Bericht : Forum B.2: Germanistik studieren – Perspektiven in Ausbildung und Beruf

Dieser Text ist der zusammenfassende Bericht zum Forum B.2 "Germanistik studieren – Perspektiven in Ausbildung und Beruf" auf dem Internationalen Colloquium "Perspektiven der Germanistik im 21. Jahrhundert", das vom 4. bis 6. April 2013 im Schloss Herrenhausen in Hannover stattfand

Functional Analysis of the Legionella pneumophila\textit{Legionella pneumophila} Nitric Oxide Regulatory Network and its Link to Quorum Sensing

Legionella pneumophila is a ubiquitous Gram-negative bacterium and the causative agent of Legionnaires’ disease and Pontiac fever. The facultative intracellular bacterium colonizes natural and man-made water systems. In the environment, Legionella resides in complex biofilms, that comprise several bacterial species and eukaryotic cells. Moreover, the pathogen can infect free-living amoebae such as Acanthamoeba castellanii and replicate intracellularly. Human infection occurs via inhalation of contaminated aerosols. In the lungs, the opportunistic pathogen infects alveolar macrophages and translocates more than 300 effector proteins into the host cell through an Icm/Dot type IV secretion system (Icm/Dot T4SS). This allows the pathogen to multiply within a unique compartment called the Legionella-containing vacuole (LCV). L. pneumophila employs the Legionella quorum sensing (Lqs) system to regulate various traits including the growth phase switch, virulence, and bacterial motility. The Lqs system is linked to the bacterial c-di-GMP metabolism through the pleiotropic transcription factor LvbR. The Lqs system comprises the autoinducer synthase LqsA, which produces the α-hydroxyketone LAI-1 (Legionella autoinducer-1, 3-hydroxypentadecan-4-one), the homologous sensor kinases LqsS and LqsT, and the response regulator LqsR. The interactions between L. pneumophila and its natural host cells in biofilms are poorly understood. In this study, we investigated the interactions of Legionella and the amoeba A. castellanii in mono-species L. pneumophila biofilms using confocal microscopy and flow cytometry. We found that the transcription factor LvbR, the response regulator LqsR, the bacterial flagellum (FlaA) and the Icm/Dot T4SS regulate the migration of A. castellanii through L. pneumophila biofilms. Furthermore, LvbR, LqsR and FlaA were found to govern the adherence and cluster formation of L. pneumophila on the surface of amoebae. The bacterial clusters were found to comprise motile (PflaA-positive) and virulent (PsidC-positive) bacteria. Macrophages and amoeba hosts of L. pneumophila synthesize nitric oxide (NO), a highly reactive gaseous molecule, which freely diffuses across membranes. NO has a bactericidal effect at high (micromolar) concentrations, however at low (nanomolar) concentrations, NO has been shown to act as a signalling molecule in many bacterial species. L. pneumophila possesses three NO sensors, Hnox1, Hnox2 and NosP. To investigate the role of the NO receptors in L. pneumophila signaling, marker-less L. pneumophila mutant strains lacking individual (Hnox1, Hnox2, or NosP) or all three NO receptors (triple knockout, TKO) were generated. We found that in the ΔnosP mutant, the lvbR promoter was upregulated, indicating that NosP negatively regulates LvbR. Furthermore, the NO receptor mutants were impaired for growth in A. castellanii and macrophages. In addition, we found that phenotypic heterogeneity of non-growing/growing bacteria in amoeba was regulated by the NO receptors. Moreover, the NO receptor mutant strains revealed an altered biofilm architecture and no longer responded to NO in biofilms. In summary, the NO receptors Hnox1, Hnox2 and NosP were shown to be involved in NO detection, replication in host cells, intracellular phenotypic heterogeneity, as well as biofilm formation and dispersion. Our results provide a deeper understanding of NO signaling in L. pneumophila and form the basis for further studies on the molecular components and mechanisms involved in intra-species and inter-kingdom NO signaling

Persistent effects of sand extraction on habitats and associated benthic communities in the German Bight

Sea-level rise demands for protection measures of endangered coastlines crucial for the local population. At the island of Sylt in the SE North Sea, shoreline erosion is compensated by replenishment with sand dredged from an offshore extraction site. We studied the long-term effects of sand extraction on bathymetry, geomorphology, habitats and benthic fauna. Sand extraction created dredging holes about 1 km in diameter and up to 20 m below the ambient seafloor level. Directly after dredging the superficial sediment layer, inside the pits was dominated by coarse sand and stones. Hydroacoustic surveys revealed only minor changes of bathymetry > 35 years after sand extraction. Obviously, backfill of the dredging pits was very slow, at a rate of a few millimeters per year, presumably resulting from low ambient sediment availability and relatively calm hydrodynamic conditions despite high wave energy during storms. Thus, a complete backfill of the deep extraction sites is likely to take centuries in this area. Hydroacoustic surveys and ground truthing showed that the backfilled material is mainly very fine sand and mud, turning the previously coarse sand surface into a muddy habitat. Accordingly, grab samples revealed significant differences in macrozoobenthos community composition, abundance and species density between recently dredged areas ( 10 years ago) and undisturbed sites (control sites). Overall, dredging turned the original association of sand-dwelling species into a muddy sediment association. Since re-establishment of disturbed benthic communities depends on previous re-establishment of habitat characteristics, the low sedimentation rates indicate that a return to a pre-dredging habitat type with its former benthic community and habitat characteristics is unlikely. Since coarse sand is virtually immobile in this area, a regeneration towards pre-dredging conditions is also unlikely without human interference (e.g., mitigation measures like depositing coarse material on the seafloor to restore the sessile epifauna)

Migration of Acanthamoeba through Legionella biofilms is regulated by the bacterial Lqs-LvbR network, effector proteins and the flagellum

The environmental bacterium Legionella pneumophila causes the pneumonia Legionnaires' disease. The opportunistic pathogen forms biofilms and employs the Icm/Dot type IV secretion system (T4SS) to replicate in amoebae and macrophages. A regulatory network comprising the Legionella quorum sensing (Lqs) system and the transcription factor LvbR controls bacterial motility, virulence and biofilm architecture. Here we show by comparative proteomics that in biofilms formed by the L. pneumophila ΔlqsR or ΔlvbR regulatory mutants the abundance of proteins encoded by a genomic 'fitness island', metabolic enzymes, effector proteins and flagellar components (e.g. FlaA) varies. ∆lqsR or ∆flaA mutants form 'patchy' biofilms like the parental strain JR32, while ∆lvbR forms a 'mat-like' biofilm. Acanthamoeba castellanii amoebae migrated more slowly through biofilms of L. pneumophila lacking lqsR, lvbR, flaA, a functional Icm/Dot T4SS (∆icmT), or secreted effector proteins. Clusters of bacteria decorated amoebae in JR32, ∆lvbR or ∆icmT biofilms but not in ∆lqsR or ∆flaA biofilms. The amoeba-adherent bacteria induced promoters implicated in motility (PflaA ) or virulence (PsidC , PralF ). Taken together, the Lqs-LvbR network (quorum sensing), FlaA (motility) and the Icm/Dot T4SS (virulence) regulate migration of A. castellanii through L. pneumophila biofilms, and - apart from the T4SS - govern bacterial cluster formation on the amoebae

From Understanding to Sustainable Use of Peatlands: The WETSCAPES Approach

Of all terrestrial ecosystems, peatlands store carbon most effectively in long-term scales of millennia. However, many peatlands have been drained for peat extraction or agricultural use. This converts peatlands from sinks to sources of carbon, causing approx. 5% of the anthropogenic greenhouse effect and additional negative effects on other ecosystem services. Rewetting peatlands can mitigate climate change and may be combined with management in the form of paludiculture. Rewetted peatlands, however, do not equal their pristine ancestors and their ecological functioning is not understood. This holds true especially for groundwater-fed fens. Their functioning results from manifold interactions and can only be understood following an integrative approach of many relevant fields of science, which we merge in the interdisciplinary project WETSCAPES. Here, we address interactions among water transport and chemistry, primary production, peat formation, matter transformation and transport, microbial community, and greenhouse gas exchange using state of the art methods. We record data on six study sites spread across three common fen types (Alder forest, percolation fen, and coastal fen), each in drained and rewetted states. First results revealed that indicators reflecting more long-term effects like vegetation and soil chemistry showed a stronger differentiation between drained and rewetted states than variables with a more immediate reaction to environmental change, like greenhouse gas (GHG) emissions. Variations in microbial community composition explained differences in soil chemical data as well as vegetation composition and GHG exchange. We show the importance of developing an integrative understanding of managed fen peatlands and their ecosystem functioning.

Psychological treatments for people with epilepsy.

BackgroundGiven the significant impact epilepsy may have on the health-related quality of life (HRQOL) of individuals with epilepsy and their families, there is increasing clinical interest in evidence-based psychological treatments, aimed at enhancing psychological and seizure-related outcomes for this group. This is an updated version of the original Cochrane Review published in Issue 10, 2017.ObjectivesTo assess the impact of psychological treatments for people with epilepsy on HRQOL outcomes.Search methodsFor this update, we searched the following databases on 12 August 2019, without language restrictions: Cochrane Register of Studies (CRS Web), which includes randomized or quasi-randomized controlled trials from the Specialized Registers of Cochrane Review Groups including Epilepsy, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946 to 09 August 2019), and PsycINFO (EBSCOhost, 1887 onwards), and from PubMed, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (ICTRP). We screened the references from included studies and relevant reviews, and contacted researchers in the field for unpublished studies.Selection criteriaWe considered randomized controlled trials (RCTs) and quasi-RCTs for this review. HRQOL was the main outcome. For the operational definition of 'psychological treatments', we included a broad range of skills-based psychological treatments and education-only interventions designed to improve HRQOL, seizure frequency and severity, as well as psychiatric and behavioral health comorbidities for adults and children with epilepsy. These psychological treatments were compared to treatment as usual (TAU), an active control group (such as social support group), or antidepressant pharmacotherapy.Data collection and analysisWe used standard methodological procedures expected by Cochrane.Main resultsWe included 36 completed RCTs, with a total of 3526 participants. Of these studies, 27 investigated skills-based psychological interventions. The remaining nine studies were education-only interventions. Six studies investigated interventions for children and adolescents, three studies investigated interventions for adolescents and adults, and the remaining studies investigated interventions for adults. Based on satisfactory clinical and methodological homogeneity, we pooled data from 11 studies (643 participants) that used the Quality of Life in Epilepsy-31 (QOLIE-31) or other QOLIE inventories (such as QOLIE-89 or QOLIE-31-P) convertible to QOLIE-31. We found significant mean changes for the QOLIE-31 total score and six subscales (emotional well-being, energy and fatigue, overall QoL, seizure worry, medication effects, and cognitive functioning). The mean changes in the QOLIE-31 total score (mean improvement of 5.23 points, 95% CI 3.02 to 7.44; P Authors' conclusionsImplications for practice: Skills-based psychological interventions improve HRQOL in adults and adolescents with epilepsy. Adjunctive use of skills-based psychological treatments for adults and adolescents with epilepsy may provide additional benefits in HRQOL when these are incorporated into patient-centered management. We judge the evidence to be of moderate certainty.Implications for researchInvestigators should strictly adhere to the CONSORT guidelines to improve the quality of reporting on their interventions. A thorough description of intervention protocols is necessary to ensure reproducibility. When examining the effectiveness of psychological treatments for people with epilepsy, the use of standardized HRQOL inventories, such as the Quality of Life in Epilepsy Inventories (QOLIE-31, QOLIE-31-P, and QOLIE-89) would increase comparability. Unfortunately, there is a critical gap in pediatric RCTs and RCTs including people with epilepsy and intellectual disabilities. Finally, in order to increase the overall quality of RCT study designs, adequate randomization with allocation concealment and blinded outcome assessment should be pursued. As attrition is often high in research that requires active participation, an intention-to-treat analysis should be carried out. Treatment fidelity and treatment competence should also be assessed. These important dimensions, which are related to 'Risk of bias' assessment, should always be reported

SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia.

The nucleoside analog cytarabine (Ara-C) is an essential component of primary and salvage chemotherapy regimens for acute myeloid leukemia (AML). After cellular uptake, Ara-C is converted into its therapeutically active triphosphate metabolite, Ara-CTP, which exerts antileukemic effects, primarily by inhibiting DNA synthesis in proliferating cells. Currently, a substantial fraction of patients with AML fail to respond effectively to Ara-C therapy, and reliable biomarkers for predicting the therapeutic response to Ara-C are lacking. SAMHD1 is a deoxynucleoside triphosphate (dNTP) triphosphohydrolase that cleaves physiological dNTPs into deoxyribonucleosides and inorganic triphosphate. Although it has been postulated that SAMHD1 sensitizes cancer cells to nucleoside-analog derivatives through the depletion of competing dNTPs, we show here that SAMHD1 reduces Ara-C cytotoxicity in AML cells. Mechanistically, dGTP-activated SAMHD1 hydrolyzes Ara-CTP, which results in a drastic reduction of Ara-CTP in leukemic cells. Loss of SAMHD1 activity-through genetic depletion, mutational inactivation of its triphosphohydrolase activity or proteasomal degradation using specialized, virus-like particles-potentiates the cytotoxicity of Ara-C in AML cells. In mouse models of retroviral AML transplantation, as well as in retrospective analyses of adult patients with AML, the response to Ara-C-containing therapy was inversely correlated with SAMHD1 expression. These results identify SAMHD1 as a potential biomarker for the stratification of patients with AML who might best respond to Ara-C-based therapy and as a target for treating Ara-C-refractory AML

In-situ estimation of ice crystal properties at the South Pole using LED calibration data from the IceCube Neutrino Observatory

The IceCube Neutrino Observatory instruments about 1 km3 of deep, glacial ice at the geographic South Pole using 5160 photomultipliers to detect Cherenkov light emitted by charged relativistic particles. A unexpected light propagation effect observed by the experiment is an anisotropic attenuation, which is aligned with the local flow direction of the ice. Birefringent light propagation has been examined as a possible explanation for this effect. The predictions of a first-principles birefringence model developed for this purpose, in particular curved light trajectories resulting from asymmetric diffusion, provide a qualitatively good match to the main features of the data. This in turn allows us to deduce ice crystal properties. Since the wavelength of the detected light is short compared to the crystal size, these crystal properties do not only include the crystal orientation fabric, but also the average crystal size and shape, as a function of depth. By adding small empirical corrections to this first-principles model, a quantitatively accurate description of the optical properties of the IceCube glacial ice is obtained. In this paper, we present the experimental signature of ice optical anisotropy observed in IceCube LED calibration data, the theory and parametrization of the birefringence effect, the fitting procedures of these parameterizations to experimental data as well as the inferred crystal properties.</p

Mechanical design of the optical modules intended for IceCube-Gen2

IceCube-Gen2 is an expansion of the IceCube neutrino observatory at the South Pole that aims to increase the sensitivity to high-energy neutrinos by an order of magnitude. To this end, about 10,000 new optical modules will be installed, instrumenting a fiducial volume of about 8 km3. Two newly developed optical module types increase IceCube’s current sensitivity per module by a factor of three by integrating 16 and 18 newly developed four-inch PMTs in specially designed 12.5-inch diameter pressure vessels. Both designs use conical silicone gel pads to optically couple the PMTs to the pressure vessel to increase photon collection efficiency. The outside portion of gel pads are pre-cast onto each PMT prior to integration, while the interiors are filled and cast after the PMT assemblies are installed in the pressure vessel via a pushing mechanism. This paper presents both the mechanical design, as well as the performance of prototype modules at high pressure (70 MPa) and low temperature (−40∘C), characteristic of the environment inside the South Pole ice

The next generation neutrino telescope: IceCube-Gen2

The IceCube Neutrino Observatory, a cubic-kilometer-scale neutrino detector at the geographic South Pole, has reached a number of milestones in the field of neutrino astrophysics: the discovery of a high-energy astrophysical neutrino flux, the temporal and directional correlation of neutrinos with a flaring blazar, and a steady emission of neutrinos from the direction of an active galaxy of a Seyfert II type and the Milky Way. The next generation neutrino telescope, IceCube-Gen2, currently under development, will consist of three essential components: an array of about 10,000 optical sensors, embedded within approximately 8 cubic kilometers of ice, for detecting neutrinos with energies of TeV and above, with a sensitivity five times greater than that of IceCube; a surface array with scintillation panels and radio antennas targeting air showers; and buried radio antennas distributed over an area of more than 400 square kilometers to significantly enhance the sensitivity of detecting neutrino sources beyond EeV. This contribution describes the design and status of IceCube-Gen2 and discusses the expected sensitivity from the simulations of the optical, surface, and radio components