Activation of Epidermal Toll-Like Receptor 2 Enhances Tight Junction Function: Implications for Atopic Dermatitis and Skin Barrier Repair

Atopic dermatitis (AD) is characterized by epidermal tight junction (TJ) defects and a propensity for Staphylococcus aureus skin infections. S. aureus is sensed by many pattern recognition receptors, including Toll-like receptor 2 (TLR2). We hypothesized that an effective innate immune response will include skin barrier repair, and that this response is impaired in AD subjects. S. aureus–derived peptidoglycan (PGN) and synthetic TLR2 agonists enhanced TJ barrier and increased expression of TJ proteins, claudin-1 (CLDN1), claudin-23 (CLDN23), occludin, and Zonulae occludens 1 (ZO-1) in primary human keratinocytes. A TLR2 agonist enhanced skin barrier recovery in human epidermis wounded by tape stripping. Tlr2−/− mice had a delayed and incomplete barrier recovery following tape stripping. AD subjects had reduced epidermal TLR2 expression as compared with nonatopic subjects, which inversely correlated (r=-0.654, P=0.0004) with transepidermal water loss (TEWL). These observations indicate that TLR2 activation enhances skin barrier in murine and human skin and is an important part of a wound repair response. Reduced epidermal TLR2 expression observed in AD patients may have a role in their incompetent skin barrier

Combining Logics to Transform Organizational Agency: Blending Industry and Art at Alessi

To understand how organizations combine conflicting institutional logics strategically to create and pursue new market opportunities, we conducted an in-depth longitudinal study of the multiple efforts of the Italian manufacturer of household goods Alessi to combine the logics of industrial manufacturing and cultural production. Over three decades, Alessi developed three different strategies to combine normative elements of the two logics, using each strategy to envision and pursue different market opportunities. By combining the logics of industrial manufacturing and cultural production, Alessi was able to envision new possibilities for value creation and to enact them through innovation in product design. The three strategies triggered a common set of mechanisms through which the purposeful combining of logics enabled the pursuit of opportunity, while each strategy structured the process differently. We develop a theoretical model linking the development of recombinant strategies to the dynamic restructuring of organizational agency and the related capacity to create and pursue new market opportunities. Our findings and theoretical insights advance understanding of the processes through which organizations challenge taken-for-granted beliefs and practices to create new market opportunities, use logics as resources to enable embedded agency, and design hybrid organizational arrangements

Comparision between relationship patterns in alopecia areata and in psychiatric disorders through the core conflictual relationship theme (CCRT) method

Objective: Several reports suggest psychological factors may play a role in the etiology or course of alopecia areata. However, empirical information about the interpersonal patterns of patients with alopecia areata at best is limited. The authors aimed at identifying possible differences between relationship patterns displayed by patients suffering from alopecia areata and those displayed by psychiatric patients. Methods: 36 alopecic patients and 55 psychiatric patients were enrolled in the study. The Core Conflictual Relationship Theme (CCRT) method is a reliable and widely adopted method for scoring relationship patterns, a basic facet of human personality. It was scored on transcriptions of psychotherapy sessions or of interviews dedicated to eliciting material for CCRT scoring, the Relationship Anecdote Paradigm (RAP) interviews. The material was rated according to the Clustered Standard Categories system. The frequencies of each CCRT component in the two samples were confronted through analysis of variance. Results: Patients with alopecia areata showed a higher frequency of the wish: 'to oppose', of the responses from others: 'upset', 'reject', and 'controlling', and of the responses of self: 'oppose', 'helpful', 'disappointed' and 'self-controlled'. The 'wish' 'to assert' was observed more frequently among the patients with a psychiatric disorder. Conclusion: The present research indicates that patients suffering from alopecia areata display relationship themes different from psychiatric patients

Aldo-Keto Reductase 1C3 Is Expressed in Differentiated Human Epidermis, Affects Keratinocyte Differentiation, and Is Upregulated in Atopic Dermatitis

Aldo-keto reductase 1C3 (AKR1C3) has been shown to mediate the metabolism of sex hormones and prostaglandin D2 (PGD2), a lipid mediator that promotes skin inflammation in atopic dermatitis (AD). As both have a role in skin function and pathology, we first sought to investigate the expression pattern of AKR1C3 in normal human epidermis. Immunofluorescence revealed a strong expression of AKR1C3 in the differentiated suprabasal layers compared with the basal layer. Western blot analysis and quantitative PCR confirmed that AKR1C3 expression was also upregulated in differentiation-induced primary human keratinocytes (PHKs). To investigate the functional role of AKR1C3 during PHK differentiation, its expression and activity (measured as PGD2 reduction to 9α,11β-PGF2 by ELISA) were impaired by small interfering RNA or 2′-hydroxyflavanone, respectively. Cytokeratin 10 (K10) and loricrin expression were then examined by western blot analysis, thus revealing altered expression of these differentiation markers. Finally, following an observation that the AD-associated mediator, PGD2, upregulated AKR1C3 expression in PHKs, we used immunofluorescence to examine AKR1C3 expression in AD and psoriasis lesions. AKR1C3 was found to be upregulated in AD but not in psoriasis lesions compared with non-lesional skin. Our work demonstrates a function for AKR1C3 in differentiation-associated gene regulation and also suggests a role in supporting inflammation in AD

Language and thought disorder in schizophrenia: brain morphological correlates.

12nonenoneA. VITA; DIECI M; GIOBBIO G.M; CAPUTO A; GHIRINGHELLI L; COMAZZI M; GARBARINI M; MENDINI A.P; MORGANTI C; TENCONI F; CESANA B; INVERNIZZI GVita, Antonio; Dieci, M; GIOBBIO G., M; Caputo, A; Ghiringhelli, L; Comazzi, M; Garbarini, M; MENDINI A., P; Morganti, C; Tenconi, F; Cesana, Bruno Mario; Invernizzi, G