Characterization of the degradation of wild-type and mutant HFE proteins during stress signalling in the endoplasmic reticulum

HFE is a transmembrane protein that becomes N-glycosylated during transport to the cell membrane. It acts to regulate cellular iron uptake by interacting with the Type 1 transferrin receptor and interfering with its ability to bind iron-loaded transferrin. There is also evidence that HFE regulates systemic iron levels by binding to the Type II transferrin receptor although the mechanism by which this occurs is still not well understood. Mutations to HFE that disrupt this function, or physiological conditions that decrease HFE protein levels, are associated with increased iron uptake, and its accumulation in tissues and organs. This is exemplified by the point mutation that results in conversion of cysteine residue 282 to tyrosine (C282Y), and gives rise to the majority of HFE-related hemochromatoses. The C282Y mutation prevents the formation of a disulfide bridge and disrupts the interaction with its co-chaperone β2-microglobulin. The resulting misfolded protein is retained within the endoplasmic reticulum (ER) where it activates the Unfolded Protein Response (UPR) and is subjected to proteasomal degradation. The absence of functional HFE at the cell surface leads to unregulated iron uptake and iron loading. While the E3 ubiquitin ligase involved in the degradation of HFE-C282Y has been identified, the mechanism by which it is targeted for degradation remains relatively obscure. The primary objective of this project was to further our understanding of how the iron regulatory HFE protein is targeted for degradation. Our studies suggest that the glycosylation status, and the active process of deglycosylation, are central to this process. We identified a number of additional factors that can contribute towards degradation and explored their regulation during ER stress conditions.

SELECTED AMERICAN VIOLIN WORKS AND THEIR EUROPEAN CONTEXT

For my dissertation, I did a study and performance of American violin works by Charles Ives, Aaron Copland, Leonard Bernstein, and John Corigliano, along with contemporaneous European works by Paul Hindemith, Bela Bartok, Igor Stravinsky, Sergei Prokofiev, and Francis Poulenc. The selected American violin works display the development of a distinctively American style and cover a significant formative period (1914-1963) of American classical music. I intend that the European works form a backdrop for setting in relief any distinctly American qualities possessed by the American works. This is because they cover a similar time period and have significant stylistic affinities and shared influences. My topic stems from a question, "What defines the American Sound?" I attempted to find the answer by looking at the time when American composers consciously searched for their identities, and declared their music to be distinctly American. I found that those distinctive qualities stemmed from three sources: folk music, jazz and hymns. Ives and Copland can be viewed as American in content for their inclusion of such elements, while Bernstein and Corigliano can also be considered as "ideologically American" for their adventurous and eclectic spirit. The simplicity derived from singing a hymn or crooning a popular song; the freedom inspired by jazz; the optimism of accepting all possibilities-these elements inform the common spirit that I found in the music of these four American composers. FIRST RECITAL Sonatafor Violin Solo Op.3112 (1924), Paul Hindemith (1895-1963) Suite Italiennefor Violin and Piano (1932), Igor Stravinsky (1882-1971) Sonatafor Violin and Piano (1963), John Corigliano (b.1938) SECOND RECITAL Second Sonatafor Violin and Piano (1914-17), Charles Ives (1874-1954) First Rhapsody for Violin and Piano (1928), Bela Bart6k (1881-1971) Violin Sonata No.1 infminor (1938-46), Sergei Prokofiev (1891-1953) THIRD RECITAL Nocturne for Violin and Piano (1926), Aaron Copland (1900-1990)Sonata for Violin and Piano, Op. 119 (1942-3, rev.1949), Francis Poulenc (1899-1963)Serenade (after Plato's "Symposium'') (1954) by Leonard Bernstein (1918-1990) The pianists were Sun Ha Yoon (Bart6k) and Grace Eunae Cho (all other repertoire).

A GOLDEN AGE: FRENCH AND SPANISH CELLO MUSIC FROM SAINT-SAENS TO CASSADO

Motivated by both the delicacy of French music, such as La Mer by Claude Debussy, and the exotic atmosphere of Spanish music, such as Zigeunerweisen by Pablo Sarasate, I decided to investigate the characteristics of French and Spanish cello music from Camille Saint-Saens to Gaspar Cassad6. French cello music flourished from the end ofthel9th to the middle of the 20th century because of the innovation of many unprecedented techniques and experimentation with a variety of sonorities. The Spanish were heavily influenced by the French due to the geographical connection. Cello virtuosi like Auguste Tolbecque, August Franchomme, Pierre Fournier, and Paul Tortelier inspired composers of their day, creating a "golden age" of cello music. This dissertation consisted of three recitals in Gildenhom Recital Hall. The first recital was held on May lOth, 2007 at 5:30pm with pianist David Ballena. The second recital was held on October 14th, 2007 at 2pm with collaborators Minna Han, piano and Jenny Wu, violin. The third recital was held on March 301 2008 at 5:30 with pianist Naoko Takao. Here is the program of the recitals: The first recital: Gabriel Faure(1856-1924): Sonate pour Violoncello et Piano Op.109(1917) Gaspar Cassad6 (1897-1966): Suite per Violoncello Solo (1926) Claude Debussy (1862-1918): Sonate pour Violoncelle et Piano (1915) The second recital: Manuel de Falla (1876-1946): Melodia (1897), Romanza (1898) Camille Saint-Saens (1835-1921): Concerto for Cello and Orchestra No.1 in A minor Op.33 (1873) Maurice Ravel (1875-1973): Sonata for Violin and Cello (1920-22) The third recital: Pablo Casals (1876-1973): Song of the Birds (1925) Edouard Lalo (1823-1892): Concerto for Cello and Orchestra in D Minor (1877) Franscis Poulenc (1899-1963): Sonata for Cello and Piano Op.l43(1940-48)

Resenha: tecnologias da informação e comunicação, função composta e regra da cadeia

Esta resenha traz uma síntese do trabalho de pesquisa realizado por Barbosa sobre o ensino de Funções Compostas e Regra da Cadeia na disciplina de Cálculo Diferencial e Integral de uma variável. A inquietação da autora reside na dificuldade apresentada pelos estudantes no entendimento destes conteúdos. Sua proposta é desenvolver uma abordagem gráfica para estes conceitos, utilizando as Tecnologias da Informação e Comunicação (TIC) como recurso para a visualização e experimentação de conjeturas pelos alunos.

Etnomatemática e discurso performático: a construção de identidades na escola

Este trabalho objetiva apresentar as reflexões decorrentes de uma pesquisa, realizada com mais de sessenta alunos em uma escola privada da cidade de São Paulo, que procurou avaliar como concebem diferentes povos africanos e indígenas, com a hipótese de que a escola, bem como a Educação que propõe, contribua para construção de representações incompletas dessas identidades. Além disso, o discurso descritivo apresentado pelos alunos foi entendido a partir do conceito de performatividade de Butler (1993), segundo o qual alguns discursos supostamente descritivos seriam capazes de, além de descrever um indivíduo ou um grupo, criar sobre tal indivíduo ou grupo uma representação de identidade vinculada à descrição feita. Associa-se tal construção às perspectivas de Vergani (2007) sobre exclusão, observando o modo como a Educação articula discursos e ideias provenientes do senso comum no cotidiano escolar para refletir sobre suas possíveis consequências, sob a perspectiva da Etnomatemática de D’Ambrosio (1999; 2011).

'Bowing from the heart': an investigation into discourses of professionalism and the work of caring for students in further education

Since their incorporation in 1993, further education (FE) colleges in England have been responsible for their own staffing and, faced with funding constraints as well as recruitment and retention targets, some have introduced a new category of staff referred to here as 'learning support workers' (LSWs). Though their employment conditions and specific duties vary considerably, LSWs' work often includes providing individual care for students. In this small-scale study, using semi-structured interviews, the perceptions of some teachers and LSWs about the nature of their relationships with each other and with students are investigated. The study is set broadly in the context of debates about the impact of public sector reform on FE colleges and teachers. A discourse analysis approach is adopted in discussion of the data. The authors conclude that although they are differently positioned in relation to traditional discourses of professionalism, both teachers and LSWs are perceived to be carrying out what Hochschild termed 'emotional labour'. The contradictory nature of emotional labour is also highlighted. Some of the implications of employing a new group of workers in FE are discussed.