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    ABSTRACT: There is a growing body of evidence linking mitochondrial dysfunction, mediated either through inherited mtDNA variation or mitochondrial proteomic deficit, to Parkinson’s disease (PD). Yet despite this, the role of somatic mtDNA point mutations and specifically point-mutational burden in PD is poorly understood. Here we take advantage of recent technical and methodological advances to examine the role of age-related and acquired mtDNA mutation in the largest study of mtDNA in post-mortem PD tissue to date.
    Full-text · Article · Nov 2015 · Neurobiology of Aging
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    ABSTRACT: The free radical theory of aging is almost 60 years old. As mitochondria are the principle source of intracellular reactive oxygen species (ROS), this hypothesis suggested a central role for the mitochondrion in normal mammalian aging. In recent years however much work has questioned the importance of mitochondrial ROS in driving aging. Conversely new evidence points to other facets of mitochondrial dysfunction which may nevertheless suggest the mitochondrion retains a critical role at the center of a complex web of processes leading to cellular and organismal aging. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Jun 2015 · Biochimica et Biophysica Acta
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    ABSTRACT: Sequencing the human genome was a huge milestone in genetic research that revealed almost the total DNA sequence required to create a human being. However, in order to function, the DNA genome needs to be expressed as an RNA transcriptome. This article reviews how knowledge of genome sequence information has led to fundamental discoveries in how the transcriptome is processed, with a focus on new system-wide insights into how pre-mRNAs that are encoded by split genes in the genome are rearranged by splicing into functional mRNAs. These advances have been made possible by the development of new post-genome technologies to probe splicing patterns. Transcriptome-wide approaches have characterised a "splicing code" that is embedded within and has a significant role in deciphering the genome, and is deciphered by RNA binding proteins. These analyses have also found that most human genes encode multiple mRNA isoforms, and in some cases proteins, leading in turn to a re-assessment of what exactly a gene is. Analysis of the transcriptome has given insights into how the genome is packaged and transcribed, and is helping to explain important aspects of genome evolution.
    Full-text · Article · Mar 2014 · Genes
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