Impairment of chaperone-mediated autophagy induces dopaminergic neurodegeneration in rats

Chaperone-mediated autophagy (CMA) involves the selective lysosomal degradation of cytosolic proteins such as SNCA (synuclein α), a protein strongly implicated in Parkinson disease (PD) pathogenesis. However, the physiological role of CMA and the consequences of CMA failure in the living brain remain elusive. Here we show that CMA inhibition in the adult rat substantia nigra via adeno-associated virus-mediated delivery of short hairpin RNAs targeting the LAMP2A receptor, involved in CMA's rate limiting step, was accompanied by intracellular accumulation of SNCA-positive puncta, which were also positive for UBIQUITIN, and in accumulation of autophagic vacuoles within LAMP2A-deficient nigral neurons. Strikingly, LAMP2A downregulation resulted in progressive loss of nigral dopaminergic neurons, severe reduction in striatal dopamine levels/terminals, increased astro- and microgliosis and relevant motor deficits. Thus, this study highlights for the first time the importance of the CMA pathway in the dopaminergic system and suggests that CMA impairment may underlie PD pathogenesis. © 2016 Taylor & Francis

High rates of obesity prevalence in adults living in Central Greece: Data from the ARGOS Study

OBJECTIVE: To investigate the prevalence of obesity in adults of a large region of Central Greece. DESIGN: The target group was adults aged 18 to 79 years who were residents of the region of Thessaly for at least one year. A sample of 852 individuals stratified for sex and age were included. Each subject underwent a thorough physical examination and body mass index (BMI) was calculated from body weight and height. Waist and hip circumferences as well as body fat content were additionally measured. RESULTS: Mean (SD) BMI for the total population was 27.5 +/- 5.5 and was significantly higher in males than in females (28.2 +/- 4.4 vs. 26.9 +/- 6.2, p102cm for men, >88cm for women), was comparable in males (40.4%) and females (35.3%). There was a positive association between obesity, central obesity, and age. The prevalence of overweight (19.5%) and obesity (9.4%) in the age-range of 18-29 years almost doubled in the next decade of age and attained the highest value, respectively, in the age-range of 50 to 59 (48.2%), and of 60 to 70 years group (38.9%). CONCLUSIONS: The rates of overweight and obesity in the population of Thessaly are relatively high with overweight being more prominent in males than in females, whereas MO was higher in females compared to males

Social network data of creative industries and cultural sector in George Town UNESCO world heritage site 2017-2018

This research draws on social network data of organisations in the creative industries and cultural sector in George Town UNESCO World Heritage Site. We collected five types of network: 1) Collaborative Network 2) Advice Network 3) Funding Network (giving and receiving) 4) Training 5) Talents. The data set also contains the background information of the organisation (anonymised) and their corresponding quantitative answers on Entrepreneurial Orientation (innovativeness, risk-taking behaviour, pro-activeness of the organisation, based on 5-point Likert scale). This data enables the identification of the type of actors and their networks, and the respective organisation's entrepreneurial orientation.This research addresses the phenomenon of creative and cultural cluster in a site with a rich cultural heritage. The project will explore questions regarding the role of different actors in developing businesses in cultural districts while preserving and disseminating their cultural heritage. Hence, the research is positioned in a wider debate regarding the links between cultural preservation, urban regeneration and tourism. The selected site is George Town, a post-British colonial town in Malaysian. The town has experienced gentrification since 1997, exacerbated with the growth of tourism and influx of external capital investment in properties, after it has been inscribed as a UNESCO World Heritage Site in 2008. Gentrification induces displacement of long-term residents and causes erosion of local culture and heritage - a global phenomenon in many World Heritage Sites. Nonetheless, a cluster of creative industries and cultural sector has been developed with involvement of various local and external actors. The development of cultural district has become an important tool for many urban planners aiming to foster the development of urban centres and revitalise neighbourhoods-in-decline. Reviewing the existing models of innovation and entrepreneurship ecosystem, there is a gap in the scope of these models in capturing civil society actors and insufficiently explaining the phenomena of cultural clusters. Thereby, they are inadequate in informing urban planning policy makers, the innovation community, cultural organisations and small businesses. The main objectives of this project are: 1) To develop a relational model of innovation and entrepreneurship ecosystem for creative and cultural districts, 2) To provide social network insights for the development of creative economy and conservation of cultural heritage in George Town. 3) To produce a policy brief on strategies for developing creative and cultural districts in George Town. This research deployed Social Network Analysis to identify actors and their networks. Understanding these networks and roles will enable the conceptual development of a novel relational model of entrepreneurship and innovation ecosystem, specifically for cultural districts. This research will collect, via face-to-face administrated questionnaires, data on network relations of actors in the creative industries and cultural sector in George Town. We used UCINET to analyse and map this network and identify its strengths and weaknesses. We also conducted six in-depth case studies of core actors in the networks to gain rich qualitative insights on how they build innovative and entrepreneurial networks. The model is applicable more generally to other small/medium size towns and cities, particularly world heritage sites, where there is a potential to build a creative and cultural district empowering local residents with development opportunities in terms of culture, social and economy.</p