Increased TIMP-3 expression alters the cellular secretome through dual inhibition of the metalloprotease ADAM10 and ligand-binding of the LRP-1 receptor

The tissue inhibitor of metalloproteinases-3 (TIMP-3) is a major regulator of extracellular matrix turnover and protein shedding by inhibiting different classes of metalloproteinases, including disintegrin metalloproteinases (ADAMs). Tissue bioavailability of TIMP-3 is regulated by the endocytic receptor low-density-lipoprotein receptor-related protein-1 (LRP-1). TIMP-3 plays protective roles in disease. Thus, different approaches have been developed aiming to increase TIMP-3 bioavailability, yet overall effects of increased TIMP-3 in vivo have not been investigated. Herein, by using unbiased mass-spectrometry we demonstrate that TIMP-3-overexpression in HEK293 cells has a dual effect on shedding of transmembrane proteins and turnover of soluble proteins. Several membrane proteins showing reduced shedding are known as ADAM10 substrates, suggesting that exogenous TIMP-3 preferentially inhibits ADAM10 in HEK293 cells. Additionally identified shed membrane proteins may be novel ADAM10 substrate candidates. TIMP-3-overexpression also increased extracellular levels of several soluble proteins, including TIMP-1, MIF and SPARC. Levels of these proteins similarly increased upon LRP-1 inactivation, suggesting that TIMP-3 increases soluble protein levels by competing for their binding to LRP-1 and their subsequent internalization. In conclusion, our study reveals that increased levels of TIMP-3 induce substantial modifications in the cellular secretome and that TIMP-3-based therapies may potentially provoke undesired, dysregulated functions of ADAM10 and LRP-1

Introduction—Food Security and Food Waste Reduction: A Social Innovation Approach to Current Social, Environmental, and Political Concerns

This chapter presents the research rationale underpinning the book. It addresses the intertwining challenges of food security and surplus food management, discussing recent data and literature. It also presents how social innovation is conceptualized in the book as the theoretical framework to analyse partnerships between business and non-profit organisations in managing food surplus. The methodology of the research is also detailed, along with the book structure

Nature-Based Solutions Accelerating Urban Sustainability Transitions in Cities: Lessons from Dresden, Genk and Stockholm Cities

Nature based solutions are amongst other practices that transition initiativeswork with when intervening in their place and change its fabric. Focusing on theactors establishing, driving and scaling these solutions in and across cities, we cometo evince that nature-based solutions have transformative social impact since theymediate new social relations and new social configurations contributing to socialinnovation in cities, and change nature perception and human-nature relations inurban contexts. We built from evidence in three city-regions that over the past yearsthey saw the proliferation of community-based and policy-based initiatives with theaim to improve sustainability, livability and the aspiration to foster inclusivity andsocial justice in their cities: the city of Dresden in Germany, the city of Genk inBelgium and the city-region of Stockholm in Sweden. We will elaborate on the differentways nature based solutions as practices of transition initiatives in cities getscaled and contribute to accelerating sustainability transitions in these city-regions.In line with this, we will draw cross-case lessons for urban planning on the tensionstransition initiatives that experiment with and institutionalize nature-based solutionsin their cities face when actively pursue acceleration strategies and pathways to scale.QC 20170919</p

A model for analysing non-profit organisations in the food recovery, management and redistribution chain

Il capitolo si concentra sulle organizzazioni non profit come principali attori nel recupero delle eccedenze alimentari, proponendo un framework interpretativo del loro ruolo e funzione