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Chez les eucaryotes, l’information génétique est transcrite en ARN messager qui subit plusieurs étapes de maturation et évènements d’assemblage avant d’être exporté hors du noyau. Ces modifications du transcrit sont effectuées par de nombreux facteurs protéiques recrutés au transcrit naissant, formant ainsi une particule ribonucléoprotéique (mRNP). La biogenèse du mRNP est étroitement liée avec la transcription et le contrôle qualité afin d’assurer l’efficacité et l’exactitude de la production de mRNPs matures. Des études récentes suggèrent que les membres du complexe THO-Sub2 pourraient être des facteurs cruciaux dans le couplage de la transcription, de la biogénèse du mRNP et de l’export. Dans notre groupe, nous avons mis en oeuvre un essai novateur pour étudier la biogénèse du mRNP et le contrôle qualité, basé sur l’expression du facteur Rho bactérien dans Saccharomyces cerevisiae. Rho interfère avec l’assemblage adéquat du mRNP et génère des transcrits aberrants qui sont dégradés par la machinerie de dégradation nucléaire. Dans cette étude, nous avons utilisé le système expérimental Rho pour mieux comprendre Rrp6 et l’implication de l’exosome dans la dégradation des transcrits liée au contrôle qualité, ainsi que pour mieux caractériser le rôle et la fonction du complexe THO-Sub2 dans le processus de biogénèse du mRNP. Les résultats obtenus révèlent une différence intéressante dans le comportement des membres du complexe THO sous l’action de Rho et dévoilent leur dépendance à la liaison à l’ARN, ce qui n’aurait pas pu être observé avec d’autres techniques expérimentales. Cela confirme le potentiel attendu du système expérimental basé sur Rho dans l’étude des facteurs protéiques impliqués dans la biogénèse et le contrôle qualité du mRNP. / In eukaryotes, the genetic information is transcribed into messenger RNA which undergoes various processing and assembly events prior to its export from the nucleus. These transcript modifications are performed by numerous protein factors recruited to the nascent transcript, thus making a messenger ribonucleoprotein particle (mRNP). mRNP biogenesis is tightly interconnected with both transcription and quality control to ensure efficiency and accuracy in production of mature mRNPs. Recent findings suggest that members of THO-Sub2 complex might be crucial factors in coupling transcription, mRNP biogenesis and export. In our group, we have implemented an innovative assay to study mRNP biogenesis and quality control, based on the expression of the bacterial factor Rho in Saccharomyces cerevisiae. Rho interferes with proper mRNP assembly and generates aberrant transcripts degraded by the nuclear degradation machinery. In this study, we use Rho experimental system to expand our findings on Rrp6 and exosome involvement in quality control degradation of transcripts, as well as to better characterize the role and function of THO-Sub2 complex in the process of mRNP biogenesis. Obtained results reveal an interesting difference in behavior of THO complex members upon Rho action and disclose their dependence on binding to the RNA, which could not be observed by other experimental techniques. This substantiates the expected potential of Rho-based experimental system in the study of protein factors involved in mRNP biogenesis and quality control.

The 1972 Paris Peace Talks between Henry Kissinger and Le Duc Tho brought the American involvement in the Vietnam War to a close by early 1973. The main sticking points theretofore were stipulations in draft cease-fire agreements allowing Northern troops to remain in the South and the National Liberation Front's participation in South Vietnam's government. President of South Vietnam Nguyen Van Thieu adamantly opposed both proposed stipulations lest his power be diluted. Thus, Kissinger had to broker a diplomatic agreement between Thieu and Le Duc Tho which was acceptable to US foreign policy viz. “peace with honor.”

The ACME collaboration has completed a measurement setting a new upper limit on the size of the electron's permanent electric dipole moment (EDM). The existence of the EDM is well motivated by theories extending the standard model of particle physics, with predicted sizes very close to the current experimental limit. The new limit was set by measuring spin precession within the metastable H state of the polar molecule thorium monoxide (ThO). A particular focus here is on the automated data acquisition system developed to search for a precession phase odd under internal and external reversal of the electric field. Automated switching of many different experimental controls allowed a rapid diagnosis of major systematics, including the dominant systematic caused by non-reversing electric fields and laser polarization gradients. Polarimetry measurements made it possible to quantify and minimize the polarization gradients in our state preparation and probe lasers. Three separate measurements were used to determine the electric field that did not reverse when we tried to switch the field direction. The new bound of |de|< 8.7 &times; 10^-29 e cm is over an order of magnitude smaller than previous limits, and strongly limits T-violating physics at TeV energy scales. / Physics

The Piwi interacting RNA pathway (piRNA) transcriptionally and post-transcriptionally silences transposons in the germline to maintain host genome integrity and faithful transmission of the genetic materials. In Drosophilaovaries, maternally loaded piRNAs kick-start piRNA biogenesis and convert precursor transcripts into piRNAs to replenish the piRNA pool during oogenesis. piRNA clusters are the genomic source of piRNA precursors, which are determined by the HP1 homolog Rhino and accessary factors. Rhino specifically binds to piRNA cluster chromatin. I was intrigued by how Rhino localizes to piRNA clusters to specify piRNA precursors. TREX is a conserved mRNA biogenesis complex composed of UAP56 and the THO complex. Identification of UAP56 as a cluster transcript-processing factor established the link between piRNA biogenesis and the general mRNA processing machinery. In my thesis, I investigated the functions of UAP56 and THO in piRNA cluster transcript processing. I characterized an RNP specific to cluster transcripts, defined by binding with both factors, which is distinct from RNP of bulk mRNA transcripts, and found that assembly of these RNPs depends on Rhino. These findings imply that piRNA precursors are specified co-transcriptionally. Additionally, I found that TREX mutants lead to a loss of Rhino binding specificity. I propose that Rhino and TREX co-transcriptionally scan for cluster and transposon sequences to establish loci that produce piRNA precursors. Surprisingly, I also discovered a piRNA-independent function for TREX in transposon silencing. I showed that TREX mutants lead to transcriptionally activation of a number of transposon families without affecting their piRNA biogenesis and piRNA mediated repressive histone modifications. I propose that TREX could mediate a conserved transposon silencing mechanism.

Au cours de la transcription, plusieurs facteurs sont assemblés sur les ARN messagers pour former des Ribonucléoparticules de messagers (mRNPs), et contrôler leur maturation, leur stabilité et leur devenir dans le cytoplasme. Afin d’assurer la production de protéines fonctionnelles, la cellule dispose de plusieurs mécanismes de régulation et de contrôle de qualité assurant la fidélité de l’information génétique transmise au niveau ARN messager et protéine.Chez la levure Saccharomyces cerevisiae, un ensemble de protéines associées au pore nucléaire, incluant la SUMO protéase Ulp1, a été impliqué dans un contrôle de qualité des mRNPs régulant leur export vers le cytoplasme. Ces données suggéraient que l’export des ARN messagers pourrait être contrôlé par la modification post-traductionnelle par le polypeptide SUMO d’un ou de plusieurs effecteurs au sein des mRNPs. Afin de mieux comprendre ces processus, nous avons combiné plusieurs approches visant à identifier ces protéines SUMOylées. En particulier, nous avons mis en place un crible protéomique visant à identifier les protéines dont l’association sur les mRNPs dépend d’Ulp1. Ce crible nous a permis de mettre en évidence une régulation par Ulp1 de l’assemblage du complexe THO sur les ARN messagers. Ce complexe, recruté sur les gènes et les mRNPs, est connu pour contribuer à l’efficacité de la transcription, prévenir l’instabilité génétique liée à la formation d’hybrides ADN matrice – ARN messager (dénommés R-loops) et permettre l’export des mRNPs. En combinant l’analyse biochimique de différentes catégories de mRNPs à des expériences d’immunoprécipitation de l’ARN, nous avons montré que l’activité de la SUMO-protéase Ulp1 est nécessaire à l’association du complexe THO sur différents ARN messagers. De plus, nous avons montré que le complexe THO est SUMOylé sur le domaine C-terminal de sa sous-unité Hpr1, et que Ulp1 régule cette modification. Enfin, cet événement de SUMOylation du complexe THO régule son association avec les mRNPs. L’analyse fonctionnelle de mutants affectant la SUMOylation du complexe THO révèle que des défauts de SUMOylation de ce complexe compromettent ses fonctions dans la transcription sans affecter l’export. De manière intéressante, nous avons observé que la présence d’un intron sur des rapporteurs LacZ diminue la sensibilité de leur expression à des inactivations ou des défauts de SUMOylation du complexe THO. Ce phénotype entraine une augmentation relative des niveaux d’ARN pré-messagers dans ces mutants, un phénomène rendant compte de la fuite cytoplasmique apparente d’ARN non épissés précédemment observée dans le mutant ulp1. L’ensemble de ces données caractérise pour la première fois un rôle de la SUMOylation dans le contrôle de l’assemblage et du devenir cellulaire des mRNPs. / During transcription, several factors associate with mRNA to form messenger Ribonucleoparticles (mRNPs), thereby controlling their processing, their stability, and their cytoplasmic fate. To ensure the production of functional proteins from these mRNAs, eukaryotic cells contain numerous regulatory and quality control systems in order to prevent aberrant mRNP accumulation and export.In the yeast Saccharomyces cerevisiae, several nuclear pore associated proteins, including the SUMO isopeptidase Ulp1, have been involved in a mRNP quality control regulating their nuclear export. These data suggested that post-translational modification by SUMO of one or several mRNP components could regulate mRNA export. In order to understand the molecular mechanisms underlying this process, we undertook several approaches to identify these SUMOylated factors. In particular, we have set up a proteomic screen to identify mRNP components whose assembly onto mRNPs depends on Ulp1 activity.This proteomic survey revealed an Ulp1-dependent regulation of THO complex assembly to mRNPs. This complex, recruited to transcribed genes and mRNPs, is known to regulate transcription elongation by preventing DNA-RNA hybrids formation (termed R-loops), and mRNP export. Through a combination of proteomic analysis of mRNPs assembled in Ulp1 mutant cells, with RNA / chromatin immunoprecipitation experiments, we demonstrate that Ulp1 controls specifically the recruitment of the THO complex within mRNPs. SUMOylation analysis further reveals that Ulp1 targets the THO complex subunit Hpr1 on its C-terminal domain for deSUMOylation. We further show that this SUMOylation event regulates THO complex association within mRNPs. Finally, functional analysis reveal that impaired deSUMOylation of the THO complex do not affect mRNP export, but disturbs expression of LacZ reporter genes, a phenotype classically associated with THO complex dysfunction. Intriguingly, the transcriptional effect of inactivation or impaired deSUMOylation of the THO complex on LacZ expression is alleviated by the presence of an intron, providing a molecular basis for previously reported pre-mRNA leakage phenotypes. Our data therefore unravels for the first time a function of SUMO in the control of mRNP assembly contributing to proper mRNP homeostasis.

This investigation of the Infancy Gospel of Thomas focuses on the question why the author of this infancy gospel narrated the mighty deeds – either received as blessings or as curses – as though the child Jesus were an adult. A possibility is that the author could have been inspired by tales from antiquity in which the heroic deeds of gods, emperors and philosophers were projected to their infancy. The study purports that the answer to this question is rather to be found in the combination of myth interpretation and societal expectations with regard to children in a Hellenistic-Semitic context. The purpose of this study is to investigate the history of the Greek manuscripts and the translation history of the Infancy Gospel of Thomas as a second century infancy gospel, secondly to identify as the most authentic text the eleventh century version thereof in Codex Sinaiticus (Gr 453) and to translate it into Afrikaans. The study demonstrates that the most likely context within which this Greek manuscript of the Infancy Gospel of Thomas was communicated most significantly was Ebionite early Christianity. By identifying and examining quotations from and allusions to the Infancy Gospel of Thomas in works by the church fathers and by comparing the Greek expressions and phrases in the Greek manuscript in Codex Sinaiticus (Gr 453) with those of versions in other Greek manuscripts and early translations, a Gnostic tradition in the message can by ruled out, while Ebionite traditions can be confirmed. The child Jesus is depicted as interacting positively with his biological family which signifies salvation for other Israelites. Such salvation manifests in the identification and recognition of the child’s divinity by the Israelite teachers. The study argues that the Greek version of the Infancy Gospel of Thomas in Codex Sinaiticus (Gr 453) represents the genre of a discursive-biographical gospel type and as a result, the narrative and argumentative structure of this infancy gospel is of great importance. So too is the phenomenon that the narrative argument of the Infancy Gospel of Thomas is cast in the form of the ancient god-child myth. In this myth the child acts as if he were an adult. This adult-like behaviour of the child Jesus is not interpreted in an allegorically way. Rather, as myth, the message is interpreted in a tautegoric manner and explained in a social scientific way. / Thesis (DLitt (Greek))--University of Pretoria, 2006. / Ancient Languages / unrestricted

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The diploma thesis is focused on the issue of consolidated financial statements, namely the change of the consolidation method, the consolidation group Energie - stavební a báňská. The theoretical part defines the basic concepts and ways of calculations related to the topic. In the analytical part, the thesis deals first with the analysis of the current economic situation of the group, as well as with the calculation of the full consolidation method. This area will proceed freely to the design part, which includes a concrete proposal for streamlining the economic results of the consolidation group. Finally, the effects of the proposed change in the consolidation method will be fully evaluated using financial analysis.