Das Kind im Drama

Die vorliegende Diplomarbeit befasst sich mit den Funktionen von Kinderrollen im deutschen Drama des 18. und 19. Jahrhunderts. Vor der Analyse der ausgewählten Dramen wird ein kurzer Einblick in die Definition von Kindheit als abstrakten Begriff und die gelebte Realität von Kindern im 18. und 19. Jahrhundert gegeben. Darauf folgt ein Abriss über die Entwicklung des deutschen Dramas im 18. Jahrhundert. Den Hauptteil dieser Arbeit bildet die Untersuchung von in 30 Theaterstücken wirkenden Kinderrollen. Dabei werden gattungsübergreifend die Positionen der Kinderfiguren innerhalb der ausgewählten Stücke erläutert und ihre Auswirkungen auf die Handlung derselben geprüft. Des Weiteren wird der Anspruch, den die Rollen an die jungen Darstellen erheben untersucht

The spectrum of HBV/HCV coinfection: epidemiology, clinical characteristics, viralinteractions and management

Abstract Monoinfection with either hepatitis B (HBV) or C virus (HCV) represents one of the major causes of chronic liver disease globally. However, in endemic areas a substantial number of patients are infected with both viruses mainly as a result of the common routes of transmission. Numerous studies have demonstrated that dually infected patients carry a greater risk of advanced liver disease, cirrhosis and hepatocellular carcinoma compared with monoinfected patients. Th e choice of treatment is based on the virological profi le of each patient taking into account the dominant virus pattern. In predominant HCV, standard combination treatment with pegylated interferon and ribavirin has proven equally eff ective in HBV/HCV-coinfected patients as well as in HCV-monoinfected patients. Strikingly, approximately 60% of patients with inactive HBV infection before HCV treatment may present HBV reactivation while others experience hepatitis B surface antigen seroconversion aft er clearing HCV, demonstrating the complexity of the interaction between the two viruses during the follow up. Th e therapeutic strategies for the predominant HBV dually infected patients are more vague, although high genetic barrier nucleos(t)ide analogues play an indisputable role. Finally, the recently approved combination treatments for chronic hepatitis C containing direct-acting antivirals may defi nitely change the treatment protocols in the future although there is no experience with these drugs in dually infected patients until today

DARC shuttles inflammatory chemokines across the blood-brain barrier during autoimmune central nervous system inflammation

Trafficking of T cells into the CNS is a pathophysiological hallmark of multiple sclerosis. Using an invitro model of the blood-brain barrier, Minten etal. reveal that the atypical chemokine receptor DARC shuttles inflammatory chemokines across the barrier, where they contribute to immune cell trafficking into the brai

Myeloid Zinc Finger 1 (Mzf1) Differentially Modulates Murine Cardiogenesis by Interacting with an Nkx2.5 Cardiac Enhancer

Vertebrate heart development is strictly regulated by temporal and spatial expression of growth and transcription factors (TFs). We analyzed nine TFs, selected by in silico analysis of an Nkx2.5 enhancer, for their ability to transactivate the respective enhancer element that drives, specifically, expression of genes in cardiac progenitor cells (CPCs). Mzf1 showed significant activity in reporter assays and bound directly to the Nkx2.5 cardiac enhancer (Nkx2.5 CE) during murine ES cell differentiation. While Mzf1 is established as a hematopoietic TF, its ability to regulate cardiogenesis is completely unknown. Mzf1 expression was significantly enriched in CPCs from in vitro differentiated ES cells and in mouse embryonic hearts. To examine the effect of Mzf1 overexpression on CPC formation, we generated a double transgenic, inducible, tetOMzf1-Nkx2.5 CE eGFP ES line. During in vitro differentiation an early and continuous Mzf1 overexpression inhibited CPC formation and cardiac gene expression. A late Mzf1 overexpression, coincident with a second physiological peak of Mzf1 expression, resulted in enhanced cardiogenesis. These findings implicate a novel, temporal-specific role of Mzf1 in embryonic heart development. Thereby we add another piece of puzzle in understanding the complex mechanisms of vertebrate cardiac development and progenitor cell differentiation. Consequently, this knowledge will be of critical importance to guide efficient cardiac regenerative strategies and to gain further insights into the molecular basis of congenital heart malformations

A global Staphylococcus aureus proteome resource applied to the in vivo characterization of host-pathogen interactions.

Data-independent acquisition mass spectrometry promises higher performance in terms of quantification and reproducibility compared to data-dependent acquisition mass spectrometry methods. To enable high-accuracy quantification of Staphylococcus aureus proteins, we have developed a global ion library for data-independent acquisition approaches employing high-resolution time of flight or Orbitrap instruments for this human pathogen. We applied this ion library resource to investigate the time-resolved adaptation of S. aureus to the intracellular niche in human bronchial epithelial cells and in a murine pneumonia model. In epithelial cells, abundance changes for more than 400 S. aureus proteins were quantified, revealing, e.g., the precise temporal regulation of the SigB-dependent stress response and differential regulation of translation, fermentation, and amino acid biosynthesis. Using an in vivo murine pneumonia model, our data-independent acquisition quantification analysis revealed for the first time the in vivo proteome adaptation of S. aureus. From approximately 2.15 × 1

Incidence and classification of pediatric diffuse parenchymal lung diseases in Germany

<p>Abstract</p> <p>Background</p> <p>Diffuse parenchymal lung diseases (DPLD) in children represent a rare and heterogeneous group of chronic pulmonary disorders. Despite substantial advances in genetics and pathomechanisms, these often lethal diseases are still under-diagnosed. This is due to the fact that (i) the incidence is low, and (ii) clinical presentation, (iii) disease classification and (iv) specific treatment options are largely unknown.</p> <p>Methods</p> <p>Here we systematically assessed the incidence, the presentation, the diagnostic yield and treatments of pediatric DPLD in Germany, using the Surveillance Unit for Rare Paediatric Disorders (ESPED).</p> <p>Results</p> <p>The incidence of DPLD was 1.32 new cases per 1 million of children per year. The majority of these children were diagnosed within the first year of life. Overall survival was 87%. Using centralized data entry and stratification tools, the patients were categorized into an advanced classification system based on diagnostic algorithms, including clinical presentations, genetics and/or histology. Combining molecular and clinical information, this survey provides an etiological overview and specific diagnostic recommendations for children with DPLD.</p> <p>Conclusions</p> <p>Standardized surveys and systematic classifications are valuable tools for the clinical handling of children with DPLD and aim to improve the disease understanding and the prognosis of these rare detrimental lung diseases.</p

A proteomics sample metadata representation for multiomics integration and big data analysis

The amount of public proteomics data is rapidly increasing but there is no standardized format to describe the sample metadata and their relationship with the dataset files in a way that fully supports their understanding or reanalysis. Here we propose to develop the transcriptomics data format MAGE-TAB into a standard representation for proteomics sample metadata. We implement MAGE-TAB-Proteomics in a crowdsourcing project to manually curate over 200 public datasets. We also describe tools and libraries to validate and submit sample metadata-related information to the PRIDE repository. We expect that these developments will improve the reproducibility and facilitate the reanalysis and integration of public proteomics datasets.publishedVersio

Resistance issues in treating chronic hepatitis B

HBV resistance is the main limitation of long-term therapy with oral HBV polymerase inhibitors, which represent the most common approach in the treatment of chronic hepatitis B. The complete suppression of HBV replication minimises the risk of resistance and therefore close monitoring with sensitive HBV DNA determinations at least every 6 months is required. Lamivudine monotherapy has the highest risk of selecting resistant mutations compared with other anti-HBV agents and is not currently considered as an optimal first-line treatment. Adefovir has a similar profile but less potency than the other nucleotide analog, tenofovir, whereas telbivudine selects for lamivudine resistance mutants and therefore its place is currently unclear. Entecavir and possibly tenofovir are the two most potent anti-HBV agents with the best resistance profile in nucleo(s)tide-naive patients, while tenofovir represents the optimal treatment for patients with lamivudine resistance. Combination of two agents without cross-resistance should be used in any patient with HBV resistance

Clinical characteristics, spontaneous clearance and treatment outcome of acute hepatitis C: A single tertiary center experience

Background and Aims: Acute hepatitis C is rarely diagnosed due to its predominantly asymptomatic course. However, early treatment results in viral eradication in a high number of patients thus, preventing chronicity. The aim of our study was to describe our experience with patients with acute hepatitis C virus (HCV) infection who presented and followed-up in our liver unit, pointing on treatment strategy, and outcome. Patients and Methods: Retrospective, descriptive study of 30 patients with acute HCV infection (26 males and 4 females) with a mean age of 32 years. Results: The source of infection was mainly injection drug use in 17/30 (56.7) and medical procedures 6/30 (20%). Twenty patients (66.6%) were symptomatic. HCV-ribonucleic acid (RNA) was detectable at presentation in 26 (86.7%) patients. The genotype distribution was: 13/26 (50%) genotype 1, 3/26 (11.5%) genotype 2, 8/26 (30.8%) genotype 3 and 2/26 (7.7%) genotype 4. Totally, 9 patients (30%) experienced spontaneous viral eradication. No significant differences could be documented between patients who spontaneously cleared the virus and those who had viral persistence. Thirteen patients (44%) were treated with peginterferon-based regimen. All patients (100%) achieved non-detectable HCV-RNA and had normal serum alanine aminotransferase levels at the end of the treatment. Eleven patients achieved sustained virologic response (SVR), one relapsed and one was lost to follow-up. The overall SVR rate was 84.6%. None of the patients required dose reduction or stopped the treatment due to side effects. Conclusion: In conclusion, early initiation of anti-viral treatment in patients with acute hepatitis C results in high-SVR rates (independently of genotype) and is well-tolerated