The Role of the Actin Regulator Cyclase-associated Protein 2 (CAP2) for Mammalian Skeletal Muscle Development.

Actin is a structural protein that is a major component of the eukaryotic cytoskeleton. It is not only important for morphology and stability of cells, but also for dynamic processes such as cell migration, adhesion, growth or contraction. In muscle cells, the highly structured complex of myosin and actin filaments is essential for the coordinated contraction of muscle fibers, which ultimately generates muscle strength. In order to achieve this function, actin filaments have to build up and rebuilt dynamically during muscle development. However, the molecular mechanisms involved are still largely unknown. The need to elucidate these mechanisms arises from the finding that a large number of human myopathies are associated with defects in the actin cytoskeleton. Previous studies identified the transcription factor SRF (serum response factor) as a major regulator of skeletal muscle development in humans and mice. In a feedback mechanism, SRF is activated in an actin-dependent manner and in turn controls the expression of actin and actin-regulatory proteins. One of the main activators of SRF is MRTF (myocardin related transcription factor), which can be sequestered by actin monomers, thus preventing translocation and subsequent activation of SRF in the nucleus. This cumulative dissertation presents two studies that aim to elucidate the underlying processes of myopathies during skeletal muscle development. In the first publication, "CAP2 deficiency delays myofibril actin cytoskeleton differentiation and disturbs skeletal muscle architecture and function", we identified a previously unknown function for the actin-regulatory protein CAP2 (cyclase-associated protein 2) during skeletal muscle development in mammals. We showed that CAP2 controls the remodeling of actin filaments in developing skeletal muscle and is therefore essential for the differentiation of muscle fibers. As a consequence of CAP2 loss, mouse mutants developed structural changes in skeletal muscles, characterized by a frequent occurrence of ring fibers, internalized nuclei and disturbed mitochondrial distribution, as well as deficits in motor functions and moderate muscle weakness. These changes reflect symptoms of human myopathies. In the second manuscript, "Cyclase-associated protein 2 (CAP2) controls MRTF-A localization and SRF activity in mouse embryonic fibroblasts", we reported that loss of CAP2 in mouse embryonic fibroblasts lead to disturbed SRF activity. Specifically, we found that CAP2 controls subcellular distribution of the SRF trans-activator MRTF in an actin-dependent mechanism. CAP2 inactivation was associated with reduced nuclear MRTF levels and impaired SRF-mediated gene expression. This suggests that CAP2-dependent actin dynamics may also control SRF activity during skeletal muscle development and that dysregulation of SRF may cause or at least contribute to the myopathy in CAP2 mutant mice

Monoid automata for displacement context-free languages

In 2007 Kambites presented an algebraic interpretation of Chomsky-Schutzenberger theorem for context-free languages. We give an interpretation of the corresponding theorem for the class of displacement context-free languages which are equivalent to well-nested multiple context-free languages. We also obtain a characterization of k-displacement context-free languages in terms of monoid automata and show how such automata can be simulated on two stacks. We introduce the simultaneous two-stack automata and compare different variants of its definition. All the definitions considered are shown to be equivalent basing on the geometric interpretation of memory operations of these automata.Comment: Revised version for ESSLLI Student Session 2013 selected paper

Digital Reading in Higher Education: A Comparison of Teacher Students with Other Student Groups

Digitale Lesefähigkeiten sind für Lehramtsstudierende in zweifacher Form bedeutsam: Sie werden im Rahmen der eigenen Ausbildung benötigt und stellen eine an Schülerinnen und Schüler zu vermittelnde Fähigkeit dar. Dass Lehramtsstudierende mit digitalen wissenschaftlichen Texten kompetent umgehen, gewann im Rahmen der digital organisierten ‹Corona-Semester› besondere Bedeutung. Vor diesem Hintergrund untersucht der vorliegende Beitrag, wie Lehramtsstudierende den Umgang mit digitaler Lektüre in Lehrveranstaltungen wahrnahmen, wie sie ihre eigene Arbeit mit diesen Texten – auch in emotionaler und motivationaler Hinsicht sowie mit Blick auf den Austausch über das Gelesene – einschätzten und welche Hilfestellung sie von Seiten der Universitäten und Hochschulen erhielten. Mithilfe einer online durchgeführten Umfrage wurden die Einschätzungen Lehramtsstudierender mit denen von Studierenden aus anderen Studiengängen (N = 4701) verglichen. Die Untersuchung hat gezeigt: Lehramtsstudierende berichteten nicht nur von grösseren Schwierigkeiten im effizienten Umgang mit Texten am Bildschirm, sondern schätzten auch ihre Konzentration und Stimmung beim Lesen negativer ein als Studierende anderer Fächer. Insgesamt stellten sich Lehramtsstudierende weniger selbstständig und intrinsisch motiviert dar als andere Studierende. Handlungsbedarf zeichnet sich insbesondere in dem Sinne ab, dass Studierenden verstärkt für das digitale Lesen adäquate Textformate bereitzustellen sind. Auch sollten Hochschulen Studierende insgesamt stärker im Umgang mit digitalen Texten unterstützen.  Digital reading skills are essential for teacher students in two ways: They are needed in the context of the students’ own education, and they represent a skill to be taught to pupils. The need for teacher students to be competent in dealing with digital scientific texts becomes particularly important in the context of the digitally organized ‹corona semesters›. In view of the above, this article examines how teacher students perceived the handling of digital texts in their courses, how they assessed their own work with these texts – also in emotional and motivational terms as well as with regard to the communication about what they read – and what support they received from their universities and colleges. With an online survey, the assessments of teacher students were compared with those of students from other fields of study (N = 4701). The study showed that teacher students seem to have greater difficulties in dealing efficiently with texts on the screen and rate their concentration and mood while reading more negatively than other students. Overall, teacher students were less self-reliant and intrinsically motivated than others. There is a need for action, particularly in the sense that students should be supplied with more adequate text formats for digital reading. Further, universities should provide students with more support in using digital texts

Serotonin controlling feeding and satiety

Serotonin has been implicated in the control of satiety for almost four decades. Historically, the insight that the appetite suppressant effect of fenfluramine is linked to serotonin has stimulated interest in and research into the role of this neurotransmitter in satiety. Various rodent models, including transgenic models, have been developed to identify the involved 5-HT receptor subtypes. This approach also required the availability of receptor ligands of different selectivity, and behavioural techniques had to be developed simultaneously which allow differentiating between unspecific pharmacological effects of these ligands and ‘true’ satiation and satiety. Currently, 5-HT1B, 5-HT2C and 5-HT6 receptors have been identified to mediate serotonergic satiety in different ways. The recently approved anti-obesity drug lorcaserin is a 5-HT2C receptor agonist. In brain, both hypothalamic (arcuate nucleus, paraventricular nucleus) and extrahypothalamic sites (parabrachial nucleus, nucleus of the solitary tract) have been identified to mediate the serotonergic control of satiety. Serotonin interacts within the hypothalamus with endogenous orexigenic (Neuropeptide Y/Agouti related protein) and anorectic (α-melanocyte stimulating hormone) peptides. In the nucleus of the solitary tract serotonin integrates peripheral satiety signals. Here, the 5-HT3, but possibly also the 5-HT2C receptor play a role. It has been found that 5-HT acts in concert with such peripheral signals as cholecystokinin and leptin. Despite the recent advances of our knowledge, many of the complex interactions between 5-HT and other satiety factors are not fully understood yet. Further progress in research will also advance the development of new serotonergic anti-obesity drugs

Combination of Constraint Systems

Summary in GermanSIGLEAvailable from TIB Hannover: RR 7403(98,118) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman