Brca1 is expressed in human microglia and is dysregulated in human and animal model of ALS

Background: There is growing evidence that microglia are key players in the pathological process of amyotrophic lateral sclerosis (ALS). It is suggested that microglia have a dual role in motoneurone degeneration through the release of both neuroprotective and neurotoxic factors. Results: To identify candidate genes that may be involved in ALS pathology we have analysed at early symptomatic age (P90), the molecular signature of microglia from the lumbar region of the spinal cord of hSOD1(G93A) mice, the most widely used animal model of ALS. We first identified unique hSOD1(G93A) microglia transcriptomic profile that, in addition to more classical processes such as chemotaxis and immune response, pointed toward the potential involvement of the tumour suppressor gene breast cancer susceptibility gene 1 (Brca1). Secondly, comparison with our previous data on hSOD1(G93A) motoneurone gene profile substantiated the putative contribution of Brca1 in ALS. Finally, we established that Brca1 protein is specifically expressed in human spinal microglia and is up-regulated in ALS patients. Conclusions: Overall, our data provide new insights into the pathogenic concept of a non-cell-autonomous disease and the involvement of microglia in ALS. Importantly, the identification of Brca1 as a novel microglial marker and as possible contributor in both human and animal model of ALS may represent a valid therapeutic target. Moreover, our data points toward novel research strategies such as investigating the role of oncogenic proteins in neurodegenerative diseases.

High-density comparative BAC mapping in the black muntjac (Muntiacus crinifrons): Molecular cytogenetic dissection of the origin of MCR 1p+4 in the X1X2Y1Y2Y3 sex chromosome system

The black muntjac (Muntiacus crinifrons, 2n = 8 female/9 male) is a critically endangered mammalian species that is confined to a narrow region of southeastern China. Male black muntjacs have an astonishing X1X2Y1Y2Y3 sex chromosome system, unparalleled i

Drama Grammatik: Dramapädagogische Ansätze für den Grammatikunterricht Deutsch als Fremdsprache

This dissertation introduces and evaluates dramagrammar, a new concept for the teaching and learning of foreign language grammar. Grammar, traditionally taught in a predominantly cognitive, abstract mode, often fails to capture the minds of foreign language learners, who are then unable to integrate this grammatical knowledge into their use of the foreign language in a meaningful way. The consequences of this approach are manifested at university level in German departments in England and Ireland, where the outcomes are unconvincing at best, abysmal at worst. Language teaching research suggests that interaction plays an important role in foreign language acquisition. Recent studies also stress the significance of grammatical knowledge in the learning process. Dramagrammar combines both interactive negotiation of meaning and explicit grammar instruction in a holistic approach, taking up the concept of drama in foreign language education and applying it to the teaching and learning of grammar. Techniques from dramatic art forms allow grammar to be experienced not only cognitively but also in social, emotional, and bodily-kinaesthetic ways. Dramagrammar lessons confront the learner with fictitious situations in which grammar is experienced 'hands-on'. Learners have to use grammatical structures in a variety of contexts, reflect upon their use, and then enlarge and enrich the dramatic situations with their newly acquired or more finely nuanced knowledge. The initial hypothesis of this dissertation is that the drammagrammar approach is beneficial to the acquisition of foreign language grammar. This hypothesis is corroborated by research findings from language teaching pedagogy and drama in education. It is further confirmed by empirical data gained from specifically designed dramagrammar modules that have been put into practice in German departments at the University of Leicester (England), the University Colleges Cork and Dublin (Ireland), the University of Bologna (Italy), as well as the Goethe-Institute Bratislava (Slovenia). The data suggests that drammagrammar has positive effects on both understanding of and attitudes towards grammar.