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Alternative pre-mRNA splicing greatly contributes to the mammalian proteomic diversity. The novel splice variants often emerge through splicing regulation at/nearby the splice sites (SS). A large group of 3′SS in human genes contain REPA (regulatory elements between the Py and 3′AG) G tracts that mostly appear in mammals as splicing silencers. However, the underlying molecular mechanisms and functional consequences remain unknown. We have identified a novel class of REPA G tracts (G)5-8 in a group of human genes including PRMT5 (protein arginine methyl transferase 5) that are significantly enriched in functional clusters of cell growth and proliferation. The PRMT5 G tracts emerged evolutionarily in mammals and repress splicing through recruitment of mainly hnRNP H that interferes with early spliceosome assembly. The splicing repression creates a shorter PRMT5 isoform (PRMT5S) that inhibits cell cycle progression contrary to the role of the full length protein (PRMT5L). Moreover, the expression of a group of genes involved in cell cycle arrest at interphase is preferentially regulated by PRMT5S. We further showed that PRMT5S is differentially expressed among cell and tissue types suggesting tissue-specific regulation. It exhibits distinct subcellular localization pattern from that of PRMT5L and opposite effects on cell cycle-specific structural dynamics of the Golgi apparatus. Moreover, these splice variants are differentially expressed during cell differentiation and PRMT5S promotes the differentiation of dendritic cells whereas PRMT5L shows the opposite effect. The expression of a large number of genes including those involved in crucial cellular processes such as differentiation and apoptosis is regulated by these splice variants of PRMT5. This study provides a direct link between the evolutionary emergence of a novel splicing regulatory G tract element and the generation of a functionally distinct protein isoform. The molecular mechanism underlying the splicing regulation by this G tract is likely common to many mammalian genes and the generation of their protein diversity. / October 2015

In addressing the client's needs for both complementary and alternative medicine (CAM) healing methods and psychotherapy (White, 2000; Saks, 2001), the psychotherapist's role is challenged. Research is needed in this area. From an applied phenomenological perspective, this research explores the problem of integration by interviewing psychotherapists who integrates their accredited psychotherapy and CAM qualifications into one practice. This research aims to ascertain what conscious experiences led these psychotherapists to integrate their two qualifications. Semi-structured interviews were conducted with such psychotherapists and the text was then thematically coded. Themes emerged from this thematic coding that describes the essences of these experiences. Such themes form the results of this dissertation. One of the main results indicated that there was a change in philosophy of life for most of the psychotherapists during their integration processes. Further the process of integration was natural and self-perpetuating and self-reinforcing for these psychotherapists. / Mr. R. L. van Niekerk

The aim of this project was to research alternative conceptions that grades 11 and 12 high school physical science learners have about projectile motion. Their performance is compared with first year university physics students. A questionnaire was designed for grade 11 and 12 learners. The understanding of university students was assessed through ex post facto scrutiny of responses to a projectile question set in their mid-year examination. The results of this study were analyzed through the responses of the learners and university students. The study revealed that the grade 11 learners performed better than their grade 12 counterparts, though the same questionnaire was used for both groups. Such differences may be associated with the fact that projectile motion is taught during the grade 11 year of study. Grade 11 learners may therefore have a better memory recall of the formal teaching of the topic and associated concepts. By contrast, grade 12 learners might have resorted to a “re-understanding” of the various concepts as they have been acquired in their own world: these are what the literature refers to as, inter alia, alternative conceptions or naïve ideas. The performance of university students was also better than that of the grades 11 and 12 learners. This may be due to a maturity factor, as well as the way in which projectile motion was dealt with in their lectures. Arising out of our analysis, we shall make a number of recommendations as to how the topic might be better taught at the secondary level. Secondary educators need to be better informed about alternative conceptions research, and preventative and remedial activities that could be adopted.

<p> Since the turn of the century, wind turbines have been rapidly growing in size and are projected to continue growing as the technology develops. These increases in size have led to increased failure rates of the glass fiber composite turbine blades. Because of this, it is of utmost importance to understand failure mechanisms in glass fiber composites and investigate new approaches to predicting failures. This has led to advancements in structural health monitoring of large composites structures by applying sophisticated sensing technologies, in attempts to evaluate material damage states and predict structural failures before they occur. This research has taken a novel approach to apply multiple ultrasonic monitoring techniques, in the form of acoustic emission and guided ultrasonic waves, simultaneously to the mechanical testing of glass fiber reinforced composite laminates. Testing of the composite laminates was conducted in the form of increasing load-unload-reload static tension tests and tension-tension fatigue tests, to measure modulus degradation of the laminates while applying the monitoring techniques. Acoustic emission was used to detect damage events that occurred within laminates in real-time and guided ultrasonic waves were applied periodically to the laminates to observe changes in wave propagation and relate back to damage severity within the laminates. Furthermore, the acoustic emission and guided ultrasonic wave datasets were combined and used to train multivariate regression models to predict modulus degradation of the laminates tested, with no prior knowledge of the laminates&rsquo; loading histories. Overall, the predictive models were able to make good predictions and showed the potential for combining multiple monitoring techniques into singular systems and statistical predictive models. This research has shown that the combination of the two measurement techniques can be implemented for more accurate and reliable monitoring of large composite structures than the techniques used individually, with minimal additional hardware. Ultimately, this research has paved the way for a new form of smart structural health monitoring, with superior predictive capabilities, which will benefit the renewable energy through reducing maintenance and repair costs and mitigating the risk of wind turbine blade failures.</p><p>

Alternative splicing is a common post-transcriptional process in eukaryote organisms by which a single gene can produce more than one distinct transcript. First discovered in the late 1970s, alternative splicing has been the focus of intense attention after the release of the human genome draft revealed a lower than expected gene number. Almost all human protein coding genes are now known to be alternatively spliced. However, how alternative splicing in humans and other well studied model organisms compares to other less characterised taxa such as protists and fungi or what is the functional role of alternative splicing remains poorly understood. Here I analyse alternative splicing in dozens of species using millions of partial transcript sequences ESTs. By applying a transcript normalisation method I showed that alternative splicing in protists and fungi is higher than previously reported and highly variable. I further observed that in representatives of both taxa, associations with translation are overrepresented among alternatively spliced genes. However, no evidence for a relationship between alternative splicing and complex phenotypes was found. Taking human lice as a model I explored the role of alternative splicing in the evolution of phenotypic variants. I found that, despite the fact that the transcriptome profiles of head and body lice are nearly identical, there are markedly differences in alternative splicing patterns. Development related functional associations were found to be enriched among genes with body lice specific alternative splicing events but not in head lice consistent with a scenario of differential patterns of alternative splicing contributing to the phenotypic innovations as human lice adapted to life in human clothing. I further explore the functional relevance of alternative splicing and its possible role in driving genomic innovations even preceding events of gene duplication. Together the work presented show that alternative splicing is widespread among previously understudied fungi and protist species and provide insights on its role in species adaptation to novel environments in using human lice as a model.

Hintergrund: Dank der modernen Medizin werden Krebserkrankungen immer häufiger und früher entdeckt. Immer mehr onkologische Patienten leben über einen langen Zeitraum mit ihrer Krebserkrankung, sodass Krebs mehr und mehr zur chronischen Erkrankung wird. Von diesen Patienten nimmt ein sehr hoher Anteil Alternativmedizin in Anspruch, oft Wissen der behandelnden Ärzte. Dabei sind sich viele Patienten der Tatsache nicht bewusst, dass zahlreiche vermeintlich natürliche alternative Heilmittel durchaus relevante Neben- und Wechselwirkungen haben können. Ziel der vorliegenden Arbeit war es, aktuelle Prävalenzwerte für die Inanspruchnahme von Alternativmedizin durch Krebspatienten zu erfassen und Patientenmerkmale zu finden, die in Zusammenhang mit der Nutzung alternativmedizinischer Methoden stehen. Methoden: Es wurden Patientendaten verwendet, die im Rahmen der multizentrischen, von der Deutschen Krebshilfe geförderten Studie „Prävalenz psychosozialer Belastungen, psychischer Störungen und ihr Behandlungsbedarf bei Tumorpatienten“ im Studienzentrum Würzburg erhoben wurden. Neben Angaben zur Nutzung von Alternativmedizin wurden mit Hilfe eines vom Patienten auszufüllenden Fragebogenheftes verschiedene soziodemographische und psychosoziale Variablen erfasst und durch medizinische Daten aus Krankenakten ergänzt. Mögliche Prädiktoren wurden mittels stufenweiser logistischer Regression ermittelt. Ergebnisse: Von den 770 Würzburger Studienteilnehmern konnten 699 im Alter zwischen 21 und 75 Jahren für die vorliegende Arbeit zur Analyse herangezogen werden. Insgesamt nutzte etwa jeder dritte Patient (33,6%) Alternativmedizin im Zusammen-hang mit der Krebserkrankung, was sich gut mit Daten aus der aktuellen Forschung deckt. 71,5% der Nutzer waren weiblich. Am häufigsten wurden Mittel aus den Kategorien „Vitamine, Mineralien, Spurenelemente“ (24% aller Patienten), „Homöopathie“ (11,6%) und „Misteltherapie“ (6,4%) angewandt. Als Bezugsquelle der alternativmedizinischen Mittel diente in der Mehrzahl der Fälle (62,5%) ein Arzt. Alle alternativmedizinischen Angebote wurden von den Anwendern hoch in ihrer Nützlichkeit bewertet. Darüber hinaus wurden soziodemographische, medizinische und psychosoziale Variablen auf einen Zusammenhang mit der Inanspruchnahme von Alternativmedizin untersucht. Entsprechend dem aktuellen Forschungsstand erwiesen sich dabei weibliches Geschlecht und höherer Bildungsstand als unabhängige Prädiktoren für die Nutzung von Alternativmedizin. Ein Zusammenhang mit dem Alter konnte hingegen nicht bestätigt werden. Im Hinblick auf krankheits- und therapieassoziierte Variablen waren der Abschluss einer Strahlentherapie und die Angabe von krebsbedingten Schmerzen von unabhängigem prädiktiven Wert, während für den Abschluss einer Chemotherapie und die Tumorlokalisation lediglich bivariate Zusammenhänge bestanden. Ein solcher Zusammenhang mit der Inanspruchnahme von Alternativmedizin konnte auch für die psychosozialen Variablen höhere psychische Belastung und geringere Lebensqualität nachgewiesen werden, die sich jedoch in der logistischen Regression nicht als unabhängige Prädiktoren bestätigten. Von den psychosozialen Variablen stellte der Wunsch nach aktiver Partizipation am Therapieprozess den einzigen unabhängigen Prädiktor für die Nutzung alternativmedizinischer Angebote dar. Schlussfolgerungen: Ein Drittel aller Krebspatienten wendet Alternativmedizin im Zusammenhang mit der Krebserkrankung an. Daher sollte die medizinische Wissenschaft es als wichtige Aufgabe sehen, fundierte Daten zu Nutzen und Sicherheit alternativmedizinischer Mittel bereitzustellen, um dieses weite Feld nicht unseriösen Anbietern zu überlassen. Auch der rein konventionell tätige Arzt sollte sich der großen Beliebtheit von Alternativ-medizin bei bestimmten Patientengruppen bewusst sein und seinen Patienten Auskunft zu alternativmedizinischen Angeboten geben können. / Background: Due to rapid advances in diagnosis and treatment of cancer the number of oncological patients is constantly growing. Among those patients the use of Complementary and Alternative Medicine (CAM) has become increasingly popular over the last decades. It is the aim of this study to investigate the prevalence of CAM-use and identify possible predictors. Methods: Data from a multicenter cross-sectional of cancer patients was used. Patients filled out a questionnaire with several different psychometric self-assessment tools. Additionally sociodemographic and medical data was collected. Bivariate analysis and stepwise logistic regression analysis was performed to identify predictors of CAM-use. Results: 699 entered the study, of which 235 (33,6%) used CAM in connection to cancer. The most popular categories of CAM were “vitamins, minerals, trace elements” (24% of all CAM users), “homeopathy” (11,6%) and “mistletoe” (6,4%). Female gender, higher education, completion of radiation therapy, pain in connection to cancer and the wish to actively participate in decision making in one’s cancer therapy could be identified as independent predictors for CAM use after logistic regression. On bivariate analysis CAM-use was associated with completion of chemotherapy, type of cancer, psychological distress and lower quality of life. There was no connection whatsoever between age and CAM-use. Conclusions: A third of all oncological patients uses CAM. Medical science should therefore try to supply well-founded data on usefulness and safety of CAM and not leave it to dubious CAM-providers. Every physician should be aware of the great popularity of CAM among certain patient groups. Even if he or she doesn’t endorse CAM-use, a physician should always be able to provide sound information regarding CAM.