The ubiquitinâproteasome system (UPS) influences gene transcription in multiple ways. One way in which the UPS impacts transcription centers on transcriptional activators, the function of which can be stimulated by components of the UPS that also trigger their destruction. Activation of transcription by the yeast activator Gcn4, for example, is attenuated by mutations in the ubiquitin-ligase that mediates Gcn4 ubiquitylation or by inhibition of the proteasome, leading to the idea that ubiquitin-mediated proteolysis of Gcn4 is required for its activity. Here, I probe the steps in Gcn4 activity that are perturbed by disruption of the UPS. I show that the ubiquitylation machinery and the proteasome control different steps in Gcn4 function, and that proteasome activity is required for the ability of Gcn4 to bind to its target genes in the context of chromatin. Curiously, the impact of proteasome inhibition on Gcn4 activity is suppressed by mutations in the ubiquitin-selective chaperone Cdc48, revealing that proteolysis per se is not required for Gcn4 activity. My data highlights the role of Cdc48 in controlling promoter occupancy by Gcn4 and support a model in which ubiquitylation of activatorsânot their destructionâis important for function.

<p> Despite the rapidly expanding body of literature relating to electronic nicotine delivery system (ENDS) use, notable gaps in the available literature are apparent. Many different models and types of ENDS are available, such as electronic cigarettes, electronic hookahs, and newer-generation ENDS devices (vapes/mods). Yet, the scientific community has been slow to identify and investigate different ENDS products other than &ldquo;e-cigarettes.&rdquo; The current project serves to bring a level of specificity to ENDS research that has not yet been seen in the published literature. The current study used a multi-site, cross-sectional, experimental design to test 1) whether endorsement of ENDS usage is affected by the language used in measurement, and 2) whether the perceived risk associated with ENDS differs by product type. Lifetime ENDS use was significantly affected by the specific terms used in measurement within a sample of 546 undergraduate students. When presented with response options for multiple ENDS types, lifetime use was 17% greater than when asking about e-cigarettes alone. Significant perceptual differences between ENDS devices were apparent. E-hookahs and vapes/mods were seen as significantly less harmful to use during pregnancy, less harmful to one&rsquo;s health, and less addictive than either cigalike e-cigarettes or conventional tobacco cigarettes. Together, these findings suggest using generic, single-item measures that only ask about e-cigarettes are problematic.</p>

<p> The human psyche is continuously producing symbols. These representations are stilled, emotively energized moments of the external world. The proposition of this thesis is that when symbols are projected onto objects, they lose capacity to elicit subjective motivation for personal responsibility to Self and culture. This research examines the questions: Do you see what I see? How does symbol integration facilitate responsibility to Self and culture? Using hermeneutic methodology, this thesis explores the meaning-making function of symbol formation, demonstrating how, through the integration of once-projected symbols, the individual can experience individuation; the becoming of true Self. Other areas of examination include symbol in relation to sign and symbol: myth and metaphor; the Self; meaning making; sameness and otherness in the function of rituals; and impact of religion on culture. This investigation also focuses on psyche&rsquo;s creation of symbol and explores how an individual&rsquo;s ability to integrate archetypal energy facilitates integration and individuation. </p>

<p> This Master&rsquo;s thesis investigated efficacy of equine assisted modality studies for individuals with Autism Spectrum Disorder. The data was collected by means of Literature Review and utilized textual analysis. All participants in the studies examined met the study eligibility criteria. The results and findings were compiled and analyzed to support the data reflected; additional studies were highlighted to aid in the comparison of the data retrieved from the four studies featured. A brief history of the synergistic relationship between horse and humans was reviewed as well as historical perspectives on equine assisted programs and their accredited organizations. The student critiqued the future of equine co-facilitated curriculum for individuals with autism, communication between equine and humans, neurophysiological adaptation and biophilia.</p>

<p> <b>Purpose:</b> Sleep-disordered breathing (SDB) is a spectrum disorder that is estimated to effect a significant proportion of the pediatric population (1-3% in USA). SDB is able to disrupt and fragment sleep through frequent arousals and intermittent hypoxia. In addition, the long term effects of SDB in pediatrics have been well-documented; decreases in intelligence quotient (IQ), executive function, school performance, and alertness have all been observed. Although surgical treatments can be quite effective, there are no widely accepted prophylactic measures to prevent SDB development. Recently, breastfeeding duration in infancy has been demonstrated to be correlated with reduced SDB (lower AHI, RAI, and higher SpO2), as well as increases in IQ, executive function, and school performance (independent of SDB). The overarching goal of this dissertation was to examine the potential effects of both breastfeeding duration and SDB severity on the neurological underpinnings associated with observed behavioral and cognitive deficits; namely, correlations with white matter structural volume and fractional anisotropy (FA) scores through diffusion tensor imaging (DTI). Here, I proposed a unique developmental hypothesis where breastfeeding may ultimately reduce SDB, enabling the preservation of rapid eye movement (REM) sleep, and leading to healthier neurological white matter development. </p><p> <b>Method:</b> Twenty-four children with SDB and 19 healthy controls were imaged using MR techniques. White matter volume was measured using the central 13 millimeters of the corpus callosum (CC). DTI of major white matter tracts was also conducted. The SDB group received neurocognitive testing to assess cognitive performance; the control group was assessed using real-world academic report cards. Finally, REM sleep was quantified in infants using overnight polysomnography (PSG), with SDB metrics and infant feeding method also measured. Results: There was no correlation between infant feeding methods and CC volume in either group, nor a significant differences between CC volumes in children with SDB versus those without. However, increased breastfeeding duration was correlated with increased left superior longitudinal fasciculus (LSLF) and left angular bundle (LAB) FA scores in healthy controls. In 8-9 month old infants, increased breastfeeding duration was also correlated with a reduced proportion of REM sleep (%TST), and children with exclusive breastfeeding had reduced SDB in infancy compared to children with any formula feeding. Finally, exclusively formula-fed infants were diagnosed with &ldquo;primary snoring&rdquo; more often than those with any amount of breastfeeding. </p><p> <b>Conclusions:</b> The findings in this dissertation revealed associations between breastfeeding, SDB, REM sleep, and white matter integrity in the brain. These results support the hypothesis that certain cognitive effects associated with SDB and infant feeding methods may have common underlying anatomical brain changes that subserve these observed phenomena.</p>

<p>Many marine invertebrates have larvae that must feed to complete development to metamorphosis. Larval feeding performance affects the amount of time larvae spend in the plankton, which affects larval mortality and dispersal, and juvenile quality. Larval feeding performance is partly determined by the abundance of edible particles in the plankton. However, the plankton also contains particles that are too large for ingestion. In this thesis I show that: 1) echinoderm larval feeding performance is reduced in environmentally realistic concentrations of inedible particles in simplified laboratory feeding environments, 2) larval feeding performance of at least one echinoid is reduced in the presence of natural inedible particles in plankton, and 3) larval feeding performance may be affected by inedible beads in the mouth. My results suggest that in nature, rates of food acquisition by larvae may depend not only on food abundance, but also on the abundance of potentially interfering non-food particles.

<p> Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and communication, is of unknown etiology, and has a prevalence of 1.5% in the U.S. Atypical language patterns and anatomical findings of brain asymmetry differences between neurotypical and individuals with ASD suggest involvement of brain lateralization aberrations in autism etiology. The literature suggests an increased frequency of non-right handedness (NRH) in ASD. This dissertation aimed to study the association between hand preference and ASD in a cohort of children with ASD using a large, well-designed, population-based case-control study, CHARGE (<i>CH</i>ildhood <i> A</i>utism <i>R</i>isks from <i>G</i>enetics and the <i>E</i>nvironment). </p><p> In Chapter 1, we evaluated the association between handedness and ASD in 2- to 5-year old children. Chapter 2 longitudinally evaluated handedness outcome of the children from Chapter 1 at age 7 and older. We then investigated the utility of a parent-reported handedness assessment of children at ages 2-5 years using established hand preference at age 7+ years as the gold standard. Finally, we investigated the association between the intronic variant rs7799109 on theFOXP2 gene and ASD as well as the gene&rsquo;s interaction effect on the association between NRH and ASD. </p><p> Our findings indicate that children with neurodevelopmental disorders show a delayed establishment of handedness lateralization in early stages of childhood with a subset of these children still remaining NRH at age 7 years. Language deficits in children at ages 2 to 5 years are associated with NRH and ASD, and is a determinant of NRH in ASD at age 7 years and older. Our study also supports current literature that hand preference may have genomic underpinnings in ASD.</p>

Eukaryotic cells respond to stress by reprogramming their gene expression program to inhibit global protein synthesis and direct translationally silenced mRNAs to cytoplasmic foci known as stress granules (SGs). SGs function as sites where mRNAs are sorted for storage, decay or translation. SGs are linked with neurodegeneration, cancer and viral infections. However, the molecular mechanisms underlying SG function during stress and in diseases are poorly understood. DEAD-box proteins (Dbps) are RNA-dependent ATPases that mediate changes in mRNA-protein complex (mRNP) structure. Several Dbps, including DDX3, are recruited to SGs and regulate mRNP entry and exit. But, it is unclear how the Dbp activity is regulated in SGs. In the work presented here, we show that human (h) Gle1 is a novel factor of SGs and it regulates SGs by modulating the dynamic equilibrium between SGs and translation through its regulation of DDX3. We further show that two alternatively spliced isoforms of the GLE1 gene perform distinct and non-overlapping functions in a cell; hGle1A is required for SG function, whereas hGle1B functions in SGs. Interestingly, our results also show that an amyotrophic lateral sclerosis (ALS)-linked mutation in GLE1 disrupts functional specificity of hGle1 isoforms and the resulting protein variant is bifunctional. Overall, this study provides insight into the critical roles of hGle1 in SG biology and also gives clues as to how mutation of GLE1 contributes towards ALS pathogenesis.

<p> The empathizing-systemizing (E-S) theory states that individuals with autism spectrum conditions (ASC) can be identified by a deficit in empathy (social skills, communication skills, and theory of mind) and a propensity for systemizing (islets of ability, obsessions with systems, and repetitive behavior). This theory has been tested in various contexts, but never with adolescents between the ages of 12 and 16. The EQ-A (Empathizing Quotient for Adolescents) and the SQ-A (Systemizing Quotient for Adolescents) were administered to 47 adolescents between the ages of 12 and 16 who had been diagnosed with ASC and 97 adolescents with no reported physical or mental disorders to discover differences in empathizing and systemizing.</p><p> To test the specific elements and predictions of the E-S theory, the EQ-A was divided into a set of three subscales derived by conceptually mapping items to factors corresponding to the concepts theoretically underlying the scale. The SQ-A was divided into subscales using factor analysis.</p><p> It was found that all four subscales resulting from the factor analysis on the SQ-A were associated with obsessions with systems. A weak positive correlation was found between the SQ-A and the EQ-A. Although the EQ-A was able to differentiate significantly between individuals with an ASC and those without, the SQ-A was not. In addition, although the EQ-A and EQ-A subscales scores correlated with similar subscales scores of the GARS-2 (a well-validated existing autism screening test), the SQ-A and its subscales did not. Implications for the E-S Theory are discussed.</p>

<p> This study explores the psychological dynamics associated with labor and birth in order to better understand the role these experiences play in women&rsquo;s psychological development. This research study utilized interpretative phenomenological analysis as a research methodology and sought to address the following questions through the theoretical perspective of psychoanalysis and social constructionism: How does the experience of pregnancy and birth impact the subjectivity of women? How do women make sense of these experiences? What role does the body play in women&rsquo;s psychological development? Does the experience of childbirth mark a unique developmental phase in the psychological life of women? In this research study, six women were asked to describe their birth narrative in full and respond to a series of open-ended questions. The results of this study indicate that pregnancy and childbirth is a porous developmental period associated with fears about capacity and feelings of omnipotence as well as multiple losses and a new sense of self. One of the more significant findings of this study is that the experience of labor and birth is felt by many women to involve feelings associated with encountering death. This finding may lead to increased understanding of why pregnancy and childbirth results in fragmentation for some women, while it appears to be a catalyst for increased subjectivity and maternal embodiment for other women.</p>