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"Funk, Wolfgang"
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Narrative(s) in Conflict
Narrative/s in Conflict presents the proceedings of an international workshop, held at the Trinity Long Room Hub Dublin in 2013, to a wider audience.This was a cross-disciplinary cooperation between the comparative research network 'Broken Narratives' (University of Vienna), the research strand 'Identities in Transformation' (Trinity College.
eBook
The Architecture of Modern Culture
These collected essays contain fundamental contributions to contemporary cultural analysis and theory as well as exemplary interpretations of film, literature and other media. Central issues of current cultural studies are addressed: cultural narratives, cultural identity, collective memory and post-colonial thinking. The oeuvre of cultural and literary critic Wolfgang Müller-Funk encompasses historic analyses such as readings of Broch, Canetti and Musil, and the heritage they passed on. Other essays move from the beginning of the 20th to the 21st century and address questions of space, time and globalization discussing, for example, Walter Benjamin and 9/11.
eBook
Abnormal Interactions between Perifollicular Mast Cells and CD8+ T-Cells May Contribute to the Pathogenesis of Alopecia Areata
Alopecia areata (AA) is a CD8+ T-cell dependent autoimmune disease of the hair follicle (HF) in which the collapse of HF immune privilege (IP) plays a key role. Mast cells (MCs) are crucial immunomodulatory cells implicated in the regulation of T cell-dependent immunity, IP, and hair growth. Therefore, we explored the role of MCs in AA pathogenesis, focusing on MC interactions with CD8+ T-cells in vivo, in both human and mouse skin with AA lesions. Quantitative (immuno-)histomorphometry revealed that the number, degranulation and proliferation of perifollicular MCs are significantly increased in human AA lesions compared to healthy or non-lesional control skin, most prominently in subacute AA. In AA patients, perifollicular MCs showed decreased TGFβ1 and IL-10 but increased tryptase immunoreactivity, suggesting that MCs switch from an immuno-inhibitory to a pro-inflammatory phenotype. This concept was supported by a decreased number of IL-10+ and PD-L1+ MCs, while OX40L+, CD30L+, 4-1BBL+ or ICAM-1+ MCs were increased in AA. Lesional AA-HFs also displayed significantly more peri- and intrafollicular- CD8+ T-cells as well as more physical MC/CD8+ T-cell contacts than healthy or non-lesional human control skin. During the interaction with CD8+ T-cells, AA MCs prominently expressed MHC class I and OX40L, and sometimes 4-1BBL or ICAM-1, suggesting that MC may present autoantigens to CD8+ T-cells and/or co-stimulatory signals. Abnormal MC numbers, activities, and interactions with CD8+ T-cells were also seen in the grafted C3H/HeJ mouse model of AA and in a new humanized mouse model for AA. These phenomenological in vivo data suggest the novel AA pathobiology concept that perifollicular MCs are skewed towards pro-inflammatory activities that facilitate cross-talk with CD8+ T-cells in this disease, thus contributing to triggering HF-IP collapse in AA. If confirmed, MCs and their CD8+ T-cell interactions could become a promising new therapeutic target in the future management of AA.
Journal Article
Thyroxine (T4) may promote re-epithelialisation and angiogenesis in wounded human skin ex vivo
There is a pressing need for improved preclinical model systems in which to study human skin wound healing. Here, we report the development and application of a serum-free full thickness human skin wound healing model. Not only can re-epithelialization (epidermal repair) and angiogenesis be studied in this simple and instructive model, but the model can also be used to identify clinically relevant wound-healing promoting agents, and to dissect underlying candidate mechanisms of action in the target tissue. We present preliminary ex vivo data to suggest that Thyroxine (T4), which reportedly promotes skin wound healing in rodents in vivo, may promote key features of human skin wound healing. Namely, T4 stimulates re-epithelialisation and angiogenesis, and modulates both wound healing-associated epidermal keratin expression and energy metabolism in experimentally wound human skin. Functionally, the wound healing-promoting effects of T4 are at least partially mediated via fibroblast growth factor/fibroblast growth factor receptor-mediated signalling, since they could be significantly antagonized by bFGF-neutralizing antibody. Thus, this pragmatic, easy-to-use full-thickness human skin wound healing model provides a useful preclinical research tool in the search for clinically relevant candidate wound healing-promoting agents. These ex vivo data encourage further pre-clinical testing of topical T4 as a cost-efficient, novel agent in the management of chronic human skin wounds.
Journal Article
Psychoanalysis, monotheism and morality : symposia of the Sigmund Freud Museum 2009-2011
International experts reflecting on psychoanalysis in relation to religion and morality. In this volume renowned experts in psychoanalysis reflect on the relationship between psychoanalysis and religion, in particular presenting various controversial interpretations of the question if and to what extent monotheism semantically and structurally fits psychoanalytic insights. Some essays augment traditional religious critiques of Freudianism with later religio-philosophical theories on, for example, femininity. Others explore the relation between psychopathology and morality from the Freudian premise that psychopathology shows in an excessive way aspects or mechanisms of the human psyche that constitute our subjectivity, and as such also our moral capacities and behaviour. This publication is GPRC-labeled (Guaranteed Peer-Reviewed Content). Contributors: Andreas De Block (University of Leuven), Fethi Benslama (University of Paris Diderot), Sergio Benvenuto (ISTC, Rome), Gohar Homayounpour (Shahid Beheshti University, Tehran), Felix de Mendelssohn (Sigmund Freud University, Vienna), Julia Kristeva (University of Paris Diderot), Lode Lauwaert (University of Leuven), Siamak Movahedi (University of Massachusetts), Wolfgang Mller-Funk (University of Vienna), Gilles Ribault (University of Paris Diderot), Cline Surprenant (University of Sussex), Inge Scholz-Strasser (Sigmund Freud Foundation), Herman Westerink (University of Vienna), Joel Whitebook (Columbia University), Moshe Zuckermann (Tel Aviv University)
eBook
Hypothalamic–Pituitary–Thyroid Axis Hormones Stimulate Mitochondrial Function and Biogenesis in Human Hair Follicles
Thyroid hormones regulate mitochondrial function. As other hypothalamic–pituitary–thyroid (HPT) axis hormones, i.e., thyrotropin-releasing hormone (TRH) and thyrotropin (TSH), are expressed in human hair follicles (HFs) and regulate mitochondrial function in human epidermis, we investigated in organ-cultured human scalp HFs whether TRH (30 nM), TSH (10 mU ml−1), thyroxine (T4) (100 nM), and triiodothyronine (T3) (100 pM) alter intrafollicular mitochondrial energy metabolism. All HPT-axis members increased gene and protein expression of mitochondrial-encoded subunit 1 of cytochrome c oxidase (MTCO1), a subunit of respiratory chain complex IV, mitochondrial transcription factor A (TFAM), and Porin. All hormones also stimulated intrafollicular complex I/IV activity and mitochondrial biogenesis. The TSH effects on MTCO1, TFAM, and porin could be abolished by K1-70, a TSH-receptor antagonist, suggesting a TSH receptor–mediated action. Notably, as measured by calorimetry, T3 and TSH increased follicular heat production, whereas T3/T4 and TRH stimulated ATP production in cultured HF keratinocytes. HPT-axis hormones did not increase reactive oxygen species (ROS) production. Rather, T3 and T4 reduced ROS formation, and all tested HPT-axis hormones increased the transcription of ROS scavengers (catalase, superoxide dismutase 2) in HF keratinocytes. Thus, mitochondrial biology, energy metabolism, and redox state of human HFs are subject to profound (neuro-)endocrine regulation by HPT-axis hormones. The neuroendocrine control of mitochondrial biology in a complex human mini-organ revealed here may be therapeutically exploitable.
Journal Article
Evaluation of Human Mesenchymal Stromal Cells as Carriers for the Delivery of Oncolytic HAdV-5 to Head and Neck Squamous Cell Carcinomas
Human multipotent mesenchymal stromal cells (hMSCs) are of significant therapeutic interest due to their ability to deliver oncolytic adenoviruses to tumors. This approach is also investigated for targeting head and neck squamous cell carcinomas (HNSCCs). HAdV-5-HexPos3, a recently reported capsid-modified vector based on human adenovirus type 5 (HAdV-5), showed strongly improved infection of both hMSCs and the HNSCC cell line UM-SCC-11B. Given that, we generated life cycle-unmodified and -modified replication-competent HAdV-5-HexPos3 vector variants and analyzed their replication within bone marrow- and adipose tissue-derived hMSCs. Efficient replication was detected for both life cycle-unmodified and -modified vectors. Moreover, we analyzed the migration of vector-carrying hMSCs toward different HNSCCs. Although migration of hMSCs to HNSCC cell lines was confirmed in vitro, no homing of hMSCs to HNSCC xenografts was observed in vivo in mice and in ovo in a chorioallantoic membrane model. Taken together, our data suggest that HAdV-5-HexPos3 is a potent candidate for hMSC-based oncolytic therapy of HNSCCs. However, it also emphasizes the importance of generating optimized in vivo models for the evaluation of hMSC as carrier cells.
Journal Article
Open Wounds and Physical Divisions
This article frames Brexit as the consequence of social and demographic fissures running through the United Kingdom, thereby arguing that Britain’s exit from the European Union is symptomatic of a specifically English rather than British crisis of national identification. It shows how such internal faultlines within the UK’s society intersect with the evocation and employment of various kinds of border imagery and border discourses in the run-up to the Brexit Referendum in 2016. For the main part of the analysis, the article sets out to broaden the by now well-established genre of “BrexLit” (Shaw, Everitt) by focusing on what could be called “Pre-BrexLit,” that is, novels written well before Brexit became a term, let alone political reality. By way of three exemplary texts—Julian Barnes’s England, England (1998), Tony Saint’s Refusal Shoes (2003), and Rupert Thomson’s Divided Kingdom (2005)—the analysis retraces how literary accounts of how to establish, maintain and control borders—both real and metaphorical, mental and physical, external and internal—prefigure some of the divisive issues around which the Brexit struggle would revolve, while at the same time avoiding the necessarily contentious and biased labels attached to post-fact Brexit literature.
Journal Article
Transduction Enhancers Enable Efficient Human Adenovirus Type 5-Mediated Gene Transfer into Human Multipotent Mesenchymal Stromal Cells
Human multipotent mesenchymal stromal cells (hMSCs) are currently developed as cell therapeutics for different applications, including regenerative medicine, immune modulation, and cancer treatment. The biological properties of hMSCs can be further modulated by genetic engineering. Viral vectors based on human adenovirus type 5 (HAdV-5) belong to the most frequently used vector types for genetic modification of human cells in vitro and in vivo. However, due to a lack of the primary attachment receptor coxsackievirus and adenovirus receptor (CAR) in hMSCs, HAdV-5 vectors are currently not suitable for transduction of this cell type without capsid modification. Here we present several transduction enhancers that strongly enhance HAdV-5-mediated gene transfer into both bone marrow- and adipose tissue-derived hMSCs. Polybrene, poly-l-lysine, human lactoferrin, human blood coagulation factor X, spermine, and spermidine enabled high eGFP expression levels in hMSCs. Importantly, hMSCs treated with enhancers were not affected in their migration behavior, which is a key requisite for many therapeutic applications. Exemplary, strongly increased expression of tumor necrosis factor (TNF)-stimulated gene 6 (TSG-6) (a secreted model therapeutic protein) was achieved by enhancer-facilitated HAdV-5 transduction. Thus, enhancer-mediated HAdV-5 vector transduction is a valuable method for the engineering of hMSCs, which can be further exploited for the development of innovative hMSC therapeutics.
Journal Article