39 research outputs found

    Chagasic Thymic Atrophy Does Not Affect Negative Selection but Results in the Export of Activated CD4+CD8+ T Cells in Severe Forms of Human Disease

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    Extrathymic CD4+CD8+ double-positive (DP) T cells are increased in some pathophysiological conditions, including infectious diseases. In the murine model of Chagas disease, it has been shown that the protozoan parasite Trypanosoma cruzi is able to target the thymus and induce alterations of the thymic microenvironment and the lymphoid compartment. In the acute phase, this results in a severe atrophy of the organ and early release of DP cells into the periphery. To date, the effect of the changes promoted by the parasite infection on thymic central tolerance has remained elusive. Herein we show that the intrathymic key elements that are necessary to promote the negative selection of thymocytes undergoing maturation during the thymopoiesis remains functional during the acute chagasic thymic atrophy. Intrathymic expression of the autoimmune regulator factor (Aire) and tissue-restricted antigen (TRA) genes is normal. In addition, the expression of the proapoptotic Bim protein in thymocytes was not changed, revealing that the parasite infection-induced thymus atrophy has no effect on these marker genes necessary to promote clonal deletion of T cells. In a chicken egg ovalbumin (OVA)-specific T-cell receptor (TCR) transgenic system, the administration of OVA peptide into infected mice with thymic atrophy promoted OVA-specific thymocyte apoptosis, further indicating normal negative selection process during the infection. Yet, although the intrathymic checkpoints necessary for thymic negative selection are present in the acute phase of Chagas disease, we found that the DP cells released into the periphery acquire an activated phenotype similar to what is described for activated effector or memory single-positive T cells. Most interestingly, we also demonstrate that increased percentages of peripheral blood subset of DP cells exhibiting an activated HLA-DR+ phenotype are associated with severe cardiac forms of human chronic Chagas disease. These cells may contribute to the immunopathological events seen in the Chagas disease

    Rank signaling links the development of invariant γΎ T cell progenitors and Aire(+) medullary epithelium

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    The thymic medulla provides a specialized microenvironment for the negative selection of T cells, with the presence of autoimmune regulator (Aire)-expressing medullary thymic epithelial cells (mTECs) during the embryonic-neonatal period being both necessary and sufficient to establish long-lasting tolerance. Here we showed that emergence of the first cohorts of Aire(+) mTECs at this key developmental stage, prior to αÎČ T cell repertoire selection, was jointly directed by Rankl(+) lymphoid tissue inducer cells and invariant VÎł5(+) dendritic epidermal T cell (DETC) progenitors that are the first thymocytes to express the products of gene rearrangement. In turn, generation of Aire(+) mTECs then fostered Skint-1-dependent, but Aire-independent, DETC progenitor maturation and the emergence of an invariant DETC repertoire. Hence, our data attributed a functional importance to the temporal development of VÎł5(+) γΎ T cells during thymus medulla formation for αÎČ T cell tolerance induction and demonstrated a Rank-mediated reciprocal link between DETC and Aire(+) mTEC maturation

    Quanto vale il marchio bio? Un'indagine edonimetrica

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    Effect of information on consumer preferences and willingness-to-pay for sparkling mock wines

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    Purpose: The purpose of this paper is to explore the role of information about alcohol content, organic labelling and packaging on consumer preferences and willingness-to-pay (WTP) of non-alcoholic sparkling mock wines. Design/methodology/approach: In a two-step study, the consumer’s expectations and overall liking of two novel brands of mock wines were investigated by focus groups followed by a common hedonic test combined with a choice experiment aimed at measuring consumer WTP. A total of 240 consumers were assigned to two tasting groups of equal size: all were presented at least one brand of mock wine, while drinkers also tasted a familiar brand of low-alcohol sweet sparkling wine. A paper-and-pencil choice experiment followed the tasting sessions. Findings: The results demonstrate that participants in blind or manipulated “informed” conditions are not able to discriminate among mock wines and wine, whereas significant differences in preferences for brands under investigation appeared when labels and other information were disclosed. In effect, drinkers and non-drinkers did not differ in hedonic scores of mock wines. While younger participants exhibited the highest scores in blind liking, the overall expected liking is significantly higher for non-drinkers and women if compared, respectively, to drinkers and men. WTP for mock wines is influenced by taste, glass bottle packaging and the organic label, while mock-wine colour is not relevant. Research limitations/implications: Although limited in sample size and representativeness, this study has brought some new insights into the consumption of non-alcoholic mock wines. In this study, a significant influence of blind sensory liking on WTP is demonstrated. This result has theoretical implications: while the effect of product information on WTP is well established, the relationship between hedonic scores and WTP – while theoretically consistent – is not so clear-cut in the literature. Further research is needed to confirm/disconfirm these findings. Practical implications: Sparkling no-alcohol mock wines, despite their sweetness, appear not different in taste to medium-to-low APV (7.5 per cent) sweet wines. Originality/value: The paper suggests that marketing of mock (no-alcohol) wines needs careful branding to elicit significant hedonic effects, while interacting sensory (blind liking) scores with price information in choice models may help to represent taste heterogeneity in WTP estimates in a better way

    Automatic analysis of eye-tracking data for augmented reality applications: A prospective outlook

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    Eye-tracking technology is becoming easier and cheaper to use, resulting in its increasing application to numerous fields of research. Recent years have seen rapid developments in this area. In light of the foregoing, in the context of Cultural Heritage (CH), the definition of a modern approach to understand how individuals perceive art is challenging. Despite the art perception is highly subjective and variable according to knowledge and experience, more recently, several scientific study and enterprises started to quantify how subjects observe art by the application of the eye-tracking technology. The aim of this study was to understand the visual behaviour of subjects looking at paintings, using eyetracking technology, in order to define a protocol for optimizing an existing Augmented Reality (AR) application that allows the visualization of digital contents through a display. The stimuli used are three famous paintings preserved at the National Gallery of Marche (Urbino, Marche Region, Italy). We applied eye-tracking to have a deeper understanding of people visual activities in front of these paintings and to analyse how digital contents eventually influence their behaviour. The description of the applied procedure and the preliminary results are presented
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