Syndecan-4 regulates cell-surface trafficking and biological activity of transglutaminase-2

Transglutaminase-2 (TG2) is a Ca2+-dependent crosslinking enzyme involved in the post-translational modification of proteins via the formation of Nε(γ-glutamyl)lysine isodipeptides. TG2 is externalised in the extracellular matrix (ECM) through an unconventional and not fully understood pathway. Under normal conditions, TG2 modulates cell adhesion, proliferation and tissue repair. Under continuous cell insult higher expression and elevated extracellular trafficking of TG2 contribute to the pathogenesis of tissue scarring. TG2 is known to have affinity for heparin, and in a previous study cell-surface heparan sulphate (HS) has been implicated in extracellular TG2 mediated RGD-independent cell adhesion, a non-enzymatic process independent from the α5β1 integrin-binding to the RGD domain on FN (Verderio et al., 2003). Hence HS proteoglycan (HSPG) could act as cell surface co-receptor for FNbound TG2 or contribute to the regulation of extracellular TG2 activity in cell adhesion and tissue repair

Syndecan-4 knockout leads to reduced extracellular transglutaminase-2 and protects against tubulointerstitial fibrosis

Transglutaminase type 2 (TG2) is an extracellular matrix crosslinking enzyme with a pivotal role in kidney fibrosis. The interaction of TG2 with the heparan sulfate proteoglycan syndecan-4 (Sdc4) regulates the cell surface trafficking, localization, and activity of TG2 in vitro but remains unstudied in vivo. We tested the hypothesis that Sdc4 is required for cell surface targeting of TG2 and the development of kidney fibrosis in CKD. Wild-type and Sdc4-null mice were subjected to unilateral ureteric obstruction and aristolochic acid nephropathy (AAN) as experimental models of kidney fibrosis. Analysis of renal scarring by Masson trichrome staining, kidney hydroxyproline levels, and collagen immunofluorescence demonstrated progressive fibrosis associated with increases in extracellular TG2 and TG activity in the tubulointerstitium in both models. Knockout of Sdc-4 reduced these effects and prevented AAN-induced increases in total and active TGF-b1. In wild-type mice subjected to AAN, extracellular TG2 colocalized with Sdc4 in the tubular interstitium and basement membrane, where TG2 also colocalized with heparan sulfate chains. Heparitinase I, which selectively cleaves heparan sulfate, completely abolished extracellular TG2 in normal and diseased kidney sections. In conclusion, the lack of Sdc4 heparan sulfate chains in the kidneys of Sdc4-null mice abrogates injury-induced externalization of TG2, thereby preventing profibrotic crosslinking of extracellular matrix and recruitment of large latent TGF-b1. This finding suggests that targeting the TG2- Sdc4 interaction may provide a specific interventional strategy for the treatment of CKD

Becoming multidimensional: an interpretative phenomenological analysis of client's experiences of transformation with teacher-led Pilates

There is a paucity of research that explores how people change without the assistance of psychotherapy. This exploratory investigation aims to make a contribution to the counselling psychology knowledge-base about the experience of psychological change without psychotherapy, and to the scant psychological knowledge-base about teacher-led structured exercise. The dissertation develops an in-depth account of eight people's meaning-making of experiences of transformation with teacher-led Pilates. Semi-structured interviews and the resultant transcripts are analysed using interpretative phenomenological analysis. The idiographic sensibility of this approach is represented using poetic condensations of individual participant's interviews. Two themes emerged from the cross-case analysis: 'weekly teacher-led Pilates classes can provide opportunities for valued interactional experiences' and 'weekly teacher-led Pilates classes can provide an invaluable arena/or transformation' . The discussion considers the characteristics of the contributors to this investigation in relation to available descriptive characteristics of people who use and participate in surveys or research about physical exercise, complementary and alternative medicine, and psychotherapy. The cross-case findings are contextualised with interactional theories, namely social psychological climate theory, attachment theory, and an embodied social cognition perspective that develops the work of phenomenological thinkers. The findings offer unexpected insights that seem to problematise key assumptions that underpin empirical psychology, psychotherapy and Pilates. The thesis draws out specific implications for the knowledge-base on which counselling psychology bases its practice

Investment determinants in self-consumption facilities: characterization and qualitative analysis in Spain

Self-consumption energy facilities are presented as viable and sustainable solutions in the energy transition scenario in which many countries are immersed. However, they rely on dispersed and private investments in the territory. Given the uneven growth in the number of self-consumption facilities in Europe, the main objective of this study is to identify and measure the investment determinants in self-consumption facilities. To this end, the main influential incentives and barriers are identified through the aggregate analysis of the regulatory framework for self-consumption in several European countries, and the empirical characterization of Spanish facilities as a multiple case study, to define the common features of the investments made. The technical, economic, and financial characterization of real self-consumption facilities in climatic zones of southern Europe is a significant contribution of the present work. There are few samples of this type in the studies published to date, which have mainly been prepared from case studies or statistical data without identifying particular facilities. Cost-related variables have been identified as the most important variables in private investment decisions, and potential influential factors on these variables that could be regulated have been pointed out as relevant. It is also worth highlighting the elaboration of an analytical framework based on this conceptual approach, which has been proven to be useful to depict regulatory scenarios and to compare the positioning for the development of self-consumption systems in different countries. A model that transfers the influence of the determining factors to the deployment of self-consumption under specific regulatory scenarios has been developed and applied to the case of Spain. As a general reflection, to increase the adoption of this kind of technology and encourage consumers to make private investments, policies for renewable energy must consider self-consumption and microgeneration as the main axis, by increasing the availability of energy when necessary. For instance, the promotion of energy storage from these kinds of facilities could receive priority treatment, as well as rewarding the electricity surplus in the interests of security of supply in a period of energy transition towards a new, more sustainable model. Incentive schemes, aids to compensate for the additional costs resulting from the battery storage or easing restrictions in terms of contracted power would foreseeably increase the rates of adoption of the technology, favoring its faster development in terms of research and development and product innovation

Sustainability reporting in view of the European sustainable finance taxonomy: Is the financial sector ready to disclose circular economy?

The European sustainable finance taxonomy requires financial and nonfinancial companies to provide investors with information about the environmental performance of their assets and economic activities. For financial institutions, making socially and environmentally responsible investments visible through a common label that guarantees specific standards for the entire European Union is crucial. Against this background, this study analyzes the evolution of sustainability reporting practices and their assurance in a sample of European financial institutions. To this end, we used a double qualitative methodological approach, based on (a) an external analysis of nonfinancial information and its relationship with the main economic-financial variables of the sample companies, and (b) a case study of a bank carried out through semi-structured interviews. This study provides an external measurement analysis of nonfinancial information in entities from different countries, which can contribute to broadening the scope and level of sustainability and circular economy accountability

Analysis of energy poverty intensity from the perspective of the regional administration: Empirical evidence from households in southern Europe

The current economic situation has increased the number of households in Europe experiencing restrictions and/or limitations of affordability of energy services, demonstrating the urgent need to intervene in those extreme cases in which households suffer the daily consequences of what is internationally defined as energy poverty. In such a context, this paper presents the results obtained in a case study characterising a sample of 615 households with demonstrated energy poverty in the region of Aragón (Spain). In parallel, the intensity of energy poverty in the studied cases is examined by measuring the percentage of energy expenditures with respect to income in the households that suffer it, and a descriptive analysis of the main determinants of energy poverty in the homes studied is presented as well as the policy implication at regional level