The 'true use of reading' : Sarah Fielding and mid eighteenth-century literary strategies.

PhDThe aim of this thesis is to explore, by examining her life and works, how Sarah Fielding (1710-68) established her identity as an author. The definition of her role involves her notions of the functions of writing and reading. Sarah Fielding attempts to invite readers to form a sense of ties by tacit understanding of her messages. As she believes that a work of literature is produced through collaboration between the writer and the reader, it is an important task in her view to show her attentiveness toward reading practice. In her consideration of reading, she has two distinct, even opposite views of her audience: on the one hand a familiar and limited circle of readers with shared moral and cultural values and on the other potential readers among the unknown mass of people. The dual targets direct her to devise various strategies. She tries to appeal to those who can endorse and appreciate her moral values as well as her learning. Her writings and letters testify that she is sensitive to the demands of the literary market, trying to lead the taste of readers by inventing new forms. The thesis opens with an overview of Sarah Fielding's career, followed by a consideration of her critical attention to the roles of reading. I go on to examine the narrative structures and strategies she deploys, with a particular emphasis on her use of the epistolary method. The following chapter deals with her attention to the reading of the moral message tangibly embodied in her educational writing. It is followed by an analysis of the activity which earned her a reputation as a learned woman. Various as the forms of her works are, they invariably reflect her attempt to balance herself between the two demands of inventiveness and familiarity

Inhibition of microglial activity alters spinal wide dynamic range neuron discharge and reduces microglial Toll-like receptor 4 expression in neuropathic rats

It is believed that neuropathic pain results from aberrant neuronal discharges although some evidence suggests that the activation of glia cells contributes to pain after an injury to the nervous system. This study aimed to evaluate the role of microglial activation on the hyper-responsiveness of wide dynamic range neurons (WDR) and Toll-like receptor 4 (TLR4) expressions in a chronic constriction injury (CCI) model of neuropathic pain in rats. Adult male Wistar rats (230 � 30 g) underwent surgery for induction of CCI neuropathy. Six days after surgery, administration of minocycline (10, 20, and 40 mg/kg, i.p.) was initiated and continued until day 14. After administration of the last dose of minocycline or saline, a behavioral test was conducted, then animals were sacrificed and lumbar segments of the spinal cord were collected for Western blot analysis of TLR4 expression. The electrophysiological properties of WDR neurons were investigated by single unit recordings in separate groups. The findings showed that after CCI, in parallel with thermal hyperalgesia, the expression of TLR4 in the spinal cord and the evoked response of the WDR neurons to electrical, mechanical, and thermal stimulation significantly increased. Post-injury administration of minocycline effectively decreased thermal hyperalgesia, TLR4 expression, and hyperresponsiveness of WDR neurons in CCI rats. The results of this study indicate that post-injury, repeated administration of minocycline attenuated neuropathic pain by suppressing microglia activation and reducing WDR neuron hyperresponsiveness. This study confirms that post-injury modulation of microglial activity is a new strategy for treating neuropathic pain

Dedication to Professor Emeritus Tsuneyuki Hanami

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Induction of podoplanin by transforming growth factor-β in human fibrosarcoma

AbstractPodoplanin/aggrus is increased in tumors and its expression was associated with tumor malignancy. Podoplanin on cancer cells serves as a platelet-aggregating factor, which is associated with the metastatic potential. However, regulators of podoplanin remain to be determined. Transforming growth factor-β (TGF-β) regulates many physiological events, including tumorigenesis. Here, we found that TGF-β induced podoplanin in human fibrosarcoma HT1080 cells and enhanced the platelet-aggregating-ability of HT1080. TGF-β type I receptor inhibitor (SB431542) and short hairpin RNAs for Smad4 inhibited the podoplanin induction by TGF-β. These results suggest that TGF-β is a physiological regulator of podoplanin in tumor cells

Patients with CDH23 mutations and the 1555A > G mitochondrial mutation are good candidates for electric acoustic stimulation (EAS)

Conclusions: CDH23 mutations and the 1555A>G mitochondrial mutation were identified among our series of electric acoustic stimulation (EAS) patients, confirming that these genes were important in hearing loss with involvement of high frequency. Successful hearing preservation as well as good outcomes from EAS indicated that patients with this combination of mutations are good candidates for EAS. Objectives: Screening for gene mutations that possibly cause hearing loss involving high frequency was performed to identify the responsible genes in patients with EAS. In addition to a review of the genetic background of the patients with residual hearing loss, the benefit of EAS for patients with particular gene mutations was evaluated. Methods: Eighteen patients (15 late-onset, 3 early-onset) with residual hearing who had received EAS were included in this study. Genetic analysis was performed to identify GJB2, CDH23, SLC26A4, and the 1555 mitochondrial mutations. Results: Three early-onset patients had CDH23 mutations. One late-onset patient had the 1555 A>G mitochondrial mutation.ArticleACTA OTO-LARYNGOLOGICA. 132(4):377-384 (2012)journal articl