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- Gorinski, Nataliya, et al.
(author)
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Attenuated palmitoylation of serotonin receptor 5-HT1A affects receptor function and contributes to depression-like behaviors
- 2019
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In: Nature Communications. - : Nature Communications. - 2041-1723. ; 10:1, s. 1-14
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Journal article (peer-reviewed)abstract
- The serotonergic system and in particular serotonin 1A receptor (5-HT1AR) are implicated in major depressive disorder (MDD). Here we demonstrated that 5-HT1AR is palmitoylated in human and rodent brains, and identified ZDHHC21 as a major palmitoyl acyltransferase, whose depletion reduced palmitoylation and consequently signaling functions of 5-HT1AR. Two rodent models for depression-like behavior show reduced brain ZDHHC21 expression and attenuated 5-HT1AR palmitoylation. Moreover, selective knock-down of ZDHHC21 in the murine forebrain induced depression-like behavior. We also identified the microRNA miR-30e as a negative regulator of Zdhhc21 expression. Through analysis of the post-mortem brain samples in individuals with MDD that died by suicide we find that miR-30e expression is increased, while ZDHHC21 expression, as well as palmitoylation of 5-HT1AR, are reduced within the prefrontal cortex. Our study suggests that downregulation of 5-HT1AR palmitoylation is a mechanism involved in depression, making the restoration of 5-HT1AR palmitoylation a promising clinical strategy for the treatment of MDD.
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- Varshosaz, Mahsa, 1985-, et al.
(author)
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A classification of product sampling for software product lines
- 2018
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In: SPLC '18 Proceedings of the 22nd International Systems and Software Product Line Conference - Volume 1. - New York, NY : Association for Computing Machinery (ACM). - 9781450363716 - 9781450364645 ; , s. 1-13
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Conference paper (peer-reviewed)abstract
- The analysis of software product lines is challenging due to the potentially large number of products, which grow exponentially in terms of the number of features. Product sampling is a technique used to avoid exhaustive testing, which is often infeasible. In this paper, we propose a classification for product sampling techniques and classify the existing literature accordingly. We distinguish the important characteristics of such approaches based on the information used for sampling, the kind of algorithm, and the achieved coverage criteria. Furthermore, we give an overview on existing tools and evaluations of product sampling techniques. We share our insights on the state-of-the-art of product sampling and discuss potential future work. © 2018 Association for Computing Machinery.
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