112 research outputs found

    Reduced TRPC Channel Expression in Psoriatic Keratinocytes Is Associated with Impaired Differentiation and Enhanced Proliferation

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    Psoriasis is a characteristic inflammatory and scaly skin condition with typical histopathological features including increased proliferation and hampered differentiation of keratinocytes. The activation of innate and adaptive inflammatory cellular immune responses is considered to be the main trigger factor of the epidermal changes in psoriatic skin. However, the molecular players that are involved in enhanced proliferation and impaired differentiation of psoriatic keratinocytes are only partly understood. One important factor that regulates differentiation on the cellular level is Ca2+. In normal epidermis, a Ca2+ gradient exists that is disturbed in psoriatic plaques, favoring impaired keratinocyte proliferation. Several TRPC channels such as TRPC1, TRPC4, or TRPC6 are key proteins in the regulation of high [Ca2+]ex induced differentiation. Here, we investigated if TRPC channel function is impaired in psoriasis using calcium imaging, RT-PCR, western blot analysis and immunohistochemical staining of skin biopsies. We demonstrated substantial defects in Ca2+ influx in psoriatic keratinocytes in response to high extracellular Ca2+ levels, associated with a downregulation of all TRPC channels investigated, including TRPC6 channels. As TRPC6 channel activation can partially overcome this Ca2+ entry defect, specific TRPC channel activators may be potential new drug candidates for the topical treatment of psoriasis

    STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing

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    Signal transducer and activator of transcription (STAT) 3 is a pleiotropic transcription factor with important functions in cytokine signaling in a variety of tissues. However, the role of STAT3 in the intestinal epithelium is not well understood. We demonstrate that development of colonic inflammation is associated with the induction of STAT3 activity in intestinal epithelial cells (IECs). Studies in genetically engineered mice showed that epithelial STAT3 activation in dextran sodium sulfate colitis is dependent on interleukin (IL)-22 rather than IL-6. IL-22 was secreted by colonic CD11c+ cells in response to Toll-like receptor stimulation. Conditional knockout mice with an IEC-specific deletion of STAT3 activity were highly susceptible to experimental colitis, indicating that epithelial STAT3 regulates gut homeostasis. STAT3IEC-KO mice, upon induction of colitis, showed a striking defect of epithelial restitution. Gene chip analysis indicated that STAT3 regulates the cellular stress response, apoptosis, and pathways associated with wound healing in IECs. Consistently, both IL-22 and epithelial STAT3 were found to be important in wound-healing experiments in vivo. In summary, our data suggest that intestinal epithelial STAT3 activation regulates immune homeostasis in the gut by promoting IL-22–dependent mucosal wound healing

    The future of dialects: Selected papers from Methods in Dialectology XV

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    Traditional dialects have been encroached upon by the increasing mobility of their speakers and by the onslaught of national languages in education and mass media. Typically, older dialects are “leveling” to become more like national languages. This is regrettable when the last articulate traces of a culture are lost, but it also promotes a complex dynamics of interaction as speakers shift from dialect to standard and to intermediate compromises between the two in their forms of speech. Varieties of speech thus live on in modern communities, where they still function to mark provenance, but increasingly cultural and social provenance as opposed to pure geography. They arise at times from the need to function throughout the different groups in society, but they also may have roots in immigrants’ speech, and just as certainly from the ineluctable dynamics of groups wishing to express their identity to themselves and to the world. The future of dialects is a selection of the papers presented at Methods in Dialectology XV, held in Groningen, the Netherlands, 11-15 August 2014. While the focus is on methodology, the volume also includes specialized studies on varieties of Catalan, Breton, Croatian, (Belgian) Dutch, English (in the US, the UK and in Japan), German (including Swiss German), Italian (including Tyrolean Italian), Japanese, and Spanish as well as on heritage languages in Canada

    The future of dialects: Selected papers from Methods in Dialectology XV

    Get PDF
    Traditional dialects have been encroached upon by the increasing mobility of their speakers and by the onslaught of national languages in education and mass media. Typically, older dialects are “leveling” to become more like national languages. This is regrettable when the last articulate traces of a culture are lost, but it also promotes a complex dynamics of interaction as speakers shift from dialect to standard and to intermediate compromises between the two in their forms of speech. Varieties of speech thus live on in modern communities, where they still function to mark provenance, but increasingly cultural and social provenance as opposed to pure geography. They arise at times from the need to function throughout the different groups in society, but they also may have roots in immigrants’ speech, and just as certainly from the ineluctable dynamics of groups wishing to express their identity to themselves and to the world. The future of dialects is a selection of the papers presented at Methods in Dialectology XV, held in Groningen, the Netherlands, 11-15 August 2014. While the focus is on methodology, the volume also includes specialized studies on varieties of Catalan, Breton, Croatian, (Belgian) Dutch, English (in the US, the UK and in Japan), German (including Swiss German), Italian (including Tyrolean Italian), Japanese, and Spanish as well as on heritage languages in Canada

    The future of dialects: Selected papers from Methods in Dialectology XV

    Get PDF
    Traditional dialects have been encroached upon by the increasing mobility of their speakers and by the onslaught of national languages in education and mass media. Typically, older dialects are “leveling” to become more like national languages. This is regrettable when the last articulate traces of a culture are lost, but it also promotes a complex dynamics of interaction as speakers shift from dialect to standard and to intermediate compromises between the two in their forms of speech. Varieties of speech thus live on in modern communities, where they still function to mark provenance, but increasingly cultural and social provenance as opposed to pure geography. They arise at times from the need to function throughout the different groups in society, but they also may have roots in immigrants’ speech, and just as certainly from the ineluctable dynamics of groups wishing to express their identity to themselves and to the world. The future of dialects is a selection of the papers presented at Methods in Dialectology XV, held in Groningen, the Netherlands, 11-15 August 2014. While the focus is on methodology, the volume also includes specialized studies on varieties of Catalan, Breton, Croatian, (Belgian) Dutch, English (in the US, the UK and in Japan), German (including Swiss German), Italian (including Tyrolean Italian), Japanese, and Spanish as well as on heritage languages in Canada

    The future of dialects: Selected papers from Methods in Dialectology XV

    Get PDF
    Traditional dialects have been encroached upon by the increasing mobility of their speakers and by the onslaught of national languages in education and mass media. Typically, older dialects are “leveling” to become more like national languages. This is regrettable when the last articulate traces of a culture are lost, but it also promotes a complex dynamics of interaction as speakers shift from dialect to standard and to intermediate compromises between the two in their forms of speech. Varieties of speech thus live on in modern communities, where they still function to mark provenance, but increasingly cultural and social provenance as opposed to pure geography. They arise at times from the need to function throughout the different groups in society, but they also may have roots in immigrants’ speech, and just as certainly from the ineluctable dynamics of groups wishing to express their identity to themselves and to the world. The future of dialects is a selection of the papers presented at Methods in Dialectology XV, held in Groningen, the Netherlands, 11-15 August 2014. While the focus is on methodology, the volume also includes specialized studies on varieties of Catalan, Breton, Croatian, (Belgian) Dutch, English (in the US, the UK and in Japan), German (including Swiss German), Italian (including Tyrolean Italian), Japanese, and Spanish as well as on heritage languages in Canada

    The future of dialects: Selected papers from Methods in Dialectology XV

    Get PDF
    Traditional dialects have been encroached upon by the increasing mobility of their speakers and by the onslaught of national languages in education and mass media. Typically, older dialects are “leveling” to become more like national languages. This is regrettable when the last articulate traces of a culture are lost, but it also promotes a complex dynamics of interaction as speakers shift from dialect to standard and to intermediate compromises between the two in their forms of speech. Varieties of speech thus live on in modern communities, where they still function to mark provenance, but increasingly cultural and social provenance as opposed to pure geography. They arise at times from the need to function throughout the different groups in society, but they also may have roots in immigrants’ speech, and just as certainly from the ineluctable dynamics of groups wishing to express their identity to themselves and to the world. The future of dialects is a selection of the papers presented at Methods in Dialectology XV, held in Groningen, the Netherlands, 11-15 August 2014. While the focus is on methodology, the volume also includes specialized studies on varieties of Catalan, Breton, Croatian, (Belgian) Dutch, English (in the US, the UK and in Japan), German (including Swiss German), Italian (including Tyrolean Italian), Japanese, and Spanish as well as on heritage languages in Canada

    The future of dialects: Selected papers from Methods in Dialectology XV

    Get PDF
    Traditional dialects have been encroached upon by the increasing mobility of their speakers and by the onslaught of national languages in education and mass media. Typically, older dialects are “leveling” to become more like national languages. This is regrettable when the last articulate traces of a culture are lost, but it also promotes a complex dynamics of interaction as speakers shift from dialect to standard and to intermediate compromises between the two in their forms of speech. Varieties of speech thus live on in modern communities, where they still function to mark provenance, but increasingly cultural and social provenance as opposed to pure geography. They arise at times from the need to function throughout the different groups in society, but they also may have roots in immigrants’ speech, and just as certainly from the ineluctable dynamics of groups wishing to express their identity to themselves and to the world. The future of dialects is a selection of the papers presented at Methods in Dialectology XV, held in Groningen, the Netherlands, 11-15 August 2014. While the focus is on methodology, the volume also includes specialized studies on varieties of Catalan, Breton, Croatian, (Belgian) Dutch, English (in the US, the UK and in Japan), German (including Swiss German), Italian (including Tyrolean Italian), Japanese, and Spanish as well as on heritage languages in Canada

    The future of dialects: Selected papers from Methods in Dialectology XV

    Get PDF
    Traditional dialects have been encroached upon by the increasing mobility of their speakers and by the onslaught of national languages in education and mass media. Typically, older dialects are “leveling” to become more like national languages. This is regrettable when the last articulate traces of a culture are lost, but it also promotes a complex dynamics of interaction as speakers shift from dialect to standard and to intermediate compromises between the two in their forms of speech. Varieties of speech thus live on in modern communities, where they still function to mark provenance, but increasingly cultural and social provenance as opposed to pure geography. They arise at times from the need to function throughout the different groups in society, but they also may have roots in immigrants’ speech, and just as certainly from the ineluctable dynamics of groups wishing to express their identity to themselves and to the world. The future of dialects is a selection of the papers presented at Methods in Dialectology XV, held in Groningen, the Netherlands, 11-15 August 2014. While the focus is on methodology, the volume also includes specialized studies on varieties of Catalan, Breton, Croatian, (Belgian) Dutch, English (in the US, the UK and in Japan), German (including Swiss German), Italian (including Tyrolean Italian), Japanese, and Spanish as well as on heritage languages in Canada
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