<p>Rho GTPase signaling regulates a wide variety of cellular functions in the developing and adult central nervous system. These molecular switches are in turn spatially and temporally regulated by an over abundance of positive and negative regulatory proteins: the activating guanine nucleotide exchange factors (GEFs) and the deactivating GTPase activating proteins (GAPs). The WAVE-associated Rac GAP (WRP) is thought to regulate key aspects of synapse development and function, and has been implicated in a form of mental retardation in humans called 3p- Syndrome. WRP is a member of the srGAP family of Rho GAP domain containing proteins, which share a characteristic domain organization and are expressed throughout the brain. Recently, one of the members of this family was found to contain a newly described inverse F-BAR (IF-BAR) domain of unknown function and to regulate cortical migration in developing neurons. This study focuses on the regulatory capacity of WRP during the development of neuronal connections in the central nervous system, and what role its loss may have on cognitive functions.</p><p>To assess these roles, biochemical studies were performed to characterize the way in which WRP's novel IF-BAR domain interacted with lipid membranes. Additionally, WRP's role in regulating neuronal function was assessed both in vitro and in vivo through the use of mouse model systems for critical genes in the WAVE complex pathway, including a conditional WRP KO mouse developed in our lab. Finally, because WRP is implicated in mental retardation, behaviors of WRP heterozygous and null mice have been evaluated.</p><p>This study shows that WRP's IF-BAR domain senses, or facilitates, outward membrane protrusions through a convex lipid-binding surface of the dimerized WRP IF-BAR domain. WRP localizes to the membranes of dendritic shafts via its IF-BAR domain where it is enriched in filopodia like projections. During dendritic filopodia formation, WRP functions to regulate the WAVE-1 complex and its downstream effectors, including the Arp2/3 complex. Loss of WRP in vivo and in vitro results in a reduction of dendritic spines, and that this is a function of WRP's role in the initiation of dendritic filopodia, not during the maturation of dendritic filopodia into mature dendritic spines. Finally, this study demonstrates that the loss of WRP results in deficits in learning and memory, linking WRP to the cognitive deficits seen in 3p- syndrome.</p> / Dissertation

Wars, conflicts, natural disasters, and poverty are several reasons why millions of children worldwide are fleeing their homes and seeking refuge in other countries. The Convention on the Rights of the Child (CRC) emphasizes the obligation of the recipient countries to promote the physical and mental recovery and integration of refugee children into society. Refugee children can in turn be perceived by the host country as long-term investments or financial burdens. The objectification of perceiving human beings as assets or burdens, rather than human, is an indication of dehumanization. Dehumanizing perceptions and views are formed by people or societies and can be spread with the help of various media platforms. This study examines 24 Swedish newspaper articles, published between the years 2015-2022, with the aim to analyze whether and how the articles use dehumanizing words, expressions, and assumptions in their representation of refugee children. To identify dehumanizing words, expressions and assumptions from the selected newspaper articles, Nick Haslam's theory of dehumanization is applied. This is a qualitative content analysis, with quantitative elements. Carol Lee Bacchi’s qualitative analysis tool, what's the problem represented to be? (WPR), is used to analyze how refugee children are represented and perceived in the newspaper articles. Upon reviewing the newspaper articles, the results were decided into four overall dehumanizing categories: 1) asset, 2) burden, 3) criminality and 4) grouping. Furthermore, the results show that the dehumanizing representations of refugee children within the newspaper articles indicates mechanistic dehumanization as well as animalistic dehumanization.