Roles of autism gene ARID1B in murine brain development and behavior

Autism spectrum disorder (ASD) and intellectual disability (ID) are highly prevalent neurodevelopmental disorders characterized by social and communication deficits, stereotyped behaviors, cognitive dysfunction, and deficits in adaptive behaviors. The pathogenesis underlying these disorders remains unknown, and thus no pharmacologic or genetic therapies are currently available. Recent progress in the field has shown that haploinsufficiency of the AT-rich interactive domain-containing 1B (ARID1B) gene is a genetic cause of ASD and ID. Our lab recently developed an Arid1b knockout mouse model to better study its role in the pathogenesis of these disorders. One theory regarding the cause of neurodevelopmental disorders is disruption of the excitatory/inhibitory balance in the brain. We previously showed that interneuron deficits lead to an excitatory/inhibitory imbalance in Arid1b knockout mice, playing a significant role in the observed behavioral phenotypes. Interneurons are highly heterogenous cell types in the brain; however, little is known regarding how the different subtypes modulate various behaviors. In chapter 2, we dissect the individual roles of the two most populous interneurons in the cerebral cortex, parvalbumin and somatostatin subtypes, in ASD/ID behaviors seen with ARID1B haploinsufficiency. We show that parvalbumin interneurons affect social and emotional behaviors, while somatostatin interneurons primarily affect stereotyped behaviors and cognitive function. In addition to interneuron deficits, several studies have also implicated altered neurite outgrowth of cortical projection neurons in ASD and ID. Furthermore, deficits in neurotrophic signaling, a master regulator of neurite outgrowth, is also frequently observed. In chapter 3, we examine a potential role of ARID1B in regulating neurite development of excitatory neurons during corticogenesis. We show that loss of the Arid1b gene leads to disrupted neurite outgrowth and altered development of the corpus callosum. Additionally, we suggest a likely role of ARID1B in the BDNF neurotrophic signaling pathway. Together, these studies provide insight into possible roles of ARID1B during neurogenesis, shedding further insight into the pathogenesis of ASD and ID

The Impact of Americanization on Intergenerational Relations: An Exploratory Study on the U.S. Territory of Guam

In-depth interviews with a sample of 60 elderly from the indigenous (Chamorro) population and the immigrant (Filipino) population examined their current lifestyles, with emphasis upon intergenerational relations. Results underscore the dramatic lifestyle changes experienced by Guam\u27s elderly in the wake of Americanization. Among these is an intergenerational language gap , wherein a majority of the grandchildren do not speak the native language of their elders. Ethnicity, mixed marriage, and length of residence on Guam are discussed as possible determinants of the language gap. The language gap is associated with lower life satisfaction for elders, as well as reduced family contact and less intergenerational assistance

The age of racial profiling in the context of terrorism

Racial profiling refers to the law enforcement practice of using only race or ethnicity as probable cause to search or arrest an individual. The public has found racial profiling to be unjustified in the context of common crime, but tends to support the practice in the context of terrorism. The current study uses an explicit judgment survey to examine the expression of prejudice and factors that influence stereotyping. The study found that participants aged 18 to 24, and those who identified with a political party, were the participants most likely to racially profile individuals with stereotypical Middle-Eastern features to be potential terrorists

Ubiquitin plays an atypical role in GPCR-induced p38 MAP kinase activation on endosomes.

Protease-activated receptor 1 (PAR1) is a G protein-coupled receptor (GPCR) for thrombin and promotes inflammatory responses through multiple pathways including p38 mitogen-activated protein kinase signaling. The mechanisms that govern PAR1-induced p38 activation remain unclear. Here, we define an atypical ubiquitin-dependent pathway for p38 activation used by PAR1 that regulates endothelial barrier permeability. Activated PAR1 K63-linked ubiquitination is mediated by the NEDD4-2 E3 ubiquitin ligase and initiated recruitment of transforming growth factor-β-activated protein kinase-1 binding protein-2 (TAB2). The ubiquitin-binding domain of TAB2 was essential for recruitment to PAR1-containing endosomes. TAB2 associated with TAB1, which induced p38 activation independent of MKK3 and MKK6. The P2Y1 purinergic GPCR also stimulated p38 activation via NEDD4-2-mediated ubiquitination and TAB1-TAB2. TAB1-TAB2-dependent p38 activation was critical for PAR1-promoted endothelial barrier permeability in vitro, and p38 signaling was required for PAR1-induced vascular leakage in vivo. These studies define an atypical ubiquitin-mediated signaling pathway used by a subset of GPCRs that regulates endosomal p38 signaling and endothelial barrier disruption

The role of sensory sensitivity in predicting food selectivity and food preferences in children with Tourette syndrome

Tourette syndrome (TS) is a neurodevelopmental disorder characterised by involuntary, repetitive and non-rhythmic motor and vocal tics. Despite suggestion that diet may affect tics, and the substantial research into children's diet, eating behaviours and sensory processing in comorbid disorders (e.g. ASD), research in TS is lacking. The present study examined differences between children with and without TS in parental reports of child selective eating, food preferences and sensitivity, and aimed to examine sensory sensitivity as a predictor of food selectivity outcomes in children with and without TS. Thirty caregivers of children with TS (M = 10 years 8 months [SD = 2.40]) and the caregivers of 30 age- and sex-matched typically developing (TD) children (M = 9 years 9 months [SD = 2.50]) completed the following measures online: Short Sensory Profile, Food Preference Questionnaire for Children, Child Eating Behaviour Questionnaire. Children with TS were reported to have significantly higher levels of food selectivity and sensory sensitivity, and less preference for fruit and vegetables than TD children. Importantly, while higher levels of overall sensory sensitivity predicted eating outcomes in the TS group, only sensitivity to taste/smell was found to be a predictor of food selectivity and preference for vegetables for both groups of children. The findings suggest that efforts to address food selectivity in children with TS may be enhanced by including strategies that address atypical sensory processing

Intra-dance variation among waggle runs and the design of efficient protocols for honey bee dance decoding

Noise is universal in information transfer. In animal communication, this presents a challenge not only for intended signal receivers, but also to biologists studying the system. In honey bees, a forager communicates to nestmates the location of an important resource via the waggle dance. This vibrational signal is composed of repeating units (waggle runs) that are then averaged by nestmates to derive a single vector. Manual dance decoding is a powerful tool for studying bee foraging ecology, although the process is time-consuming: a forager may repeat the waggle run 1- >100 times within a dance. It is impractical to decode all of these to obtain the vector; however, intra-dance waggle runs vary, so it is important to decode enough to obtain a good average. Here we examine the variation among waggle runs made by foraging bees to devise a method of dance decoding. The first and last waggle runs within a dance are significantly more variable than the middle run. There was no trend in variation for the middle waggle runs. We recommend that any four consecutive waggle runs, not including the first and last runs, may be decoded, and we show that this methodology is suitable by demonstrating the goodness-of-fit between the decoded vectors from our subsamples with the vectors from the entire dances

Supporting the learning of deaf students in higher education: a case study at Sheffield Hallam University

This article is an examination of the issues surrounding support for the learning of deaf students in higher education (HE). There are an increasing number of deaf students attending HE institutes, and as such provision of support mechanisms for these students is not only necessary but essential. Deaf students are similar to their hearing peers, in that they will approach their learning and require differing levels of support dependant upon the individual. They will, however, require a different kind of support, which can be technical or human resource based. This article examines the issues that surround supporting deaf students in HE with use of a case study of provision at Sheffield Hallam University (SHU), during the academic year 1994-95. It is evident that by considering the needs of deaf students and making changes to our teaching practices that all students can benefit

Girls’ and boys’ problem talk: Implications for emotional closeness in friendships.

This research highlights the critical role of gender in the context of problem talk and social support in adolescents’ friendships. Early- and middle-adolescents’ (N = 314 friend dyads; Ms = 13.01 and 16.03 years) conversations about problems were studied using observation and a short-term longitudinal design. Mean-level gender differences emerged in that girls participated in problem talk more than boys and responded in a more positive and engaged manner to friends’ statements about problems (e.g., by saying something supportive, asking a question) than did boys. Interestingly, boys used humor during problem talk more than girls. Despite mean-level differences, there were not gender differences in the functional significance of participating in problem talk and positive engaged responses in that these behaviors predicted increased friendship closeness for both boys and girls. In contrast, humor during problem talk predicted increased closeness only for boys, highlighting an understudied pathway to closeness in boys’ friendships