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Ferreira, Rodrigues Sara [Verfasser]. "Propagation of Tau pathology in Alzheimer disease / Sara Ferreira Rodrigues." Bonn : Universitäts- und Landesbibliothek Bonn, 2020. http://d-nb.info/121914049X/34.
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Canter, Rebecca Gail. "4D mapping of network-specific pathological propagation in Alzheimer's disease." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/107868.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2016.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 113-132).
Alzheimer's disease (AD) causes a devastating loss of memory and cognition for which there is no cure. Without effective treatments that slow or reverse the course of the disease, the rapidly aging population will require astronomical investment from society to care for the increasing numbers of AD patients. Additionally, the financial and emotional burden on families of affected individuals will be profound. Traditional approaches to the study of AD use either biochemical assays to probe cellular pathophysiology or non-invasive imaging platforms to investigate brain-wide network alterations. Though decades of research using these tools have advanced the field significantly, our increased understanding of AD has not led to successful interventions. One reason for this impediment may be that the tools used in neither approach can achieve the spatial and temporal precision necessary to study the consequences of molecular insults across the brain over time. In this thesis, I capitalize on recent advances in tissue processing technologies to gain a network-level perspective on the molecular and cellular progression of AD. First, I present optimized methods for in situ proteomic phenotyping of large-volume tissue specimens. Then, I use the techniques to map amyloid-beta (A[beta]) aggregates at the whole-brain scale across disease stages in a mouse model of AD. The spatially-unbiased, temporally-precise map demonstrates hierarchical susceptibility of increasingly large, memory-related brain networks to A[beta] deposition. Importantly, the 4D nature of the map reveals that subcortical nodes and white matter tracts of the Papez memory circuit exhibit unique, early vulnerability to A[beta] aggregates. Finally, using large-volume labeling approaches, I confirm the molecular findings by showing disease-specific A[beta] aggregation in human samples from the early hub regions. Together, this data unites desperate observations of network-level deficits and identifies critical locations of early A[beta] deposition in the brain. By linking molecular and network observations, I begin to provide biological explanations for the clinical manifestation of AD. This perspective can guide earlier patient identification and refine experimental approaches to developing cognitively efficacious treatments. These discoveries emphasize the necessity of multi-level investigations in neuroscience research and highlight the potential impacts of tools that enable researchers to bridge the gap.
by Rebecca Gail Canter.
Ph. D.
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Elizabeth, Murphy A. "UTILIZING DROSOPHILA PRIMARY NEURONS TO STUDY HUMAN TAU PROPAGATION: AN IN VITRO MODEL OF ALZHEIMER'S DISEASE." Ohio University Honors Tutorial College / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1524831015975217.
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Domert, Jakob. "Neuron-to-neuron propagation of neurodegenerative proteins; relation to degradative systems." Doctoral thesis, Linköpings universitet, Avdelningen för neuro- och inflammationsvetenskap, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-134667.
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Alzheimer’s disease (AD) and Parkinson’s disease (PD) are defined by neurodegeneration and accumulations of misfolded proteins that spread through the brain in a well characterized manner. In AD these accumulations consist mainly of β-amyloid (Aβ) and tau, while in PD, α-synuclein (α-syn) make up the characteristic lewy pathology. The general aim of this thesis was to investigate mechanisms associated with neurotoxic peptide activity by Aβ, tau and α-syn in relation to cellular degradation and transfer with a cell-to-cell transfer model system. We found that intercellular transfer of oligomeric Aβ occurs independently of isoform. However, the amount of transfer correlates with each isoforms ability to resist degradation or cellular clearance. The Aβ1-42 isoform showed particular resistance to clearance, which resulted in higher levels of cell-to-cell transfer of the isoform and lysosomal stress caused by accumulation. As Aβ accumulations can inhibit the proteasomal degradation we investigated how reduced proteasomal degradation affected neuron-like cells. We found increased levels of phosphorylated tau protein, disturbed microtubule stability and impaired neuritic transport after reduced proteasomal activity. These changes was partly linked to c-Jun and ERK 1/2 kinase activity. We could also show that α-syn transferred from cell-to-cell in our model system, with a higher degree of transfer for the larger oligomer and fibrillar species. Similar to Aβ, α-syn mainly colocalized with lysosomes, before and after transfer. Lastly, we have developed our cell-to-cell transfer system into a model suitable for high throughput screening (HTS). The type of cells have been upgraded from SH-SY5Y cells to induced pluripotent stem cells (iPSCs), with a differentiation profile more similar to mature neurons. The next step will be screening a small molecular library for substances with inhibitory effect on cell-to-cell transfer of Aβ peptides. The importance of the degradative systems in maintaining protein homeostasis and prevent toxic accumulations in general is well known. Our findings shows the importance of these systems for neurodegenerative diseases and also highlight the link between degradation and cell-to-cell transfer. To restore or enhance the degradative systems would be an interesting avenue to treat neurodegenerative diseases. Another way would be to inhibit the transfer of misfolded protein aggregates. By using the HTS model we developed, a candidate substance with good inhibitory effect on transfer can hopefully be found.
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Davidson, Andrew Doran. "Fundamental Principles of Tremor Propagation in the Upper Limb." BYU ScholarsArchive, 2016. https://scholarsarchive.byu.edu/etd/6509.
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Although tremor is the most common movement disorder, there exist few effective tremor-suppressing devices, in part because the characteristics of tremor throughout the upper limb are unknown. To clarify, optimally suppressing tremor requires a knowledge of the mechanical origin, propagation, and distribution of tremor throughout the upper limb. Here we present the first systematic investigation of how tremor propagates between the shoulder, elbow, forearm, and wrist. We simulated tremor propagation using a linear, time-invariant, lumped-parameter musculoskeletal model relating joint torques and the resulting joint displacements. The model focused on the seven main degrees of freedom (DOF) from the shoulder to the wrist and included coupled joint inertia, damping, and stiffness. We deliberately implemented a simple model to focus first on the most basic effects. Simulating tremorogenic joint torque as a sinusoidal input, we used the model to establish fundamental principles describing how input parameters (torque location and frequency) and joint impedance (inertia, damping, and stiffness) affect tremor propagation. We expect that the methods and principles presented here will serve as the groundwork for future refining studies to understand the origin, propagation, and distribution of tremor throughout the upper limb in order to enable the future development of optimal tremor-suppressing devices.
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Kim, Louis Y. (Louis Yongchul). "Estimating network structure and propagation dynamics for an infectious disease : towards effective vaccine allocation." Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/91397.
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Thesis: S.M., Massachusetts Institute of Technology, Sloan School of Management, Operations Research Center, 2014.76
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 67-72).
In the event of a pandemic influenza outbreak, such as the 2009-2010 H1N1 "Swine Flu" episode, it is crucial to effectively allocate limited resources in order to minimize the casualties. Design of effective resource allocation strategies requires good understanding of the underlying contact network and of the propagation dynamics. In this thesis we develop a parameter estimation method that learns the network structure, among a family of graphs, and disease dynamics from the recorded infection curve, assuming that the disease dynamics follow an SIR process. We apply the method to data collected during the 2009-2010 H1N1 epidemic and show that the best-fit model, among a scale-free network and a small-world network, indicates the scale-free network. Given the knowledge of the network structure we evaluate different vaccination strategies. As a benchmark, we allow the vaccination decisions to depend on the state of the epidemic and we show that random vaccination (which is the current practice), does not efficiently halt the spread of influenza. Instead, we propose vaccine allocation strategies that exploit the underlying network structure and provide a reduction in the number of infections by over 6 times compared to the current practice. In addition, more realistic scenario involves random encounters between agents. To test this hypothesis, we introduced a dynamic network formation on top of the static network model. We apply the estimation method to the dynamic network model and show a small improvement in estimating the infection dynamics of the 2009-2010 H1N1 influenza.
by Louis Y. Kim.
S.M.
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Wann, Steven R. "In vitro isolation and propagation of mammatoxin-resistant aspen." Diss., Georgia Institute of Technology, 1985. http://hdl.handle.net/1853/5742.
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Chen, Chien-Hung. "Optimization and decision strategies for medical preparedness and emergency response." Diss., Georgia Institute of Technology, 2013. http://hdl.handle.net/1853/52939.
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The public health emergencies, such as bioterrorist attacks or pandemic outbreaks, have gained serious public and government attentions since the 2001 anthrax attacks and the SARS outbreak in 2003. These events require large-scale and timely dispensing of critical medical countermeasures for protection of the general population.
This thesis research focuses on developing mathematical models, real-time algorithms, and computerized decision support systems that enable (1) systematic coordination to tackle multifaceted nature of mass dispensing, (2) fast disease propagation module to allow immediate mitigation response to on-site uncertainties, and (3) user-friendly platform to facilitate modeling-solution integration and cross-domain collaboration. The work translates operations research methodologies into practical decision support tools for public health emergency professionals.
Under the framework of modeling and optimizing the public health infrastructure for biological and pandemic emergency responses, the task first determines adequate number of point-of-dispensing sites (POD), by placing them strategically for best possible population coverage. Individual POD layout design and associated staffing can thus be optimized to maximize throughput and/or minimize resource requirement for an input throughput. Mass dispensing creates a large influx of individuals to dispensing facilities, thus raising the risk of high degree of intra-facility infections. Our work characterizes the interaction between POD operations and disease propagation.
Specifically, fast genetic algorithm-based heuristics were developed for solving the integer-programming-based facility location instances. The approach has been applied to the metro-Atlanta area with a population of 5.2 million people spreading over 11 districts. Among the 2,904 instances, the state-of-the-art specialized integer programming solver solved all except one instance to optimality within 300,000 CPU seconds and solved all except 5 to optimality within 40,000 CPU seconds. Our fast heuristic algorithm returns good feasible solutions that are within 8 percent to optimality in 15 minutes. This algorithm was embedded within an interactive web-based decision support system, RealOpt-Regional©. The system allows public health users to contour the region of interest and determine the network of PODs for their affected population. Along with the fast optimization engine, the system features geographical, demographical, and spatial visualization that facilitate real-time usage. The client-server architecture facilities front-end user interactive design on Google Maps© while the facility location mathematical instances are generated and solved in the back-end server.
In the analysis of disease propagation and mitigation strategies, we first extended the 6-stage ordinary differential equation-based (ODE) compartmental model to accommodate POD operations. This allows us to characterize the intra-facility infections of highly contagious diseases during local outbreak when large dispensing is in process. The disease propagation module was then implemented into the CDC-RealOpt-POD© discrete-event-simulation-optimization. CDC-RealOpt-POD is a widely used emergency response decision support system that includes simulation-optimization for determining optimal staffing and operations. We employed the CDC-RealOpt-POD environment to analyze the interactions between POD operations and disease parameters and identified effective mitigation strategies. The disease propagation module allows us to analyze the efficient frontier between operational efficiencies and intra-POD infections. Emergency response POD planners and epidemiologists can collaborate under the familiar CDC-RealOpt-POD environment, e.g., design the most efficient plan by designing and analyzing both POD operations and disease compartmental model in a unified platform. Corresponding problem instances are formed automatically by combining and transforming graphical inputs and numerical parameters from users.
To facilitate the operations of receiving, staging and storage (RSS) of medical countermeasures, we expanded the CDC-RealOpt-POD layout design functions by integrating it with the process flow. The resulting RSS system allows modeling of both system processes along with spatial constraints for optimal operations and process design. In addition, agent-based simulation was incorporated inside where integrated process flow and layout design allow analysis of crowd movement and congestion. We developed the hybrid agent behavior where individual agents make decision through system-defined process flow and autonomous discretion. The system was applied successfully to determine guest movement strategies for the new Georgia Aquarium Dolphin Tales exhibit. The goal was to enhance guest experience while mitigating overall congestion.
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Gibb, Matthew Michael James. "Myocardial microstructure and its role in propagation dynamics." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:69a1a65e-9a71-422c-86e8-c347cfabf21a.
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Computational modelling and simulation, in close interaction with experiments, has provided invaluable insight into the biochemical, mechanical and electrophysiological function and dysfunction of the heart. However, limitations in imaging techniques and computing resources have precluded the analysis of tissue architecture near the cellular scale and the effect of this architecture on cardiac function. It is the wider aim of this thesis to develop a framework to characterise cardiac microstructure and to investigate the role of microstructure in cardiac propagation dynamics and arrhythmogenesis. An initial modelling study elucidates the effect of blood vessels in sustaining arrhythmic episodes, and how the accurate modelling of fibre direction in the vicinity of the vessels mitigates this detrimental mechanism. A mathematical model of fibre orientation in a simple geometry around blood vessels has been developed, based on information obtained from highly detailed histological and MRI datasets. A simulation regime was chosen, guided by the vasculature extracted from whole heart MRI images, to analyse ventricular wavefront propagation for different orientations and positions of blood vessels. Our results demonstrate not only that the presence of the blood vessels encourages curvature in the activation wavefront around the blood vessels, but further that vessels act to restrict and prolong phase singularities. When compared to a more simplistic implementation of fibre orientation, the model is shown to weaken wavefront curvature and reduce phase singularity anchoring. Having established the importance of microstructural detail in computational models, it seems expedient to generate accurate data in this regard. An automated registration toolchain is developed to reconstruct histological slices based on coherent block face volumes, in order to present the first 3-D sub-cellular resolution images of cardiac tissue. Although mesoscopic geometry is faithfully reproduced throughout much of the dataset, low levels of transformational noise obfuscate tissue microstructure. These distortions are all but eradicated by a novel transformational diffusion algorithm, with characteristics that outperform any previous method in the literature in this domain, with respect to robustness, conservation of geometry and extent of information transfer. Progress is made towards extracting microstructural models from the resultant histological volumes, with a view to incorporating this detail into simulations and yielding a deeper understanding of the role of microstructure in arrhythmia.
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Eusebio, A. "Mechanisms and consequences of beta oscillatory activity propagation in the basal ganglia-cortical network in Parkinson's disease." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1356885/.
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Excessive neural synchronisation in the beta frequency band (10-35 Hz) is a hallmark of Parkinson’s disease (PD) but the mechanisms underlying the generation and propagation of such oscillatory activity and its links with movement impairment remain partly unclear. Patients receiving deep brain stimulation of the subthalamic nucleus (STN DBS) provide a unique opportunity to address these issues by either recording the neuronal activity from the implanted electrodes or driving the network to study the behavioural and neurophysiological effects of stimulation. The studies outlined in this thesis bring further understanding into the mechanisms by which beta oscillations pervade every level of the basal ganglia – cortical network, how they impair movement and how they are modified by the usual treatments of PD such as dopamine or STN DBS. We performed a series of experiments involving PD patients either in the post-operative phase of DBS or chronically stimulated, and in an animal model of PD to study the effect of beta frequency STN stimulation on movement, the effect of high frequency STN stimulation on beta oscillations and the network properties underlying its vulnerability to beta frequencies. The findings of these studies suggest the existence of anatomically segregated subthalamo-cortical networks, with specific properties and susceptibility to resonate variably impaired in PD patients. We propose that excessive beta oscillations in PD are primarily due to a failing damping system rather than a net increase in their generation, and that dopaminergic drugs act to partially restore this damping system, while high frequency DBS suppresses pathological local beta activity. / Abstract in French: Les oscillations neuronales dans la bande beta (10-35 Hz) sont caractéristiques de la maladie de Parkinson (MP). Toutefois, les mécanismes qui sous-tendent la genèse et la propagation des ces activités et leurs liens avec les troubles moteurs restent obscurs. La chirurgie de stimulation des noyaux sous-thalamiques (NST) permet d’enregistrer l’activité neuronale par l’électrode implantée et d’étudier les effets moteurs et neurophysiologiques de la stimulation. Les travaux présentés dans cette thèse ont pour but d’améliorer la compréhension de l’origine de la diffusion des oscillations beta dans le réseau subthalamo-cortical, de leur retentissement sur la motricité et de l’influence des traitements de la MP sur celles-ci. Nous avons effectué une série d’expériences chez des patients parkinsoniens et chez un modèle animal de la MP pour étudir les effets de la stimulation du NST dans la bande beta sur la motricité, ceux de la stimulation à haute fréquence du NST sur les oscillations beta et les propriétés de réseau à l’origine de sa vulnérabilité aux fréquences beta. Les résultats de ces travaux suggèrent l’existence de réseaux subthalamo-corticaux distincts, présentant des propriétés et une susceptibilité à la résonance propres, et qui seraient atteints de façon variable selon les patients, possiblement en rapport avec la variabilité clinique de la MP. Nous proposons que les oscillations beta dans la MP sont principalement dues à la faillite du système d’atténuation plutôt qu’à une augmentation de leur genèse, que les traitements dopaminergiques restaurent partiellement ce système d’atténuation alors que la stimulation à haute fréquence du NST supprime cette activité.
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Eusebio, Alexandre. "Mechanisms and consequences of beta oscillatory activity propagation in the basal ganglia-cortical network in Parkinson's disease." Paris 6, 2011. http://www.theses.fr/2011PA066711.
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Les oscillations neuronales dans la bande beta (10-35 Hz) sont caractéristiques de la maladie de Parkinson (MP). Toutefois, les mécanismes qui sous-tendent la genèse et la propagation des ces activités et leurs liens avec les troubles moteurs restent obscurs. La chirurgie de stimulation des noyaux sous-thalamiques (NST) permet d’enregistrer l’activité neuronale par l’électrode implantée et d’étudier les effets moteurs et neurophysiologiques de la stimulation. Les travaux présentés dans cette thèse ont pour but d’améliorer la compréhension de l’origine de la diffusion des oscillations beta dans le réseau subthalamo-cortical, de leur retentissement sur la motricité et de l’influence des traitements de la MP sur celles-ci. Nous avons effectué une série d’expériences chez des patients parkinsoniens et chez un modèle animal de la MP pour étudir les effets de la stimulation du NST dans la bande beta sur la motricité, ceux de la stimulation à haute fréquence du NST sur les oscillations beta et les propriétés de réseau à l’origine de sa vulnérabilité aux fréquences beta. Les résultats de ces travaux suggèrent l’existence de réseaux subthalamo-corticaux distincts, présentant des propriétés et une susceptibilité à la résonance propres, et qui seraient atteints de façon variable selon les patients, possiblement en rapport avec la variabilité clinique de la MP. Nous proposons que les oscillations beta dans la MP sont principalement dues à la faillite du système d’atténuation plutôt qu’à une augmentation de leur genèse, que les traitements dopaminergiques restaurent partiellement ce système d’atténuation alors que la stimulation à haute fréquence du NST supprime cette activité
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Dujardin, Simon. "De la cellule au primate, propagation physiopathologique de la protéine Tau." Thesis, Lille 2, 2015. http://www.theses.fr/2015LIL2S019/document.
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Tau est une protéine stabilisatrice des microtubules majoritairement exprimée au niveau neuronal qui existe en six isoformes différentes appelées isoformes 3R ou 4R en fonction de l’inclusion de 3 ou 4 séquences répétées dans leur domaine de liaison aux microtubules. Dans une vingtaine de pathologies neurodégénératives appelées tauopathies, des protéines Tau anormalement modifiées s’agrègent formant des lésions intracellulaires appelées dégénérescence neurofibrillaire (DNF). Selon les tauopathies, la morphologie des lésions, leur composition en isoformes ainsi que l’évolution spatio-temporelle de la pathologie diffèrent. Dans la plupart des cas, les tauopathies sont sporadiques mais quelques mutations du gène codant Tau (MAPT) causent des formes familiales de démences fronto-temporales. Dans certaines tauopathies sporadiques comme la maladie d’Alzheimer, la DNF est initiée dans des régions spécifiques et évolue ensuite de manière stéréotypée. Ces stades neuropathologiques sont bien définis, mais les mécanismes expliquant cette évolution restent méconnus. Récemment, certaines études ont proposé que des espèces pathologiques de la protéine Tau sont capables de se déplacer activement de région en région suivant des connections neuro-anatomiques propageant ainsi la pathologie Tau dans le cerveau.Dans ce contexte, nous avons démontré à la fois in vitro, en utilisant un système de chambre microfluidique mais également in vivo dans un nouveau modèle de rat, que la protéine Tau est activement et physiologiquement transférée de cellule en cellule. De manière intéressante, la pathologie Tau qui se développe dans l’hippocampe des rats se propage également de région en région. Ce modèle étant basé sur une technologie de vectorisation virale, nous avons pu tester différentes constructions pour montrer qu’étonnamment, la pathologie Tau induite par des espèces mutées ou des isoformes 3R est restreinte autour du site d’initiation et ne propage pas aussi loin que pour les espèces sauvages 4R. La protéine Tau ainsi que la DNF se propagent donc de cellules en cellules mais les mécanismes expliquant cette propagation restent inconnus. Pour aborder cette question, et connaissant l’importance des vésicules extracellulaires (EVs) dans les mécanismes de communication intercellulaire, nous avons analysé leur implication dans le transfert de la protéine Tau. Nous avons purifié des EVs in vitro depuis des surnageants de culture mais également in vivo depuis des échantillons de liquide céphalorachidien de primates ainsi que des échantillons de fluide interstitiel cérébral de rat. Nous avons ainsi démontré que la protéine Tau est sécrétée de manière physiologique sous forme libre mais également au sein de EVs issues du bourgeonnement de la membrane plasmique nommées ectosomes. Il apparaît aussi qu’en cas de surexpression ou de présence de DNF, la protéine Tau est retrouvée dans des exosomes, des EVs issues de la voie endosomes/lysosomes.Ces résultats nous montrent que la protéine Tau se propage de neurone en neurone physiologiquement mais aussi durant des processus pathologiques. Il semble aussi exister des espèces particulières de protéine Tau plus promptes à se propager que d’autres. Ces différences pourraient en partie expliquer les différents phénotypes observés au sein des tauopathies. Nous avons aussi démontré que la protéine Tau est sécrétée via plusieurs voies de sécrétions qui pourraient refléter différents stades physiopathologiques. Des études complémentaires sont nécessaires notamment pour 1-clairement identifier les mécanismes de sortie et d’entrée de Tau dans les neurones. 2-comprendre si certaines espèces vont spécifiquement induire la pathologie dans les neurones secondaires et s’il est possible de les bloquer grâce à des thérapies ciblées. Et 3-identifier les raisons qui expliquent les vulnérabilités de certaines populations cellulairesTau is a microtubule-associated protein mainly expressed in neurons. There are six different isoforms of this protein bearing either 3 or 4 microtubule-binding domains and called 3R-Tau or 4R-Tau. During the course of tauopathies, Tau proteins are abnormally modified and aggregate in specific intracellular lesions called neurofibrillary degeneration (NFD). According to tauopathies, the morphology of lesions, their isoforms’ composition and the spatiotemporal evolution of the pathology are different. Moreover, tauopathies are mostly sporadic but some mutations on Tau gene (MAPT) induce rare forms of familial fronto-temporal dementia. In some sporadic tauopathies like Alzheimer’s disease, the NFD is initiated in specific brain areas and evolves stereotypically in well-defined neuropathological stages. The mechanisms underlying such evolutions are mainly unknown but recently, different studies had proposed that some pathological species of Tau protein are able to actively move from region-to-region following neuro-anatomical connections and to spread the Tau pathology intra-cerebrally by this way.Within this context, we have demonstrated either in vitro using a microfluidic chamber system or in vivo using a new rat model, that Tau proteins are actively and physiologically transferred from cell-to-cell. Interestingly, in this model we could also follow the development of the Tau pathology inside the rats’ hippocampus but also its propagation from region-to-region. This model is based on a viral vector technology; therefore, we were able to test different construct and to show that surprisingly, Tau pathology induced by mutated or 3R-Tau species is restricted to the vicinity of the initiation site and do not propagate as far as the wild-type 4R-Tau species.Tau proteins as well as NFD are cell-to-cell propagating but the mechanisms underlying this phenomenon are still unknown. In order to address this point and knowing the significance of extracellular vesicles (EVs) in the intercellular communication mechanisms, we analysed their implication in the transfer of Tau proteins. We purified EVs in vitro from culture supernatants but also in vivo from primates’ cerebrospinal fluid samples and rats’ cerebral interstitial fluid samples. We demonstrated that Tau proteins are secreted physiologically in a free form but also within specific EVs named ectosomes and coming from a budding of the plasma membrane. Also, it seems that when Tau is overexpressed and when NFD is present, Tau proteins are retrieved within EVs named exosomes and derived from the endosomes/lysosomes pathway.These results clearly show that Tau proteins are propagating from neuron to neuron physiologically but also during pathological processes. It seems also that some specific Tau species are more prone to propagate than others. These differences could partly contribute to the different phenotypes observed among tauopathies. We have also demonstrated that Tau proteins are secreted via several pathways of secretion that could reflect different pathophysiological stages. Some complementary studies are needed particularly to 1- clearly identify the cellular mechanisms of Tau exit and entry. 2- to understand if some Tau species will specifically induce Tau pathology in secondary neurons and if it is possible to block this phenomenon thanks to targeted therapy. And 3- to identify the reasons that explain the vulnerability of some specific cell populations to Tau pathology propagation
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Cavichioli, Jose Carlos [UNESP]. "Enxertia hipocotiledonar e convencional de maracujazeiro-amarelo sobre três porta-enxertos." Universidade Estadual Paulista (UNESP), 2008. http://hdl.handle.net/11449/106210.
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cavichioli_jc_dr_ilha.pdf: 512413 bytes, checksum: cd81d5957ea863badb365f4bca783ea8 (MD5)A cultura do maracujazeiro-amarelo (Passiflora edulis f. flavicarpa Deg.) tem sofrido com várias doenças, o que tem comprometido severamente a produção, determinando a migração da cultura. Dentre as doenças, a morte prematura de plantas tem se destacado, causando prejuízos nas lavouras do Estado de São Paulo. Essa doença tem sido associada a fungos do solo, como Fusarium oxysporum f. passiflorae, Fusarium solani, Phytophthora sp. e também a bactéria, como Xanthomonas axonopodis f. passiflorae. As medidas de controle da morte prematura são preventivas, e, uma vez afetada pelos patógenos, a planta morrerá, pois não há controle curativo. A aplicação de defensivos químicos não tem sido eficiente na solução do problema da morte prematura de plantas. A enxertia do maracujazeiro-amarelo em portaenxerto resistente é uma técnica promissora para o controle desta doença. Esse trabalho teve como objetivo verificar o desempenho de plantas de maracujazeiro-amarelo (Passiflora edulis f. flavicarpa) enxertadas em três diferentes espécies de maracujazeiro, em dois sistemas de enxertia, em área com e sem histórico de morte prematura. Foram conduzidos três experimentos, sendo dois em viveiro e um no campo, no município de Adamantina, SP, na região da Nova Alta Paulista, no período de dezembro de 2005 a julho de 2007. Pelos resultados verificou-se que os dois métodos de enxertia utilizados foram bem sucedidos para as três espécies de maracujazeiros estudadas. A utilização de P. giberti e P. alata como portaenxerto para P. edulis Sims f. flavicarpa são medidas promissoras para o controle da morte prematura de plantas. Plantas enxertadas sobre P. giberti apresentaram menor vigor a partir dos 180 dias, menor porte vegetativo, frutos com menor diâmetro e peso e menor produtividade.
The yellow passion fruit (Passiflora edulis Sims f. flavicarpa Deg.) has been suffering with many diseases, what have been severely compromising the crop yield, determining the migration of the culture. Amongst the diseases, the premature death of plants has detached, causing crop losses the State of São Paulo. This disease has been associated with soil fungi, as Fusarium oxysporum f. passiflorae, Fusarium solani, Phytophthora sp, and also bacteria, as Xanthomonas axonopodis f. passiflorae. Measures to control premature death of plants are preventive, and, once affected by pathogens, the plant will die because there is no curative control. The application of chemical defensives has not been effective to solve the plants premature deaths. The grafting of yellow passion fruit in resistant rootstock is a promising technique for this disease control. This work aimed to evaluate the performance of yellow passion fruit grafted on three rootstocks, in two systems of grafting, cultivated in sites with or without disease history. Three experiments were carried out, two in nursery and one in the field, in Adamantina, SP, from December 2005 to July 2006. It was concluded that the two methods of grafting utilized were successful for the three species of Passiflora. The use of P. giberti and P. alata as rootstocks for P. edulis f. flavicarpa are promising measures for the control of premature death of plants. Plants grafting on P. giberti presented lower vigor form the 180 days, lower vegetative growth, fruits with lower diameter and weight and lower yield.
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Cavichioli, Jose Carlos. "Enxertia hipocotiledonar e convencional de maracujazeiro-amarelo sobre três porta-enxertos /." Ilha Solteira : [s.n.], 2008. http://hdl.handle.net/11449/106210.
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Orientador: Luiz de Souza CorrêaBanca: Aparecida Conceição Boliani
Banca: Shizuo Seno
Banca: João Carlos de Oliveira
Banca: Aloísio Costa Sampaio
Resumo: A cultura do maracujazeiro-amarelo (Passiflora edulis f. flavicarpa Deg.) tem sofrido com várias doenças, o que tem comprometido severamente a produção, determinando a migração da cultura. Dentre as doenças, a morte prematura de plantas tem se destacado, causando prejuízos nas lavouras do Estado de São Paulo. Essa doença tem sido associada a fungos do solo, como Fusarium oxysporum f. passiflorae, Fusarium solani, Phytophthora sp. e também a bactéria, como Xanthomonas axonopodis f. passiflorae. As medidas de controle da morte prematura são preventivas, e, uma vez afetada pelos patógenos, a planta morrerá, pois não há controle curativo. A aplicação de defensivos químicos não tem sido eficiente na solução do problema da morte prematura de plantas. A enxertia do maracujazeiro-amarelo em portaenxerto resistente é uma técnica promissora para o controle desta doença. Esse trabalho teve como objetivo verificar o desempenho de plantas de maracujazeiro-amarelo (Passiflora edulis f. flavicarpa) enxertadas em três diferentes espécies de maracujazeiro, em dois sistemas de enxertia, em área com e sem histórico de morte prematura. Foram conduzidos três experimentos, sendo dois em viveiro e um no campo, no município de Adamantina, SP, na região da Nova Alta Paulista, no período de dezembro de 2005 a julho de 2007. Pelos resultados verificou-se que os dois métodos de enxertia utilizados foram bem sucedidos para as três espécies de maracujazeiros estudadas. A utilização de P. giberti e P. alata como portaenxerto para P. edulis Sims f. flavicarpa são medidas promissoras para o controle da morte prematura de plantas. Plantas enxertadas sobre P. giberti apresentaram menor vigor a partir dos 180 dias, menor porte vegetativo, frutos com menor diâmetro e peso e menor produtividade.
Abstract: The yellow passion fruit (Passiflora edulis Sims f. flavicarpa Deg.) has been suffering with many diseases, what have been severely compromising the crop yield, determining the migration of the culture. Amongst the diseases, the premature death of plants has detached, causing crop losses the State of São Paulo. This disease has been associated with soil fungi, as Fusarium oxysporum f. passiflorae, Fusarium solani, Phytophthora sp, and also bacteria, as Xanthomonas axonopodis f. passiflorae. Measures to control premature death of plants are preventive, and, once affected by pathogens, the plant will die because there is no curative control. The application of chemical defensives has not been effective to solve the plants premature deaths. The grafting of yellow passion fruit in resistant rootstock is a promising technique for this disease control. This work aimed to evaluate the performance of yellow passion fruit grafted on three rootstocks, in two systems of grafting, cultivated in sites with or without disease history. Three experiments were carried out, two in nursery and one in the field, in Adamantina, SP, from December 2005 to July 2006. It was concluded that the two methods of grafting utilized were successful for the three species of Passiflora. The use of P. giberti and P. alata as rootstocks for P. edulis f. flavicarpa are promising measures for the control of premature death of plants. Plants grafting on P. giberti presented lower vigor form the 180 days, lower vegetative growth, fruits with lower diameter and weight and lower yield.
Doutor
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Mutlu, Justine. "Connectivité fonctionnelle au repos : relation avec la topographie et la propagation des atteintes structurales, fonctionnelles et moléculaires dans la maladie d'Alzheimer." Thesis, Normandie, 2017. http://www.theses.fr/2017NORMC005/document.
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L’amélioration des techniques d’imagerie cérébrale a permis de grandes avancées dans la compréhension et la prédiction des mécanismes physiopathologiques de la Maladie d’Alzheimer (MA). Récemment, des travaux ont émis l’hypothèse d’une neurodégénérescence transneuronale selon laquelle les maladies neurodégénératives cibleraient des réseaux fonctionnels spécifiques où elles apparaitraient et se propageraient. Cette thèse visait à tester cette hypothèse dans le cadre de la MA en étudiant les liens entre la connectivité fonctionnelle au repos et les atteintes structurales, métaboliques et moléculaires. Un premier volet a été consacré à la caractérisation des atteintes fonctionnelles, structurales et métaboliques au sein des réseaux ventral et dorsal du cortex cingulaire postérieur (CCP) dans le Mild Cognitive Impairment (MCI) et la MA. Cette étude transversale a suggéré une vulnérabilité plus précoce (dès le stade de MCI) du réseau ventral en atrophie et en connectivité fonctionnelle au repos tandis que l’hypométabolisme était présent dans les deux réseaux chez les MCI et les MA. Le second volet a permis d’évaluer l’influence de la connectivité spécifique (de la région la plus atteinte) versus de la connectivité globale (d’une région avec le reste du cerveau, particulièrement élevée dans les régions hubs) sur la topographie et la propagation de l’atrophie, de l’hypométabolisme et des dépôts amyloïdes sur 18 mois dans la MA. Cette étude longitudinale a révélé que l’atrophie apparaitrait et se propagerait via la connectivité spécifique en évitant les régions hubs qui sont davantage vulnérables à l’hypométabolisme et aux dépôts amyloïdesAdvances in neuroimaging techniques have allowed considerable improvement of the understanding and the prediction of the pathophysiological processes of Alzheimer’s disease (AD). Recent findings suggested a transneuronal spread hypothesis of neurodegeneration according to which neurodegenerative disease would target specific functional networks among which it would appear and spread. This thesis aimed at assessing this hypothesis in AD by studying the relationships between resting-state functional connectivity and structural, metabolic and molecular alterations. Firstly, we identified the functional, structural and metabolic alterations within the ventral and the dorsal posterior cingulate cortex (PCC) networks in Mild Cognitive Impairment (MCI) and AD. This transversal study suggested an early vulnerability (since the MCI stage) of the ventral network regarding atrophy and resting-state functional connectivity disruptions while hypometabolism concerned both ventral and dorsal networks in MCI and AD patients. Secondly, we assessed the relative influence of the specific connectivity (of the region the most disrupted) versus the global connectivity (of one region with the rest of the brain, especially high in hub regions) on the topography and the propagation of atrophy, hypometabolism and amyloid deposition over 18 months in AD. This longitudinal study revealed that atrophy would appear and propagate through the specific connectivity by avoiding hub regions which would be more vulnerable to the hypometabolism and amyloid deposition
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Girardi, Eduardo Augusto. "Métodos alternativos de produção de mudas cítricas em recipientes na prevenção da morte súbita dos citros." Universidade de São Paulo, 2005. http://www.teses.usp.br/teses/disponiveis/11/11136/tde-05072005-154651/.
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A Morte Súbita dos Citros (MSC) é uma nova doença que afeta a citricultura paulista, podendo levar à morte de milhões de plantas cítricas enxertadas sobre limão 'Cravo' (Citrus limonia Osbeck), com um impacto comparável ao do vírus da Tristeza dos Citros durante as décadas de 30 e 40. Técnicas alternativas na propagação dos citros podem contornar os efeitos da MSC, seja diretamente, pela produção de subenxertos tolerantes, ou indiretamente, pelo emprego de estaquia de citros e interenxertia em combinações copa/porta-enxerto incompatíveis, mas sobre porta-enxertos tolerantes à MSC. O presente trabalho visou avaliar diferentes métodos de produção de mudas cítricas em recipientes que proporcionem possível prevenção futura das plantas à MSC em condições de campo, através de três experimentos. 1) desenvolvimento de onze porta-enxertos para fins de subenxertia, em diferentes recipientes. Os recipientes usados foram tubetes de 290 mL, sacolas de 1,7L e porta-enxertos transplantados de tubetes de 75mL para sacolas de 1,7L e 4,5L; 2) viabilização de produção de mudas de laranja 'Pêra' (Citrus sinensis L. Osbeck) sobre porta-enxertos citrumelo 'Swingle' (Poncirus trifoliata x Citrus paradisi) e limão 'Volkameriano' (Citrus volkameriana Pasquale), através de interenxertos de laranjas 'Valência' e 'Hamlin'(Citrus sinensis L. Osbeck), tangerina 'Sunki' (Citrus sunki Hort. ex Tanaka) e tangerina 'Cleópatra' (Citrus reshni Hort. ex Tanaka); 3) produção de mudas cítricas e subenxertos a partir de estacas enraizadas de citrumelo 'Swingle'. Utilizaram-se estacas herbáceas, semi-lenhosas e lenhosas obtidas de porta-enxertos de seis meses de idade, submetidas a imersão em solução com IBA 0 ou 500mg L-1 e a enxertia antes do enraizamento. Porta-enxertos produzidos diretamente em sacolas de 1,7L atingiram ponto ideal de subenxertia em menor tempo, ou seja, cerca de 100 a 150 dias após a semeadura, além de permitir a obtenção de plantas maiores e com sistema radicular adequado em mesmo espaço de tempo, quando se necessitar de subenxertos mais vigorosos no campo. A interenxertia se mostrou uma técnica promissora para propagação de citros, especialmente no caso de viabilizar o plantio de laranja 'Pêra' sobre citrumelo 'Swingle' em áreas afetadas pela MSC. Contudo, determina um ciclo de produção mais prolongado e com maior percentagem de descarte de mudas, levando-se até 17 meses para a formação da muda a partir da semeadura do porta-enxerto. Estacas herbáceas com um par de folhas são as mais indicadas para enraizamento e multiplicação de citrumelo 'Swingle'.Citrus Sudden Death (CSD) is a new disease detected in the citrus industry in São Paulo State, Brazil. It affects all citrus varieties budded on Rangpur Lime (Citrus limonia Osbeck), causing lost of vigor and leaf brightness, root system destruction, yield reduction, degeneration of rootstock phloem tissue and death of plants in few months. CSD has a great potential to destroy millions of plants such as Citrus Tristeza Virus has caused between 1930 and 1940. Alternative production methods of container-grown citrus nursery trees could prevent some effects of CSD, for instance, by the use of tolerant inarchings, citrus cuttings, or even interstocks in incompatible scion/rootstock combinations. This work evaluated the following alternative production methods of citrus aiming to prevent occurrence of CSD in groves: 1) production of citrus inarchings using eleven rootstocks in four container types: 290mL tubes and 1,7L and 4,5L plastic bags; 2) production of 'Pera' sweet orange (Citrus sinensis L. Osbeck) nursery trees on incompatible 'Swingle' citrumelo (Poncirus trifoliata x Citrus paradisi) and 'Volkamer' lemon (Citrus volkameriana Pasquale) with four interstocks: 'Valencia' and 'Hamlin' sweet oranges (Citrus sinensis L. Osbeck), 'Sunki' mandarin (Citrus sunki Hort. ex Tanaka) and 'Cleópatra' mandarin (Citrus reshni Hort. ex Tanaka); 3) production of citrus inarchings and nursery trees using 'Swingle' citrumelo cuttings. Herbaceous, semi-hardwood and hardwood cuttings were used and were submitted to IBA solution (0 or 500mg L-1) and budded before rooting. Production of inarchings directly sowed in 1,7L containers resulted in rootstocks ready for use about 100 to 150 days after sowing with more vigorous plants and well shaped root system. Interstocking is a promising citrus propagation technique especially regarding incompatible combinations, and could allow the use of 'Pera' sweet orange on 'Swingle' citrumelo in areas affected by CSD. On the other hand, the production cycle is longer, up to 17 months from sowing, besides producing a higher percentage of inadequate plants. Twoleaf herbaceous cuttings are indicated for appropriate rooting and multiplication of 'Swingle' citrumelo.
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Courte, Josquin. "Étude de la propagation prion-like de l'alpha-synucléine dans des réseaux de neurones reconstruits Reconstruction of directed neuronal networks in a microfluidic device with asymmetric microchannels Neurotoxicity of the Cyanotoxin BMAA Through Axonal Degeneration and Intercellular Spreading." Thesis, Sorbonne université, 2019. https://accesdistant.sorbonne-universite.fr/login?url=http://theses-intra.upmc.fr/modules/resources/download/theses/2019SORUS053.pdf.
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Les maladies neurodégénératives (telles que les maladies de Parkinson et d’Alzheimer) sont caractérisées par l’agrégation de protéines mal repliées en dépôts insolubles. Ces dépôts engendrent des dysfonctions cellulaires, et semblent donc avoir un rôle fondamental dans le développement de ces pathologies. L’apparition de ces dépôts se fait de façon stéréotypée dans des sous-groupes de patients. Notamment, dans la maladie de Parkinson, la petite protéine présynaptique alpha-synucléine (aSyn) est le composant principal d’agrégats dénommés corps de Lewy et neurites de Lewy. Les corps et neurites de Lewy apparaissent suivant un patron dénommé « staging de Braak » dans une sous-partie conséquente des patients. Dans une certaine mesure, le patron d’apparition des agrégats semblent suivre la connectivité neuro-anatomique entre les régions cérébrales, ce qui suggère que l’agrégation puisse se propager dans les réseaux neuronaux.L’étude des maladies prions telles que le kuru ou la maladie de Creutzfeldt-Jakob a mis en évidence un mécanisme original de propagation du mérepliement des protéines. La protéine PrP s’agrégeant dans ces pathologies est en effet capable d’adopter au moins deux conformations radicalement distinctes. L’une, pathologique, forme des agrégats, tandis que la forme fonctionnelle ne s’agrège pas. Par des mécanismes encore mal compris, mais qui potentiellement similaires à la formation de fibres amyloïdes, la protéine pathologique est en mesure de convertir la protéine fonctionnelle en sa forme anormale, et à l’inclure dans des agrégats. La forme anormale de la protéine est donc capable de s’auto-propager, et cela de cellule à cellule et d’organisme à organisme. De nombreuses similitudes dans les caractéristiques biochimiques et moléculaires des agrégats présents dans les maladies neurodégénératives non prions ont mené à l’hypothèse que l’agrégation protéique se fait suivant des modalités similaires aux maladies à prions. Suivant ce scénario, l’agrégation protéique est en mesure de se propager de neurone à neurone dans le cerveau via les connexions neuronales, et ainsi suivre un patron stéréotypé dépendant de l’interconnexion des régions successivement touchées. Cette hypothèse est dénommée « prion-like ».Cependant, les mécanismes expliquant la génération d’un patron stéréotypé de développement prion-like des agrégats d’aSyn restent obscurs. Le but de ma thèse a été d’aborder les déterminants de la propagation de l’agrégation de l’aSyn dans des réseaux de neurones hétérogènes grâce à des modèles in vitro. J’ai tout d’abord évalué si différentes régions du cerveau de souris mises en culture primaire présentaient la même vulnérabilité au recrutement de l’aSyn soluble dans des agrégats pathologiques introduits dans le milieu extracellulaire. J’ai pu mettre en évidence que la vulnérabilité de neurones striataux, corticaux et hippocampaux était fortement différente, et que le facteur déterminant cette vulnérabilité était le niveau d’expression endogène de l’aSyn. J’ai ensuite développé un système de culture permettant la reconstruction contrôlée de réseaux de neurones binaires in vitro, composés de neurones primaires murins, dont les connexions sont parfaitement orientées d’un compartiment vers l’autre, un prérequis pour l’étude de la propagation d’un agent pathogène auto-propagatif. Un tel système est parfaitement original, et n’avait jamais été publié auparavant. J’ai finalement modélisé la propagation prion-like de l’aSyn dans de tels réseaux, en y introduisant des agrégats exogènes d’aSyn fluorescents dans le compartiment « présynaptique » et en évaluant la propagation de l’agrégation au compartiment « postsynaptique ». Ce transfert ne peut se faire que via les connexions neuronales poussant depuis le compartiment présynaptique, les deux compartiments étant fluidiquement isolés. [...]Neurodegenerative diseases such as Parkinsons’s or Alzheimer’s diseases are characterized by the aggregation of misfolded proteins in insoluble inclusions. These inclusions trigger cellular dysfnctions and are therefore thought to play an important role in the development of these pathologies. They appear following a conserved pattern in subgroups of patients. In Parkinson’s disease, the small presynaptic protein alpha-synuclein (aSyn) is the main component of protein deposits termed Lewy bodies and Lewy neurites. These appear following a stereotypical pattern known as “Braak staging” in a consequent subset of patients. The pattern of inclusion formation partly follows neuroanatomical connectivity, suggesting that protein aggregation propagates in neural networks. Prion diseases such as kuru or Creutzfeldt-Jakob’s disease have revealed an original mechanism for propagating protein misfolding. The PrP protein, aggregated in these diseases, is able to have two radically distinct conformations. The pathological one aggregates in supramolecular assemblies, while the functional one does not. Through an incompletely understood mechanism which might share similarities with the formation of amyloid fibrils, the pathological form of the protein is able to convert the functional form into the pathological one, recruiting it into aggregates. The abnormal form of the protein is thus able to self-propagate, from cell to cell and from organism to organism. Numerous biochemical and molecular characteristics of aggregates detected in neurodegenerative diseases are shared with the prion aggregates. It is thus hypothesized that protein aggregation in neurodegenerative diseases unfolds in a similar manner to prion aggregation. In this scenario, protein aggregation is able to be transmitted from neuron to neuron following neuroanatomical connectivity, and thus propagates in a stereotypical manner in neural networks following axonal tracts. This scenario is named “prion-like hypothesis”. However, how the prion-like propagation of aSyn generates the conserved pattern of aggregates in the brain of patients is still unknown. The aim of my PhD thesis has been to decipher parameters impacting the prion-like propagation of aSyn in heterogeneous neural networks with in vitro models. I first assessed if specific neuronal populations cultured from various regions of the mouse brain exhibited the same vulnerability to the prion-like recruitment of aSyn in pathological aggregates following their exposure to exogenous aSyn fibrils. I was able to demonstrate that cortical, striatal and hippocampal primary neuronal cultures had a significant difference in their vulnerability to prion-like seeding of aSyn aggregation. I also demonstrated that this vulnerability was due to the differential expression of aSyn in these populations. I then developed a culture system allowing for the controlled reconstruction of primary murine neurons networks. This system allows for the perfect filtration of axonal outgrowth in one direction, thus allowing the reconstruction of fully oriented binary networks. Axonal growth orientation is a prerequisite to the in vitro study of pathogens propagation in neural networks. This system is the first to achieve this level of axonal filtration while allowing synaptic connectivity between the two compartments. I finally modeled aSyn prion-like propagation in these reconstructed networks by selectively introducing exogenous fluorescent aSyn fibrils in the “presynaptic” compartment and following aggregation propagation to the “postsynaptic” compartment. This propagation can only occur through crossing axons, as the two compartments are fluidically isolated. I demonstrated that anterograde aSyn prion-like propagation was relatively inefficient in this experimental framework. Indeed, while a small quantity of exogenous fibrils are transferred to postsynaptic neurons, they are not able to seed endogenous aSyn aggregation in those. [...]
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Stehle, Juliette. "Réseaux de proximité humaine : Analyse, modélisation, et processus dynamiques." Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM4086.
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Les technologies modernes permettent d'avoir des renseignements toujours plus précis sur les interactions entre individus. Dans ce contexte, la collaboration SocioPatterns a permis de développer une infrastructure mesurant, avec une très grande résolution temporelle, la proximité face-à-face d'individus volontaires, portant des badges de radio-identification. Cette infrastructure a été déployée dans divers contextes, tels que des conférences scientifiques, un musée, une école ou encore un service hospitalier. La simple analyse de ces données représente un enjeu majeur pour l'étude de la dynamique humaine et soulève des questions aussi fondamentales que la recherche d'outils et de techniques d'analyse adaptés. Cette thèse présente la caractérisation statistique de la dynamique de proximité physique, mise en relation avec le contexte et les autres métadonnées disponibles, telles que l'âge, le sexe des individus, ou bien la structure de leurs réseaux sociaux virtuels. Si la structure des contacts diffère considérablement selon le contexte, les distributions empiriques des durées des interactions et entre interactions sont très similaires. Un modèle individu-centré, présenté dans cette thèse, propose des règles d'interactions microscopiques simples susceptibles de donner lieu à cette structure macroscopique complexe des temps d'interaction. Enfin, la caractérisation de la dynamique des contacts entre individus constitue une étape cruciale pour comprendre les mécanismes de propagation de maladies telles que la grippe dans une populationModern technologies allow to access to more and more detailed information on human interactions. In this context, the SocioPatterns collaboration has allowed to develop an infrastructure based on radio-identification devices, that records human proximity patterns at a fine grained resolution, among voluntary individuals. This infrastructure has been deployed in diverse contexts, such as scientific conferences, a museum, a primary school, or a hospital department. The mere analysis of these data represents a high stake for the study of human dynamics and raises fundamental issues such as the need of adequate tools and analysis techniques. This thesis presents the statistical characterization of physical proximity dynamics, put into relation with the context and other available metadata such as the age, the gender of participants or the structure of their virtual social networks. Although contact patterns considerably differ amongst the various contexts, the empirical distributions of interaction durations and of inter-contact times are very similar. An agent-based model, presented in this thesis, suggests simple microscopic interaction rules able to produce the complex macrostructure of interaction durations. In the last place, the characterization of contact dynamics constitutes a determining step for understanding spreading mechanisms of diseases such as the influenza. The human proximity data have allowed to analyze the level of information needed on contact dynamics for the elaboration of epidemiological models of contagion. Such models allow to better estimate the impact of public health strategies, e.g. the closure of school classes and targeted vaccinations
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Quax, Rick. "Modeling and simulating the propagation of infectious diseases using complex networks." Thesis, Atlanta, Ga. : Georgia Institute of Technology, 2008. http://hdl.handle.net/1853/24827.
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Lemos, Oriel Filgueira de. "Mutagênese e tecnologia in vitro no melhoramento genético da pimenta-do-reino (Piper nigrum L.)." Universidade de São Paulo, 2003. http://www.teses.usp.br/teses/disponiveis/11/11137/tde-07042003-161151/.
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O presente trabalho teve por objetivo desenvolver tecnologia in vitro e associá-la à mutagênese, e avaliar plantas V 5 e V6 quanto aos caracteres agronômicos de produção em área de ocorrência da doença fusariose, visando ao melhoramento genético da pimenta-do-reino para obtenção de plantas tolerantes e/ou resistentes à doença fusariose. A aplicação das técnicas in vitro iniciou-se através da obtenção de plantas doadoras de explantes, a partir de estacas em casa-de-vegetação e, de sementes e embriões zigóticos in vitro. O processo de micropropagação foi desenvolvido a partir de gemas de plantas obtidas in vitro através do estabelecimento de condições adequadas de cultivo em meios de cultura apropriados para multiplicação de gemas, enraizamento e obtenção de "plantlets", e de tipo de substrato para aclimatação e formação de mudas. Após a definição deste processo, gemas de plantas de casa-de-vegetação foram submetidas a diferentes tratamentos de assepsia e as sobreviventes micropropagadas. Seleção in vitro foi estabelecida ao cultivar isolados patogênicos do fungo Fusarium solani f. sp. piperis em meio Czapek-Dox e, através da curva de crescimento foi estabelecido o período de 28 dias de cultivo mais adequado para obtenção de filtrado da cultura do fungo. Diferentes concentrações de filtrado e formas de esterilização foram testadas em meio de cultura de multiplicação de gemas e determinou-se a concentração de 55% do filtrado do fungo (v/v) sob a esterilização por duas autoclavagens, adequada para causar 100% de mortalidade de gemas susceptíveis à doença. Simultaneamente, testes de radiossensitividade foram desenvolvidos através da irradiação gama em gemas in vitro e a dose de 20Gy foi escolhida para indução de mutações. As gemas irradiadas que passaram por vários ciclos de multiplicação e sobreviveram ao agente seletivo, filtrado de cultura do fungo, estão sendo clonadas para serem submetidas à seleção artificial com esporos do fungo em casa-de-vegetação, seleção natural em campo de ocorrência da doença e avaliação agronômica. Testes indicaram, a concentração de 2x10 6 esporos/ml em suspensão e a aplicação no solo do fungo adequada para seleção em casa-de-vegetação. As plantas V5 e V6 avaliadas em campo quanto a mortalidade e caracteres de produção apresentaram performance semelhante às plantas da cultivar original quanto à média de comprimento de espiga (8,4 cm), peso (4,42g) e número de frutos (40 frutos) por espiga, peso de 100 frutos (10,67g) e rendimento de pimenta preta (> 30%). Entretanto, melhores resultados para a média de produção de pimenta verde (3.290g) e sobrevivência em área de ocorrência da fusariose. As análises por componentes principais e variáveis canônicas apresentaram divergência genética entre as plantas originadas por estacas que sofreram irradiação gama e aquelas da cultivar original.The purposes of the present work were to develop in vitro technology, associating it with mutagenesis, and to evaluate the V5 and V6 plants based on agronomical characters of production in Fusarium incidence areas, aiming at the genetic improvement of black pepper to obtain tolerant and/or resistant plants to the disease. The use of in vitro techniques started with the production of explant donor plants from greenhouse-grown cuttings and from seeds and in vitro zygotic embryos. The micropropagation process was developed using young shoots of in vitro plants by establishment of proper growing conditions in culture media for multiplication, rooting and production of plantlets, and by determining a suitable substrate type for acclimatization and growing of plantlets. After the process was defined, young shoots obtained from greenhouse grown plants underwent different aseptic treatments and the surviving plantlets were micropropagated. In vitro selection was carried out by cultivating pathogenic isolates of Fusarium solani f. sp. piperis in Czapek-Dox medium and, by using a growing curve, the most suitable growing period (28 days) for obtaining the fungus culture filtrate was defined. Different filtrate concentrations and sterilization techniques were tested in culture medium for young shoot multiplication. A concentration of 55% (v/v) of fungus filtrate under sterilization by double autoclavation was considered adequate to cause 100% mortality of fusariosis susceptible young shoots. Simultaneously, radiosensitivity tests were carried out through gamma irradiation of in vitro young shoots and dose of 20Gy was selected for mutation induction. Irradiated young shoots which underwent several multiplication cycles and survived the selective agent, fungus culture filtrate, are being cloned in order to be submitted to artificial selection with the fungus spores in greenhouse, to natural selection in a disease incidence area and to agronomical evaluation. These tests indicated that the concentration of 2x10 6 spores/ml in suspension and the application of the fungus on soil were appropriate for greenhouse selection. The V5 and V6 plants evaluated in field conditions for mortality and production characters showed similar performance to the original cultivar plants regarding average height (8.4 cm), weight (4.42g) and number of fruits (40 fruits) per spike, weight of 100 fruits (10.67g) and black pepper yield (>30%). However, better results were observed for average green pepper production (3,290g) and survival rates in a fusariosis incidence area. Analyses of principal components and canonic variables evidenced genetic divergence between plants grown from gamma-irradiated cuttings and the original cultivar ones.
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Skřížala, Martin. "Využití neuronových sítí v klasifikaci srdečních onemocnění." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2008. http://www.nusl.cz/ntk/nusl-217210.
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This thesis discusses the design and the utilization of the artificial neural networks as ECG classifiers and the detectors of heart diseases in ECG signal especially myocardial ischaemia. The changes of ST-T complexes are the important indicator of ischaemia in ECG signal. Different types of ischaemia are expressed particularly by depression or elevation of ST segments and changes of T wave. The first part of this thesis is orientated towards the theoretical knowledges and describes changes in the ECG signal rising close to different types of ischaemia. The second part deals with to the ECG signal pre-processing for the classification by neural network, filtration, QRS detection, ST-T detection, principal component analysis. In the last part there is described design of detector of myocardial ischaemia based on artificial neural networks with utilisation of two types of neural networks back – propagation and self-organizing map and the results of used algorithms. The appendix contains detailed description of each neural networks, description of the programme for classification of ECG signals by ANN and description of functions of programme. The programme was developed in Matlab R2007b.
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Goumas, Dimitrios. "Possibilites de detection d'erwinia chrysanthemi pv. Dianthicola (hellmers) dickey 1979-agent de la bacteriose du dahlia sp. Evaluation des methodes immunoenzymatiques pour le controle sanitaire du materiel de propagation." Paris 6, 1987. http://www.theses.fr/1987PA066405.
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La bacteriose a e. Chrysanthemi pv. Dianthicola (echr) facteur limitant de la production du dahlia est transmise par la multiplication vegetative. Afin de proposer une methode de diagnostic plus precise que la detection visuelle, les methodes immunoenzymatiques ont ete etudiees et adaptees pour la detection d'echr dans les tissus du dahlia. La methode das-elisa (double antibody sandwich) est evaluee par rapport aux methodes de diagnostic de reference (isolement et immunofluorescence). Son utilisation, pour l'analyse sanitaire du materiel de propagation vis-a-vis d'echr seul et associe eventuellemnt a la mosaique du dahlia (damy), est etudiee en vue d'une selection sanitaire. Les etudes effectuees pour optimiser les reactifs, pour determiner les parametres pouvant modifier la reaction antigene-anticorps
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Ahmed, Muhammad Faisal, of Western Sydney Hawkesbury University, of Science Technology and Environment College, and of Science Food and Horticulture School. "Studies on the tissue culture and potential for the development of a genetic transformation system for avocados (Persea americana Mill.)." THESIS_CSTE_SFH_Ahmed_M.xml, 2002. http://handle.uws.edu.au:8081/1959.7/3.
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The avocado industry needs improved cultivars with better agronomic traits such as increased resistance to pests and diseases. These could be developed with biotechnological approaches to breeding such as the use of genetic engineering. a prerequisite to the use of this technique if the development of an efficient in vitro regeneration system. The objective of this study therefore, was to develop a tissue culture protocol suitable for the propagation and transformation of avocado. To do this, the effects of the preconditioning of mother plants, different explant sources, growth regulator pretreatments of explants and different compositions of the growth medium were examined. The results of these confirmed that avocado is typical of woody plants, as avocado tissues shows a decrease in morphogenetic capacity as they age, and the most juvenile explant, the embryonic shoot axis, showed the highest potential for shoot regeneration. Regrowth of explants after removal of the first flush of shoots resulted in the production of shoot bases in vitro. Shoot bases were most efficiently produced when embryonic axes were dissected transversely to the axis of growth. This study has resulted in the production of an efficient system for the production of multiple shoots from embryonic shoot tissues of avocado through the induction of shoot bases. This tissue culture system could be extended to the use of somatic tissues as a source of explants. If shoot bases can be established from such tissues, this will provide a means by which avocado can be clonally propagated and provides a system by which genetic transformation and other techniques of biotechnology can be applied to the production of new and superior cultivars.Doctor of Philosophy (PhD)
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Bendifallah, Maya. "Development of Inhibitors of Amyloid Fibril Propagation." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS578.
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L'α-Synuclein (αSyn) fibrillaire, impliqué dans la maladie de Parkinson et d’autres synucleinopathies, peut se propager entre cellules de manière « prion-like » et cette propagation est liée à la progression de la maladie. Durant cette étude, nous nous sommes tournés vers les chaperons moléculaires impliqués dans l’agrégation de l’αSyn ou bien dans sa toxicité afin de trouver des candidats capables d’interférer avec la propagation. Nous avons ensuite testé l’effet des chaperons capables de se lier aux fibres d’αSyn sur l’internalisation des fibres d’αSyn par les cellules Neuro-2a. Nous démontrons que l’interaction avec l’αSyn agrégeant avec αB-crystallin (αBc) ou Carboxyl terminus of Hsc70-interacting protein (CHIP) a mené à la formation de fibres qui sont moins internalisées par les cellules. Enfin, en passant par une stratégie de pontage chimique optimisé couplé à la spectrométrie de masse, nous avons identifié les zones d’interaction entre l’αSyn fibrillaire et soit αBc, soit CHIP. Ces résidus issus des chaperons, se trouvant à proximité des fibres d’αSyn dans les complexes, pourraient être développés dans des mini-chaperons peptidiques, capables d’enrober la surface des fibres et ainsi de bloquer la liaison à la membrane et l’internalisation des fibres. De surcroît, des polypeptides issus des partenaires précédemment identifiés d’αSyn ont été testé pour leur liaison aux fibres et leur effet sur la propagation des fibresFibrillar α-Synuclein (αSyn) is the molecular hallmark of Parkinson’s Disease and other synucleinopathies. Its prion-like propagation between cells is linked to disease progression. In this study, we looked to molecular chaperones previously implicated in αSyn fibrillation and/or toxicity to identify proteins capable of binding αSyn fibrillar aggregates in order to target their propagation. We further assessed the effect of the fibril-binding chaperones on internalization of αSyn fibrils by Neuro-2a cells. We demonstrate that the interaction of aggregating αSyn with αB-crystallin (αBc) or Carboxyl terminus of Hsc70-interacting protein (CHIP) led to the formation of fibrils that are less internalized by cells. Finally, using an optimized chemical cross-linking and mass spectrometry strategy, we identified the interaction areas between fibrillar αSyn and either αBc or CHIP. These chaperone residues, located proximally to αSyn fibrils, could be subsequently developed into peptidic mini chaperones, capable of coating the fibril surface and thereby blocking fibrillar cell binding and internalization. Furthermore, polypeptides derived from previously identified αSyn binding partners were tested for their binding to αSyn fibrils and subsequent effect on fibril propagation
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La, Peyre Jerome F. "Studies on the oyster pathogen Perkinsus marinus (Apicomplexa): Interactions with host defenses of Crassostrea virginica and Crassostrea gigas, and in vitro propagation." W&M ScholarWorks, 1993. https://scholarworks.wm.edu/etd/1539616724.
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The disease caused by the protozoan Perkinsus marinus has been a major source of mortality in the eastern oyster, Crassostrea virginica. Variations in susceptibility to P. marinus infection among eastern oysters collected from the Chesapeake Bay and Gulf of Mexico, as well as between eastern and Pacific (Crassostrea gigas) oysters were determined. Since oyster host defense may play a role in determining susceptibility to pathogen infection, cellular and humoral defense activities of the oyster and their interactions with P. marinus were investigated. Procedures also had to be established to isolate, purify, and propagate in vitro, P. marinus. Eastern oysters from all sites were found to be highly susceptible to the pathogen. Cellular and humoral activities were significantly affected by heavy intensity of P. marinus infection. Prevalence and intensity of P. marinus infection were lower in Pacific oysters than in eastern oysters. Pacific oysters may offer a less favorable environment for the development of P. marinus compared to eastern oysters for at least two possible reasons: the elevated cellular and humoral activities may degrade the parasite more effectively, and lower plasma protein levels may limit parasite growth. Incubation of merozoites with hemocytes of eastern and Pacific oysters in vitro suggested that limited intracellular killing of P. marinus occurred but that killing was not mediated by oxygen metabolites. Perkinsus marinus was successfully propagated in vitro in a culture medium containing most of the known constituents of cell-free oyster hemolymph. Cultures of the parasite were initiated from heart fragments of infected oysters. The cultured protozoan was similar in morphology to P. marinus, enlarged in fluid thioglycollate medium, reacted with polyclonal antibodies raised against hypnospores and was infective. Continuous cultures of P. marinus could also be initiated from hypnospores. Two types of division, progressive cleavage and successive bipartition of the mother cell protoplast, were observed.
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Landureau, Maud. "Développement d'outils thérapeutiques ciblant les agrégats d'alpha-synucléine dans les synucléinopathies Mapping of Three Alpha-Synuclein Fibrillar Polymorphs Surfaces Internalization and Degradation of Different Alpha-Synuclein Strains by Neurons or Astrocytes." Thesis, université Paris-Saclay, 2021. http://www.theses.fr/2021UPASL022.
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L'agrégation d'alpha-synucléine et la propagation de ces agrégats de neurone à neurone ont, de manière récurrente, été montrées comme étant au cœur du processus physiopathologique de différentes maladies neurodégénératives telles que la maladie de Parkinson, les démences à corps de Lewy ou les atrophies multisystématisées. Bien que ces synucléinopathies aient en commun la présence de dépôts fibrillaires riches en alpha-synucléine, les phénotypes pathologiques sont différents. Notre hypothèse est que la présence de différentes "souches" d'alpha-synucléines fibrillaires présentant différentes affinités, tropismes, propriétés d'internalisation et de propagation pourrait expliquer l'hétérogénéité physiopathologique et clinique retrouvée dans la maladie de Parkinson et les autres synucléinopathies. Le but de ce projet était de déterminer comment interférer avec la liaison et la propagation "prion-like" de ces assemblages d'alpha-synucléines dans les neurones. Dans cet objectif, nous avons caractérisé les surfaces de trois souches d’alpha-synucléine. Dans un premier temps, nous avons mis en place des approches in vitro de protéolyses ménagées et de marquages hydrogène-deutérium combinées à la spectrométrie de masse qui nous ont permis de cartographier la surface d'agrégats fibrillaires d'alpha-synucléines générés in vitro. Dans un second temps, nous avons étudié la prise charge de différentes souches d’alpha-synucléine par des cultures primaires de neurones ou d’astrocytes afin d’analyser les caractéristiques de dégradation des souches in cellulo, liées à leurs spécificités de surface déterminées préalablement. La cartographie réalisée ouvre la voie, à long terme, au développement d’outils diagnostics ou thérapeutiques hautement spécifiques capables de reconnaitre spécifiquement différentes souches d’alpha-synucléine ou d’inhiber la propagation de cellule à cellule de ces agrégats afin de ralentir ou d'arrêter la progression de la maladieThe aggregation of alpha-synuclein and the spread of aggregates from neuron to neuron have been consistently shown to be at the heart of the pathophysiological process of devasting neurodegenerative diseases like Parkinson's disease, dementia with Lewy bodies or multiple system atrophy. While fibrillar alpha-synuclein rich deposits are a common hallmark of synucleinopathies, distinct pathological phenotypes are observed. We hypothesize that different "strains" of fibrillar alpha-synuclein with different affinity/tropism, internalization and seeding properties, may account for the patho-physiological and clinical heterogeneity in Parkinson's disease and other synucleinopathies. We aim to determine a way to interfere with the binding to neurons of distinct alpha-synuclein assemblies and their prion-like propagation. To this end, we mapped the surface of three distinct alpha-synuclein strains. First, we implemented limited proteolysis and hydrogene-deuterium approaches combined to mass spectrometry in order to map, in vitro, the solvent exposed-surfaces of fibrillar alpha-synuclein assemblies generated in vitro. Second, we studied the processing of different alpha-synuclein strains using primary cultures of neurons and astrocytes in order to analyze the strain degradation characteristics in cellulo, related to the surface specificities determined in vitro. Mapping the surfaces of those assemblies and identification of exposed and protected strain-specific sequences open the way, in the long term, for developing highly specific binders that might either detect specific alpha-synuclein strains or inhibit cell-to-cell propagation disease progression
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Fournet, Julie. "Contacts entre individus : analyse et application à l'étude de la propagation de maladies infectieuses." Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM4043/document.
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Les contacts face-à-face entre individus permettent de caractériser les réseaux sociaux et jouent un rôle prépondérant dans la compréhension des mécanismes de propagation des épidémies dans une population. De récentes avancées technologiques ont rendu possible l'acquisition de données précises sur les interactions humaines. Cette thèse présente, dans un premier temps, l'analyse de données de contacts collectées trois années de suite (2011, 2012 et 2013) dans un lycée français entre des étudiants de classes préparatoires. L'analyse a montré que la plupart des contacts se produisent entre étudiants de même classe et que les structures des contacts sont très similaires d'un jour sur l'autre. Dans un second temps, on compare différentes méthodes de collecte de données qui permettent d'obtenir des informations de nature différente (par exemple existence d'un contact face-à-face vs existence d'une amitié).L'utilisation de données rapportant les amitiés entre les étudiants ne permet pas d'obtenir une bonne estimation du réseau de contact (i.e., les amitiés ne correspondent pas forcément à des contacts face-à-face et vice versa) résultant en une sous-estimation du risque épidémique dans cette population.Dans la dernière partie, nous essayons de reproduire les biais provenant du réseau d'amitié en échantillonnant le réseau de contact. Ceci pourrait nous donner des indications sur comment compenser ces biais et comment utiliser des données incomplètes pour obtenir des prédictions fiables sur le risque épidémiqueFace-to-face contacts between individuals contribute to shape social networks and play an important role in determining how infectious diseases can spread within a population. Recently, technological advances have made it possible to obtain accurate data on human interactions.This thesis first presents the analysis of contact data collected three years in a row (2011, 2012 and 2013) in a French high school among students of "classes préparatoires" (i.e., studies taking place after high school and preparing for admission to higher education colleges). The analysis showed that most contacts occur within students of same classes and that contact patterns are very similar from one day to the next.Then, we compare different methods of data collection which allow to gather information of different nature (for instance existence of a face-to-face contact vs existence of a friendship).The use of data reporting friendships does not allow to obtain a good estimation of the contact network (i.e., friendships do not correspond necessarily to face-to-face contacts and vice versa) resulting in an underestimation of the epidemic risk in that population.Finally, we try to reproduce the biases coming from the friendship network by sampling the contact network. This might give hints on how to compensate these biases and how to use the information contained in incomplete data sets to obtain accurate predictions of the epidemic risk
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Tshilenge, Mfumu Jean-Claude. "Proposition d'une méthode organisationnelle pour la surveillance de la propagation des maladies chroniques et épidémiques : Application au système de santé de la RDC." Thesis, Université Grenoble Alpes, 2020. http://www.theses.fr/2020GRALM029.
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La surveillance de la propagation des maladies épidémiques constitue une préoccupation majeure dans le domaine de la Santé Publique des populations. Au XVIIème siècle voit le jour une discipline scientifique appelée épidémiologie qui se définit comme étant l’étude de la distribution des problèmes de santé et de leurs déterminants dans les populations humaines et application de cette étude à la prévention des problèmes de santé. On distingue deux modes de surveillance : active et passive. En surveillance active, l’enquêteur va chercher l’information auprès des participants, est pratiquée lors des grandes enquêtes transversales qui passent par l’échantillonnage de la population. En mode passif, la surveillance se fait sur base des informations que les formations sanitaires remontent vers les agences sanitaires.En République Démocratique du Congo, les autorités sanitaires ont adopté et adapté en 2011 une stratégie de surveillance intégrée des maladies et de la riposte proposée par l’Organisation Mondiale de la Santé en faveur des pays aux ressources très limitées. La mise en oeuvre de cette stratégie manquait un cadre organisationnel que nous proposons à travers notre travail de recherche.Nous proposons une méthode d’innovation organisationnelle dénommée CHICKEN dont la mise en oeuvre vise à contribuer aux problématiques soulevées par les professionnels de la pyramide sanitaire de la RDC à savoir : (i) améliorer la qualité de données sanitaires par la mise en place des modèles des processus réutilisables par les personnels de santé pour savoir bien identifier et confirmer des cas d’une pathologie ; (ii) mettre en place des outils d’analyses pour détecter les facteurs déterminants des épidémies selon leur périodicité dans le temps et dans l’espace tout en assurant des rappels automatiques aux formations sanitaires en manque de données ; et (iii) faciliter la coopération des acteurs pour améliorer ou optimiser l’anticipation des propagations des maladies épidémiquesMonitoring the spread of epidemic diseases is a major concern in the area of public health. In 17th century, a scientific discipline called epidemiology was born. It is defined as the study of the distribution of health problems and their determinants in human populations and the application of this study to the prevention of health problems. There are two modes of surveillance: active and passive. In active surveillance, the investigator will seek information from participants, is practiced during large cross-sectional surveys which involve sampling the population. In passive mode, surveillance is carried out on the basis of information that the health facilities send back to the health agencies.In the Democratic Republic of Congo, the health authorities adopted and adapted in 2011 an IDSR (Integrated Disease Surveillance and Response) strategy proposed by the World Health Organization in favor of the low-income and middle-income countries. The implementation of this strategy failed due to the lack of an organizational framework that we would propose through our research work.We propose an organizational innovation method called CHICKEN whose process and object models contribute to the problems raised by health professionals in the health pyramid of the DRC namely to : (i) improve the quality of health data by setting up process models that can be reused by health workers to properly identify and confirm the suspected cases of a pathology; (ii) set up analysis tools to detect the determinants of epidemics according to their periodicity in time and space while ensuring automatic reminders to health units in lack of data; and (iii) facilitate the cooperation between actors that can improve or optimize the anticipation of the spread of epidemic diseases
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Zhu, Seng. "Study of the mechanism of Tunneling nanotubes formation and their role in aggregate proteins transfer between cells." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS377.
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Les Tunneling nanotubes (TNT) sont des protrusions cellulaires à base d'actine qui médient la communication cellulaire en transférant des cargos cellulaires. Les différents types de communication intercellulaires sont de plus en plus considérés comme des cibles potentielles pour le traitement de différentes maladies, telles que les maladies infectieuses liées aux virus et bactéries, les cancers ou les maladies neurodégénératives. Des études récentes ont mis en évidence un mécanisme de propagation d'agrégats protéiques ressemblant à la propagation du prion dans diverses maladies neurodégénératives non infectieuses telles que la maladie d'Alzheimer (AD), la démence frontotemporelle (FTD), la maladie de Parkinson (PD) et la maladie de Huntington. Ces maladies se caractérisent par l'accumulation de protéines mal repliées dans le cerveau des patients. Ainsi, on peut envisager de nouvelles stratégies thérapeutiques pour bloquer la propagation des protéines anormales dans tout le cerveau. Il a été démontré que les TNT pourraient jouer un rôle essentiel dans la propagation des agrégats de prions au sein du système nerveux central (SNC) et périphérique. Par conséquent, l'étude du mécanisme de la formation de TNT pourrait fournir de nouvelles idées sur le mécanisme de propagation de la maladie et de nouvelles cibles thérapeutiques. L'objectif de ma thèse était d'étudier le rôle du transfert des agrégats de protéines par les TNT entre les cellules et d'étudier le mécanisme de formation des TNT. Dans notre laboratoire, nous avons déjà montré que les TNT permettent le transfert de prions entre les cellules. Dans la première partie de mon doctorat, j'ai confirmé que les transferts d'agrégats de prions entre les cellules de CAD neuronales se faisaient par les TNT à l'intérieur de vésicules endocytiques (Zhu et al., 2015). De plus, en collaboration avec un collègue, nous avons fourni des preuves que les agrégats de prions pourraient être transférés entre des astrocytes primaires et des neurones et que ce transfert était médié par un contact cellulaire (Victoria et al., 2016). J'ai également collaboré à une autre étude où nous avons montré que les agrégats d'α-synucléine (caractéristiques de la maladie de Parkinson) peuvent être transférés entre les cellules à l'intérieur des lysosomes, et que ce transfert intercellulaire est médié par les TNT (Abounit et al., 2016). Dans mon deuxième projet, afin d'étudier le mécanisme de la formation de TNT, j'ai effectué un crible à haut débit pour les Rab GTPase. J'ai trouvé que Rab8 et Rab11 peuvent favoriser la formation des TNT, et que les cascades Rab8-VAMP3, Rab11-ERM et Rab8-Rab11 sont impliquées dans la formation des TNT. Mes données suggèrent que la polymérisation de l'actine et le trafic de membranes sont impliqués dans la formation des TNT. Ces résultats permettent d'éclairer le mécanisme de la formation des TNT et de fournir des preuves moléculaires que les Rab GTPases régulent ce processusTunneling nanotubes are actin-based cell protrusions that mediate cell-to-cell communication by transferring cellular cargos. The different types of intercellular communication are increasing by being considered as potential targets for the treatment of various diseases, such as infectious diseases linked to viruses and bacteria, cancers or neurodegenerative diseases. Recent studies have highlighted a prion-like mechanism of propagation of protein misfolding in a variety of common, non-infectious, neurodegenerative diseases such as Alzheimer’s disease (AD), Frontotemporal dementia (FTD), Parkinson’s disease (PD), and Polyglutamine (PolyQ) diseases, which are characterized by the accumulation of misfolded proteins in the brain of patients. Thus, new therapeutic strategies to block propagation of protein misfolding throughout the brain can be envisaged. It has been shown that TNTs might play a critical role in spreading of prion aggregates within the CNS and from the periphery. Therefore, the study of mechanism of TNT formation could provide new insights on the mechanism of disease propagation and novel therapeutic targets. The aim of my thesis was to study the role of TNT-mediate protein aggregates transfer between cells and to investigate the mechanism of TNT formation. In our lab, we already reported TNT mediate prion transfer between cells. In the first part of my PhD, I further confirmed that prion aggregates transfer between neuronal CAD cells through TNT inside endocytic vesicles (Zhu et al., 2015). Furthermore in collaboration with a colleague, we provided evidences that prion aggregates could transfer between primary astrocytes and neurons and the transfer was mediated by cell-to-cell contact (Victoria et al., 2016). I also collaborated to another study where we showed that α-synuclein aggregates (Parkinson’s disease) can transfer between cells inside lysosomes, and the intercellular transfer is mediated by TNTs (Abounit et al., 2016).In my second project, in order to investigate the mechanism of TNT formation, I performed a High-content screening of Rab GTPase. I found that Rab8 and Rab11 can promote TNT formation, that Rab8-VAMP3, Rab11-ERM and Rab8-Rab11 cascades are involved in TNT formation. My data suggests that both actin polymerization and membrane trafficking are involved in TNT formation. These results help to shed light on the mechanism of TNT formation, and provide molecular evidences that Rab GTPases regulate this process
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Chakouch, Mashhour. "Viscoelastic properties of in vivo thigh muscle and in vivo phantom using magnetic resonance elastography (MRE)." Thesis, Compiègne, 2015. http://www.theses.fr/2015COMP2236/document.
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Résumé de l'étude in vitro. L'objectif de cette étude in vitro était de créer un fantôme avec la même architecture musculaire (fibre, aponévrose ...) et les mêmes propriétés mécaniques que le muscle en condition passive et active. Deux fantômes homogènes ont été fabriqués avec différentes concentrations de plastisol pour simuler les propriétés élastiques du muscle en condition passive (50% plastisol) et active (70% de plastisol). Pour cela, des fils en Téflon (d = 0,9 mm) ont été insérés dans la partie supérieure du fantôme (50%) pour représenter les fibres musculaires. De plus, une feuille en matière plastique (8 x 15 cm) a également été placée au milieu du fantôme pour imiter la structure de l'aponévrose. Ensuite, des tests ERM ont été effectués à 90 Hz avec deux stimulateurs pneumatiques de différentes formes (tube en silicone, membrane circulaire) pour analyser l'effet du type du stimulateur sur la propagation des ondes. La longueur d'onde a été mesurée à partir des images phase et les propriétés élastiques (module de cisaillement) ont été calculées. Les deux fantômes (50% et 70%) ont montré des propriétés élastiques similaires à celles du muscle à l’état passif (2,40 ± 0,18 kPa) et actif (6,24 ± 0,21 kPa). Le stimulateur en forme de tube a donné des valeurs plus élevées (environ 1,2 kPa à 1,53 kPa). L'analyse du comportement des ondes a révélé un glissement le long de la feuille plastique. Ce phénomène a aussi été observé in vivo le long de l’aponévrose. L'onde a également été sensible à la présence des fils en téflon car des coupures, des trous, ont été identifiés au cours de la propagation de l’onde. Une nouvelle méthode de post-traitement a été créée pour mesurer les paramètres G' et G" à partir de tests ERM réalisés à plusieurs fréquences (60, 80, 100 Hz) et en utilisant des modèles rhéologiques. Cette méthode a été testée sur un fantôme (50%) qui n’avait pas d’inclusion. Les résultats des mesures viscoélastiques (G', G") ont été validés avec la technique HFVS (Hyper-Fréquence viscoélastique Spectroscopy). Des valeurs similaires, G' et G’’, ont été obtenues avec les deux techniques. Ce dernier résultat valide la nouvelle méthode de post-traitement pour mesurer les propriétés viscoélastiques. Résumé de l'étude in vivo. L'objectif de cette étude in vivo a été de développer des protocoles ERM pour caractériser les propriétés élastiques (module de cisaillement) des neuf muscles de la cuisse. Ces tests ont été effectués à une seule fréquence (90 Hz). Différents modules de cisaillement ont été trouvés entre les muscles. Le gracilis a révélé des propriétés élastiques plus élevées que les autres muscles. Ces différentes élasticités peuvent être dues à différentes compositions physiologiques et architecturales entre les tissus. Ensuite, les propriétés viscoélastiques des muscles ischio (ST, SM, et la BC) et du muscle Gr ont été déterminées en appliquant la nouvelle méthode de post-traitement des données (précédemment validée sur le fantôme 50%) avec des tests ERM multi fréquences (70, 90 et 120 Hz) et en utilisant des modèles rhéologiques. Les résultats ont montré que deux modèles rhéologiques, Zener et springpot, peuvent être utilisés pour mesurer les propriétés viscoélastiques des muscles à l’état passif. De plus, des résultats similaires ont été trouvés entre G "/ G ', obtenus expérimentalement à 90 Hz, et la valeur α du modèle de springpotSummary of the vitro studies. The objective of this in vitro study was to create a phantom witch the same muscle architecture (fiber, aponeurosis …) and mechanical properties of muscle in passive and active states. Two homogeneous phantoms were manufactured with different concentrations of plastisol to simulate the muscle elastic properties in passive (50% of plastisol) and active (70% of plastisol) muscle conditions. Moreover, teflon tubing pipes (D = 0.9 mm) were thread in the upper part of the phantom (50%) to represent the muscle fibers and a plastic sheet (8 x 15 cm) was also included in the middle of the phantom to mimic the aponeurosis structure. Subsequently, MRE tests were performed at 90Hz with two different pneumatic drivers, tube and round shapes, to analyze the effect of the type of driver on the wave propagation. The wavelength was measured from the phase images and the elastic properties (shear modulus) were calculated. Both phantoms revealed elastic properties which were in the same range as in vivo muscle in passive (2.40 ± 0.18 kPa) and active (6.24 ± 0.21 kPa) states. The impact of the type of driver showed higher values with the tube (range: 1.2 kPa to 1.53 kPa). The analysis of the wave behavior revealed a sliding along the plastic sheet as it was observed for in vivo muscle study. The wave was also sensitive to the presence of the fibers where gaps were identified. A new post processing method was established to measure G’ and G” from experimental multi frequencies (60, 80, 100 Hz) MRE (MMRE) tests and rheological models. This method was tested on the phantom (50%) made without fiber. Cross validation of the viscoelastic (G’, G”) results was made with Hyper-Frequency Viscoelastic Spectroscopy (HFVS). Both techniques showed similar range of values for G’ and G” at the same frequencies. This last result validated our new data processing for the viscoelastic measurement. Summary of the in vivo studies. The objective of this in vivo study was to develop MRE protocols to characterize the elastic properties (shear modulus) of the nine thigh muscles. These tests were performed at a single frequency (90Hz). Different shear moduli were found between the muscles. The gracilis revealed the highest elastic properties compared to all the other muscles. These different elasticities may be due to different physiological and architectural compositions between the tissues. Then the viscoelastic properties of the ischio (ST, SM, and BC) and Gr muscles were determined based on our new data-processing method (validated on the phantom 50%) using MMRE tests (70, 90 and 120Hz) and rheological models. The results revealed that two rheological models, zener and springpot, can be used to measure the viscoelastic properties in passive state. A similar trend was found between the experimental ratios G”/G’ obtained at 90 Hz and the α value of the springpot model. The present MRE muscle protocol, and the viscoelastic data base, could be used as non-invasive diagnostic tools to evaluate tissue alterations, the progression of diseases, and the effect of treatments, such as the ongoing therapeutic trials for Duchenne muscular dystrophy
31
Huang, Yu-Fen, and 黃玉芬. "Inferring Drug-Disease Associations from Chemical, Genomic and Disease Phenotype Data Using Heterogeneous Network Propagation." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/63230664966352052537.
Full textAbstract:
碩士國立清華大學
資訊系統與應用研究所
101
During the last few years, the knowledge of drug, disease phenotype and protein has been rapidly accumulated and more and more scientists have been draw attention to inferring drug-disease associations by computational method. Development of an integrated approach for systematic discovering drug-disease associations by those informational data is an important issue. We combine three weighted networks of drug, genomic and disease phenotype data from available experimental data and knowledge then infer drug-disease associations by a hetero-network propagation approach. In the experiments, we adopt prostate cancer and colorectal cancer as our test data. We select the manually curated associations from comparative toxicogenomics database as our benchmark. The ranked results show that our proposed method obtains high specificity and sensitivity and clearly outperforms previous methods. We clearly demonstrate the feasibility and benefits of using network-based analyses of chemical, genomic and phenotype data to reveal drug-disease associations. The potential associations which were inferred by our method drew the biologists’ attention and provide new perspectives for toxicogenomics and drug reposition evaluation.
32
Cunha, Carolina. "Role of glial cells as contributors to the onset and propagation of als disease." Doctoral thesis, 2017. http://hdl.handle.net/10451/32317.
Full textAbstract:
Tese de doutoramento, Farmácia (Biologia Celular e Molecular), Universidade de Lisboa, Faculdade de Farmácia, 2017Amyotrophic lateral sclerosis (ALS) is a motor neuron (MN) disease comprehending critical neuroinflammatory pathways, where microglia and astrocytes play a crucial role. ALS onset events are largely unknown and identification of disease steps during progression and dissemination, including the possible role of exosomes, are not clarified. Several models were used to improve data validity and deepen knowledge in ALS. We identified innovative targets to regulate microglia M1 polarization, including NLRP3-inflammasome, HMGB1 alarmin and MFG-E8/lactadherin, and demonstrated the sorting of microglial microRNA(miR) 155/miR-146a into exosomes. We showed that ALS NSC-34 MNs and their exosomes are enriched in miR-124, which are captured and drive early N9-microglia M1 polarization, with later development of M1/M2 subpopulations containing increased miR-124/miR-146a/miR-155. Moving from in vitro models to the spinal cord of the SOD1G93A ALS mouse model, we observed that depressed intercellular communication and increased miR-155 were early disease events preceding the inflammatory status of the symptomatic stage. Upregulated CX3CL1-CX3CR1, connexin-43/pannexin-1 and miR-124/miR-125b/miR-146a/miR-21 emerged as candidate targets for pathological neuroinflammation. Reduced MN number, together with aberrant/reactive astrocytes showing deficient glutamate transporters and GFAP, additionally characterized such state. Differently deregulated profiles of microglia isolated from the spinal cord of 7-day old SOD1G93A mice, after short- and long-term cultures, highlighted that cells present transient phenotypes accordingly to ALS environmental progression-stimuli and ultimately acquire a less responsive phenotype to stimulation. Astrocytes isolated from these mice promoted diverse inflammatory polarized subtypes in wild-type and ALS microglia, thus accounting to microglia heterogeneous populations, while strengthened deregulated microglia-astrocyte cross-talk as part of ALS neurodegenerative mechanisms. Our studies in ALS models reveal early promising biomarkers and novel targets to control excessive neuroinflammation and spread, including exosomal microRNAs. Due to multiple microglia phenotypes induced by MNs and their exosomes, and by reactive astrocytes, in the ALS disease, differentiated and combined therapeutic approaches may be recommended.
Santa Casa da Misericórdia de Lisboa, programa de Investigação Científica em Esclerose Lateral Amiotrófica, projeto ELA-2015-002, The EU Joint Programme-Neurodegenerative Disease Research (JPND), projeto JPCOFUND/003/2015
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Manitz, Juliane. "Statistical Inference for Propagation Processes on Complex Networks." Doctoral thesis, 2014. http://hdl.handle.net/11858/00-1735-0000-0022-5F38-B.
Full textAbstract:
Die Methoden der Netzwerktheorie erfreuen sich wachsender Beliebtheit, da sie die Darstellung von komplexen Systemen durch Netzwerke erlauben. Diese werden nur mit einer Menge von Knoten erfasst, die durch Kanten verbunden werden. Derzeit verfügbare Methoden beschränken sich hauptsächlich auf die deskriptive Analyse der Netzwerkstruktur. In der hier vorliegenden Arbeit werden verschiedene Ansätze für die Inferenz über Prozessen in komplexen Netzwerken vorgestellt. Diese Prozesse beeinflussen messbare Größen in Netzwerkknoten und werden durch eine Menge von Zufallszahlen beschrieben. Alle vorgestellten Methoden sind durch praktische Anwendungen motiviert, wie die Übertragung von Lebensmittelinfektionen, die Verbreitung von Zugverspätungen, oder auch die Regulierung von genetischen Effekten. Zunächst wird ein allgemeines dynamisches Metapopulationsmodell für die Verbreitung von Lebensmittelinfektionen vorgestellt, welches die lokalen Infektionsdynamiken mit den netzwerkbasierten Transportwegen von kontaminierten Lebensmitteln zusammenführt. Dieses Modell ermöglicht die effiziente Simulationen verschiedener realistischer Lebensmittelinfektionsepidemien. Zweitens wird ein explorativer Ansatz zur Ursprungsbestimmung von Verbreitungsprozessen entwickelt. Auf Grundlage einer netzwerkbasierten Redefinition der geodätischen Distanz können komplexe Verbreitungsmuster in ein systematisches, kreisrundes Ausbreitungsschema projiziert werden. Dies gilt genau dann, wenn der Ursprungsnetzwerkknoten als Bezugspunkt gewählt wird. Die Methode wird erfolgreich auf den EHEC/HUS Epidemie 2011 in Deutschland angewandt. Die Ergebnisse legen nahe, dass die Methode die aufwändigen Standarduntersuchungen bei Lebensmittelinfektionsepidemien sinnvoll ergänzen kann. Zudem kann dieser explorative Ansatz zur Identifikation von Ursprungsverspätungen in Transportnetzwerken angewandt werden. Die Ergebnisse von umfangreichen Simulationsstudien mit verschiedenstensten Übertragungsmechanismen lassen auf eine allgemeine Anwendbarkeit des Ansatzes bei der Ursprungsbestimmung von Verbreitungsprozessen in vielfältigen Bereichen hoffen. Schließlich wird gezeigt, dass kernelbasierte Methoden eine Alternative für die statistische Analyse von Prozessen in Netzwerken darstellen können. Es wurde ein netzwerkbasierter Kern für den logistischen Kernel Machine Test entwickelt, welcher die nahtlose Integration von biologischem Wissen in die Analyse von Daten aus genomweiten Assoziationsstudien erlaubt. Die Methode wird erfolgreich bei der Analyse genetischer Ursachen für rheumatische Arthritis und Lungenkrebs getestet. Zusammenfassend machen die Ergebnisse der vorgestellten Methoden deutlich, dass die Netzwerk-theoretische Analyse von Verbreitungsprozessen einen wesentlichen Beitrag zur Beantwortung verschiedenster Fragestellungen in unterschiedlichen Anwendungen liefern kann.
34
Ruttum, Joanne C. "Development of in vitro lily scale budlets as related to virus elimination." Thesis, 1991. http://hdl.handle.net/1957/36587.
Full textAbstract:
Lily hybrids vary in their ability to produce
virus-free (VF) bulblets when grown from virus-infected
scales in tissue culture. Asiatic hybrids typically
produce a higher percentage of in vitro VF scale bulblets
than do Lilium longiflorum cultivars. Three hypotheses
concerning the cause of this variation are tested on five
lily hybrids: an Asiatic hybrid, two L. longiflorum
cultivars, an Oriental hybrid and L. candidum.
The first hypothesis states that VF scale bulblets
originate from wound tissue that is naturally low in virus
concentration and blocks the passage of virus particles
from one cell to the next. The second hypothesis says that
scale-to-bulblet vascular connections, which serve as virus
pathways, occur in hybrids showing high percentages of
virus-infected scale bulblets, while connections are absent
in those hybrids with low numbers of virus-infected
bulblets. The third hypothesis concerns the virus
concentration in the scale at the site of bulblet origin:
bulblets of hybrids producing large numbers of VF bulblets
originate from scale tissues low in virus concentration;
bulblets of low percentage VF bulblet hybrids originate
from scale tissues high in virus concentration.
The first two hypotheses are not supported by the
results of this study. First, lily bulblets do not
originate from wound tissue. Second, scale-to-bulblet
vascular connections consistently occur in 'Enchantment,'
an Asiatic hybrid, and occasionally occur in L. candidum.
Vascular connections are not detected in the low VF bulblet
producers, L. longiflorum cultivars 'Ace' and 'Nellie
White,' nor are they seen in the Oriental hybrid
'Stargazer.'
Speculative support exists for the third hypothesis
concerning uneven virus concentration in the scale.
Distinct virus particles are observed with the electron
microscope in the double virus-infected L. longiflorum
cultivars and not in the other singly-infected lilies. The
doubly-infected lilies produce a continuous layer of
divided cells in the adaxial subepidermis of the scale
where bulblets originate, whereas the singly-infected
lilies produce cell division masses in the same area but
only beneath forming bulblets.
This study suggests that virus particles in
L. longiflorum cultivars are more uniformly distributed
than particles in the other lilies examined. This occurs
not only at the site of bulblet origin but also throughout
the scale mesophyll. Whether this is due to concurrent
viral infection or to hybrid variation is unknown.Graduation date: 1992
35
Clayton, Kevin A. "Amyloid plaque deposition accelerates tau propagation via activation of microglia in a humanized app mouse model." Thesis, 2021. https://hdl.handle.net/2144/42695.
Full textAbstract:
Alzheimer’s disease is characterized by the formation of two major pathological hallmarks: amyloid plaques and neurofibrillary tangles. Although there have been many studies to understand the role of microglia in Alzheimer’s disease, it is not yet known how microglia can promote disease progression while actively phagocytosing amyloid plaques or phosphorylated tau (p-tau). Through stereotaxic injection of adeno-associated virus expressing mutant P301L tau (AAV-P301L-tau) into the medial entorhinal cortex (MEC) of both wild-type (WT) and APPNL-G-F mice, we demonstrate how amyloid plaques exacerbate p-tau propagation to the granule cell layer (GCL) of the hippocampus. However, in mice receiving the colony-stimulating factor 1 receptor inhibitor (PLX5622), ~95% of microglia were depleted, which dramatically reduced p-tau propagation to the GCL. Although microglia depletion curtailed p-tau propagation, it also led to reduced plaque compaction and an increase in overall amyloid-beta (Aβ) plaque presence. Additionally, we found microglia depletion resulted in greater p-tau aggregation in dystrophic neurites surrounding amyloid plaques. We investigated neurodegenerative microglia (MGnD), which are activated in response to amyloid plaques, for their propensity to release extracellular vesicles in comparison to homeostatic microglia. We discovered that MGnD, identified by Clec7a or Mac2 staining, strongly express Tumor susceptibility gene 101 (Tsg101), which is an ESCRT-1 protein and a marker for extracellular vesicles (EVs). To further investigate EV release and MGnD, a novel lentivirus expressing fluorescent mEmerald conjugated to CD9 (mE-CD9) was constructed and injected into the MEC of both WT and APPNL-G-F mice which allowed for visualization of mE-CD9+ puncta around individual microglia. CD9 is a tetraspanin and also a marker for EVs. We observed that the number of mEmerald+ particles surrounding MGnD was three-fold higher compared to non-diseased, homeostatic microglia. Sequential injection of mE-CD9 and AAV-P301L-tau into the MEC revealed that microglia-derived EVs encapsulate pathologic p-tau, which is augmented by the MGnD phenotype. Taken together, these data provide strong evidence that MGnD exhibit increased secretion of tau-containing EVs, providing a possible mechanism for how amyloid deposition indirectly exacerbates tau propagation.
36
Mohamed, Nguyen-Vi. "La sécrétion de la protéine tau : mécanisme de propagation de la pathologie de tau dans la maladie d’Alzheimer." Thèse, 2016. http://hdl.handle.net/1866/15973.
Full text
37
Huang, Ling-Yu, and 黃齡玉. "Propagation of infectious bursal disease virus in DF-1 cells and purification of virus particles by gel filtration." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/18241066971046205893.
Full text
38
Tai-Yuan, Chen, and 陳泰元. "The non-sterile propagation and mode of action of Streptomyces griseobrunneus S3 for controlling disease caused by Pythium aphanidermatum and Rhizoctonia solani AG4." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/93024043115365492523.
Full textAbstract:
碩士國立中興大學
植物病理學系
93
柒、英文摘要 The non-sterile propagation and mode of action of Streptomyces griseobrunneus S3 for controlling diseases caused by Pythium aphanidermatum and Rhizoctonia solani AG4. Chen Tai-Yuan The main objectives of this investigation were to establish a non-sterile propagation system (NSPS) for biological control application of Streptomyces griseobrunneus S3 (SGS3) and to explore the mode of action of the disease control observed. The tested biological control agent SGS3, originally isolated by Lai (2003) from citrus rhizosphere, has been shown having great potential for biofungicide application. The main attributes known pertaining to its effectiveness as biocontrol agent included the excellence in chitin and β-1,3-glucan degradation, and as well the antibiotic and sporulating activities. And for the biofungicide application, a pilot scale liquid fermentation technique platform was established; the yield of spore suspension of SGS3 reached 5x1011 cfu/ml. The establishment of a NSPS discussed in this investigation was aimed to provide a grower do-it-yourself (DIY) system for the mass propagation and reactivation of the fermenter produced spore biomass right before application and thus to reduce the cost of the biofungicide application. In a preliminary screening trial where that sterile culture system was applied, the provision of wheat bran at 3% was found the best among the tested grain varieties as natural substrate for supporting the spore production of SGS3 in a broth culture system. Urea at 0.2% was found to be an appropriate nitrogen supplement for boosting up the antibiotic activity of the produced broth culture. For the serial trials conducted to establish the NSPS technique, the test bacterium was cultured with the test growth medium without autoclave sterilization. In a NSPS broth culture using wheat bran as the major growth substrate, the growth of SGS3 appeared to fluctuate during the culturing period mainly because the presence of certain microbial contaminants. A 5-minute boiling treatment of the wheat bran broth medium was found helpful in reducing the interference of the contaminating microbes thus provided significantly increased yield. However, with the optimization of the cultural substrate formulation, the applied inoculants, and the buffer capacity of the growth medium, the interference of the contaminating microbes became non-significant and the boiling treatment appeared not necessary. In an optimized cultural condition using wheat bran broth as major nutrient constituent, the growth of SGS3 was greatly improved by the addition of 100 mM K2HPO4 and 0.1% oyster shell powder; the spore yield of SGS3 reached approximately 2x1012 cfu/ml 3 days after incubation. The stimulatory effect of K2HPO4 addition appeared to be associated with the buffer capacity provided. In addition to SGS3, the optimized NSPS established appeared to work for Streptomyces sp. S1, Streptomyces sp. S4, Streptomyces saraceticus S31; the spore yield all reached 1012 cfu/ml level except that of S31 which yielded only to 1010 cfu/ml. The usefulness of the established system in Streptomyces sp. biofungicide application was clearly indicated further by the fact that the disease control effectiveness provided by the NSPS broth culture was equibalent to that by the original fermenter produced culture broth. For seedling damping offs caused by Pythium aphanidermatum and Rhizoctonia solani AG4, effective disease control was demonstrated. By drenching treatment with SGS3 broth cultures at 100X in dilution 2 days (for P. aphanidermatum) to 4 days (for R. solani AG4) before seeding, the percent infection of the two diseases was reduced by 77 to 64%, respectively, as compared to the water treated control. A comparable disease control effectiveness was also demonstrated when SGS3 was applied by seed coating. What worth to mention is that when the pre-seeding drenching treatment was combined with seed coating, the percent infection of both targeted diseases was reduced over 81%; the protective effect was equivalent to that by the compared chemical treatment- metalaxyl (applied at 350 g a.i./ml for P. aphanidermatum) and pencycuron (applied at 250 g a.i./ml for R. solani AG4). The effectiveness of disease control appeared to be dosage dependent which relies primarily on the presence of SGS3 spore propagules. The role of metabolites present in the broth culture (i.e. cultural filtrate) appeared to be minor as regards to the disease control demonstrated although its presence did contribute some additive effect in counteracting the fungal invasion. Upon artificial inoculation of SGS3, the microscopic examination revealed that the applied bacterial spores germinate readily, grew on, coiled up and even penetrated the mycelia of P. aphanidermatum and R. solani AG4. The mycoparasitism led to rapid increase of electrolytes from the host fungal mycelia, and the parasitized mycelia appeared to be killed within 24 hours. The mycoparasitic effect was manifested by the formation of eroded concave lesion reflecting the functioning of chitin/glucan degrading enzymes; the activity was greatly stimulated by the addition of chitin whereas was repressed by the addition of glucose. The killing of target fungi, as revealed by fluorescen diacetate/propidium iodide vital staining, was detected before dismantling of the fungal cell became apparent indicating the involvement of antibiotics during the process. The fast and lethal mycoparasitic activity well illustrated how SGS3 helps plants fight with the fungal pathogens. As for the disease control, the effect of SGS3 application on the disease resistance was investigated using tomato as a model. An enhanced expression of PR-1 (pathogenesis related protein 1) gene, indicating the induction of resistance gene expression, was detected consistently from foliar tissue after drenching treatment of SGS3. As the induced PR-1 gene expression was detected from the culture broth treated rather than the culture filtrate treated plants, the existence of SGS3 propagules again appeared to be critical. The data herein presented indicates clearly the disease control by SGS3 is a result of multiple mode of action including mycoparasitism, antibiotic activity, and induced resistance. The effective disease control equivalent to that by chemical fungicides was demonstrated. The success of NSPS development warrant the innundative application of the viable, active SGS3 propagules in practical application.
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Mitchell, Richard Glen. "Factors affecting the successful deployment of Pinus patula as rooted cuttings." Thesis, 2005. http://hdl.handle.net/10413/4474.
Full textAbstract:
Summary:
The future mass propagation of elite families of Pinus patula by cuttings is a realistic
method of deployment if the short-term performance of cuttings and seedlings are
confirmed at harvesting. This will impact significantly on the future outlook of forestry in
South Africa as softwood yields are improved substantially through the introduction of
material of high genetic value in commercial plantings. This, however, will require
significant changes in future silviculture and other management practices as foresters and
plantation staff learn to regenerate, maintain, and schedule the harvesting of cutting
stands according to a different set of demands as a result of the change in plant type.
Contrary to operational experience, cutting survival was similar to seedling survival in all
field studies. This indicates that factors other than those that were studied and reported
on, such as planting techniques, may be contributing to mortality. Also, due to the
different root structure of cuttings they may be more fragile. The similar survival
observed in these trials, therefore, may have been due to the close supervision given to
the planting operations by the research staff. Although survival was similar, both plant
types survived unacceptably poorly in the majority of studies with an average stocking of
approximately 50% at one year. It is therefore anticipated that commercial stands will
require several blanking operations in order to achieve an acceptable stocking in excess
of 85% by the following planting season. The reduction in expected profitability as a
result of blanking costs, delayed establishment, and the loss of improved genetic plant
material, indicates that this is an area that still requires further research irrespective of
what plant type is being planted.
The pathogen, Fusarium circinatum, was commonly isolated from the planting stock
before and after planting in two studies. Due to its virulent nature, it was assumed that
mortality on the trees on which F. circinatum was isolated was principally due to this
pathogen. At planting all plants were observed to be healthy and free of disease
indicating that this pathogen maybe carried from the nursery to the field in a cryptic form,
either inside or outside the plant tissue , which results in the death of the newly planted
tree. In two field studies, where F. circinatum was commonly isolated, the application of
Benomyl fungicide and to some extent the biological control agent Trichoderma
harzianum at planting appeared to improve survival although this improvement was not
significant. Laboratory studies, designed to determine alternatives to Benomyl fungicide,
indicated that three fungicides (Octave, Folicur and Tilt), three sterilants (Sporekill®,
Prasin®and Citex®) , as well as a biological control agent (T.harzianum), were all highly
successful in controlling F. circinatum colony growth in vitro. It is recommended that
these products undergo nursery testing , where the plant material is inoculated with F.
circinatum spores, in order to test their efficacy and possible phytotoxicity in vivo before
commercial application.
Post-planting survival was also affected by site climate . Greater temperature extremes, as
well as lower humidity and less rainfall resulted in poor survival. Plant dimension at
planting was found to interact with site quality where it was a significant factor on a poor
quality site. Optimal cutting dimensions at planting was a root collar diameter of 2.8 - 3.2
mm, and a stem height greater than 7 cm at planting for cuttings produced in cavities
90 ml in volume. Optimal seedling dimensions at planting were a root collar diameter of
1.8 - 2 mm, and a stem height of 10 - 15 cm for seedlings produced in cavities 80 ml in
volume.
In a separate study, plant morphological criteria influenced medium-term growth, where
greater root mass and thicker cutting root collar diameters at planting improved field
growth performance for seven years after planting. A greater root mass at planting was
achieved by raising cuttings in containers that could support greater medium volume.
From the study it was concluded that cuttings should be raised for an approximate period
of 9 months in container cavities no smaller than 80 ml in volume and possess an oven-dry
root mass of 0.3 - 0.5 g at planting. In addition to similar survival, the cuttings in this
study grew either similarly to, or in some cases out-performed, the seedlings that were
used as a control.
Several other published studies indicate that hedge maturation poses the greatest threat to
the success of softwood cutting deployment. This is especially true in clonal forestry and
methods to maintain juvenility, such as cold storage of shoots and cryopreservation,
require further research before clonal plantations of P. patula can be realised. In the
studies carried out on family hedges in this report, the effect of donor hedge maturation
was found to influence nursery management practice and the characteristics of rooted
cuttings. The nursery data indicates that rooting efficiency, root system quality, and stem
size and form, all decline with increasing hedge age particularly from two years after the
date of sowing. A decline in root system quality was particularly apparent and was
observed prior to a decline in rooting efficiency. If field trials indicate poorer
performance from older hedges , it may be necessary to determine whether the causes are
purely ontogenetic, morphological, or both before drawing final conclusions about hedge
longevity. Until such results are known, it is recommended that P. patula cuttings should
be propagated from seedling donors maintained as hedges , approximately 15 cm high, for
a period not more than three years from the date of sowing.Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2005.
40
Ojelade, Babatube Solomon. "Regeneration potential of selected medicinal plants used to treat human and livestock diseases in Limpopo Province of South Africa." Diss., 2017. http://hdl.handle.net/11602/1069.
Full textAbstract:
MSCAGR ( Plant Production)Many high valued tree species of medicinal significance in the Limpopo Province, South Africa exhibit seed dormancy, and also contain aromatic oils which inhibit rooting of their stem cuttings. These plant species are under pressure due to human over-exploitation. The main objective of this study was to investigate effects of rooting hormones on the rooting ability that will help in domesticating some of the selected high valued medicinal plants, Elaeodendron transvaalense (bushveld saffron), Brackenridgea zanguebarica (yellow peeling plane), and Warburgia salutaris (pepper-bark tree). Stem cuttings of these plant species were prepared and treated with various concentrations (500, 1000 and 2000 ppm) of IBA, IAA and NAA in different growth media (Natural soil, farm soil and hygromix) at a nursery house. 180 experimental units were sown and arranged in Randomized Complete Block Design (RCBD), each treatment replicated five times and then monitored for a period of three months. Data were only obtained from Brackenridgea zanguebarica as other species dried up two weeks after sprouting. The two variables measured from the experiments were sprouted stems and number of leaves. The data obtained were subjected to analysis of variance and least significant difference (LSD) at 5% probability level was used to compare treatment using STATISTICA software analysis package. The hormone, hormone concentration, growth media and their interactions had effect on sprouted stems and number of leaves produced on Brackenridgea zanguebarica cuttings, with no record of rooting ability. IBA (500 ppm and 1000 ppm) and control (without rooting hormone) showed high significant results with natural soil and farm soil in terms of leaf production compared to the hygromix, which is significantly lower from others. IBA at the various concentrations (500, 1000 and 2000 ppm) and the control gave the highest percentage sprouted stem on both natural soil and farm soil as compared with other hormones at the same
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