La réparation par excision de nucléotides (NER) permet l'élimination des lésions provoquant une distorsion de la double hélice de l’ADN. Ces lésions sont induites par plusieurs agents environnementaux comme les rayons UV, ainsi que par certaines drogues chimio- thérapeutiques tel que le cisplatine. Des défauts dans la NER conduisent à de rares maladies autosomiques héréditaires : La xérodermie pigmentaire (XP), le syndrome de Cockayne (CS), le syndrome de sensibilité aux UVSS et la trichothiodystrophie (TTD). Ces maladies sont associées soit à une prédisposition élevée au cancer de la peau et / ou à de graves anomalies du développement neurologique. Le groupe de patients XP-A représente le deuxième groupe (XP) le plus fréquent, et possède la forme la plus sévère combinant cancer de la peau avec un haut risque de dégénérescence neurologique. À date, aucune explication n`a été proposée pour les symptômes neurologiques observés chez ces patients. Nous avions suggéré ainsi que la protéine XPA possède d`autres fonctions dans d`autres processus cellulaires, ceci en interagissant avec des partenaires protéiques différents de ceux déjà connus. Afin de confirmer cette hypothèse nous avions réalisé une étude protéomique à grande échelle en combinant la spectrométrie de masse à une immunoprécipitation en Tandem d`affinité (TAP), afin d`identifier de nouvelles protéines interagissant directement avec XPA. Nous avions montré que XPA peut interagir avec MRE11, la protéine clé de la réparation par recombinaison homologue. Des études additionnelles sont requises pour confirmer cette interaction et comprendre sa fonction / To maintain genome integrity and ensure the continuation of transcription, helix distorting DNA lesions induced by UV and other environmental mutagens are eliminated through a highly-versatile DNA repair pathway: nucleotide excision repair (NER). Mutations in 11 genes (XPC, XPE, XPB, XPD, XPG, XPA, XPG, TTD-A, CSA, CSB and UVSSA), among the 30 genes directly involved in NER, have been associated with the human genetic disorders: xeroderma pigmentosum (XP), cockayne syndrome (CS), trichothiodystrophy (TTD), and UV-sensitive syndrome (UVSS). Patients of these syndromes display a wide variety of clinical features that range from normal development with extreme predisposition to cancer, to neurodevelopmental defects associated with premature aging abnormalities. The connection between DNA damage and neurodegeneration remains unclear, i.e. cannot be explained by a DNA-repair deficiency alone, implying that various repair factors perform other functions beyond the repair process. XP-A is the second most common form of XP. XP-A cells have very low levels of NER activity and are sensitive to killing by UV light. It is one of the most severely affected XP groups, with the onset of cutaneous features, skin cancer, ocular features, and severe early onset neurological disease. Therefore we hypothesize that XPA interacts with cellular proteins that regulate its functions either in UV damage repair or in neurological development. To test this, our major aim was to carry out a large-scale proteomics investigation to identify novel interacting partners for XPA in the absence or presence of genotoxic stress, thus providing clues on the origins of neurodegeneration observed in many XP-A patients. We provide evidence that XPA can interact with MRE11, the key factor in repair of double strand breraks by homologous Recombination. Future experiments will be aimed at determining the impact of the XPA/MRE11 interaction functions in cells.

Made available in DSpace on 2016-04-27T16:57:40Z (GMT). No. of bitstreams: 1 Alexandre Kruger Zocolotti.pdf: 9994415 bytes, checksum: b48568ef8a6e79cad2d1cd9480137cb4 (MD5) Previous issue date: 2015-11-10 / The research presented here focused on investigating conceptions of the processes of teaching and learning mathematics teachers trained in areas related to this discipline and who have attended a course in Educational Complementation. An empirical study was conducted with four teachers of mathematics - two teachers who worked in the Secondary School and two teachers who worked in high school - who had training in those molds. The theoretical study involved conceptions, teaching knowledge and training of mathematics teachers, with special attention to the models of teacher education in force in Brazil. For data collection, two different elements were used: semistructured interviews and observations of the practice of each of the surveyed teachers. In the data analysis, it was perceived details that have identified how each participant understands the processes of teaching and learning of mathematics. These details, which combine aspects that reveal knowledge of each of the teachers showed differences in expressed or mathematical knowledge in everyday practice observed, each of the participants. The conclusion of the study highlights the need for a discussion on the restructuring of Pedagogical Supplementary courses, as well as the urgency of a survey that reveals, at national level, the number of mathematics teachers who have been trained through these courses / A pesquisa aqui apresentada teve como foco investigar concepções sobre os processos de ensino e de aprendizagem de professores de Matemática formados em áreas afins a essa disciplina e que frequentaram um curso de Complementação Pedagógica. Um estudo empírico foi conduzido com quatro professores de Matemática duas docentes que atuavam no Ensino Fundamental II e dois docentes que atuavam no Ensino Médio - que possuíam formação nos moldes citados. O referencial teórico estudado envolveu concepções, saberes docentes e formação de professores de Matemática, com especial atenção aos modelos de formação docente vigentes no Brasil. Para a coleta de dados, foram utilizados dois elementos diferentes: entrevistas semiestruturadas e observações da prática de cada um dos professores pesquisados. Na análise dos dados, foram percebidos detalhes que permitiram identificar como cada um dos participantes entende os processos de ensino e de aprendizagem da Matemática. Esses detalhes, que reúnem aspectos que revelam saberes de cada um dos docentes, mostraram diferenças no conhecimento matemático manifestado ou na prática cotidiana observada, de cada um dos participantes. A conclusão do trabalho aponta a necessidade de uma discussão sobre a reestruturação dos Cursos de Complementação Pedagógica, bem como a urgência de um levantamento que revele, a nível nacional, o número de professores de Matemática que foram formados por esses cursos

Jesus' story has been retold in various forms and fashions for centuries. Jesus novels, a subset of the historical fiction genre, are one of the latest means of not only re-imagining the man from Galilee but also of rewriting the canonical Gospels. This thesis explores the Christological portraits constructed in four of those novels while also using the novels to examine the intertextual play of these Gospel rewrites with their Gospel progenitors. Chapter 1 offers a prolegomenon to the act of fictionalizing Jesus that discusses the relationship between the person and his portraits and the hermeneutical circle created by these texts as they both rewrite the Gospels and stimulate a rereading of them. It also establishes the "preposterous" methodology that will be used when reexamining the Gospels "post" reading the novels. Chapters 2 to 5 offer four case studies of "complementing" and "competing" novels and the techniques they use to achieve these aims: Anne Rice's Christ the Lord: Out of Egypt; Neil Boyd's The Hidden Years; Nino Ricci's Testament; and José Saramago's The Gospel according to Jesus Christ. Chapter 6 begins an examination of a specific interpretive circle based upon Jesus' temptation in the wilderness. Beginning with the synoptic accounts of that event, the chapter then turns to how Jesus' testing has been reinterpreted and presented in two of the novels. Returning to the Gospel of Matthew's version of the Temptation, chapter 7 offers a "preposterous" examination of that pericope, which asks novel questions of the text and its role with Matthew's narrative context based on issues raised by the Gospel rewrites. The thesis concludes by suggesting that Jesus novels, already important examples of the reception history of the Gospels, can also play a helpful role in re-interpreting the Gospels themselves.

SLOVENE NATIONAL THEATRE IN LJUBLJANA Author Report Of The Diploma Work Author: Bc. Petr Hýl Supervisor: doc. ing. arch. Zdeněk Makovský