Invited Review: Decoding the pathophysiological mechanisms that underlie RNA dysregulation in neurodegenerative disorders: a review of the current state of the art

Altered RNA metabolism is a key pathophysiological component causing several neurodegenerative diseases. Genetic mutations causing neurodegeneration occur in coding and noncoding regions of seemingly unrelated genes whose products do not always contribute to the gene expression process. Several pathogenic mechanisms may coexist within a single neuronal cell, including RNA/protein toxic gain-of-function and/or protein loss-of-function. Genetic mutations that cause neurodegenerative disorders disrupt healthy gene expression at diverse levels, from chromatin remodelling, transcription, splicing, through to axonal transport and repeat-associated non-ATG (RAN) translation. We address neurodegeneration in repeat expansion disorders [Huntington's disease, spinocerebellar ataxias, C9ORF72-related amyotrophic lateral sclerosis (ALS)] and in diseases caused by deletions or point mutations (spinal muscular atrophy, most subtypes of familial ALS). Some neurodegenerative disorders exhibit broad dysregulation of gene expression with the synthesis of hundreds to thousands of abnormal messenger RNA (mRNA) molecules. However, the number and identity of aberrant mRNAs that are translated into proteins – and how these lead to neurodegeneration – remain unknown. The field of RNA biology research faces the challenge of identifying pathophysiological events of dysregulated gene expression. In conclusion, we discuss current research limitations and future directions to improve our characterization of pathological mechanisms that trigger disease onset and progression

Performance of prunus rootstocks in the 2001 NC-140 peach trial

Fourteen Prunus rootstock cultivars and selections budded with either \u27Redtop\u27, \u27Redhaven\u27 or \u27Cresthaven\u27 peach were planted at 11 locations in North America in 2001 in a randomized block design with a tree spacing of 5 by 6 m and 8 replicates. This test planting was a NC-140 Cooperative Regional Rootstock Project (www.nc140.org). There were 14 rootstocks, which included three peach seedling rootstocks: \u27Lovell\u27, \u27Bailey\u27, and Guardian® \u27BY520-9\u27 [selection SC-17] and 11 clonal rootstocks. Clonal rootstocks included peach × almond hybrids \u27BH-4\u27 and \u27SLAP\u27 (\u27Cornerstone\u27); peach × plum hybrids \u27K146-43\u27 (\u27Controller 5\u27), \u27K146- 44\u27, and \u27P30-135\u27 (\u27Controller 9\u27); interspecific plum hybrids \u27Hiawatha\u27, \u27Jaspi\u27 and \u27Julior\u27; interspecific Prunus hybrids \u27Cadaman®\u27 and \u27VVA-1\u27 (Krymsk® 1); and Prunus pumila selection \u27Pumiselect®\u27. The largest trees were from Georgia, Maryland, and South Carolina. \u27BH-4\u27, \u27SLAP\u27, SC-17, Lovell, and \u27Cadaman®\u27 were the most vigorous rootstocks. \u27Jaspi\u27, \u27K146-43\u27, \u27K146-44\u27 and \u27VVA-1\u27 were the least vigorous, having trunk circumferences 30-40% smaller than Lovell. No rootstock had a significantly higher survival rate than Lovell at all locations. \u27Julior\u27, \u27Jaspi\u27, and \u27VVA-1\u27 had significantly more root suckers. Cumulative fruit yields were highest on the peach seedling, peach × almond, and \u27Cadaman®\u27 rootstocks. Lowest cumulative yields were from trees on \u27Jaspi\u27, \u27VVA-1\u27, and \u27K146-44\u27 rootstocks. Fruit weight was significantly larger on \u27BH-4\u27, \u27SLAP\u27 and \u27Bailey\u27 rootstocks. \u27Bailey\u27 and \u27Jaspi\u27 had the highest and lowest cumulative yield efficiency, respectively