<p> Impairments in various aspects of language, including the manipulation and comprehension of verbal and written language, are common in pediatric populations. Some disorders of language are secondary to other clinical presentations, while others, such as dyslexia (or reading disability [RD]), language impairment (LI), speech sound disorder (SSD), and autism spectrum disorders (ASD), have primary deficits in language skills. Each of these is a distinct disorder with unique clinical presentations and deficits. For instance, children with RD have deficits in reading and the use of written language, while those with LI have deficits in the manipulation and comprehension of verbal language. Additionally, children with SSD have difficulties in the production of speech sounds, while children with ASD may have delays or regressions in language and an inability to use complex, proper syntax and pragmatics. However, there is substantial comorbidity of these disorders, as children affected with one of these disorders are more likely to have or develop another disorder than their typically developing peers. These 'disorders&mdash;RD, LI, SSD, and ASD&mdash;are complex traits, with significant environmental and genetic components contributing to each. Similar to their phenotypic relationships, there is limited evidence that these disorders may share genetic contributors. In fact, these shared genetic components may explain the common phenotypic comorbidities of these disorders. Therefore, the overall goal of this project is to determine whether and to what extent RD, LI, SSD, and ASD share genetic associations with the hypothesis that these disorders have common genetic contributors. To accomplish this goal, I assess whether genetic associations were shared among these disorders or specific to individual disorders. First, I expand the association of the RD environmental risk factor, prenatal exposure to nicotine, to include LI and show the association of dopamine-related genes <i> ANKK1</i> and <i>DRD2</i> to LI. Second, two RD risk genes, <i> DCDC2</i> and <i>KIAA0319</i>, located within the DYX2 locus on chromosome 6p22, show associations with both LI and SSD. Third, I identify <i> ZNF385D</i> as a novel risk gene for subjects affected with comorbid RD and LI. I also assess the neuroimaging implications of DYX2 genes and <i> ZNF385D</i>, specifically in regards to cortical thickness, fiber tract volume, and fractional anisotropy. Finally, two LI risk genes, <i>ATP2C2 </i> and <i>CMIP</i> located within the SLI1 locus on chromosome 16, are associated with language skills of subjects with ASD. Taken together, these results characterize the relationship of previously identified risk genes to other related language disorders and identify novel risk genes that specifically contribute to language comorbidity. Shared genetic associations among these language disorders appear to be commonplace as opposed to the exception. However, the question remains of how these genetic variants interact with each other and other genes/exposures to ultimately lead to one or more of these language deficits seen clinically.</p>

<p> The worm <i>Caenorhabditis elegans</i> is a well-studied model organism in numerous aspects of its biology. This small free living nematode has less than 1,000 cells, but shows clear conservation in both signaling and behavior to mammals in aspects of appetite control. This is of importance to humans, where failure of appetite control is a major factor in the unprecedented obesity epidemic that we see today. </p><p> In general, worm behavior reflects its internal nutritional state and the availability and quality of food. Specifically, worms show a behavioral state that mimics aspects of the mammalian behavioral satiety sequence, which has been termed satiety quiescence. We have used locomotion tracking and Hidden Markov Model analysis to identify worm behavioral state over time, finding quiescence along with the established worm locomotive behaviors roaming and dwelling. Using this analysis as well as more conventional cell biology and genetic approaches we have further investigated satiety signaling pathways. We have found that the neuron ASI is a major center of integration of signals regarding the internal nutritional state of the worms as well as the nutritional content of its environment. Our results show that cGMP causes levels of the TGF&beta; ligand to be increased in fasted worms, which is then released and binds to its receptor on the RIM and RIC neurons. This signaling connects nutritional state to behavioral response, promoting the sleep-like behavioral state satiety quiescence. Additionally, we have begun a candidate approach examining several other groups of signaling molecules for potential roles in satiety quiescence signaling including cannabinoids, multidrug resistance proteins, and neuropeptides. The result of this investigation is a better understanding of mechanisms of satiety quiescence signaling as well as a new tool that provides highly quantitative, unbiased, and automated data to aid in our ongoing work.</p>

Made available in DSpace on 2016-12-23T14:37:56Z (GMT). No. of bitstreams: 1 Thais Prando Oliveira.pdf: 1106882 bytes, checksum: 9256d7e852794b97281e6e4eb3eefbd2 (MD5) Previous issue date: 2012-08-20 / Esta pesquisa investigou, em uma abordagem psicogenética, aspectos do funcionamento cognitivo de crianças por meio de um jogo regras com base na teoria de Piaget. Participaram do estudo 21 crianças, de ambos os sexos, com idades de oito e doze anos, de uma escola pública de Ensino Fundamental de Vitória-ES. A coleta de dados ocorreu em três encontros por dupla, utilizando-se como instrumento o jogo Lig-4 e um protocolo contendo questões e situações-problema. O primeiro encontro foi realizado em duas etapas: uma de aprendizagem e outra de prática do jogo. O segundo em dois momentos, sendo um destinado à prática do jogo e outro à primeira avaliação do nível de análise heurística. No terceiro realizou-se a prática do jogo e a segunda avaliação do nível de análise heurística. Os dados foram analisados por meio de níveis de análise heurística formulados em relação aos Sistemas Cognitivos I e II propostos por Piaget. Entre os resultados, verificou-se que a situação destinada à primeira avaliação e a ampliação da prática do jogo, não possibilitaram uma melhora expressiva no nível de análise heurística dos participantes de ambas as idades na segunda avaliação. No entanto, comparando-se o desempenho das crianças das duas idades, constatou-se que o das de doze anos foi superior ao das de oito anos, sendo que no Sistema Cognitivo I elas alcançaram níveis mais complexos do que no Sistema Cognitivo II. Conclui-se que o jogo Lig-4 mostrou-se adequado para a análise de Sistemas Cognitivos, fornecendo subsídios para trabalhos de avaliação e intervenção / This research has investigated, in a psychogenetic approach, childrens cognitive function aspects through a game of rules based on Piagets theory. Twenty-one children participated in this study, from both genders, ages varying from eight to twelve, from a public elementary school from Vitória ES. Data gathering occurred in three meeting per pair, utilizing the game lig-4 and a protocol containing questions and problem-situations. The first meeting was made in two phases: learning and game practice. The second one, in two moments, being one destined to game practice and, the other one, to the first assessment of heuristic analysis level. On the third meeting there were more game practice and the second assessment on heuristic analysis level. Data was analyzed using heuristic analysis levels formulated in relation to Cognitive Systems I and II proposed by Piaget. Among the results, it was verified that the situation destined to the first assessment and game practice expansion did not offer an expressive improvement on heuristic analysis level in the participants from both ages on the second assessment. However, comparing both participants performances, it was stated that the twelve-year-olds performances was superior than the eight-year-olds , taking in consideration that on Cognitive System I they ve achieved more complex levels than on Cognitive System II. It was concluded that, the game lig-4 was adequate to analyze Cognitive Systems, providing resources for evaluation and intervention jobs