Targeting Several CAG Expansion Diseases by a Single Antisense Oligonucleotide

To date there are 9 known diseases caused by an expanded polyglutamine repeat, with the most prevalent being Huntington's disease. Huntington's disease is a progressive autosomal dominant neurodegenerative disorder for which currently no therapy is available. It is caused by a CAG repeat expansion in the HTT gene, which results in an expansion of a glutamine stretch at the N-terminal end of the huntingtin protein. This polyglutamine expansion plays a central role in the disease and results in the accumulation of cytoplasmic and nuclear aggregates. Here, we make use of modified 2′-O-methyl phosphorothioate (CUG)n triplet-repeat antisense oligonucleotides to effectively reduce mutant huntingtin transcript and protein levels in patient-derived Huntington's disease fibroblasts and lymphoblasts. The most effective antisense oligonucleotide, (CUG)7, also reduced mutant ataxin-1 and ataxin-3 mRNA levels in spinocerebellar ataxia 1 and 3, respectively, and atrophin-1 in dentatorubral-pallidoluysian atrophy patient derived fibroblasts. This antisense oligonucleotide is not only a promising therapeutic tool to reduce mutant huntingtin levels in Huntington's disease but our results in spinocerebellar ataxia and dentatorubral-pallidoluysian atrophy cells suggest that this could also be applicable to other polyglutamine expansion disorders as well

Molecular analysis of the myosin gene family in Arabidopsis thaliana

Myosin is believed to act as the molecular motor for many actin-based motility processes in eukaryotes. It is becoming apparent that a single species may possess multiple myosin isoforms, and at least seven distinct classes of myosin have been identified from studies of animals, fungi, and protozoans. The complexity of the myosin heavy-chain gene family in higher plants was investigated by isolating and characterizing myosin genomic and cDNA clones from Arabidopsis thaliana . Six myosin-like genes were identified from three polymerase chain reaction (PCR) products (PCR1, PCR11, PCR43) and three cDNA clones (ATM2, MYA2, MYA3). Sequence comparisons of the deduced head domains suggest that these myosins are members of two major classes. Analysis of the overall structure of the ATM2 and MYA2 myosins shows that they are similar to the previously-identified ATM1 and MYA1 myosins, respectively. The MYA3 appears to possess a novel tail domain, with five IQ repeats, a six-member imperfect repeat, and a segment of unique sequence. Northern blot analyses indicate that some of the Arabidopsis myosin genes are preferentially expressed in different plant organs. Combined with previous studies, these results show that the Arabidopsis genome contains at least eight myosin-like genes representing two distinct classes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43437/1/11103_2004_Article_BF00040695.pd

Effect of Deficit Irrigation and Fertilization on Cucumber

Soil water budgets are essential in determining the proper timing and amount of irrigation. Organic fertilizers can be substituted for commercial fertilizers; however, information is sparse on the interaction of irrigation management and nutrient source on cucumber (Cucumis sativus L.) production. This study evaluated nutrient source and irrigation management on growth and yield of cucumber grown in the arid area of Egypt. A field experiment was conducted using cucumber grown in northern Egypt at Shibin El-Kom in 2006 and 2007 to evaluate water use and fertilizer rate and type. Three irrigation deficits and seven fertilization types were arranged in a randomized split-plot design with irrigation rates as main plots and fertilizer treatments within irrigation rates. Irrigation treatments were a ratio of crop evapotranspiration (ET) as: 1.0 ET, 0.84 ET, and 0.64 ET. Fertilizer treatments were applied at the recommended rate of N either as a commercial fertilizer or with organic manure. Chlorophyll a and b, leaf area index, and yield were greatest with the lowest ratios of male to female flowers when adequate water and high N were used (1.0 ET with chicken manure at 7 Mg/ha). Seasonal water use was 498 and 471 mm for 1.0 ET in 2006 and 2007 plantings over the 125 d growing season, respectively. The yield reduction coefficient averaged 0.77. An optimal scheduling was statistically developed based on crop response in deficit irrigation to achieve maximum yield for different uniformity coefficient variation values. Cucumber performance was significantly affected by both irrigation and nutrient deficiencies