Indiana University-Purdue University Indianapolis (IUPUI) / The relationship between gene copy number and protein expression levels has not thoroughly been examined in humans or mouse models of Down syndrome (DS) in relationship to developmental changes in the trisomic brain. Found on human chromosome 21 (Hsa21) and triplicated in DS, Dual-specificity tyrosine-phosphorylated regulated kinase 1A (DYRK1A) has been linked in DS to neurological deficits by restricting cell growth and proliferation. Little information exists regarding DYRK1A during perinatal development and how its expression may lead to cognitive deficits, and none exists that explores the gene-to-protein relationship during these critical time periods. This study aims to 1) Quantify variable DYRK1A expression across development as a function of age, sex, and brain region in trisomic Ts65Dn mice compared to euploid counterparts and 2) establish that the spatiotemporal pattern of developmental DYRK1A in the brain is not influenced solely by gene copy number, and that reduction of Dyrk1a in euploid and trisomic mice does not result in a corresponding global reduction of DYRK1A expression. DYRK1A was quantified in three areas of the postnatal brain at seven ages using the Ts65Dn mouse, the most studied model of DS, and found that trisomic expression is significantly increased on postnatal day ([P]6), declining by the third week to near euploid levels. We also uncovered a sexual dimorphic expression of DYRK1A when comparing animals of different sexes within the same genotype. Data from Dyrk1a knockdown mice indicated that reducing only Dyrk1a in euploid and in otherwise trisomic animals yields highly variable levels of DYRK1A, dependent on sex and tissue type, supporting the non-intuitive relationship between gene dosage and protein expression. These data emphasize the need to understand the age-dependent regulation of antecedent conditions that are causing changes in Dyrk1a expression in the brain.

The purpose of this study was to examine whether cut-points developed for the general population provide different estimates of physical activity (PA) levels in adults with Down syndrome (DS) compared to cut-points developed specifically in adults with DS. This study also attempted to objectively measure the PA levels of adults with DS and to determine if they meet the recommended amount of PA to obtain health benefits. Thirteen adults with DS wore an accelerometer to determine time spent in moderate, vigorous, and moderate-to-vigorous PA. Results indicated that different sets of cut-points responded differently in classifying moderate and vigorous PA levels, as well as in classifying whether participants met the recommended amount of PA for health benefits, as evidenced by the different estimates of moderate-to-vigorous PA in 10 minute bouts. Results also indicated that population specific cut-points should be used for assessment of PA levels in persons with DS.

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Previous research has indicated found that individuals with Down syndrome (DS) have difficulties in processing auditory information for the planning of movements relative to their peers with undifferentiated developmental handicaps. This modality-specific information-processing difficulty has been found for the preprogramming of goal-directed aiming movements (Le Clair & Elliott, 1995) and in simple reaction times (Davis, Sparrow, & Ward, 1991; Hermelin, 1964). The purpose of the present study was to assess whether or not a model of atypical cerebral specialization for the perception of speech sounds, proposed by Elliott and colleagues, could explain these findings. Thus, participants performed a choice reaction aiming task under three conditions. Colour-coded targets were cued by a visual cue at the target location, a visual cue remote from the target location, or a verbal cue identifying the target. Results revealed that while the reaction times did nCit differ between the two groups with handicaps, the participants with DS, unlike the two control groups, had significantly longer movement times in the verbal than in two visual conditions. These results support the model of biological dissociation. / Thesis / Master of Science (MS)

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Neste trabalho foi estudado o crescimento de fibras monocristalinas de LiYF4 (YLF) dopadas com Er3+ ou Nd3+ pelo método de micro-pulling-down (-PD) no modo resistivo. Para otimização do processo de crescimento foi, desenvolvida nova metodologia de confecção de cadinhos, de forma a torná-los mais rígidos permitindo sua utilização em mais de uma experiência, aumentando a reprodutibilidade do processo. A câmara de crescimento também foi modificada para obtenção de vácuo da ordem de 10-7 torr. Devido ao tratamento térmico do sistema sob alto vácuo, antes da fusão do material, não foram observados transientes iniciais no processo de puxamento das fibras de YLF dopadas. Foram crescidas fibras de YLF:Nd com concentrações de 0,5, 1 e 1,5 mol% e fibras de YLF:Er com 1, 10, 20 mol %, com diâmetros da ordem de 0,7 mm e comprimentos de até 120mm. Devido a problemas mecânicos do sistema, o ancoramento das fibras, ou seja, o equilíbrio na interface sólidoliquido, mostrou-se muito difícil, sendo necessárias várias correções nos parâmetros de crescimento para estabilização da interface sólido-líquido resultando na formação de defeitos, principalmente na superfície, em regiões ao longo das fibras. Nas condições do presente estudo, o uso de uma atmosfera estática mostrou-se desfavorável. Testes de ganho efetuados com a fibra de YLF:Nd dopada com 1,5mol%, mostraram um ganho superior às perdas comprovando seu potencial para ação laser. / In the present work, we studied the growth of single crystal fibers of LiYF4 (YLF) doped with Er3+ or Nd3+ by the resistive micro-pulling-down (-PD) tecnhique. A new method for crucible preparation was developed to improve the growth process. The use of better-built crucibles allows their use in more than one experiment, increasing the process reproducibility. The growth chamber was also modified to achieve vacuum of approximately 10-7 torr. The previous thermal treatment under high vacuum before charge melting eliminate the initial transient reported in previous works of YLF doped fibers growth. Single crystal fibers of YLF:Nd (0.5, 1 e 1.5 mol%) and YLF:Er (1, 10 and 20 mol %), with 0.7 mm diameters and up to 120mm of length were grown. Mechanical problems in the micro-PD system equipment made difficult the control of the solid-liquid interface, and several corrections on the experimental parameters were necessary during the growth process, resulting in defects formation, mainly on the fibers surface. In the experimental conditions of this work, the use of a static atmosphere showed not appropriate for elimination of spurious contamination from ambient atmosphere. The Nd:YLF (1.5mol%) fiber demonstrated a gain higher that the losses, demonstrating the viability for laser action.