Neural stem cells in development and cancer

Neural stem cells are defined by their unique ability to undergo self-renewal divisions. By dividing asymmetrically, a stem cell simultaneously produces a daughter cell that retains stem cell identity, whereas the other starts to differentiate and contributes to a continuous supply of neural cell types. Drosophila neuroblasts provide an excellent model system to study asymmetric stem cell divisions. The first part of this thesis will concentrate on the important adaptor protein Miranda which ensures the asymmetric segregation of cell fate determinants to the differentiating ganglion mother cell during neuroblast mitosis. The dynamic apical-then-basal localization pattern and the requirement for both Myosin II and Myosin VI suggested that Miranda is actively transported to the basal pole as a myosin cargo. However, immunofluorescence studies combined with time-lapse confocal microscopy and FRAP analyses revealed that Miranda reaches the basal cortex by passive diffusion throughout the cell rather than by long range myosin-directed transport. Instead, myosins play an indirect role in asymmetric Miranda localization. The formation of active Myosin II filaments in early prophase results in the exclusion of Miranda from the apical cortex. In the cytoplasm, Miranda diffuses three-dimensionally through the cell and becomes restricted to the basal half of the metaphase neuroblast by Myosin VI to facilitate its interaction with a putative basal cortical anchor. There is growing evidence that deregulation of the self-renewing process of stem cells may be an early event in tumorigenesis and that many cancers contain a small population of so called cancer stem cells which are responsible for maintenance and growth of tumors. The second part of the thesis will report on the isolation of cells with stem-like features from a murine mouse model of oligodendroglioma with activated EGFR signaling and loss of the tumor suppressor p53 in the postnatal stem cell lineage. Although oligodendroglioma-derived progenitor cells share many similarities with normal neural stem cells, they have increased self-renewing and proliferation capacities and in addition, undergo aberrant differentiation. They are multipotential, however, when induced to differentiate they preferentially generate cells of the oligodendrocytic lineage recapitulating the properties of the tumor they originate from. Brain cancer derived stem-like cells generate new tumors following intracranial injections that faithfully reproduce the phenotype of the parental tumor qualifying them as cancer stem cells. Interestingly, neural stem cells isolated from tumor prone mice long before oligodendroglioma occurrence show similar, but less severe alterations in their self-renewing and differentiation capacities. Importantly, they never form orthotopic tumors and thus were referred to as premalignant stem cells. The overproduction of oligodendrocytic cells is caused by a defect in asymmetric cell division that is very likely accompanied with genetic instabilities and epigenetic alterations. This results strengthen the hypothesis that early defects in neural stem cells, together with additional genetic alterations lead to the progression to a more malignant stem cell type which is responsible for tumor growth and maintenance

Experimental analysis of cell function using cytoplasmic streaming

This laboratory exercise investigates the phenomenon of cytoplasmic streaming in the fresh water alga Nitella. Students use the fungal toxin cytochalasin D, an inhibitor of actin polymerization, to investigate the mechanism of streaming. Students use simple statistical methods to analyze their data. Typical student data are provided

Contemporary mass balance on a cold Eastern Alpine ice cap as a potential link to the Holocene climate

Alpine cold ice caps are sensitive indicators of local climate. The adequate interpretation of this information in an ice core requires detailed in situ glaciological and meteorological records, of which there are few. The Weißseespitze summit ice cap (3499 m) presents an ideal case to compare past and present climate and mass balance, with limited ice flow, but close to 6000 years locked into about 10 m of ice. First-ever meteorological observations at the ice dome have revealed that over 3 years of observation most of the accumulation took place between October and December and from April to June. In the colder winter months, between January and March, wind erosion prevents accumulation. Melt occurred between June and September, ice was only affected during short periods, mainly in August, which caused ice losses of up to 0.6 m (i.e. ~ 5% of the total ice thickness). Historical data points at a loss of of 34.9 ± 10.0 m between 1893 and 2018 and almost balanced conditions between 1893 and 1914. The local evidence of ice loss lays the basis for the interpretation of past gaps in the ice core records as past warm/melt events

New glacier evidence for ice-free summits during the life of the Tyrolean Iceman

Detailed knowledge of Holocene climate and glaciers dynamics is essential for sustainable development in warming mountain regions. Yet information about Holocene glacier coverage in the Alps before the Little Ice Age stems mostly from studying advances of glacier tongues at lower elevations. Here we present a new approach to reconstructing past glacier low stands and ice-free conditions by assessing and dating the oldest ice preserved at high elevations. A previously unexplored ice dome at Weißseespitze summit (3500 m), near where the “Tyrolean Iceman” was found, offers almost ideal conditions for preserving the original ice formed at the site. The glaciological settings and state-of-the-art micro-radiocarbon age constraints indicate that the summit has been glaciated for about 5900 years. In combination with known maximum ages of other high Alpine glaciers, we present evidence for an elevation gradient of neoglaciation onset. It reveals that in the Alps only the highest elevation sites remained ice-covered throughout the Holocene. Just before the life of the Iceman, high Alpine summits were emerging from nearly ice-free conditions, during the start of a Mid-Holocene neoglaciation. We demonstrate that, under specific circumstances, the old ice at the base of high Alpine glaciers is a sensitive archive of glacier change. However, under current melt rates the archive at Weißseespitze and at similar locations will be lost within the next two decades

A comparison of soil amendment with either anaerobically digested or fresh cattle manure and its impact on genetic diversity, microbial activity and physiological community profile

Póster presentado en el congreso I Global Soil Biodiversity Conference, celebrado en Dijon, Francia, del 2 al 5 de diciembre de 2014In recent years, small-and mid-scale biogas plants have thrived in Europe and led to a change in land-use. Manures that used to be applied to agricultural soils are now used for energy generation in biogas reactors and instead digestateis applied to agricultural soils. Here we present the results of a study simulating soil amendment with either anaerobically digested or fresh cattle manure and its effect on the microbial community.Peer Reviewe

Multi-sensor monitoring and data integration reveal cyclical destabilization of the Äußeres Hochebenkar rock glacier

This study investigates rock glacier destabilization based on the results of a unique in situ and remote-sensing-based monitoring network focused on the kinematics of the rock glacier in Äußeres Hochebenkar (Austrian Alps). We consolidate, homogenize, and extend existing time series to generate a comprehensive dataset consisting of 14 digital surface models covering a 68-year time period, as well as in situ measurements of block displacement since the early 1950s. The digital surface models are derived from historical aerial imagery and, more recently, airborne and uncrewed-aerial-vehicle-based laser scanning (ALS and ULS, respectively). High-resolution 3D ALS and ULS point clouds are available at annual temporal resolution from 2017 to 2021. Additional terrestrial laser scanning data collected in bi-weekly intervals during the summer of 2019 are available from the rock glacier front. Using image correlation techniques, we derive velocity vectors from the digital surface models, thereby adding rock-glacier-wide spatial context to the point-scale block displacement measurements. Based on velocities, surface elevation changes, analyses of morphological features, and computations of the bulk creep factor and strain rates, we assess the combined datasets in terms of rock glacier destabilization. To additionally investigate potential rotational components of the movement of the destabilized section of the rock glacier, we integrate in situ data of block displacement with ULS point clouds and compute changes in the rotation angles of single blocks during recent years. The time series shows two cycles of destabilization in the lower section of the rock glacier. The first lasted from the early 1950s until the mid-1970s. The second began around 2017 after approximately 2 decades of more gradual acceleration and is currently ongoing. Both destabilization periods are characterized by high velocities and the development of morphological destabilization features on the rock glacier surface. Acceleration in the most recent years has been very pronounced, with velocities reaching 20–30 m a−1 in 2020–2021. These values are unprecedented in the time series and suggest highly destabilized conditions in the lower section of the rock glacier, which shows signs of translational and rotational landslide-like movement. Due to the length and granularity of the time series, the cyclic destabilization process at the Äußeres Hochebenkar rock glacier is well resolved in the dataset. Our study highlights the importance of interdisciplinary, long-term, and continuous high-resolution 3D monitoring to improve process understanding and model development related to rock glacier rheology and destabilization

Stigma of Mental Illness in Germans and Turkish Immigrants in Germany: The Effect of Causal Beliefs

Background: Stigma poses an additional burden for people suffering from mental illness, one that often impairs their social participation and can prevent them from seeking adequate help. It is therefore crucial to understand how stigma develops in order to counteract it by setting up effective evidence-based anti-stigma interventions. The present study examines the effect of causal beliefs on stigmatizing behavioral intentions, namely people's desire to distance themselves from persons with mental illness. In addition, we draw cross-cultural comparisons between native Germans and Turkish immigrants to investigate the influence of culture on stigma and causal beliefs and to broaden knowledge on the biggest immigrant group in Germany and on immigrants in Western countries in general.Methods:n = 302 native Germans and n = 173 Turkish immigrants were presented either a depression or a schizophrenia vignette. Then, causal beliefs, emotional reaction and desire for social distance were assessed with questionnaires. Path analyses were carried out to investigate the influence of causal beliefs on the desire for social distance and their mediation by emotional reactions for Germans and Turkish immigrants, respectively.Results: We found an influence of causal beliefs on the desire for social distance. Emotional reactions partly mediated this relationship. Causal attribution patterns as well as the relationship between causal attributions and stigma varied across both subsamples and mental illnesses. In the German subsample, the ascription of unfavorable personal traits resulted in more stigma. In the Turkish immigrant subsample, supernatural causal beliefs increased stigma while attribution to current stress reduced stigma.Conclusion: Our study has implications for future anti-stigma interventions that intend to reduce stigmatization of mentally ill people. Targeting the ascription of unfavorable personal traits and supernatural causal attributions as well as promoting current stress as the cause for mental illness appears to be of particular importance. Also, the mediating influence of emotional responses to causal beliefs needs to be addressed. Furthermore, differential interventions across cultural groups and specific mental illnesses may be appropriate