RESUMO
OBJECTIVE: This study evaluated human Blood Oxygen Level-Dependent (BOLD) responses in primary and higher-order olfactory regions of older adults, using odor memory and odor identification tasks. The goal was to determine which olfactory and memory regions of interest are more strongly engaged in older populations comparing these two odor training tasks. METHODS: Twelve adults 55-75 years old (75% females) without intranasal or major neurological disorders performed repetitive odor memory and identification tasks using a 3-tesla magnetic resonance scanner. Odors were presented intermittently at 10-second bursts separated by 20-second intervals of odorless air. Paired t-tests were used to compare differences in the degree of activation between odor identification and odor memory tasks within individuals. An FDR cluster-level correction of p<0.05 was used for multiplicity of tests (with a cluster-defining threshold set at p<0.01 and 10 voxels). RESULTS: Odor identification compared to memory (ie, odor identification > odor memory) contrasts had several areas of significant activation, including many of the classical olfactory brain regions as well as the hippocampus. The opposite contrast (odor memory > odor identification) included the piriform cortex, though this was not significant. Both tasks equally activated the piriform cortex, and thus when the two tasks are compared to each other this area of activation appears to be either absent (OI > OM) or only weakly observed (OM > OI). CONCLUSION: These findings from a predominantly African American sample suggest that odor identification tasks may be more potent than memory tasks in targeted olfactory engagement in older populations. Furthermore, repetitive odor identification significantly engaged the hippocampus - a region relevant to Alzheimer's disease - more significantly than did the odor memory task. If validated in larger studies, this result could have important implications in the design of olfactory training paradigms.
RESUMO
Through a combination of in silico research and reviews of previous work, mechanisms by which nonsense-mediated mRNA decay (NMD) affects the inheritance and expressivity of Waardenburg syndrome is realized. While expressivity and inheritance both relate to biochemical processes underlying a gene's function, this research explores how alternative splicing and premature termination codons (PTC's) within mRNAs mutated in the disease are either translated into deleterious proteins or decayed to minimize expression of altered proteins. Elucidation of splice variants coupled with NMD perpetuating the various symptoms and inheritance patterns of this disease represent novel findings. By investigating nonsense mutations that lie within and outside the NMD boundary of these transcripts we can evaluate the effects of protein truncation versus minimized protein expression on the variable expressivity found between Type I and Type III Waardenburg syndrome, PAX3, while comparatively evaluating EDN3 and SOX10's role in inheritance of Type IV subtypes of the disease. This review will demonstrate how alternative splicing perpetuates or limits NMD activity by way of PTC positioning, thereby affecting the presentation of Waardenburg syndrome.
