Because microRNAs have recently been involved in cardiac disease, we analyzed microRNA (miRNA) expression profiles of failing human ischemic hearts and uncovered several differentially expressed miRNAs, with miRNA-216a (miR-216a) being strongly increased in expression. Interestingly, predictive algorithms identified many cell-death-related genes as potential direct target genes of miR-216a, one of them being Beclin-1 (Becn1), an autophagy-regulating gene. Because cardiomyocyte demise due to apoptosis and autophagy is a major cellular event in heart failure, this proposal focuses not only on miR-216a and its role in cell death during myocardial repair, but also on identifying other miRNAs that are involved in regulating autophagy in cardiomyocytes. We hypothesize 1) that post-transcriptional mechanisms regulate cell viability by autophagy and 2) that changes in miR-216a expression directly influences cardiac autophagy and remodeling The key objectives are: 1) Identify genes that are directly regulated by miR-216a and 2) define the role of miR-216a regulating cell death in ischemic heart disease; 3) Establish the therapeutic value of miR-216 silencing in cardiac disease and 4) identify other autophagy-regulating miRNAs by high-throughput screening. For objective 1, we will take a bioinformatics approach by combining large-scale proteomics and microarray analyses on genetic and pharmacological models of miR-216a silencing. In objective 2 we will modulate miR-216a expression in vitro and in vivo and expect miR-216a expression levels to directly reflect the degree of cardiac remodeling, by directly affecting autophagy. For objective 3, we will use a pharmacological approach to silence miR-216a in the setting of ischemic heart disease and anticipate subsequent attenuation of post-MI remodeling, revealing a new potential therapeutic strategy in human cardiac disease. For objective 4, we will establish a high content screening (HCS) assay to identify all miRNAs that functionally regulate autophagy in cardiomyocytes in response to cell stresses inducing/inhibiting autophagy and pathological cardiac remodeling. Keywords: ischemic heart disease, microRNA, autophagy, autophagy-modulating microRNAs, pathological cardiac remodeling.

Dutch healthcare accounts for 7-8% of the total greenhouse gas emissions. In hospitals, at least 20% of this derives from the operating theatre. This includes waste, inhalation gases for anaesthesia, energy for air refreshment and medicine residues in waste water. To change the behaviour of all stakeholders, we assembled a very diverse team to make the operating theatre greener by gaining insight in the biggest polluters. This project aims to fill knowledge gaps but also to provide tools that enhance trust, acceptance and a change in behaviour for the myriad of stakeholders.

In response to high-profile financial reporting scandals, one of the most profound changes in audit regulation of the past decade is the instalment of public oversight of the auditing profession. The objective is to ensure trust in the financial markets and enhance investor protection and the public interest. Motivated by the debate on the effectiveness of public oversight, which is not uncontested, and the paucity of empirical evidence, the proposed research investigates economic consequences of public oversight and specifically the impact of disclosure of inspection outcomes on information asymmetry and the cost of capital in the equity and debt market.

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Some people have difficulties with reading, writing or math, have a low IQ or have difficulties understanding health information. These people are on average less healthy. Yet, little collaboration exists with this group in health research. We want to change this and collaborate on a structural basis. We do this with a permanent advisory group with people from this group. The advisory group advises health scientists on research. We want to encourage fellow scientists to ask the advisory group for advice more often. In addition, we want advisory group members to be able to participate as researchers in some studies.