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Autoimmune vitiligo is associated with gain-offunction by a transcriptional regulator that elevates expression of HLA-A∗02:01 in vivo
No full textHLA-A is a class I major histocompatibility complex receptor that presents peptide antigens on the surface of most cells. Vitiligo, an autoimmune disease in which skin melanocytes are destroyed by cognate T cells, is associated with variation in the HLA-A gene; specifically HLA-A∗02:01, which presents multiple vitiligo melanocyte autoantigens. Refined genetic mapping localizes vitiligo risk in the HLA-A region to an SNP haplotype ∼20-kb downstream, spanning an ENCODE element with many characteristics of a transcriptional enhancer. Convergent CTCF insulator sites flanking the HLA-A gene promoter and the predicted transcriptional regulator, with apparent interaction between these sites, suggests this element regulates the HLA-A promoter. Peripheral blood mononuclear cells from healthy subjects homozygous for the high-risk haplotype expressed 39% more HLA-A RNA than cells from subjects carrying nonhigh-risk haplotypes (P = 0.0048). Similarly, RNAseq analysis of 1,000 Genomes Project data showed more HLA-A mRNA expressed in subjects homozygous for the high-risk allele of lead SNP rs60131261 than subjects homozygous for the low-risk allele (P = 0.006). Reporter plasmid transfection and genomic run-on sequence analyses confirm that the HLA-A transcriptional regulator contains multiple bidirectional promoters, with greatest activity on the high-risk haplotype, although it does not behave as a classic enhancer. Vitiligo risk associated with the MHC class I region thus derives from combined quantitative and qualitative phenomena: a SNP haplotype in a transcriptional regulator that induces gainof-function, elevating expression of HLA-A RNA in vivo, in strong linkage disequilibrium with an HLA-A allele that confers ∗02:01 specificity
Developing Expression in Brass Performance and Teaching
No full textDeveloping Expression in Brass Performance and Teaching helps university music teachers, high school band directors, private teachers, and students develop a vibrant and flexible approach to brass teaching and performance that keeps musical expression central to the learning process. Strategies for teaching both group and applied lessons will help instructors develop more expressive use of articulation, flexibility in sound production, and how to play with better intonation.
The author shares strategies from today’s best brass instrument performers and teachers for developing creativity and making musical expression central to practicing and performing. These concepts presented are taken from over thirty years of experience with musicians like Wynton Marsalis, Barbara Butler, Charles Geyer, Donald Hunsberger, Leonard Candelaria, John Haynie, Bryan Goff, members of the Chicago Symphony and New York Philharmonic and from leading music schools such as the Eastman School of Music, The University of North Texas and The Florida State University.
The combination of philosophy, pedagogy, and common sense methods for learning will ignite both musicians and budding musicians to inspired teaching and playing
What if the Black Officer Was Female? Race and Gender Characteristics in Arrest Practices
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Phantom Fictions: María Luisa Bombal, Pía Barros and the Anxiety of Authorship
No full textThis research demonstrates the ways in which the work of Sandra M. Gilbert and Susan Gubar on the topic of the anxiety of authorship within female writers provides a legitimate and robust framework for exploring women\u27s literary development in Chilean literature. By studying María Luisa Bombal\u27s novella The Final Mist (1935) alongside Pia Barros’ short story \u22Scents of Wood and Silence\u22 (1991), this research demonstrates how two female Chilean authors, linked through time by genre, metaphor, and style, offer a unique image of the struggle of women writers against the anxiety of authorship and inferiorization instigated by the patriarchal literary tradition. Gilbert and Gubar argue that female writers must seek out literary foremothers in order to legitimize their art. This paper utilizes Gilbert and Gubar’s framework to explore the ways in which Barros\u27 short story interacts with Bombal\u27s novella as a literary foremother. It does so primarily by analyzing the shared metaphors present in the stories, such as the portrayals of phantom men as embodiments of the unique female experience and creation, with male partners being presented as representations of a male dominated literary culture. It also engages in the shared styles of writing, focusing on the way in which the authors demonstrate the longing for language by their emphasis on silence, which also serves as a depiction of the struggle of the woman writer against her male precursor within Gilbert and Gubar\u27s framework. Lastly, this research investigates the ways in which both Barros and Bombal used genre to expand the literary canon, blurring the lines between male points of view, which demand reality be considered transparent and objective, and the experiences of the female protagonists who incorporate and legitimize hidden, subjective experiences as a valid form of narration.http://opus.ipfw.edu/stu_symp2016/1007/thumbnail.jp