My dissertation analyzes how eighteenth-century novels were still invested in the continuation of the romance and need to be read in the historical context of English interactions with other cultures, in particular those of the Ottoman Empire. Chapter One sets up the racial model of romance and demonstrates how it fit into English politics by contrasting the reinterpretations of Aphra Behn's Oroonoko (1688) throughout the eighteenth century as the protagonist's cultural affiliations shifts from Islamic to "pagan" African as the prose narrative's use of romance tropes to support Behn's royalist politics is replaced, eventually leading to the narrative's association with the abolition of the transatlantic slave trade. Chapter Two shifts to the establishment of the "Arabick Interest" in Restoration and early eighteenth- century England by examining the contesting reactions to the influence of Islam on English identity through its analysis of England's translations between 1671 and 1708 of the philosophical romance Muhammad Ibn Tufayl's Hayy Ibn Yaqzan as well as the anxieties causes by a Protestant -Islamic connection in Daniel Defoe's Robinson Crusoe (1719). The second half of this dissertation adds the discussion of women as another "third term" like romance and Islamic influence. Chapter Three's discussion of Samuel Johnson's Rasselas (1759) and Charlotte Lennox's The Female Quixote (1752) both use romance elements to reference an older form of history writing, one in which the boundaries between romance and fact are porous, to critique English concepts of difference, especially those of gender or culture, in favor of a more universalized view of the world. Their works responded to a mid eighteenth-century shift as England began to emerge as a global power. Chapter Four combines the elements of race, religion and gender from the preceding chapters in its reading of Charlotte Dacre's Zofloya (1806), of which I argue that even though she does not explicitly argue for increased legal rights or social freedoms for women, Dacre's presentations of the dangers to society through its enforcement of feminine passivity implicitly demonstrates a need to create a society where women are educated to be free subjects and independent of patriarchal control

Face mask-wearing practices and their impact on the visual field bear particular importance in the coronavirus disease 2019 (COVID-19) pandemic era. This case series examines 10 participants with no history of ocular impairment or visual field defects who underwent age-corrected visual field testing in both eyes with different types of face masks. Wearing duckbill N95 masks was consistently associated with increased accuracy errors in the inferior altitudinal visual field when compared to wearing surgical masks or no masks. These findings support public health guidance that has previously attributed the risks of falls and accidents to face mask wearing.

Background

CYFIP1, a protein that interacts with FMRP and regulates protein synthesis and actin dynamics, is overexpressed in Dup15q syndrome as well as autism spectrum disorder (ASD). While CYFIP1 heterozygosity has been rigorously studied due to its loss in 15q11.2 deletion, Prader-Willi and Angelman syndrome, the effects of CYFIP1 overexpression, as is observed in patients with CYFIP1 duplication, are less well understood.

Methods

We developed and validated a mouse model of human CYFIP1 overexpression (CYFIP1 OE) using qPCR and western blot analysis. We performed a large battery of behavior testing on these mice, including ultrasonic vocalizations, three-chamber social assay, home-cage behavior, Y-maze, elevated plus maze, open field test, Morris water maze, fear conditioning, prepulse inhibition, and the hot plate assay. We also performed RNA sequencing and analysis on the basolateral amygdala.

Results

Extensive behavioral testing in CYFIP1 OE mice reveals no changes in the core behaviors related to ASD: social interactions and repetitive behaviors. However, we did observe mild learning deficits and an exaggerated fear response. Using RNA sequencing of the basolateral amygdala, a region associated with fear response, we observed changes in pathways related to cytoskeletal regulation, oligodendrocytes, and myelination. We also identified GABA-A subunit composition changes in basolateral amygdala neurons, which are essential components of the neural fear conditioning circuit.

Conclusion

Overall, this research identifies the behavioral and molecular consequences of CYFIP1 overexpression and how they contribute to the variable phenotype seen in Dup15q syndrome and in ASD patients with excess CYFIP1.

The integrin alpha3beta1 mediates cellular adhesion to the matrix ligand laminin-5. A second integrin ligand, the urokinase receptor (uPAR), associates with alpha3beta1 via a surface loop within the alpha3 beta-propeller (residues 242-246) but outside the laminin binding region, suggesting that uPAR-integrin interactions could signal differently from matrix engagement. To explore this, alpha3-/- epithelial cells were reconstituted with wild-type (wt) alpha3 or alpha3 with Ala mutations within the uPAR-interacting loop (H245A or R244A). Wt or mutant-bearing cells showed comparable expression and adhesion to laminin-5. Cells expressing wt alpha3 and uPAR dissociated in culture, with increased Src activity, up-regulation of SLUG, and down-regulation of E-cadherin and gamma-catenin. Src kinase inhibition or expression of Src 1-251 restored the epithelial phenotype. The H245A and R244A mutants were unaffected by coexpression of uPAR. We conclude that alpha3beta1 regulates both cell-cell contact and matrix adhesion, but through distinct protein interaction sites within its beta-propeller. These studies reveal an integrin- and Src-dependent pathway for SLUG expression and mesenchymal transition.

Injury-initiated epithelial to mesenchymal transition (EMT) depends on contextual signals from the extracellular matrix, suggesting a role for integrin signaling. Primary epithelial cells deficient in their prominent laminin receptor, alpha3beta1, were found to have a markedly blunted EMT response to TGF-beta1. A mechanism for this defect was explored in alpha3-null cells reconstituted with wild-type (wt) alpha3 or point mutants unable to engage laminin 5 (G163A) or epithelial cadherin (E-cadherin; H245A). After TGF-beta1 stimulation, wt epithelial cells but not cells expressing the H245A mutant internalize complexes of E-cadherin and TGF-beta1 receptors, generate phospho-Smad2 (p-Smad2)-pY654-beta-catenin complexes, and up-regulate mesenchymal target genes. Although Smad2 phosphorylation is normal, p-Smad2-pY654-beta-catenin complexes do not form in the absence of alpha3 or when alpha3beta1 is mainly engaged on laminin 5 or E-cadherin in adherens junctions, leading to attenuated EMT. These findings demonstrate that alpha3beta1 coordinates cross talk between beta-catenin and Smad signaling pathways as a function of extracellular contact cues and thereby regulates responses to TGF-beta1 activation.

Allohexaploid bread wheat (Triticum aestivum L.) provides approximately 20% of calories consumed by humans. Lack of genome sequence for the three homeologous and highly similar bread wheat genomes (A, B, and D) has impeded expression analysis of the grain transcriptome. We used previously unknown genome information to analyze the cell type-specific expression of homeologous genes in the developing wheat grain and identified distinct co-expression clusters reflecting the spatiotemporal progression during endosperm development. We observed no global but cell type- and stage-dependent genome dominance, organization of the wheat genome into transcriptionally active chromosomal regions, and asymmetric expression in gene families related to baking quality. Our findings give insight into the transcriptional dynamics and genome interplay among individual grain cell types in a polyploid cereal genome.

The inability of neurons to regenerate long axons within the CNS is a major impediment to improving outcome after spinal cord injury, stroke, and other CNS insults. Recent advances have uncovered an intrinsic program that involves coordinate regulation by multiple transcription factors that can be manipulated to enhance growth in the peripheral nervous system. Here, we use a systems genomics approach to characterize regulatory relationships of regeneration-associated transcription factors, identifying RE1-Silencing Transcription Factor (REST; Neuron-Restrictive Silencer Factor, NRSF) as a predicted upstream suppressor of a pro-regenerative gene program associated with axon regeneration in the CNS. We validate our predictions using multiple paradigms, showing that mature mice bearing cell type-specific deletions of REST or expressing dominant-negative mutant REST show improved regeneration of the corticospinal tract and optic nerve after spinal cord injury and optic nerve crush, which is accompanied by upregulation of regeneration-associated genes in cortical motor neurons and retinal ganglion cells, respectively. These analyses identify a role for REST as an upstream suppressor of the intrinsic regenerative program in the CNS and demonstrate the utility of a systems biology approach involving integrative genomics and bio-informatics to prioritize hypotheses relevant to CNS repair.