889 resultados para Esclerose lateral amiotrófica


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The lateral septum is associated with the regulation of innate behavior, motivation, and locomotion. Its complex interconnections with cognitive and affective regions such as the hippocampus, hypothalamus, and medial septum have made it an attractive region for studying how motivation regulates behavior in context-specific settings. This GABAergic brain region’s main output is the lateral hypothalamus, which provides downstream signaling of motor commands. Even though stimulation of lateral septum projections to the hypothalamus have shown to decrease running speed in free behaving mice, characterizing movement kinematics due to LS activation has not been studied. GABAergic medium spiny neurons of the lateral septum were selectively activated through the use of optogenetic techniques in transgenic mice. Photostimulation of the lateral septum at theta frequencies caused a non-significant decrease in head and back speed. 3D motion analysis of body movement under photostimulation was quantified, revealing a slow, linear decrease of body speed as photostimulation progressed. These results support the role of lateral septum activation in movement regulation and shed light on the specific manner in which stimulation of the LS gradually decreases movement speed.

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A functional nervous system requires the precise arrangement of all nerve cells and their neurites. To achieve this correct assembly, a myriad of molecular guidance cues works together to direct the outgrowth of neurites to their correct positions. The small nematode C. elegans provides the ideal model system to study the complex mechanisms of neurite guidance due to its relatively simple nervous system, composed of 302 neurons. I used two mechanosensory neurons, called the posterior lateral microtubule (PLM), to investigate the role of the ephrin and Eph receptor protein family in neurite termination in C. elegans. Activation of the C. elegans Eph receptor VAB-1 on the PLM growth cone is sufficient to cause PLM termination, but the identity and location of the activating ligand has not been established. In my thesis I investigated the ability of the ephrin ligand EFN-1 to activate VAB-1 to cause PLM termination when expressed on the same cell (in cis) and on opposing cells (in trans) to the receptor. I showed that EFN-1 is able to activate VAB-1 in cis and in trans to cause PLM termination. I also assessed the hypodermal seam cells as the source of the ephrin stop cue using fluorescently labelled and seam cell mutant transgenic worms. I found that although the PLM shows consistent termination on the seam cell V2 in wild type worms independent of PLM length, this process is not significantly disrupted in seam cell mutants. With this information I have created a new hypothesis that the PLM neurite is able the provide a positional cue for the developing seam cells, and have created a new transgenic strain which can be used to assess the impact of PLM and ALM cell ablation on seam cell position. My research is the first to demonstrate the ability of an ephrin ligand to activate its ephrin receptor in cis, and further research can investigate if this finding has in vivo applications.

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The spacing of adjacent wheel lines of dual-lane loads induces different lateral live load distributions on bridges, which cannot be determined using the current American Association of State Highway and Transportation Officials (AASHTO) Load and Resistance Factor Design (LRFD) or Load Factor Design (LFD) equations for vehicles with standard axle configurations. Current Iowa law requires dual-lane loads to meet a five-foot requirement, the adequacy of which needs to be verified. To improve the state policy and AASHTO code specifications, it is necessary to understand the actual effects of wheel-line spacing on lateral load distribution. The main objective of this research was to investigate the impact of the wheel-line spacing of dual-lane loads on the lateral load distribution on bridges. To achieve this objective, a numerical evaluation using two-dimensional linear elastic finite element (FE) models was performed. For simulation purposes, 20 prestressed-concrete bridges, 20 steel bridges, and 20 slab bridges were randomly sampled from the Iowa bridge database. Based on the FE results, the load distribution factors (LDFs) of the concrete and steel bridges and the equivalent lengths of the slab bridges were derived. To investigate the variations of LDFs, a total of 22 types of single-axle four-wheel-line dual-lane loads were taken into account with configurations consisting of combinations of various interior and exterior wheel-line spacing. The corresponding moment and shear LDFs and equivalent widths were also derived using the AASHTO equations and the adequacy of the Iowa DOT five-foot requirement was evaluated. Finally, the axle weight limits per lane for different dual-lane load types were further calculated and recommended to complement the current Iowa Department of Transportation (DOT) policy and AASHTO code specifications.

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Sound localisation is defined as the ability to identify the position of a sound source. The brain employs two cues to achieve this functionality for the horizontal plane, interaural time difference (ITD) by means of neurons in the medial superior olive (MSO) and interaural intensity difference (IID) by neurons of the lateral superior olive (LSO), both located in the superior olivary complex of the auditory pathway. This paper presents spiking neuron architectures of the MSO and LSO. An implementation of the Jeffress model using spiking neurons is presented as a representation of the MSO, while a spiking neuron architecture showing how neurons of the medial nucleus of the trapezoid body interact with LSO neurons to determine the azimuthal angle is discussed. Experimental results to support this work are presented.

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[ES]En este proyecto se ha desarrollado un prototipo de un videojuego en 2D con perspectiva lateral. El juego es fundamentalmente un juego de peleas en el que se usa una pelota para combatir. El objetivo es derrotar al rival, consiguiendo que la pelota le golpee y evitando recibir golpes mediante el uso de los controles apropiados. Está ambientado en un mundo futurista y los combates tienen lugar en naves espaciales o planetas alienígenas. Para el desarrollo de este juego se ha empleado el motor de videojuegos Unity 5, además de recursos creados por la propia autora u obtenidos de diversas fuentes de contenido open-source.

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Thesis (Master's)--University of Washington, 2016-08

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On-site detection of inoculum of polycyclic plant pathogens could potentially contribute to management of disease outbreaks. A 6-min, in-field competitive immunochromatographic lateral flow device (CLFD) assay was developed for detection of Alternaria brassicae (the cause of dark leaf spot in brassica crops) in air sampled above the crop canopy. Visual recording of the test result by eye provides a detection threshold of approximately 50 dark leaf spot conidia. Assessment using a portable reader improved test sensitivity. In combination with a weather-driven infection model, CLFD assays were evaluated as part of an in-field risk assessment to identify periods when brassica crops were at risk from A. brassicae infection. The weather-driven model overpredicted A. brassicae infection. An automated 7-day multivial cyclone air sampler combined with a daily in-field CLFD assay detected A. brassicae conidia air samples from above the crops. Integration of information from an in-field detection system (CLFD) with weather-driven mathematical models predicting pathogen infection have the potential for use within disease management systems.

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Thesis (Master's)--University of Washington, 2016-08

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A mamografia é, atualmente, o principal método de diagnóstico imagiológico da patologia mamária, sendo, por isso, essencial a produção consistente de imagens mamográficas de elevada qualidade. Assim, e uma vez que a mamografia visa a maximização da visualização do tecido mamário, o principal objetivo deste estudo consiste em investigar a apresentação mamográfica do músculo grande peitoral na incidência oblíqua médio-lateral (OML) da mama. Pretendeu-se relacionar os padrões técnicos de aquisição de imagem à forma de apresentação do referido músculo, avaliando-os de acordo com os atuais critérios de qualidade de imagem. As imagens mamográficas foram recolhidas a partir de duas instituições hospitalares de referência do Porto, sendo posteriormente efetuada uma análise e tratamento estatístico dos indicadores qualitativos e quantitativos de qualidade das mesmas. Numa análise global por instituição, e tendo por base estes indicadores, a instituição que utiliza uma angulação fixa do potter-bucky, independentemente do biótipo corporal da paciente, apresentou resultados melhores, indicando assim que a existência de falhas devido a erros de posicionamento é menor por comparação aos critérios de qualidade padrão. Constatou-se, portanto, que a angulação do potter-bucky tem um impacto relevante e estatisticamente significativo na qualidade das imagens mamográficas.

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Strigolactones are a group of plant compounds of diverse but related chemical structures. They have similar bioactivity across a broad range of plant species, act to optimize plant growth and development, and promote soil microbe interactions. Carlactone, a common precursor to strigolactones, is produced by conserved enzymes found in a number of diverse species. Versions of the MORE AXILLARY GROWTH1 (MAX1) cytochrome P450 from rice and Arabidopsis thaliana make specific subsets of strigolactones from carlactone. However, the diversity of natural strigolactones suggests that additional enzymes are involved and remain to be discovered. Here, we use an innovative method that has revealed a missing enzyme involved in strigolactone metabolism. By using a transcriptomics approach involving a range of treatments that modify strigolactone biosynthesis gene expression coupled with reverse genetics, we identified LATERAL BRANCHING OXIDOREDUCTASE (LBO), a gene encoding an oxidoreductase-like enzyme of the 2-oxoglutarate and Fe(II)-dependent dioxygenase superfamily. Arabidopsis lbo mutants exhibited increased shoot branching, but the lbo mutation did not enhance the max mutant phenotype. Grafting indicated that LBO is required for a graft-transmissible signal that, in turn, requires a product of MAX1. Mutant lbo backgrounds showed reduced responses to carlactone, the substrate of MAX1, and methyl carlactonoate (MeCLA), a product downstream of MAX1. Furthermore, lbo mutants contained increased amounts of these compounds, and the LBO protein specifically converts MeCLA to an unidentified strigolactone-like compound. Thus, LBO function may be important in the later steps of strigolactone biosynthesis to inhibit shoot branching in Arabidopsis and other seed plants.

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Introdução: A esclerose sistémica (ES) é uma doença reumática rara, onde se verifica uma reacção auto-imune, afectando o tecido conjuntivo. De etiologia desconhecida, esta patologia, dividide-se em dois subtipos: limitada e difusa, tendo como processos característicos e inter-relacionados: a lesão vascular, a reacção autoimune e a fibrose. As células NK modulam as doenças auto-imunes através das suas capacidades citotóxicas e de produção de citocinas. Deste modo procedeu-se ao estudo imunofenotípico e funcional de duas sub-populações de células Natural Killer (NK) (NK CD56dim e NK CD56bright). Métodos: Recorrendo à citometria de fluxo, caracterizamos fenotipicamente as células NK, com base na expressão de CD49e, CD29 e LAIR-1; funcionalmente, com base nas citocinas TNF-α e IFN-γ e citotoxicamente, com base na granzima B e na perforina. Resultados: Os nossos resultados sugerem uma diminuição da percentagem e valor absoluto de células NK totais e suas subpopulações, NK CD56dim e NK CD56bright, em doentes com ES, sobretudo na presença de úlceras digitais (UD) e fibrose pulmonar (FP). Observamos ainda uma diminuição da expressão de CD49e e um aumento da expressão de LAIR-1, nas células NK, em doentes com ES, principalmente nos que não apresentavam UD e FP. Num modo geral observou-se um aumento da frequência de células NK a expressar granzima B e perforina e um aumento da expressão destas duas proteínas. Conclusão: Concluímos que as células NK poderão ter um papel importante na fisiopatologia da ES, pelas alterações fenotípicas e funcionais, podendo, futuramente vir a ser utilizados na monitorização da severidade desta doença.

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