52 research outputs found

    HPRT Deficiency Coordinately Dysregulates Canonical Wnt and Presenilin-1 Signaling: A Neuro-Developmental Regulatory Role for a Housekeeping Gene?

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    We have used microarray-based methods of global gene expression together with quantitative PCR and Western blot analysis to identify dysregulation of genes and aberrant cellular processes in human fibroblasts and in SH-SY5Y neuroblastoma cells made HPRT-deficient by transduction with a retrovirus stably expressing an shRNA targeted against HPRT. Analysis of the microarray expression data by Gene ontology (GO) and Gene Set Enrichment Analysis (GSEA) as well as significant pathway analysis by GeneSpring GX10 and Panther Classification System reveal that HPRT deficiency is accompanied by aberrations in a variety of pathways known to regulate neurogenesis or to be implicated in neurodegenerative disease, including the canonical Wnt/β-catenin and the Alzheimer's disease/presenilin signaling pathways. Dysregulation of the Wnt/β-catenin pathway is confirmed by Western blot demonstration of cytosolic sequestration of β-catenin during in vitro differentiation of the SH-SY5Y cells toward the neuronal phenotype. We also demonstrate that two key transcription factor genes known to be regulated by Wnt signaling and to be vital for the generation and function of dopaminergic neurons; i.e., Lmx1a and Engrailed 1, are down-regulated in the HPRT knockdown SH-SY5Y cells. In addition to the Wnt signaling aberration, we found that expression of presenilin-1 shows severely aberrant expression in HPRT-deficient SH-SY5Y cells, reflected by marked deficiency of the 23 kDa C-terminal fragment of presenilin-1 in knockdown cells. Western blot analysis of primary fibroblast cultures from two LND patients also shows dysregulated presenilin-1 expression, including aberrant proteolytic processing of presenilin-1. These demonstrations of dysregulated Wnt signaling and presenilin-1 expression together with impaired expression of dopaminergic transcription factors reveal broad pleitropic neuro-regulatory defects played by HPRT expression and suggest new directions for investigating mechanisms of aberrant neurogenesis and neuropathology in LND and potential new targets for restoration of effective signaling in this neuro-developmental defect

    Fruit nitrogen content of sixteen strawberry genotypes grown in an advanced matted row production system

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    In the perennial strawberry production system, removal of the harvested crop represents a loss of nitrogen (N) that may be influenced by cultivar. Eight strawberry (Fragaria xananassa Duch.) cultivars and eight numbered selections grown in advanced matted row culture were compared over three seasons for removal of N in the harvested crop. Replicated plots were established in 1999, 2000, and 2001 and fruited the following year. \u27Allstar\u27, \u27Cavendish\u27, \u27Earliglow\u27, \u27Honeoye\u27, \u27Jewel\u27, \u27Northeaster\u27, \u27Ovation\u27, and \u27Latestar\u27 and selections B37, B51, B244-89, B683, B753, B781, B793, and B817 were compared for yield and fruit N concentration. Harvest removal of N (HRN) was calculated from total season yield and fruit N concentration at peak harvest. There were significant differences in HRN among genotypes, ranging from 1.80 to 2.96 g N per meter of row for numbered selections B781 and B37, respectively. Among cultivars, HRN ranged from 2.01 to 3.56 g.m(-1) for \u27Ovation\u27 and \u27Jewel\u27, respectively. The amount of HRN was largely determined by yield, however, there were also significant genotype differences in fruit N concentration, ranging from 0.608 to 0.938 mg N per gram fresh weight for B244-89 and \u27Jewel\u27, respectively. These differences indicate that N losses in the harvested crop are genotype dependent

    The Hemlock Society membership: Comparisons between 1983 and 1995 surveys and the general population

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    While most Right to Die studies have examined the ethical and moral implications of assisted suicide, few have investigated the active membership of Right to Die organizations. Two studies, one in 1983 and one in 1995, have surveyed The Hemlock Society USA membership in an effort to identify those who are actively involved in the Right to Die social movement. This study compares the social demographic descriptors of members of the Hemlock Society at these two different points in time: from the 1983 survey to the California portion of the 1995 survey and between all three Hemlock samples and the General Social Survey. The most significant findings of this study demonstrate that the population of the Hemlock Society is increasing in religiosity and continues to be defined as a well-educated and healthy membership. The Hemlock Society membership over-represents the female population, those over 55 years of age, divorcees and widows/ widowers, atheists, and those who are well-educated compared to the general population. Additionally, Hemlock Society members appear to be healthy adults who are still living on their own as opposed to depending on their families for assistance. In other words, the Hemlock Society members constitute a unique and dynamic group of individuals

    A heat unit model for predicting bloom dates in Rubus

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    ‘Navaho’ and ‘Apache’ blackberry plants were maintained at 10, 15, 20, 25, 30, or 35 °C in growth chambers to determine optimum temperature for budbreak and flowering (fewest days to flowering). In a separate experiment, bloom dates were observed for a collection of 117 Rubus genotypes over four seasons. Using these phenological data, predictive linear and curvilinear models were tested using a range of cardinal temperatures. The growth chamber experiment indicated optimum temperatures for bloom were 25.6 °C for ‘Apache’ and 29.2 °C for ‘Navaho’. For the field observations, time to bloom was best defined by a linear model with base and optimum temperatures of 6 and 25 °C and a curvilinear model defined by base and optimum temperatures of 4 and 27 °C, respectively. Based on the linear growing degree hour (GDH) model, heat units to bloom varied among cultivars in the collection from 9,200 GDH for ‘Chickasaw’ to 18,900 GDH for ‘Merton Thornless’
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