59 research outputs found

    The Robber Bride: a Dystopian Female World in Margaret Atwood’s Mythology

    Get PDF
    The aim of this paper is to show how Atwood’s reformulations of myths contain hidden political messages from ancient and modern history and can be interpreted from Fredric Jameson’s views on ‘symbolic acts,’ discourse and the ideology of form. Several scholars have explored the symbolic relationship between the three major protagonists in The Robber Bride and fragments of the omnipotent image of the Neolithic deity the White Goddess. As the symbolic counterparts of Diana, Venus and Hecate in the novel, Tony, Roz and Charis demonstrate how women’s integrity has been crippled and how the restoration of female principle is just a utopian idea. However, our analysis has revealed that the younger generation of “goddesses” does not bring hope to the female gender in either the present or the future. Augusta, Paula and Erin symbolize oversimplified and parodied versions of the destructive Hecate in an unpromising world and “the not-good place” that resembles a dystopia

    Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>The relationship between relative metabolic disturbances and developmental disorders is an emerging research focus. This study compares the nutritional and metabolic status of children with autism with that of neurotypical children and investigates the possible association of autism severity with biomarkers.</p> <p>Method</p> <p>Participants were children ages 5-16 years in Arizona with Autistic Spectrum Disorder (n = 55) compared with non-sibling, neurotypical controls (n = 44) of similar age, gender and geographical distribution. Neither group had taken any vitamin/mineral supplements in the two months prior to sample collection. Autism severity was assessed using the Pervasive Development Disorder Behavior Inventory (PDD-BI), Autism Treatment Evaluation Checklist (ATEC), and Severity of Autism Scale (SAS). Study measurements included: vitamins, biomarkers of vitamin status, minerals, plasma amino acids, plasma glutathione, and biomarkers of oxidative stress, methylation, sulfation and energy production.</p> <p>Results</p> <p>Biomarkers of children with autism compared to those of controls using a t-test or Wilcoxon test found the following statistically significant differences (p < 0.001): Low levels of biotin, plasma glutathione, RBC SAM, plasma uridine, plasma ATP, RBC NADH, RBC NADPH, plasma sulfate (free and total), and plasma tryptophan; also high levels of oxidative stress markers and plasma glutamate. Levels of biomarkers for the neurotypical controls were in good agreement with accessed published reference ranges. In the Autism group, mean levels of vitamins, minerals, and most amino acids commonly measured in clinical care were within published reference ranges.</p> <p>A stepwise, multiple linear regression analysis demonstrated significant associations between several groups of biomarkers with all three autism severity scales, including vitamins (adjusted R<sup>2 </sup>of 0.25-0.57), minerals (adj. R<sup>2 </sup>of 0.22-0.38), and plasma amino acids (adj. R<sup>2 </sup>of 0.22-0.39).</p> <p>Conclusion</p> <p>The autism group had many statistically significant differences in their nutritional and metabolic status, including biomarkers indicative of vitamin insufficiency, increased oxidative stress, reduced capacity for energy transport, sulfation and detoxification. Several of the biomarker groups were significantly associated with variations in the severity of autism. These nutritional and metabolic differences are generally in agreement with other published results and are likely amenable to nutritional supplementation. Research investigating treatment and its relationship to the co-morbidities and etiology of autism is warranted.</p

    Effect of a vitamin/mineral supplement on children and adults with autism

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Vitamin/mineral supplements are among the most commonly used treatments for autism, but the research on their use for treating autism has been limited.</p> <p>Method</p> <p>This study is a randomized, double-blind, placebo-controlled three month vitamin/mineral treatment study. The study involved 141 children and adults with autism, and pre and post symptoms of autism were assessed. None of the participants had taken a vitamin/mineral supplement in the two months prior to the start of the study. For a subset of the participants (53 children ages 5-16) pre and post measurements of nutritional and metabolic status were also conducted.</p> <p>Results</p> <p>The vitamin/mineral supplement was generally well-tolerated, and individually titrated to optimum benefit. Levels of many vitamins, minerals, and biomarkers improved/increased showing good compliance and absorption. Statistically significant improvements in metabolic status were many including: total sulfate (+17%, p = 0.001), S-adenosylmethionine (SAM; +6%, p = 0.003), reduced glutathione (+17%, p = 0.0008), ratio of oxidized glutathione to reduced glutathione (GSSG:GSH; -27%, p = 0.002), nitrotyrosine (-29%, p = 0.004), ATP (+25%, p = 0.000001), NADH (+28%, p = 0.0002), and NADPH (+30%, p = 0.001). Most of these metabolic biomarkers improved to normal or near-normal levels.</p> <p>The supplement group had significantly greater improvements than the placebo group on the Parental Global Impressions-Revised (PGI-R, Average Change, p = 0.008), and on the subscores for Hyperactivity (p = 0.003), Tantrumming (p = 0.009), Overall (p = 0.02), and Receptive Language (p = 0.03). For the other three assessment tools the difference between treatment group and placebo group was not statistically significant.</p> <p>Regression analysis revealed that the degree of improvement on the Average Change of the PGI-R was strongly associated with several biomarkers (adj. R<sup>2 </sup>= 0.61, p < 0.0005) with the initial levels of biotin and vitamin K being the most significant (p < 0.05); both biotin and vitamin K are made by beneficial intestinal flora.</p> <p>Conclusions</p> <p>Oral vitamin/mineral supplementation is beneficial in improving the nutritional and metabolic status of children with autism, including improvements in methylation, glutathione, oxidative stress, sulfation, ATP, NADH, and NADPH. The supplement group had significantly greater improvements than did the placebo group on the PGI-R Average Change. This suggests that a vitamin/mineral supplement is a reasonable adjunct therapy to consider for most children and adults with autism.</p> <p>Trial Registration</p> <p><b>Clinical Trial Registration Number: </b><a href="http://www.clinicaltrials.gov/ct2/show/NCT01225198">NCT01225198</a></p

    Complexity in the genetic architecture of leukoaraiosis in hypertensive sibships from the GENOA Study

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Subcortical white matter hyperintensity on magnetic resonance imaging (MRI) of the brain, referred to as leukoaraiosis, is associated with increased risk of stroke and dementia. Hypertension may contribute to leukoaraiosis by accelerating the process of arteriosclerosis involving penetrating small arteries and arterioles in the brain. Leukoaraiosis volume is highly heritable but shows significant inter-individual variability that is not predicted well by any clinical covariates (except for age) or by single SNPs.</p> <p>Methods</p> <p>As part of the Genetics of Microangiopathic Brain Injury (GMBI) Study, 777 individuals (74% hypertensive) underwent brain MRI and were genotyped for 1649 SNPs from genes known or hypothesized to be involved in arteriosclerosis and related pathways. We examined SNP main effects, epistatic (gene-gene) interactions, and context-dependent (gene-environment) interactions between these SNPs and covariates (including conventional and novel risk factors for arteriosclerosis) for association with leukoaraiosis volume. Three methods were used to reduce the chance of false positive associations: 1) false discovery rate (FDR) adjustment for multiple testing, 2) an internal replication design, and 3) a ten-iteration four-fold cross-validation scheme.</p> <p>Results</p> <p>Four SNP main effects (in <it>F3</it>, <it>KITLG</it>, <it>CAPN10</it>, and <it>MMP2</it>), 12 SNP-covariate interactions (including interactions between <it>KITLG </it>and homocysteine, and between <it>TGFB3 </it>and both physical activity and C-reactive protein), and 173 SNP-SNP interactions were significant, replicated, and cross-validated. While a model containing the top single SNPs with main effects predicted only 3.72% of variation in leukoaraiosis in independent test samples, a multiple variable model that included the four most highly predictive SNP-SNP and SNP-covariate interactions predicted 11.83%.</p> <p>Conclusion</p> <p>These results indicate that the genetic architecture of leukoaraiosis is complex, yet predictive, when the contributions of SNP main effects are considered in combination with effects of SNP interactions with other genes and covariates.</p

    Copper-Triggered Aggregation of Ubiquitin

    Get PDF
    Neurodegenerative disorders share common features comprising aggregation of misfolded proteins, failure of the ubiquitin-proteasome system, and increased levels of metal ions in the brain. Protein aggregates within affected cells often contain ubiquitin, however no report has focused on the aggregation propensity of this protein. Recently it was shown that copper, differently from zinc, nickel, aluminum, or cadmium, compromises ubiquitin stability and binds to the N-terminus with 0.1 micromolar affinity. This paper addresses the role of copper upon ubiquitin aggregation. In water, incubation with Cu(II) leads to formation of spherical particles that can progress from dimers to larger conglomerates. These spherical oligomers are SDS-resistant and are destroyed upon Cu(II) chelation or reduction to Cu(I). In water/trifluoroethanol (80∶20, v/v), a mimic of the local decrease in dielectric constant experienced in proximity to a membrane surface, ubiquitin incubation with Cu(II) causes time-dependent changes in circular dichroism and Fourier-transform infrared spectra, indicative of increasing β-sheet content. Analysis by atomic force and transmission electron microscopy reveals, in the given order, formation of spherical particles consistent with the size of early oligomers detected by gel electrophoresis, clustering of these particles in straight and curved chains, formation of ring structures, growth of trigonal branches from the rings, coalescence of the trigonal branched structures in a network. Notably, none of these ubiquitin aggregates was positive to tests for amyloid and Cu(II) chelation or reduction produced aggregate disassembly. The early formed Cu(II)-stabilized spherical oligomers, when reconstituted in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) liposomes and in POPC planar bilayers, form annular and pore-like structures, respectively, which are common to several neurodegenerative disorders including Parkinson's, Alzheimer's, amyotrophic lateral sclerosis, and prion diseases, and have been proposed to be the primary toxic species. Susceptibility to aggregation of ubiquitin, as it emerges from the present study, may represent a potential risk factor for disease onset or progression while cells attempt to tag and process toxic substrates
    corecore