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1.
Curr Alzheimer Res ; 17(10): 904-915, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33327913

RESUMO

OBJECTIVE: Alzheimer disease (AD) is a chronic neurodegenerative disorder that affects millions of individuals worldwide. Symptoms include memory dysfunction and deficits in attention, planning, language, and overall cognitive function. Olfactory dysfunction is a common symptom of AD and evidence supports that it is an early marker. Furthermore, olfactory bulb and entorhinal cortex atrophy are well described in AD. However, in AD, no studies have assessed the olfactory cortex as a whole and if sex effects are observed. METHODS: Magnetic Resonance Imaging was used to scan 39 participants with an average age of 72 years and included men and women. AAL Single-Subject Atlas (implemented in PNEURO tool - PMOD 3.8) was used to determine the volume of the olfactory cortex and the hippocampus. Olfactory cortex volume was lower in both men and women AD cases compared with controls. This decrease was more apparent in the left olfactory cortex and was influenced by age. As expected, hippocampal volume was also significantly reduced in AD. However, this was only observed in the male cohort. A significant correlation was observed between levels of education and hippocampal volume in controls that were not detected in the AD participants. Asymmetry was observed in the olfactory cortex volume when comparing left and right volumes in both the control and AD participants, which was not observed in the hippocampus. RESULTS: These data highlight the importance of the role of olfactory cortical atrophy in the pathogenesis of AD and the interplay between the olfactory deficits and degeneration of olfactory regions in the brain.


Assuntos
Doença de Alzheimer/patologia , Atrofia/patologia , Processamento de Imagem Assistida por Computador , Córtex Olfatório/patologia , Idoso , Encéfalo/patologia , Disfunção Cognitiva/fisiopatologia , Estudos de Coortes , Feminino , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Fatores Sexuais
2.
PLoS One ; 9(10): e110134, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25335079

RESUMO

Integrated analysis of genomic and transcriptomic level changes holds promise for a better understanding of colorectal cancer (CRC) biology. There is a pertinent need to explain the functional effect of genome level changes by integrating the information at the transcript level. Using high resolution cytogenetics array, we had earlier identified driver genes by 'Genomic Identification of Significant Targets In Cancer (GISTIC)' analysis of paired tumour-normal samples from colorectal cancer patients. In this study, we analyze these driver genes at three levels using exon array data--gene, exon and network. Gene level analysis revealed a small subset to experience differential expression. These results were reinforced by carrying out separate differential expression analyses (SAM and LIMMA). ATP8B1 was found to be the novel gene associated with CRC that shows changes at cytogenetic, gene and exon levels. Splice index of 29 exons corresponding to 13 genes was found to be significantly altered in tumour samples. Driver genes were used to construct regulatory networks for tumour and normal groups. There were rearrangements in transcription factor genes suggesting the presence of regulatory switching. The regulatory pattern of AHR gene was found to have the most significant alteration. Our results integrate data with focus on driver genes resulting in highly enriched novel molecules that need further studies to establish their role in CRC.


Assuntos
Adenosina Trifosfatases/genética , Neoplasias Colorretais/genética , Processamento Alternativo , Biomarcadores/metabolismo , Neoplasias Colorretais/patologia , Análise Citogenética , Éxons , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Análise de Componente Principal
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