuropeptides." Thesis, Queen's University Belfast, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390877.
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Pell, Gavin. "Structural and functional analysis of Cellvibrio hemicellulases." Thesis, University of Newcastle Upon Tyne, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.413943.
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Snowden, B. W. "Structural and functional studies of herpesvirus glycoproteins." Thesis, University of Leeds, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.355709.
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Payne, Karl Alex Peter. "Structural and functional studies of aminopeptidase P." Thesis, University of Leeds, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.435785.
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