Return migration and re-migration of Brazilian-Japanese and the role of identity in their migration

published_or_final_versionInternational and Public AffairsMasterMaster of International and Public Affair

Neuropathologic features in the hippocampus and cerebellum of three older men with fragile X syndrome

<p>Abstract</p> <p>Background</p> <p>Fragile X syndrome (FXS) is the most common inherited form of intellectual disability, and is the most common single-gene disorder known to be associated with autism. Despite recent advances in functional neuroimaging and our understanding of the molecular pathogenesis, only limited neuropathologic information on FXS is available.</p> <p>Methods</p> <p>Neuropathologic examinations were performed on post-mortem brain tissue from three older men (aged 57, 64 and 78 years) who had received a clinical or genetic diagnosis of FXS. In each case, physical and cognitive features were typical of FXS, and one man was also diagnosed with autism. Guided by reports of clinical and neuroimaging abnormalities of the limbic system and cerebellum of individuals with FXS, the current analysis focused on neuropathologic features present in the hippocampus and the cerebellar vermis.</p> <p>Results</p> <p>Histologic and immunologic staining revealed abnormalities in both the hippocampus and cerebellar vermis. Focal thickening of hippocampal CA1 and irregularities in the appearance of the dentate gyrus were identified. All lobules of the cerebellar vermis and the lateral cortex of the posterior lobe of the cerebellum had decreased numbers of Purkinje cells, which were occasionally misplaced, and often lacked proper orientation. There were mild, albeit excessive, undulations of the internal granular cell layer, with patchy foliar white matter axonal and astrocytic abnormalities. Quantitative analysis documented panfoliar atrophy of both the anterior and posterior lobes of the vermis, with preferential atrophy of the posterior lobule (VI to VII) compared with age-matched normal controls.</p> <p>Conclusions</p> <p>Significant morphologic changes in the hippocampus and cerebellum in three adult men with FXS were identified. This pattern of pathologic features supports the idea that primary defects in neuronal migration, neurogenesis and aging may underlie the neuropathology reported in FXS.</p

FMR1 premutation and full mutation molecular mechanisms related to autism

Fragile X syndrome (FXS) is caused by an expanded CGG repeat (>200 repeats) in the 5′ un-translated portion of the fragile X mental retardation 1 gene (FMR1) leading to a deficiency or absence of the FMR1 protein (FMRP). FMRP is an RNA-binding protein that regulates the translation of a number of other genes that are important for synaptic development and plasticity. Furthermore, many of these genes, when mutated, have been linked to autism in the general population, which may explain the high comorbidity that exists between FXS and autism spectrum disorders (ASD). Additionally, premutation repeat expansions (55 to 200 CGG repeats) may also give rise to ASD through a different molecular mechanism that involves a direct toxic effect of FMR1 mRNA. It is believed that RNA toxicity underlies much of the premutation-related involvement, including developmental concerns like autism, as well as neurodegenerative issues with aging such as the fragile X-associated tremor ataxia syndrome (FXTAS). RNA toxicity can also lead to mitochondrial dysfunction, which is common in older premutation carriers both with and without FXTAS. Many of the problems with cellular dysregulation in both premutation and full mutation neurons also parallel the cellular abnormalities that have been documented in idiopathic autism. Research regarding dysregulation of neurotransmitter systems caused by the lack of FMRP in FXS, including metabotropic glutamate receptor 1/5 (mGluR1/5) pathway and GABA pathways, has led to new targeted treatments for FXS. Preliminary evidence suggests that these new targeted treatments will also be beneficial in non-fragile X forms of autism

The Use of Transcranial Direct Current Stimulation for Long-Term Learning

Transcranial Direct Current Stimulation (tDCS) is a non-invasive means of electrical brain stimulation that can influence the neural activity of the underlying cortex, and is becoming a popular means of cognitive enhancement. However, some meta-analyses arrive at inconclusive results, and the efficacy of tDCS is controversial, especially during the earlier years of this dissertation work. One reason that could account for the low reliability between some studies is the possibility of delayed effects that may not occur until some hours or days after a session. Evidence for this phenomenon has been accruing with longitudinal studies and is thought to relate to downstream effects of the stimulation on promoting LTP and LTP-like plasticity within task-relevant neurons. The primary aim of this thesis is to explore the conditions under which such long-term changes can occur, and the extent to which they can influence human learning. To do so, three empirical studies were conducted. First, we established that tDCS could improve cognitive function during a week-long period of working memory (WM) training, with follow-up effects lasting up to a year. Our second study investigated the neural underpinnings of these longitudinal effects by using EEG to show greater evoked responses to a visual flicker roughly 24 hours after tDCS. Finally, we repeated our WM training design, but manipulated the stimulation timing window (before, during, or after task performance), in order to optimize our protocol to manifest greater long-term effects. However, we unexpectedly found that tDCS actually impaired performance relative to sham, particularly when applied before or after training. Post-hoc analyses looking at the combined data from our first and third experiments revealed an interesting baseline-dependency that may reconcile our discrepant results. We found that tDCS was only effective for individuals who started off with either low or high WM ability, but ineffective or possibly even detrimental for individuals starting off with more average ability levels. Overall, this thesis argues for a promising outlook for the use of tDCS for increasing long-term learning, but cautions that the strength and direction of effects can vary wildly depending on a variety of individual difference and other factors

Tracking the imagined audience: A case study on Nike’s use of Twitter for B2C interaction

Social media platforms have become the new centre of attention in business-to-consumer (B2C) communication. These interactions provide a rich source of information for businesses in terms of their customers’ preferences, backgrounds and behaviour. We introduce a multi-disciplinary theoretical and methodological framework based on studies in marketing, communication and computer-mediated communication, which aims to inform marketing professionals and academic researchers on how social media can facilitate B2C engagement

FMR1 premutation and full mutation molecular mechanisms related to autism.

Fragile X syndrome (FXS) is caused by an expanded CGG repeat (&gt;200 repeats) in the 5' un-translated portion of the fragile X mental retardation 1 gene (FMR1) leading to a deficiency or absence of the FMR1 protein (FMRP). FMRP is an RNA-binding protein that regulates the translation of a number of other genes that are important for synaptic development and plasticity. Furthermore, many of these genes, when mutated, have been linked to autism in the general population, which may explain the high comorbidity that exists between FXS and autism spectrum disorders (ASD). Additionally, premutation repeat expansions (55 to 200 CGG repeats) may also give rise to ASD through a different molecular mechanism that involves a direct toxic effect of FMR1 mRNA. It is believed that RNA toxicity underlies much of the premutation-related involvement, including developmental concerns like autism, as well as neurodegenerative issues with aging such as the fragile X-associated tremor ataxia syndrome (FXTAS). RNA toxicity can also lead to mitochondrial dysfunction, which is common in older premutation carriers both with and without FXTAS. Many of the problems with cellular dysregulation in both premutation and full mutation neurons also parallel the cellular abnormalities that have been documented in idiopathic autism. Research regarding dysregulation of neurotransmitter systems caused by the lack of FMRP in FXS, including metabotropic glutamate receptor 1/5 (mGluR1/5) pathway and GABA pathways, has led to new targeted treatments for FXS. Preliminary evidence suggests that these new targeted treatments will also be beneficial in non-fragile X forms of autism