12 research outputs found

    Treatment of a language activation maintenance deficit in Wernicke's aphasia

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    This study demonstrates a novel and effective treatment approach for a person with Wernicke’s aphasia and severe short-term memory impairment. The treatment targets the ability to access and maintain activation of phonological and lexical-semantic representations of words, using varying time intervals between stimulus and response during word repetition. Effects seem to reflect improvement in the ability to maintain activation and connection strength to allow better word processing. The robust response to the treatment indicates great potential of this approach with someone who has difficulty with semantic and phonological processing of words

    Second Interview with Ann Davis Thomas

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    A second interview with Ann Davis Thomas, daughter of London architect Arthur Joseph Davis (1878-1951). Discusses her father’s partnership with Charles Mèwes, his work on buildings such as the Ritz Hotel, the Morning Post and the Royal Automobile Club, and the ocean liners Aquitania and Queen Mary in the early 20th century

    Interview with Ann Davis Thomas

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    An interview with Ann Davis Thomas, daughter of London architect Arthur Joseph Davis (1878-1951). Discusses her father’s partnership with Charles Mèwes, his work on buildings such as the Ritz Hotel, the Morning Post and the Royal Automobile Club, and the ocean liners Aquitania and Queen Mary in the early 20th century

    IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ

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    Fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic scleroderma (SSc), are commonly associated with high morbidity and mortality, thereby representing a significant unmet medical need. Interleukin 11 (IL11)-mediated cell activation has been identified as a central mechanism for promoting fibrosis downstream of TGFβ. IL11 signaling has recently been reported to promote fibroblast-to-myofibroblast transition, thus leading to various pro-fibrotic phenotypic changes. We confirmed increased mRNA expression of IL11 and IL11Rα in fibrotic diseases by OMICs approaches and in situ hybridization. However, the vital role of IL11 as a driver for fibrosis was not recapitulated. While induction of IL11 secretion was observed downstream of TGFβ signaling in human lung fibroblasts and epithelial cells, the cellular responses induced by IL11 was quantitatively and qualitatively inferior to that of TGFβ at the transcriptional and translational levels. IL11 blocking antibodies inhibited IL11Rα-proximal STAT3 activation but failed to block TGFβ-induced profibrotic signals. In summary, our results challenge the concept of IL11 blockade as a strategy for providing transformative treatment for fibrosis

    Image_2_IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ.tif

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    Fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic scleroderma (SSc), are commonly associated with high morbidity and mortality, thereby representing a significant unmet medical need. Interleukin 11 (IL11)-mediated cell activation has been identified as a central mechanism for promoting fibrosis downstream of TGFβ. IL11 signaling has recently been reported to promote fibroblast-to-myofibroblast transition, thus leading to various pro-fibrotic phenotypic changes. We confirmed increased mRNA expression of IL11 and IL11Rα in fibrotic diseases by OMICs approaches and in situ hybridization. However, the vital role of IL11 as a driver for fibrosis was not recapitulated. While induction of IL11 secretion was observed downstream of TGFβ signaling in human lung fibroblasts and epithelial cells, the cellular responses induced by IL11 was quantitatively and qualitatively inferior to that of TGFβ at the transcriptional and translational levels. IL11 blocking antibodies inhibited IL11Rα-proximal STAT3 activation but failed to block TGFβ-induced profibrotic signals. In summary, our results challenge the concept of IL11 blockade as a strategy for providing transformative treatment for fibrosis.</p

    DataSheet_2_IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ.csv

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    Fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic scleroderma (SSc), are commonly associated with high morbidity and mortality, thereby representing a significant unmet medical need. Interleukin 11 (IL11)-mediated cell activation has been identified as a central mechanism for promoting fibrosis downstream of TGFβ. IL11 signaling has recently been reported to promote fibroblast-to-myofibroblast transition, thus leading to various pro-fibrotic phenotypic changes. We confirmed increased mRNA expression of IL11 and IL11Rα in fibrotic diseases by OMICs approaches and in situ hybridization. However, the vital role of IL11 as a driver for fibrosis was not recapitulated. While induction of IL11 secretion was observed downstream of TGFβ signaling in human lung fibroblasts and epithelial cells, the cellular responses induced by IL11 was quantitatively and qualitatively inferior to that of TGFβ at the transcriptional and translational levels. IL11 blocking antibodies inhibited IL11Rα-proximal STAT3 activation but failed to block TGFβ-induced profibrotic signals. In summary, our results challenge the concept of IL11 blockade as a strategy for providing transformative treatment for fibrosis.</p
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