The histone demethylase Jumonji domain-containing protein 3 (JMJD3) regulates fibroblast activation in systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) fibroblasts remain activated even in the absence of exogenous stimuli. Epigenetic alterations are thought to play a role for this endogenous activation. Trimethylation of histone H3 on lysine 27 (H3K27me3) is regulated by Jumonji domain-containing protein 3 (JMJD3) and ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) in a therapeutically targetable manner. The aim of this study was to explore H3K27me3 demethylases as potential targets for the treatment of fibrosis. METHODS: JMJD3 was inactivated by small interfering RNA-mediated knockdown and by pharmacological inhibition with GSKJ4. The effects of targeted inactivation of JMJD3 were analysed in cultured fibroblasts and in the murine models of bleomycin-induced and topoisomerase-I (topoI)-induced fibrosis. H3K27me3 at the FRA2 promoter was analysed by ChIP. RESULTS: The expression of JMJD3, but not of UTX, was increased in fibroblasts in SSc skin and in experimental fibrosis in a transforming growth factor beta (TGFβ)-dependent manner. Inactivation of JMJD3 reversed the activated fibroblast phenotype in SSc fibroblasts and prevented the activation of healthy dermal fibroblasts by TGFβ. Pharmacological inhibition of JMJD3 ameliorated bleomycin-induced and topoI-induced fibrosis in well-tolerated doses. JMJD3 regulated fibroblast activation in a FRA2-dependent manner: Inactivation of JMJD3 reduced the expression of FRA2 by inducing accumulation of H3K27me3 at the FRA2 promoter. Moreover, the antifibrotic effects of JMJD3 inhibition were reduced on knockdown of FRA2. CONCLUSION: We present first evidence for a deregulation of JMJD3 in SSc. JMJD3 modulates fibroblast activation by regulating the levels of H3K27me3 at the promoter of FRA2. Targeted inhibition of JMJD3 limits the aberrant activation of SSc fibroblasts and exerts antifibrotic effects in two murine models

Local public transport and neighbourhood satisfaction: The effect on older adults' subjective wellbeing

The Covid-19 pandemic has impacted older adults in terms of both physical (high mortality rate) and psychological health. In these challenging times more than ever, exploring which dimensions affect the older people's subjective wellbeing is relevant. As the literature has shown, older people prefer to age in place: the living environment and the presence of local services (including public transport) play a key role. The effects of social environment on older people's mobility, especially during the Covid-19 pandemic period remain a less studied topic. Within this context, the paper aims to explore the role of satisfaction with neighbourhood, local public transport, and socio-demographic characteristics in influencing subjective wellbeing in Italy, during the Covid-19 pandemic. A survey has been addressed to people aged over 65 years old in three Italian cities (Milan, Padua, and Varese). A structural equation model and an ordered logit model have been performed. Results show that older adults who are satisfied with their neighbourhood and are happy with the local public transport characteristics are more likely to have higher subjective wellbeing. Moreover, men, older adults living alone, and those who have suffered from an income reduction, due to the pandemic, show lower levels of subjective wellbeing

CD30-positive primary cutaneous anaplastic large cell lymphoma with coexistent pseudocarcinomatous hyperplasia

CD30-positive primary cutaneous anaplastic large cell lymphoma (C-ALCL) is an indolent type of cutaneous lymphoma with favourable clinical prognosis. Pseudocarcinomatous hyperplasia (PCH) is a rare benign epithelial condition that can resemble invasive squamous cell carcinoma both clinically and histopathologically. PCH predominantly occurs in CD30-positive lymphoproliferative disorders. We report a 75-year-old woman with PCH in a multifocal C-ALCL located on the scalp and right retroauricular area, which rapidly responded to treatment with psoralen ultraviolet A photochemotherapy. Comprehensive virological analyses for potential oncogenic viruses, including Epstein-Barr virus, human herpesvirus-8, human papillomaviruses, the recently discovered cutavirus and nine different human polyomaviruses, were negative

Proposal for a EU quality label for aerospace education

The paper presents a possible roadmap for the definition of a European quality label for aerospace related higher education degrees. The proposal is the result of a two-years long Horizon 2020 project that has involved a great portion of the European stakeholders in aerospace: Universities, research centres, industries (both small and large) networks, associations and accreditation agencies. The core concept established is that it is possible to establish a sector-specific, content based, quality system, that can complement the existing national or European accreditation systems, providing added value to the internal and/or external quality assurance processes that are in place in most EU countries. The tools and processes proposed are sufficiently simple to be manageable by Universities in addition to their national accreditation processes or as stand-alone assessment. The main goal of the proposed process is the evaluation of the quality of the aerospace curricula in the European context, whereas the accreditation of the programme can be seen as an optional extension of the process, subject to further national regulations. The process is proposed in view of the awarding of a sector-specific, content based, quality label, to be issued by an appropriate legally recognized and qualified institution. 8 field tests with volunteering universities throughout Europe have been performed. They experienced the method as very practical and to the point.Flight Performance and Propulsio