The non-canonical Wnt signaling pathway regulates the actin cytoskeleton controlling cell migration, cell polarity, and cell survival. The protein Profilin1 is a downstream effector of the non-canonical Wnt pathway and directly binds to actin to facilitate cytoskeleton rearrangement. Profilin1 binds to monomeric actin and brings it to the FH1 (Formin Homology 1) domain of Daam1. The neighboring FH2 (Formin Homology 2) domain nucleates actin and caps the growing end of the completed actin filament. It is currently unknown which amino acids on Profilin1 facilitate binding to Daam1 and actin in non-canonical Wnt signaling. In this study, I identified two residues on the Xenopus protein Profilin1- Tyrosine 131 and Serine 135- that play a role in non-canonical Wnt signaling. In this study, I was able to show that non-canonical Wnt signaling leads to the phosphorylation of Tyrosine 131. Mutating Tyrosine 131 to Alanine (Tyr131Ala) causes a cytokinesis defect preventing gastrulation in Xenopus embryos. Additionally, overexpression of PFN1-Tyr131Ala prevents Wnt5a-mediated actin fiber formation and increases multinucleation in HeLa cells. Mutating Serine 135 to Alanine (PFN1-Ser135Ala) lowers the binding affinity of Profilin1 to the FH1 domain of Daam1 but does not affect cytokinesis. The evidence presented in this study suggests that Tyr131 regulates gastrulation, while Ser135 plays a role in modulating binding of Profilin1 to Daam1. Further research into the molecular mechanism of regulation of Tyr131 and Ser135 in non-canonical Wnt signaling would be a major step in uncovering the mechanism of actin polymerization and a better understanding of cell signaling during vertebrate gastrulation. / Biology

Clinical profile of children with Autism Spectrum Disorder in a developmental clinic in Western Cape Abstract Introduction Autism Spectrum Disorder (ASD) is increasingly being recognised as a significant neurodevelopmental condition in African countries. There is some evidence to suggest that the children who present with ASD in Africa may be diagnosed late and have a more severe clinical picture. The purpose of this study was to describe the clinical profile of children with ASD in the neurodevelopmental clinic at Red Cross War Memorial Children's Hospital in Western Cape Province South Africa. Methods We sampled patients with a previous or new diagnosis who attended our clinic during the period January to July 2017. Consenting participants were administered a questionnaire with sociodemographic and clinical questions, clinical details of medical and developmental diagnosis were extracted from medical records and children. were further assessed using the Autism Diagnostic Observation Schedule version 2 (ADOS-2). Results A total of 32 patients were recruited into the study with 26 out of 32 (81%) being boys. On assessment as part of the study, all participants met DSM 5 criteria for the diagnosis of ASD. Most participants (94%) had not experienced general developmental regression but a substantial proportion (39%) had reported early regression of language milestones. Almost half of participants (48%) had self-injurious behaviour reported, 25% had associated motor difficulty and 10% comorbid epilepsy. More than half of participants (53%) required substantial support in day-to-day activities. Most participants (81%) were administered module 1 of the ADOS-2 reflecting the high proportion of children in the sample who were either preverbal or using only single words. Conclusions Children seen in this clinical sample reflected the more severe end of the autism spectrum with a significant proportion having associated comorbidities such as epilepsy, and motor difficulties. The phenotypic profile on the ADOS 2 in this study correlated well with clinical assessments.

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Teachers are subject to multiple stressors in their profession and often experience significant distress, which has been found to be linked with harsh and punitive behaviors. These behaviors have been found to influence students negatively, particularly those with vulnerable temperaments. Prior research has also found such negative teacher behavior to be associated with hierarchical social structures in classrooms. While many researchers have attributed this hierarchical structure to teacher modeling—normalizing negative displays of behavior or treating favored students preferentially—student personality may also be a factor. Students high in neuroticism have been found to be particularly vulnerable to stress and often withdrawn. Students high in extraversion, however, have been found to be sociable and to experience positive emotions more frequently. Some evidence suggests these students may also be more likely to form transitive friendships, in which person A is friends with person B, person B is friends with person C, and person A is also friends with C, creating more cohesive networks of friends. It is possible that one reason hierarchical classroom social structures emerge in classrooms in which teachers display negative behaviors is that students higher in extraversion support each other and help maintain each other’s positive emotions, while students higher in neuroticism are more likely to withdraw and experience more negative emotions. Students higher in extraversion may be more likely to occupy higher-status positions in the classroom social structure both because they have more frequent contact with one another, and because other students are more likely to hope to befriend those who are happier and have more friends. The current study will simulate fourth- and fifth-grade classrooms to investigate the relationship between teacher behavior, student personality, student emotions, and student social network structure. Results suggest that extraversion is associated with a greater likelihood of being embedded in transitive triads and greater popularity in the friendship social network. However, there is little evidence that neuroticism is associated with students’ position in the student social network or that teacher behavior is related to the structure of student social networks

The Wnt signaling pathway is highly conserved in metazoan animals. Wnt signaling regulates an array of cellular processes that include motility, polarity, cell fate determination, primary axis formation and organogenesis and recently have been implicated in stem cell renewal. Deregulated Wnt signaling has tragic consequences for the developing embryo and is a causative factor for a number of pleiotropic human pathologies such as cancers of the breast, colon and skin, skeletal defects and human birth defect disorders including the most common human neural tube closure defect: spina bifida. Modulation of the actin cytoskeleton via the non-canonical Wnt signaling pathway mediate cell polarity and cell migration that are required for proper vertebrate gastrulation and subsequent neurulation. However, the mechanism(s) by how the non-canonical pathway mediates this actin cytoskeleton modulation is not fully understood. Identifying and characterizing novel signaling components of the non-canonical pathway remain essential to understand its role during embryogenesis. The Formin-homology protein Dishevelled associated activator of morphogenesis 1 (Daam1) was previously characterized as an essential component for non-canonical Wnt-dependent regulation of cytoskeletal reorganization and cell migration. Daam1 and Daam2 are members of the Daam family of proteins but the role of Daam2 in early embryonic development however remains conflicting as to whether it functions in the canonical or non-canonical Wnt signaling pathway. In this thesis, I cloned and functionally characterized the role of Xenopus Daam2 in the Wnt signaling pathway. Co-immunoprecipitation assays confirm the binding of Daam2 with Dishevelled (Dvl) as well as the domains within those proteins required for interaction. Interestingly the binding of Daam2 and Dvl was subject to Wnt regulation. Sub-cellular localization immunofluorescence studies using mammalian cell culture system reveal Daam2 is cytoplasmic and regulates the actin cytoskeleton by modulating the actin filament formation. In Xenopus embryos, Daam2 is temporally expressed at very low levels maternally and its expression increases during neurulation and remains subsequently elevated after neurulation. Daam2 expression is spatially refined to areas of highly dynamic actin reorganization such as mesoderm, notochord and neural tube. The knockdown of Daam2 in Xenopus embryos specifically produces neural tube closure defect suggesting a role in non-canonical signaling. Indeed studies examining the role of Daam2 in canonical Wnt signaling found no role for this protein in canonical Wnt signaling. These studies taken together identify Daam2 as an important Wnt signaling component that functions in the non-canonical Wnt signaling pathway and regulates neural tube morphogenesis. / Biology