Interactions between endothelin receptor B and transcription factors Sox10 and Pax3 in the melanocyte lineage

Genetic interactions that underlie developmental processes such as cell differentiation and pattern formation are complex and difficult to elucidate. Neural Crest (NC) cells and their derivatives offer an optimal system in which to probe for these complex interactions as they acquire different cell fates and constitute a variety of structures. The transcription factors Sox10 and Pax3 as well as the transmembrane receptor Endothelin receptor b (Ednrb) are temporally and spatially co-expressed early in NC cells and mutations in these genes lead to similar hypopigmentation phenotypes due to a reduced number of NC-derived melanocyte precursors, the melanoblasts. The goal of this study was to establish whether Sox10 and Ednrb or Pax3 and Ednrb interact to promote normal murine melanocyte development. Crosses of Sox10 or Pax3 with Ednrb heterozygous mutants showed that the double heterozygous hypopigmentation phenotype was significantly more pronounced than phenotypes of single heterozygotes, implying that a synergistic interaction exists between Sox10 and Ednrb and Pax3 and Ednrb. This interaction was further explored by the attempt to rescue the Sox10 and Pax3 hypopigmentation phenotypes by the transgenic addition of Ednrb to melanoblasts. Pigmentation was completely restored in the Sox10 and partially restored in the Pax3 mutant mice. The comparison of the number of melanoblasts in transgenic and non-transgenic Sox10 mutant embryos showed that the transgenic rescue occurred as early as E11.5, a critical time for melanoblast population expansion. Cell survival assays indicated that the rescue was not due to an effect of the transgene on melanoblast survival. A novel phenotype arose when studying the interaction between Ednrb and Pax3. Newborns appeared normal but by 3.5 weeks of age, the affected pups were smaller than normal littermates and developed a dome-shaped head; some also developed thoracic kyphosis. Affected pups were dead by 4 weeks of age: 80% were Pax3Sp/+ and 75% were female. When compared to normal littermates, affected mice had brains with enlarged 4th ventricles and more glia while skeletal staining showed kyphosis, wider rib cages and pelvic differences. An epistatic interaction resulting from the mixing of genetic backgrounds that is exacerbated in the presence of Pax3 heterozygosity is suspected.

Interactions between Endothelin Receptor B and Transcription Factors Sox10 and Pax3 in the Melanocyte Lineage

Genetic interactions that underlie developmental processes such as cell differentiation and pattern formation are complex and difficult to elucidate. Neural Crest (NC) cells and their derivatives offer an optimal system in which to probe for these complex interactions as they acquire different cell fates and constitute a variety of structures. The transcription factors Sox10 and Pax3 as well as the transmembrane receptor Endothelin receptor b (Ednrb) are temporally and spatially co-expressed early in NC cells and mutations in these genes lead to similar hypopigmentation phenotypes due to a reduced number of NC-derived melanocyte precursors, the melanoblasts. The goal of this study was to establish whether Sox10 and Ednrb or Pax3 and Ednrb interact to promote normal murine melanocyte development. Crosses of Sox10 or Pax3 with Ednrb heterozygous mutants showed that the double heterozygous hypopigmentation phenotype was significantly more pronounced than phenotypes of single heterozygotes, implying that a synergistic interaction exists between Sox10 and Ednrb and Pax3 and Ednrb. This interaction was further explored by the attempt to rescue the Sox10 and Pax3 hypopigmentation phenotypes by the transgenic addition of Ednrb to melanoblasts. Pigmentation was completely restored in the Sox10 and partially restored in the Pax3 mutant mice. The comparison of the number of melanoblasts in transgenic and non-transgenic Sox10 mutant embryos showed that the transgenic rescue occurred as early as E11.5, a critical time for melanoblast population expansion. Cell survival assays indicated that the rescue was not due to an effect of the transgene on melanoblast survival. A novel phenotype arose when studying the interaction between Ednrb and Pax3. Newborns appeared normal but by 3.5 weeks of age, the affected pups were smaller than normal littermates and developed a dome-shaped head; some also developed thoracic kyphosis. Affected pups were dead by 4 weeks of age: 80% were Pax3Sp/+ and 75% were female. When compared to normal littermates, affected mice had brains with enlarged 4th ventricles and more glia while skeletal staining showed kyphosis, wider rib cages and pelvic differences. An epistatic interaction resulting from the mixing of genetic backgrounds that is exacerbated in the presence of Pax3 heterozygosity is suspected.

Women Creators: Artistry and Sacrifice in the Novels of Virginia Woolf

This thesis examines different facets of feminine artistry in Virginia Woolf's novels with the purpose of defining her conception of women artists and the role sacrifice plays in it. The project follows characters in "Mrs. Dalloway," "To the Lighthouse," and "Between the Acts" as they attempt to create art despite society's restrictions; it studies the suffering these women experience under regimented institutions and arbitrary gender roles. From Woolf’s earlier texts to her last, she embraces the uncertainty of identity, even as she portrays the artist’s sacrifice in the early-to-mid twentieth century, specifically as the creative female identity fights to adapt to male-dominated spaces. Through a close-reading approach coupled with biographical and historical research, this thesis concludes that although the narratives of Woolf's novels demand the woman artist sacrifice for the sake of pursuing creation, Woolf praises the attempt and considers it a crueler fate to live with unfulfilled potential.

Square and compass: Freemasonry's tools for constructing a global civil society

The concept of a global civil society is gaining greater acceptance among International Relations (IR) scholars, yet few studies exist that look at the role of fraternal organizations and their influence in constructing this realm. Freemasonry, one of the oldest fraternal orders, exerts a powerful influence on its membership through its symbolism, architecture and ritual, based on the tenets of mutual respect and tolerance towards all human beings. Such principles helped in creating a body of practices and institutions as early as the eighteenth century which two hundred years later were identified and conceptualized as global civil society. ^ The allegations of anti-Masons and conspiracy theorists offer a continuous account of Masonry's influence on the political scene since its modern founding in 1717 Great Britain. Conspiracy theorists portray the coming of a New World Order, orchestrated and directed by a secret hierarchy of Masons/Illuminati. Even though the lens of conspiracy theories paints a distorted view of reality, it does focus attention to Freemasonry's activities as a major player in politics over the span of three centuries. Not only do such theories challenge the novelty of practices that make up a global civil society, but also the notion that it is an inclusive and growing sector that unites people across the globe. They also provide a valuable critique by pointing out the inconsistencies and discriminatory practices of Masonry as contrasted with the lofty ideals and aims for humanity. ^ The Masonic influence in the social world is perceived as one that reflects the liberal worldview where the nation-state and power structures are in pursuit of human progress, or profit. The symbolism of Masonry, however, carries a message that can be characterized as representing republican ideals. Masonic symbolism and ritual create spaces of meaning where the contradictions between the ideals and the structures of inequality and elitism can be resolved. Freemasonry as a symbolic system proclaiming their inherent republican values does have a global reach. However, the effectiveness of these values is bounded by the constraints that are inherent in a liberal world dominated by nation-states. ^

Disease and hygiene in the construction of a nation: The public sphere, public space, and the private domain in Buenos Aires, 1871–1910

The maturation of the public sphere in Argentina during the late nineteenth and early twentieth centuries was a critical element in the nation-building process and the overall development of the modern state. Within the context of this evolution, the discourse of disease generated intense debates that subsequently influenced policies that transformed the public spaces of Buenos Aires and facilitated state intervention within the private domains of the city’s inhabitants. Under the banner of hygiene and public health, municipal officials thus Europeanized the nation’s capital through the construction of parks and plazas and likewise utilized the press to garner support for the initiatives that would remedy the unsanitary conditions and practices of the city. Despite promises to the contrary, the improvements to the public spaces of Buenos Aires primarily benefited the porteño elite while the efforts to root out disease often targeted working-class neighborhoods. The model that reformed the public space of Buenos Aires, including its socially differentiated application of aesthetic order and public health policies, was ultimately employed throughout the Argentine Republic as the consolidated political elite rolled out its national program of material and social development.

The Fate of Spermatogonial Stem Cells in the Cryptorchid Testes of RXFP2 Deficient Mice

The environmental niche of the spermatogonial stem cell pool is critical to ensure the continued generation of the germ cell population. To study the consequences of an aberrant testicular environment in cryptorchidism we used a mouse model with a deletion of Rxfp2 gene resulting in a high intra-abdominal testicular position. Mutant males were infertile with the gross morphology of the cryptorchid testis progressively deteriorating with age. Few spermatogonia were identifiable in 12 month old cryptorchid testes. Gene expression analysis showed no difference between mutant and control testes at postnatal day 10. In three month old males a decrease in expression of spermatogonial stem cell (SSC) markers Id4, Nanos2, and Ret was shown. The direct counting of ID4+ cells supported a significant decrease of SSCs. In contrast, the expression of Plzf, a marker for undifferentiated and differentiating spermatogonia was not reduced, and the number of PLZF+ cells in the cryptorchid testis was higher in three month old testes, but equal to control in six month old mutants. The PLZF+ cells did not show a higher rate of apoptosis in cryptorchid testis. The expression of the Sertoli cell FGF2 gene required for SSC maintenance was significantly reduced in mutant testis. Based on these findings we propose that the deregulation of somatic and germ cell genes in the cryptorchid testis, directs the SSCs towards the differentiation pathway. This leads to a depletion of the SSC pool and an increase in the number of PLZF+ spermatogonial cells, which too, eventually decreases with the exhaustion of the stem cell pool. Such a dynamic suggests that an early correction of cryptorchidism is critical for the retention of the SSC pool.