93 research outputs found
Der Mordfall Marinus Schöberl. Arbeitspapier 1/2004
Im Zentrum der Studie steht die Ermordung von Marinus Schöberl in Potzlow / Uckermark, die im November 2002, vier Monate nach der Tat, bekannt wurde. Die Tat wurde von maßgeblichen lokalen Persönlichkeiten, von der überregionalen Presse und von Brandenburger wie Berliner Antifa-Kreisen als rechtsextreme Tat wahrgenommen und verurteilt. Sie wurde häufig als exemplarischer Fall von rechtsextremer Gewalt oder zur Veranschaulichung anderer Gesichtspunkte angeführt. Ein genaueres Hinsehen zeigt indes, dass die schlimmsten Verbrechen aus trivialen, also alltagsnahen Umständen hervorgehen. Der Wunsch nach einer Symmetrie zwischen extremen Taten und ihren Ursachen verweist auf unsere eigene Fassungslosigkeit und eine Strategie, das Alltagsleben als „gute Normalität“ zu konstruieren, in der „das Böse“ und „die Extremen“ keinen Platz haben. Der Mord an Marinus Schöberl zeigt, dass Gewaltexzesse und Alltagsnormalität zusammengehören. Die Lebensgeschichte, die soziale und biographische Situation der Beteiligten lassen sich unter der Perspektive ihrer Zugehörigkeiten, Orientierungen, Wahrnehmungen und Verhaltensweisen betrachten. Welche sozialen Voraussetzungen und welche Dynamiken waren für das Tatgeschehen charakteristisch? Wie stellt sich der Fall dar, wenn wir ihn als die individuelle Kombination von generellen, also allgemein verbreiteten und bekannten sozialen Mustern betrachten? Wir fragen in diesem Sinne nach einer „individuellen Allgemeinheit des Falls“, nach den „sozialen Bestandteilen“ des Tatgeschehens. In der vorliegenden Studie gehen wir davon aus, dass die Wahrscheinlichkeit für Gewalttätigkeiten mit bestimmten sozialökonomischen Faktoren zusammenhängt. Im ersten Teil zeigen wir, inwiefern diese Faktoren in der Uckermark gegeben sind. Zum zweiten geht es uns darum, die innere Strukturlogik des konkreten Gewalthandelns zu rekonstruieren, das schließlich in den Mord an Marinus Schöberl mündete. In einem dritten Teil werden einige Überlegungen vorgestellt, wie einzelne der identifizierten Problemfelder praktisch angegangen werden können
Zelluläre Modulatoren der Ektodomänenspaltung von APP
The processing of APP occurs in two alternative ways: upon release of the ectodomain by α-secretase, the neuroprotective APPsα-fragment is produced. But if APP is cleaved by the β-secretase the Aβ-peptide can be produced. To be able to influence the production of Aβ-peptides, it is essential to understand how it is decided if cleavage occurs by α- or β-secretase.
At present little is known about the control of the alternate processing. Until now, the molecular mechanisms and especially the responsible cellular modulators are not understood in detail or not yet identified. To get a better understanding of cellular regulatory processes and to identify novel cellular modulators of APP ectodomain shedding, the present work chose two approaches: on the one hand cellular mechanisms of TMEM59-mediated inhibition
ectodomain shedding of APP were investigated. On the other hand a genome-wide RNAi screening in Drosophila cells was performed in order to identify novel cellular modulators of
APP ectodomain shedding in human cells.
TMEM59 was identified as a novel modulator of APP ectodomain shedding in a cDNA expression screening in the lab (Neumann et al., 2006; Schobel et al., 2008; Schobel et al., 2006). TMEM59 is a Golgi protein that inhibits on the one hand processing and maturation of APP and on the other hand Golgi glycosylation reactions (Fischer, 2008). My own work could verify these effects of TMEM59 and its homolog TMEM59L on processing and maturation of APP. In particular, it was shown that these effects are not only true for
transiently expressed APP but also for endogenous levels of APP. In detailed immunofluorescence studies it was shown that TMEM59 colocalizes with different markers
of the Golgi subcompartments and that therefore TMEM59 is present throughout the whole Golgi apparatus. This finding points to a more general modulation of Golgi glycosylation
reactions by TMEM59. To test if TMEM59-dependet modulation of Golgi glycosylation reactions also affects APP secretases ADAM10 and BACE1, which are also glycosylated
proteins, the activities of these proteases were investigated. It was shown that proteolytic activities were not changed, ruling out that impairment of secretase activities by TMEM59 could cause the observed inhibition of APP processing. But interestingly, studies of intracellular APP transport could show that TMEM59 caused retention of APP in the Golgi apparatus and blockage of transport towards the cell surface and into endosomal compartments. Since APP is cleaved by α-secretase at the plasma membrane and by β-secretase in endosomes it is likely that a TMEM59-dependent APP transport block causes the observed inhibition of APP ectodomain shedding. For further validation of TMEM59 and its homolog TMEM59L as modulators of APP ectodomain shedding, a double knockdown study
was performed. In this approach effects on APP ectodomain shedding could also be established, affirming TMEM59 and its homolog TMEM59L as modulators of APP ectodomain shedding with novel cellular mechanisms.
In order to identify novel cellular modulators of APP ectodomain shedding a genome wide RNAi screening in Drosophila cells was performed and candidate genes were investigated in human cells in present work. Initially a suitable Drosophila reporter cell line expressing a reporter construct of APP ectodomain shedding (HRP-APP) was established. Other constructs were used to monitor general secretion (GLuc) and transfection efficiency (FLuc). Using
Kuzbanian, the α-secretase in Drosophila (Sapir et al., 2005), as a positive control guaranteed that transfection of cDNAs into Drosophila cells did not interfere with uptake of dsRNAs or efficiency of RNAi and that the reporter construct HRP-APP is normally produced and
processed in reporter cells. After successful establishment of the reporter cell line the genome wide RNAi was performed in two steps: a primary screening revealed approx. 300 candidate genes out of which 43 could be confirmed in a secondary screening to be modulators of APP
ectodomain shedding. The RNAi screening was verified by the several-fold appearance of Kuzbanian among the top modulators. For further investigation of the top candidates human ortholog genes were identified. The 30 human candidate genes were investigated in RNAi
studies in human SH-SY5Y cells. In these cells, APP is processed by α-secretase ADAM10 as well as by β-secretase BACE1. Therefore effects on both shedding products (APPsα and APPsβ) were investigated upon depletion of candidate genes using siRNAs. It is known that siRNAs produce a high rate of off target effects, to this end a robust validation strategy was developed. Candidate genes were first depleted with two different siRNA pools and their effects on APP shedding were compared. Afterwards the remaining 12 candidate genes were depleted using single siRNA sequences and the effects were compared to those of the siRNA
pool. Only when a reproduction of effects was obtained in a next step correlation of knockdown and phenotype were assessed. Using these steps of validation 5 candidate genes
could be verified as modulators of APP shedding in human cells: next to genes coding for a histone protein (HIST1H4C), a ribosomal protein (RPL36AL), a protein of the minor spliceosom (ZMAT5), an unknown gene (METTL16) and the gene VPS24 („vacuolar protein sorting-associated protein 24“), coding for a protein of intracellular protein transport, were identified. VPS24 was chosen for further validation by a pathway analysis. VPS24 belongs to the ESCRT machinery („endosomal sorting complex required for transport“) and therefore participates in endosomal-lysosomal protein transport. In further RNAi studies other members of the ESCRT machinery were depleted in human cells and effects on APP shedding were compared to VPS24 depletion. For most of the ESCRT members a consistent reduction in APPsβ production could be observed. To engross these results VPS24 was depleted by using an alternative RNAi system. With this stable knockdown approach, the knockdown phenotype could be confirmed. This stepwise validation strategy for candidate genes of the initial Drosophila RNAi screening verified VPS24 as a modulator of APP ectodomain shedding in human cells
How to tell a data story
At Stadt.Geschichte.Basel, more than 70 historians research the history of Basel from the Celts to the present. The focus is on current and little-researched topics such as the industrial and commercial history of the 19th and 20th centuries or the history of migration. The city's history is not viewed in isolation, but is interwoven regionally and internationally at the economic, political and cultural levels. It is published in 10 printed volumes. In addition, selected historical aspects are presented in the form of data stories. To facilitate this process, the Stadt.Geschichte.Basel research data management team has developed a guide. It walks through the questions that led to the development, production and publication of the data story
Photorhabdus luminescens genes induced upon insect infection
This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens
Deriving Facilitators for Electronic Health Record Implementation: A Systematic Literature Review of Opportunities and Challenges
Electronic Health Records aim to remove information asymmetries between healthcare providers and contribute to improved healthcare quality and safety. Nevertheless, the successful and comprehensive implementation remains challenging and complex. Recently, increased interest of patients in their healthcare and enhanced technological opportunities led to new challenges and an emerging amount of research. To achieve an overarching overview of facilitators for EHR implementation, the perspectives of relevant stakeholders were considered. Therefore, we conducted a multidisciplinary systematic literature review involving five databases from public health, information systems, and interdisciplinary research. As a result, we first identified opportunities and challenges according to the stakeholder groups, environmental context, and implementation stages. Second, we derived five facilitators (individual stakeholder readiness, change management, accessibility and ownership, EHR structure, and external factors). Therefore, we lay a state-of-the-art foundation for EHR implementation for scientific studies and development activities in practice with our research
An investigation of the mediating role of personality and family functioning in the association between attachment styles and eating disorder status
Background: This study examined relationships between attachment style, eating disorders (EDs), personality variables and family functioning. Methods: In our study, 253 women (M = 25.72 years, SD = 8.73) were grouped into one of four categories either according to self-reported ED diagnosis or by exceeding cut-offs for a clinical diagnosis on the Eating Disorder Examination Questionnaire (EDE-Q) or Short Evaluation of Eating Disorders (SEED): anorexia nervosa (AN), bulimia nervosa (BN), other eating disorder (O-ED), no eating disorder (Non-ED). The ED group (AN, BN, O-ED) included 106 women (M = 24.74 years, SD = 7.71), and the Non-ED group 147 women (M = 26.42 years, SD = 9.37). Approximately half of the ED group had a comorbid disorder (59.4%), while the majority of the Non-ED group had no psychological disorder (89.1%). Results: Participants with an ED were significantly more often insecurely attached (Adult Attachment Scale; AAS), emotionally unstable, less extraverted (Big-Five-Test of Personality; B5T) and showed less positive family functioning (Experiences in Personal Social Systems Questionnaire; EXIS.pers). Results showed partial mediation for attachment and EDs through neuroticism, extraversion and family functioning. Discussion: The study found further evidence for elevated problems with attachment, personality, and family experiences in individuals with EDs, while suggesting mechanisms that may link these constructs. Implications for research and practice were discussed. Conclusion: This study supports findings that acknowledge the mediating role played by personality factors and family functioning in the relationship between attachment and EDs
Layering of surface snow and firn at Kohnen Station, Antarctica - noise or seasonal signal?
The density of firn is an important property for monitoring and modeling the ice sheet as well as to model the pore close-off and thus to interpret ice core-based greenhouse gas records. One feature, which is still in debate, is the potential existence of an annual cycle of firn density in low-accumulation regions. Several studies describe or assume seasonally successive density layers, horizontally evenly distributed, as seen in radar data. On the other hand, high-resolution density measurements on firn cores in Antarctica and Greenland showed no clear seasonal cycle in the top few meters. A major caveat of most existing snow-pit and firn-core based studies is that they represent one vertical profile from a laterally heterogeneous density field. To overcome this, we created an extensive dataset of horizontal and vertical density data at Kohnen Station, Dronning Maud Land on the East Antarctic Plateau. We drilled and analyzed three 90 m long firn cores as well as 160 one meter long vertical profiles from two elongated snow trenches to obtain a two dimensional view of the density variations. The analysis of the 45 m wide and 1 m deep density fields reveals a seasonal cycle in density. However, the seasonality is overprinted by strong stratigraphic noise, making it invisible when analyzing single firn cores. Our density dataset extends the view from the local ice-core perspective to a hundred meter scale and thus supports linking spatially integrating methods such as radar and seismic studies to ice and firn cores
In vitro interaction network of a synthetic gut bacterial community
A key challenge in microbiome research is to predict the functionality of microbial communities based on community membership and (meta)-genomic data. As central microbiota functions are determined by bacterial community networks, it is important to gain insight into the principles that govern bacteria-bacteria interactions. Here, we focused on the growth and metabolic interactions of the Oligo-Mouse-Microbiota (OMM12) synthetic bacterial community, which is increasingly used as a model system in gut microbiome research. Using a bottom-up approach, we uncovered the directionality of strain-strain interactions in mono- and pairwise co-culture experiments as well as in community batch culture. Metabolic network reconstruction in combination with metabolomics analysis of bacterial culture supernatants provided insights into the metabolic potential and activity of the individual community members. Thereby, we could show that the OMM12 interaction network is shaped by both exploitative and interference competition in vitro in nutrient-rich culture media and demonstrate how community structure can be shifted by changing the nutritional environment. In particular, Enterococcus faecalis KB1 was identified as an important driver of community composition by affecting the abundance of several other consortium members in vitro. As a result, this study gives fundamental insight into key drivers and mechanistic basis of the OMM12 interaction network in vitro, which serves as a knowledge base for future mechanistic in vivo studies
Study of exclusive one-pion and one-eta production using hadron and dielectron channels in pp reactions at kinetic beam energies of 1.25 GeV and 2.2 GeV with HADES
We present measurements of exclusive ensuremathπ+,0 and η production in pp reactions at 1.25GeV and 2.2GeV beam kinetic energy in hadron and dielectron channels. In the case of π+ and π0 , high-statistics invariant-mass and angular distributions are obtained within the HADES acceptance as well as acceptance-corrected distributions, which are compared to a resonance model. The sensitivity of the data to the yield and production angular distribution of Δ (1232) and higher-lying baryon resonances is shown, and an improved parameterization is proposed. The extracted cross-sections are of special interest in the case of pp → pp η , since controversial data exist at 2.0GeV; we find \ensuremathσ=0.142±0.022 mb. Using the dielectron channels, the π0 and η Dalitz decay signals are reconstructed with yields fully consistent with the hadronic channels. The electron invariant masses and acceptance-corrected helicity angle distributions are found in good agreement with model predictions
Common Motifs in the Response of Cereal Primary Metabolism to Fungal Pathogens are not Based on Similar Transcriptional Reprogramming
During compatible interactions with their host plants, biotrophic plant–pathogens subvert host metabolism to ensure the sustained provision of nutrient assimilates by the colonized host cells. To investigate, whether common motifs can be revealed in the response of primary carbon and nitrogen metabolism toward colonization with biotrophic fungi in cereal leaves, we have conducted a combined metabolome and transcriptome study of three quite divergent pathosystems, the barley powdery mildew fungus (Blumeria graminis f.sp. hordei), the corn smut fungus Ustilago maydis, and the maize anthracnose fungus Colletotrichum graminicola, the latter being a hemibiotroph that only exhibits an initial biotrophic phase during its establishment. Based on the analysis of 42 water-soluble metabolites, we were able to separate early biotrophic from late biotrophic interactions by hierarchical cluster analysis and principal component analysis, irrespective of the plant host. Interestingly, the corresponding transcriptome dataset could not discriminate between these stages of biotrophy, irrespective, of whether transcript data for genes of central metabolism or the entire transcriptome dataset was used. Strong differences in the transcriptional regulation of photosynthesis, glycolysis, the TCA cycle, lipid biosynthesis, and cell wall metabolism were observed between the pathosystems. However, increased contents of Gln, Asn, and glucose as well as diminished contents of PEP and 3-PGA were common to early post-penetration stages of all interactions. On the transcriptional level, genes of the TCA cycle, nucleotide energy metabolism and amino acid biosynthesis exhibited consistent trends among the compared biotrophic interactions, identifying the requirement for metabolic energy and the rearrangement of amino acid pools as common transcriptional motifs during early biotrophy. Both metabolome and transcript data were employed to generate models of leaf primary metabolism during early biotrophy for the three investigated interactions
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