“Like Following a Mirage”: Memory and Empowerment in Alice Munro’s “The Bear Came Over the Mountain”

La nouvelle “The Bear Came Over the Mountain” d’Alice Munro est une étude sur la douleur, la perte, la trahison et, en premier lieu, une réflexion sur le principe féminin. La nouvelle a attiré l’attention d’autres écrivains – en particulier celle de Jonathan Franzen qui la classe parmi les plus belles réussites de Munro ; ou Sarah Polly qui a réalisé Away from Her, l’adaptation d’un texte fort ambigu. Le présent article souhaite revenir sur cette ambigüité. À première vue, la nouvelle décrit la tragédie d’une femme qui sombre peu à peu dans la maladie d’Alzheimer : Fiona doit apprendre à vivre avec ses défaillances mémorielles et accepter de quitter son foyer. Munro ne se satisfait jamais de présenter le point de vue limité d’un personnage. Elle laisse entrevoir, par le biais de subtiles suggestions, que le choix de Fiona de s’écarter du monde social relève d’un désir de se venger de mari volage. En d’autres termes, cet article suggère que Fiona joue la malade pour reprendre sa vie en main et ainsi échapper à l’amour hypocrite de son époux. De cette manière, la nouvelle devient l’une des illustrations récentes les plus fortes de l’ambition de Munro de décrire les femmes dans leur vie de tous les jours et d’explorer les moyens mis en œuvre pour en améliorer les conditions

Would You Publish This Book? Material Production, Canadian Criticism, and The Theatre of Form

The publication of Canadian literary criticism in its historically recognizable forms of academic discourse has dramatically decreased due to shifts in government funding policies and widespread changes in the book publishing industry. The cultural implication of this material shift in the sheer quantity of criticism published is significant: publishers are unreceptive to books about Canadian literature. Decreases in the production of Canadian criticism shift the cultural paradigms by substituting more broadly marketable cultural objects for more esoteric objects aligned with the discourse of nation as it is disseminated through critical acts. With funding from the Ontario Arts Council, the Canada Council and the Aid to Scholarly Publications Program, ECW Press published Ric Knowles's The Theatre of Form and the Production of Meaning: Contemporary Canadian Dramaturgies in 1999 at a financial loss. Most commentary on Canadian criticism does not consider the factors accounting for the material solidity, just as most academics really don't consider the issue of profit or loss associated with the production of the scholarly book as a central factor in the evaluation of the publishability of their scholarly work

Contrast Enhanced Micro-Computed Tomography Resolves the 3-Dimensional Morphology of the Cardiac Conduction System in Mammalian Hearts

The general anatomy of the cardiac conduction system (CCS) has been known for 100 years, but its complex and irregular three-dimensional (3D) geometry is not so well understood. This is largely because the conducting tissue is not distinct from the surrounding tissue by dissection. The best descriptions of its anatomy come from studies based on serial sectioning of samples taken from the appropriate areas of the heart. Low X-ray attenuation has formerly ruled out micro-computed tomography (micro-CT) as a modality to resolve internal structures of soft tissue, but incorporation of iodine, which has a high molecular weight, into those tissues enhances the differential attenuation of X-rays and allows visualisation of fine detail in embryos and skeletal muscle. Here, with the use of a iodine based contrast agent (I2KI), we present contrast enhanced micro-CT images of cardiac tissue from rat and rabbit in which the three major subdivisions of the CCS can be differentiated from the surrounding contractile myocardium and visualised in 3D. Structures identified include the sinoatrial node (SAN) and the atrioventricular conduction axis: the penetrating bundle, His bundle, the bundle branches and the Purkinje network. Although the current findings are consistent with existing anatomical representations, the representations shown here offer superior resolution and are the first 3D representations of the CCS within a single intact mammalian heart

Transcriptomic and Epigenetic Regulation of Disuse Atrophy and the Return to Activity in Skeletal Muscle

Physical inactivity and disuse are major contributors to age-related muscle loss. Denervation of skeletal muscle has been previously used as a model with which to investigate muscle atrophy following disuse. Although gene regulatory networks that control skeletal muscle atrophy after denervation have been established, the transcriptome in response to the recovery of muscle after disuse and the associated epigenetic mechanisms that may function to modulate gene expression during skeletal muscle atrophy or recovery have yet to be investigated. We report that silencing the tibialis anterior muscle in rats with tetrodotoxin (TTX)—administered to the common peroneal nerve—resulted in reductions in muscle mass of 7, 29, and 51% with corresponding reductions in muscle fiber cross-sectional area of 18, 42, and 69% after 3, 7, and 14 d of TTX, respectively. Of importance, 7 d of recovery, during which rodents resumed habitual physical activity, restored muscle mass from a reduction of 51% after 14 d TTX to a reduction of only 24% compared with sham control. Returning muscle mass to levels observed at 7 d TTX administration (29% reduction). Transcriptome-wide analysis demonstrated that 3714 genes were differentially expressed across all conditions at a significance of P ≤ 0.001 after disuse-induced atrophy. Of interest, after 7 d of recovery, the expression of genes that were most changed during TTX had returned to that of the sham control. The 20 most differentially expressed genes after microarray analysis were identified across all conditions and were cross-referenced with the most frequently occurring differentially expressed genes between conditions. This gene subset included myogenin (MyoG), Hdac4, Ampd3, Trim63 (MuRF1), and acetylcholine receptor subunit α1 (Chrna1). Transcript expression of these genes and Fboxo32 (MAFbx), because of its previously identified role in disuse atrophy together with Trim63 (MuRF1), were confirmed by real-time quantitative RT-PCR, and DNA methylation of their promoter regions was analyzed by PCR and pyrosequencing. MyoG, Trim63 (MuRF1), Fbxo32 (MAFbx), and Chrna1 demonstrated significantly decreased DNA methylation at key time points after disuse-induced atrophy that corresponded with significantly increased gene expression. Of importance, after TTX cessation and 7 d of recovery, there was a marked increase in the DNA methylation profiles of Trim63 (MuRF1) and Chrna1 back to control levels. This also corresponded with the return of gene expression in the recovery group back to baseline expression observed in sham-operated controls. To our knowledge, this is the first study to demonstrate that skeletal muscle atrophy in response to disuse is accompanied by dynamic epigenetic modifications that are associated with alterations in gene expression, and that these epigenetic modifications and gene expression profiles are reversible after skeletal muscle returns to normal activity

Gene expression profiling of alveolar soft-part sarcoma (ASPS)

<p>Abstract</p> <p>Background</p> <p>Alveolar soft-part sarcoma (ASPS) is an extremely rare, highly vascular soft tissue sarcoma affecting predominantly adolescents and young adults. In an attempt to gain insight into the pathobiology of this enigmatic tumor, we performed the first genome-wide gene expression profiling study.</p> <p>Methods</p> <p>For seven patients with confirmed primary or metastatic ASPS, RNA samples were isolated immediately following surgery, reverse transcribed to cDNA and each sample hybridized to duplicate high-density human U133 plus 2.0 microarrays. Array data was then analyzed relative to arrays hybridized to universal RNA to generate an unbiased transcriptome. Subsequent gene ontology analysis was used to identify transcripts with therapeutic or diagnostic potential. A subset of the most interesting genes was then validated using quantitative RT-PCR and immunohistochemistry.</p> <p>Results</p> <p>Analysis of patient array data versus universal RNA identified elevated expression of transcripts related to angiogenesis (ANGPTL2, HIF-1 alpha, MDK, c-MET, VEGF, TIMP-2), cell proliferation (PRL, IGFBP1, NTSR2, PCSK1), metastasis (ADAM9, ECM1, POSTN) and steroid biosynthesis (CYP17A1 and STS). A number of muscle-restricted transcripts (ITGB1BP3/MIBP, MYF5, MYF6 and TRIM63) were also identified, strengthening the case for a muscle cell progenitor as the origin of disease. Transcript differentials were validated using real-time PCR and subsequent immunohistochemical analysis confirmed protein expression for several of the most interesting changes (MDK, c-MET, VEGF, POSTN, CYP17A1, ITGB1BP3/MIBP and TRIM63).</p> <p>Conclusion</p> <p>Results from this first comprehensive study of ASPS gene expression identifies several targets involved in angiogenesis, metastasis and myogenic differentiation. These efforts represent the first step towards defining the cellular origin, pathogenesis and effective treatment strategies for this atypical malignancy.</p

Protein-Energy Wasting and Mortality in Chronic Kidney Disease

Protein-energy wasting (PEW) is common in patients with chronic kidney disease (CKD) and is associated with an increased death risk from cardiovascular diseases. However, while even minor renal dysfunction is an independent predictor of adverse cardiovascular prognosis, PEW becomes clinically manifest at an advanced stage, early before or during the dialytic stage. Mechanisms causing loss of muscle protein and fat are complex and not always associated with anorexia, but are linked to several abnormalities that stimulate protein degradation and/or decrease protein synthesis. In addition, data from experimental CKD indicate that uremia specifically blunts the regenerative potential in skeletal muscle, by acting on muscle stem cells. In this discussion recent findings regarding the mechanisms responsible for malnutrition and the increase in cardiovascular risk in CKD patients are discussed. During the course of CKD, the loss of kidney excretory and metabolic functions proceed together with the activation of pathways of endothelial damage, inflammation, acidosis, alterations in insulin signaling and anorexia which are likely to orchestrate net protein catabolism and the PEW syndrome

Canadian Authors and Their Literary Agents (pp 93-120)

This essay provides an account of Canadian authors and their literary agents, from 1890-1990, in the context of recent ideas about book history and the material production of texts. My aim is to provide a new way of understanding how Canadian literature was produced and disseminated during a century marked by enormous shifts in the status and conception of the author. The paper weaves together biography, history, economics, copyright law, government policies on culture, and literary analysis in order to illustrate the role that literary agents played in the formation of Canadian authors' careers. It seeks to correct the frequently made, but incorrect assertion that professional literary agencies were not operating in Canada until the 1950s. In providing a chronological overview of the connection between Canadian authors and their associations with professional and informal agents in Canada, the US, and Britain, the essay provides the beginnings of a more detailed history of the nature of literary collaboration that existed over a turbulent century

Nobody Gets Hurt Bullfighting Canadian-Style: Rereading Frank Davey's "Surviving the Paraphrase"

Although Frank Davey's "Surviving the Paraphrase" has been canonized and appropriated by Canadian theorists as a crucial resistance narrative, critics have not focussed on the essay as a literary document that is related to the author's career, his consciousness, or his life. The fiction of Davey's life encodes his own stance as the author of the text. "Surviving the Paraphrase" can be read as a confession and redemption narrative; it traces Davey's personal sense of loss in moving east as a loss of self and voice, and his desire to redeem himself (reclaim his voice) by positing a non-centralist vision of recovery through form (which Davey equates with the authenticity of "writing as writing"). By the end of the essay, thematic criticism has been identified with power structures that need to be destroyed in order to create a milieu in which no writer is excluded. The essay's appeal lies both in the contradictions between loyalty and liberation it embodies and in the way these contradictions are presented as relevant issues to a professional community faced with questions about its own identity and future