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The use of parasites as biological tags for discrimination of fish stocks has become a commonly used approach in fisheries management. Metazoan parasite community analysis and anisakid nematode population genetics based on a mitochondrial cytochrome marker were applied in order to assess the usefulness of the two parasitological methods for stock discrimination of beaked redfish Sebastes mentella of three fishing grounds in the North East Atlantic. Multivariate, model-based approaches demonstrated that the metazoan parasite fauna of beaked redfish from East Greenland differed from Tampen, northern North Sea, and Bear Island, Barents Sea. A joint model (latent variable model) was used to estimate the effects of covariates on parasite species and identified four parasite species as main source of differences among fishing grounds; namely Chondracanthus nodosus, Anisakis simplex s.s., Hysterothylacium aduncum, and Bothriocephalus scorpii. Due to its high abundance and differences between fishing grounds, Anisakis simplex s.s. was considered as a major biological tag for host stock differentiation. Whilst the sole examination of Anisakis simplex s.s. on a population genetic level is only of limited use, anisakid nematodes (in particular, A. simplex s.s.) can serve as biological tags on a parasite community level. This study confirmed the use of multivariate analyses as a tool to evaluate parasite infra-communities and to identify parasite species that might serve as biological tags. The present study suggests that S. mentella in the northern North Sea and Barents Sea is not sub-structured.
19(S)-hydroxy-eicosatetraenoic acid (19(S)-HETE) belongs to a family of arachidonic acid metabolites produced by cytochrome P450 enzymes, which play critical roles in the regulation of cardiovascular, renal and pulmonary functions. Although it has been known for a long time that 19(S)-HETE has vascular effects, its mechanism of action has remained unclear. In this study we show that 19(S)-HETE induces cAMP accumulation in the human megakaryoblastic leukemia cell line MEG-01. This effect was concentration-dependent with an EC50 of 520 nM, insensitive to pharmacological inhibition of COX-1/2 and required the expression of the G-protein Gs. Systematic siRNA-mediated knock-down of each G-protein coupled receptor (GPCR) expressed in MEG-01 followed by functional analysis identified the prostacyclin receptor (IP) as the mediator of the effects of 19(S)-HETE, and the heterologously expressed IP receptor was also activated by 19(S)-HETE in a concentration-dependent manner with an EC50 of 567 nM. Pretreatment of isolated murine platelets with 19(S)-HETE blocked thrombin-induced platelets aggregation, an effect not seen in platelets from mice lacking the IP receptor. Furthermore, 19(S)-HETE was able to relax mouse mesenteric artery- and thoracic aorta-derived vessel segments. While pharmacological inhibition of COX-1/2 enzymes had no effect on the vasodilatory activity of 19(S)-HETE these effects were not observed in vessels from mice lacking the IP receptor. These results identify a novel mechanism of action for the CYP450-dependent arachidonic acid metabolite 19(S)-HETE and point to the existence of a broader spectrum of naturally occurring prostanoid receptor agonists.
The first step in methanol metabolism in methylotrophic yeasts, the oxidation of methanol and higher alcohols with molecular oxygen to formaldehyde and hydrogen peroxide, is catalysed by alcohol oxidase (AOX), a 600-kDa homo-octamer containing eight FAD cofactors. When these yeasts are grown with methanol as the carbon source, AOX forms large crystalline arrays in peroxisomes. We determined the structure of AOX by cryo-electron microscopy at a resolution of 3.4 Å. All residues of the 662-amino acid polypeptide as well as the FAD are well resolved. AOX shows high structural homology to other members of the GMC family of oxidoreductases, which share a conserved FAD binding domain, but have different substrate specificities. The preference of AOX for small alcohols is explained by the presence of conserved bulky aromatic residues near the active site. Compared to the other GMC enzymes, AOX contains a large number of amino acid inserts, the longest being 75 residues. These segments are found at the periphery of the monomer and make extensive inter-subunit contacts which are responsible for the very stable octamer. A short surface helix forms contacts between two octamers, explaining the tendency of AOX to form crystals in the peroxisomes.
Simple cells in primary visual cortex were famously found to respond to low-level image components such as edges. Sparse coding and independent component analysis (ICA) emerged as the standard computational models for simple cell coding because they linked their receptive fields to the statistics of visual stimuli. However, a salient feature of image statistics, occlusions of image components, is not considered by these models. Here we ask if occlusions have an effect on the predicted shapes of simple cell receptive fields. We use a comparative approach to answer this question and investigate two models for simple cells: a standard linear model and an occlusive model. For both models we simultaneously estimate optimal receptive fields, sparsity and stimulus noise. The two models are identical except for their component superposition assumption. We find the image encoding and receptive fields predicted by the models to differ significantly. While both models predict many Gabor-like fields, the occlusive model predicts a much sparser encoding and high percentages of ‘globular’ receptive fields. This relatively new center-surround type of simple cell response is observed since reverse correlation is used in experimental studies. While high percentages of ‘globular’ fields can be obtained using specific choices of sparsity and overcompleteness in linear sparse coding, no or only low proportions are reported in the vast majority of studies on linear models (including all ICA models). Likewise, for the here investigated linear model and optimal sparsity, only low proportions of ‘globular’ fields are observed. In comparison, the occlusive model robustly infers high proportions and can match the experimentally observed high proportions of ‘globular’ fields well. Our computational study, therefore, suggests that ‘globular’ fields may be evidence for an optimal encoding of visual occlusions in primary visual cortex.
The sequenced genome of the poly-extremophile Exiguobacterium sp. S17, isolated from modern stromatolites at Laguna Socompa (3,570 m), a High-Altitude Andean Lake (HAAL) in Argentinean Puna revealed a putative proteorhodopsin-encoding gene. The HAAL area is exposed to the highest UV irradiation on Earth, making the microbial community living in the stromatolites test cases for survival strategies under extreme conditions. The heterologous expressed protein E17R from Exiguobacterium (248 amino acids, 85% sequence identity to its ortholog ESR from E. sibiricum) was assembled with retinal displaying an absorbance maximum at 524 nm, which makes it a member of the green-absorbing PR-subfamily. Titration down to low pH values (eventually causing partial protein denaturation) indicated a pK value between two and three. Global fitting of data from laser flash-induced absorption changes gave evidence for an early red-shifted intermediate (its formation being below the experimental resolution) that decayed (τ1 = 3.5 μs) into another red-shifted intermediate. This species decayed in a two-step process (τ2 = 84 μs, τ3 = 11 ms), to which the initial state of E17-PR was reformed with a kinetics of 2 ms. Proton transport capability of the HAAL protein was determined by BLM measurements. Additional blue light irradiation reduced the proton current, clearly identifying a blue light absorbing, M-like intermediate. The apparent absence of this intermediate is explained by closely matching formation and decay kinetics.
This thesis addresses the reconstruction of the topographic evolution and the climate dynamics of the Early Cenozoic North American Cordillera through integrated geochronology, sedimentology, stable isotope, and clumped isotope thermometry studies. It encompasses the scientific disciplines of geochemistry, tectonics, and Earth surface processes.
Bacterial sugar symporters in the Major Facilitator Superfamily (MFS) use the H+ (and in a few cases Na+) electrochemical gradients to achieve active transport of sugar into the cell. Because a number of structures of MFS sugar symporters have been solved recently, molecular insight into the transport mechanism is possible from detailed functional analysis. We present here a comparative electrophysiological study of the lactose permease (LacY), the fucose permease (FucP) and the xylose permease (XylE), which reveals common mechanistic principles and differences. In all three symporters energetically downhill electrogenic sugar/H+ symport is observed. Comparison of the pH dependence of symport at symmetrical pH exhibits broad bell-shaped pH profiles extending over 3 to 6 pH units and a decrease at extremely alkaline pH ≥ 9.4 and at acidic to neutral pH = 4.6–7.5. The pH dependence can be described by an acidic to neutral apparent pK (pKapp) and an alkaline pKapp. Experimental evidence suggests that the alkaline pKapp is due to H+ depletion at the protonation site, while the acidic pKapp is due to inhibition of deprotonation. Since previous studies suggest that a single carboxyl group in LacY (Glu325) may be the only side chain directly involved in H+ translocation and a carboxyl side chain with similar properties has been identified in FucP (Asp46) and XylE (Asp27), the present results imply that the pK of this residue is switched during H+/sugar symport in all three symporters.
Capoeta damascina was earlier considered by many authors as one of the most common freshwater fish species found throughout the Levant, Mesopotamia, Turkey, and Iran. However, owing to a high variation in morphological characters among and within its various populations, 17 nominal species were described, several of which were regarded as valid by subsequent revising authors. Capoeta damascina proved to be a complex of closely related species, which had been poorly studied. The current study aims at defining C. damascina and the C. damascina species complex. It investigates phylogenetic relationships among the various members of the C. damascina complex, based on mitochondrial and nuclear DNA sequences. Phylogenetic relationships were projected against paleogeographical events to interpret the geographic distribution of the taxa under consideration in relation to the area’s geological history. Samples were obtained from throughout the geographic range and were subjected to genetic analyses, using two molecular markers targeting the mitochondrial cytochrome oxidase I (n = 103) and the two adjacent divergence regions (D1-D2) of the nuclear 28S rRNA genes (n = 65). Six closely related species were recognized within the C. damascina complex, constituting two main lineages: A western lineage represented by C. caelestis, C. damascina, and C. umbla and an eastern lineage represented by C. buhsei, C. coadi, and C. saadii. The results indicate that speciation of these taxa is rather a recent event. Dispersal occurred during the Pleistocene, resulting in present-day distribution patterns. A coherent picture of the phylogenetic relationships and evolutionary history of the C. damascina species complex is drawn, explaining the current patterns of distribution as a result of paleogeographic events and ecological adaptations.
Objectives: Assessment of the clinical severity of Fabry disease (FD), an X-linked, rare, progressive disorder based on a genetic defect in alpha-galactosidase is challenging, especially regarding cardiac involvement. The aim of the study was to evaluate the diagnostic value of cardiac troponin I (cTnI) in discriminating FD patients with cardiac involvement in a large FD patient cohort.
Methods: cTnI levels were measured with a contemporary sensitive assay in plasma samples taken routinely from FD patients. The assay was calibrated to measure cTnI levels ≥0.01 ng/ml. Elevated cTnI values (cut-off ≥0.04 ng/ml) were correlated with clinical data.
Results: cTnI was assessed in 62 FD patients (median age: 47 years, males: 36%). Elevated cTnI levels were detected in 23 (37%) patients. Patients with a cTnI elevation were older (median 55 years versus 36 years, p<0.001). Elevated cTnI levels were associated with the presence of a LVH (16/23 versus 1/39; OR 65.81, CI: 6.747–641.859; p<0.001). In almost all patients with a left ventricular hypertrophy (LVH) elevated cTnI levels were detected (16/17, 94%). Absolute cTnI levels in patients with LVH were higher than in those without (median 0.23 ng/ml versus 0.02 ng/ml; p<0.001). A cTnI level <0.04ng/ml had a high negative predictive value regarding the presence of a LVH (38/39, 97%). In a control group of non-FD patients (n = 17) with LVH (due to hypertension) none showed cTnI levels ≥0.01 ng/ml.
Conclusions: Elevated cTnI levels are common in FD patients, reflecting cardiac involvement. FD patients might benefit from a continuous cTnI monitoring.
The worldwide use of neonicotinoid pesticides has caused concern on account of their involvement in the decline of bee populations, which are key pollinators in most ecosystems. Here we describe a role of non-neuronal acetylcholine (ACh) for breeding of Apis mellifera carnica and a so far unknown effect of neonicotinoids on non-target insects. Royal jelly or larval food are produced by the hypopharyngeal gland of nursing bees and contain unusually high ACh concentrations (4–8 mM). ACh is extremely well conserved in royal jelly or brood food because of the acidic pH of 4.0. This condition protects ACh from degradation thus ensuring delivery of intact ACh to larvae. Raising the pH to ≥5.5 and applying cholinesterase reduced the content of ACh substantially (by 75–90%) in larval food. When this manipulated brood was tested in artificial larval breeding experiments, the survival rate was higher with food supplemented by 100% with ACh (6 mM) than with food not supplemented with ACh. ACh release from the hypopharyngeal gland and its content in brood food declined by 80%, when honeybee colonies were exposed for 4 weeks to high concentrations of the neonicotinoids clothianidin (100 parts per billion [ppb]) or thiacloprid (8,800 ppb). Under these conditions the secretory cells of the gland were markedly damaged and brood development was severely compromised. Even field-relevant low concentrations of thiacloprid (200 ppb) or clothianidin (1 and 10 ppb) reduced ACh level in the brood food and showed initial adverse effects on brood development. Our findings indicate a hitherto unknown target of neonicotinoids to induce adverse effects on non-neuronal ACh which should be considered when re-assessing the environmental risks of these compounds. To our knowledge this is a new biological mechanism, and we suggest that, in addition to their well documented neurotoxic effects, neonicotinoids may contribute to honeybee colony losses consecutive to a reduction of the ACh content in the brood food.
We explored the potential of Smac mimetics, which antagonize Inhibitor of Apoptosis (IAP) proteins, for chemosensitization of neuroblastoma (NB). Here, we report that Smac mimetics, e.g. BV6, prime NB cells for chemotherapeutics including the topoisomerase II inhibitor doxorubicin (DOX) and vinca alkaloids such as Vincristine (VCR), Vinblastine (VBL) and Vinorelbine (VNR). Additionally, BV6 acts in concert with DOX or VCR to suppress long-term clonogenic growth. While BV6 causes rapid downregulation of cellular IAP (cIAP)1 protein and nuclear factor-kappaB (NF-κB) activation, DOX/BV6- or VCR/BV6-induced apoptosis occurs independently of NF-κB or TNFα signaling, since overexpression of dominant-negative IκBα superrepressor or the Tumor Necrosis Factor (TNF)α-blocking antibody Enbrel fail to block cell death. Mechanistic studies reveal that Receptor-interacting protein (RIP)1 is required for DOX/BV6-, but not for VCR/BV6-induced apoptosis, since transient or stable knockdown of RIP1 or the pharmacological RIP1 inhibitor necrostatin-1 significantly reduce apoptosis. By comparison, VCR/BV6-mediated apoptosis critically depends on the mitochondrial pathway. VCR/BV6 cotreatment causes phosphorylation of BCL-2 during mitotic arrest, enhanced activation of BAX and BAK and loss of mitochondrial membrane potential (MMP). Additionally, overexpression of BCL-2 profoundly suppresses VCR/BV6-induced apoptosis. Thus, BV6 sensitizes NB cells to chemotherapy-induced apoptosis via distinct initial signaling mechanisms depending on the chemotherapeutic drug. These findings provide novel mechanistic insights into Smac mimetic-mediated chemosensitization of NB.
Unusual Deep Water sponge assemblage in South China - witness of the end-Ordovician mass extinction
(2015)
There are few sponges known from the end-Ordovician to early-Silurian strata all over the world, and no records of sponge fossils have been found yet in China during this interval. Here we report a unique sponge assemblage spanning the interval of the end-Ordovician mass extinction from the Kaochiapien Formation (Upper Ordovician-Lower Silurian) in South China. This assemblage contains a variety of well-preserved siliceous sponges, including both Burgess Shale-type and modern type taxa. It is clear that this assemblage developed in deep water, low energy ecosystem with less competitors and more vacant niches. Its explosion may be related to the euxinic and anoxic condition as well as the noticeable transgression during the end-Ordovician mass extinction. The excellent preservation of this assemblage is probably due to the rapid burial by mud turbidites. This unusual sponge assemblage provides a link between the Burgess Shale-type deep water sponges and the modern forms. It gives an excellent insight into the deep sea palaeoecology and the macroevolution of Phanerozoic sponges, and opens a new window to investigate the marine ecosystem before and after the end-Ordovician mass extinction. It also offers potential to search for exceptional fossil biota across the Ordovician-Silurian boundary interval in China.
Bei dem letzten Update des Genocide Alert Monitors wurde in sozialen Medien wiederholt darauf aufmerksam gemacht, dass fast sämtliche Massenverbrechen angeblich in muslimischen Staaten stattfänden. Der Islam wurde von den Kommentatoren als gewalttätige Religion bezeichnet und Muslime hauptverantwortlich für die über 21.000 im 1. Quartal 2016 getöteten Menschen gemacht. Anlass genug, die erfassten Situationen auf religiöse Identitäten von Tätern und Opfern zu analysieren...
Indignados and occupy: channeling political dissatisfaction through an anti-institutional approach
(2016)
This is the fourth post in the blog series „Movements and Institutions“.
Between 2011 and 2012 many public spaces in global North were indefinitely occupied by people dissatisfied with the political system. The origin of this dissatisfaction, however, is not clear. This article rejects that the origin was either a popular longing for direct democracy or for an end to neoliberalism. It problematizes the frequent assumption that voting is a proper way to account for the will of the people: The manifestation of thousands of Indignados and Occupiers pointed to the idea that elections are not a sufficient method for expressing political will. This article goes further to suggest that voting is not a neutral method either.
This is the fifth post in the blog series „Movements and Institutions“.
The article traces a formalization process within the Interventionist Left (IL). Against theoretical expectations that would assume a de-radicalization of aims and repertoires of protest, we find that due to the network’s multi-track strategy, and the claim to radicalize existing social debates, the IL did not de-radicalize despite a formalization process and a partial integration into established systems.
This is the third post in the blog series „Movements and Institutions“.
The relationship of social movements and institutions should not just be seen as one where political demands can influence policy change in a targeted organization or political system. With a focus on instituting practices, instead of resulting institutions, we can understand all social institutions as institutionalizations, as constantly moving processes with the potential for radical change.
The behaviour of electronic circuits is influenced by ageing effects. Modelling the behaviour of circuits is a standard approach for the design of faster, smaller, more reliable and more robust systems. In this thesis, we propose a formalization of robustness that is derived from a failure model, which is based purely on the behavioural specification of a system. For a given specification, simulation can reveal if a system does not comply with a specification, and thus provide a failure model. Ageing usually works against the specified properties, and ageing models can be incorporated to quantify the impact on specification violations, failures and robustness. We study ageing effects in the context of analogue circuits. Here, models must factor in infinitely many circuit states. Ageing effects have a cause and an impact that require models. On both these ends, the circuit state is highly relevant, an must be factored in. For example, static empirical models for ageing effects are not valid in many cases, because the assumed operating states do not agree with the circuit simulation results. This thesis identifies essential properties of ageing effects and we argue that they need to be taken into account for modelling the interrelation of cause and impact. These properties include frequency dependence, monotonicity, memory and relaxation mechanisms as well as control by arbitrary shaped stress levels. Starting from decay processes, we define a class of ageing models that fits these requirements well while remaining arithmetically accessible by means of a simple structure.
Modeling ageing effects in semiconductor circuits becomes more relevant with higher integration and smaller structure sizes. With respect to miniaturization, digital systems are ahead of analogue systems, and similarly ageing models predominantly focus on digital applications. In the digital domain, the signal levels are either on or off or switching in between. Given an ageing model as a physical effect bound to signal levels, ageing models for components and whole systems can be inferred by means of average operation modes and cycle counts. Functional and faithful ageing effect models for analogue components often require a more fine-grained characterization for physical processes. Here, signal levels can take arbitrary values, to begin with. Such fine-grained, physically inspired ageing models do not scale for larger applications and are hard to simulate in reasonable time. To close the gap between physical processes and system level ageing simulation, we propose a data based modelling strategy, according to which measurement data is turned into ageing models for analogue applications. Ageing data is a set of pairs of stress patterns and the corresponding parameter deviations. Assuming additional properties, such as monotonicity or frequency independence, learning algorithm can find a complete model that is consistent with the data set. These ageing effect models decompose into a controlling stress level, an ageing process, and a parameter that depends on the state of this process. Using this representation, we are able to embed a wide range of ageing effects into behavioural models for circuit components. Based on the developed modelling techniques, we introduce a novel model for the BTI effect, an ageing effect that permits relaxation. In the following, a transistor level ageing model for BTI that targets analogue circuits is proposed. Similarly, we demonstrate how ageing data from analogue transistor level circuit models lift to purely behavioural block models. With this, we are the first to present a data based hierarchical ageing modeling scheme. An ageing simulator for circuits or system level models computes long term transients, solutions of a differential equation. Long term transients are often close to quasi-periodic, in some sense repetitive. If the evaluation of ageing models under quasi-periodic conditions can be done efficiently, long term simulation becomes practical. We describe an adaptive two-time simulation algorithm that basically skips periods during simulation, advancing faster on a second time axis. The bottleneck of two-time simulation is the extrapolation through skipped frames. This involves both the evaluation of the ageing models and the consistency of the boundary conditions. We propose a simulator that computes long term transients exploiting the structure of the proposed ageing models. These models permit extrapolation of the ageing state by means of a locally equivalent stress, a sort of average stress level. This level can be computed efficiently and also gives rise to a dynamic step control mechanism. Ageing simulation has a wide range of applications. This thesis vastly improves the applicability of ageing simulation for analogue circuits in terms of modelling and efficiency. An ageing effect model that is a part of a circuit component model accounts for parametric drift that is directly related to the operation mode. For example asymmetric load on a comparator or power-stage may lead to offset drift, which is not an empiric effect. Monitor circuits can report such effects during operation, when they become significant. Simulating the behaviour of these monitors is important during their development. Ageing effects can be compensated using redundant parts, and annealing can revert broken components to functional. We show that such mechanisms can be simulated in place using our models and algorithms. The aim of automatized circuit synthesis is to create a circuit that implements a specification for a certain use case. Ageing simulation can identify candidates that are more reliable. Efficient ageing simulation allows to factor in various operation modes and helps refining the selection. Using long term ageing simulation, we have analysed the fitness of a set of synthesized operational amplifiers with similar properties concerning various use cases. This procedure enables the selection of the most ageing resilient implementation automatically.
Purpose: In secondary progressive Multiple Sclerosis (SPMS), global neurodegeneration as a driver of disability gains importance in comparison to focal inflammatory processes. However, clinical MRI does not visualize changes of tissue composition outside MS lesions. This quantitative MRI (qMRI) study investigated cortical and deep gray matter (GM) proton density (PD) values and T1 relaxation times to explore their potential to assess neuronal damage and its relationship to clinical disability in SPMS.
Materials and Methods: 11 SPMS patients underwent quantitative T1 and PD mapping. Parameter values across the cerebral cortex and deep GM structures were compared with 11 healthy controls, and correlation with disability was investigated for regions exhibiting significant group differences.
Results: PD was increased in the whole GM, cerebral cortex, thalamus, putamen and pallidum. PD correlated with disability in the whole GM, cerebral cortex, putamen and pallidum. T1 relaxation time was prolonged and correlated with disability in the whole GM and cerebral cortex.
Conclusion: Our study suggests that the qMRI parameters GM PD (which likely indicates replacement of neural tissue with water) and cortical T1 (which reflects cortical damage including and beyond increased water content) are promising qMRI candidates for the assessment of disease status, and are related to disability in SPMS.
Heutzutage unterliegen insbesondere aquatische Ökosysteme durch den permanenten Anstieg nicht-heimischer Arten einem folgenreichen Wandel. Dabei stellt der Biodiversitätsverlust nur den Endpunkt einer biologischen Invasion dar. Dazwischen wirken sich Faktoren wie Konkurrenz-, Prädationsdruck oder die Übertragung von Krankheitserregern wie z.B. Parasiten auf den Rückgang der Arten aus. Als integraler Bestandteil eines jeden Ökosystems spielen Parasiten bei Invasionsprozessen eine entscheidende Rolle und können durch ihren Einfluss auf heimische und nicht-heimischen Arten Invasionen begünstigen. Fische übernehmen aufgrund ihrer vielseitigen Bedeutung im Nahrungsnetz eine Schlüsselfunktion als Wirte diverser Parasitenarten und sind deshalb ausgezeichnete Untersuchungsobjekte, um durch nicht-heimische Arten verursachte Veränderungen in Nahrungsnetzstrukturen oder Parasitenfaunen aquatischer Ökosysteme aufzudecken.
Vor diesem Hintergrund wurde die vorliegende kumulative Dissertation angefertigt, welche auf drei (ISI-) Einzelpublikationen basiert. Die Arbeit beschäftigte sich unter Verwendung morphologischer und molekularbiologischer Methoden schwerpunktmäßig mit der Parasitendiversität und Nahrungsökologie zweier eingeschleppter Fischarten in stark anthropogen beeinflussten deutschen Fließgewässern. Dabei handelte es sich um die hauptsächlich durch das Ballastwasser von Schiffen verbreitete invasive Schwarzmundgrundel Neogobius melanostomus aus den Flüssen Rhein und Main sowie den von Hobby-Aquarianern in den durch Industrieabwässer thermisch belasteten Gillbach ausgesetzten Zebrabuntbarsch Amatitlania nigrofasciata. Unter Berücksichtigung nahrungsökologischer und räumlich-zeitlicher Aspekte sollten die parasitologischen Risiken und Konsequenzen, welche durch das Einschleppen nicht-heimischer Fischarten auftreten, aufgezeigt werden, um übergeordnet die Folgenabschätzung auf dem Gebiet der Invasionsbiologie zu verbessern. Das Nahrungsspektrum beider Fischarten wies sowohl räumliche (zwischen den Flüssen und Standorten), als auch zeitliche (monatlich) Variationen auf, was die Anpassungsfähigkeit bzw. die optimale Nutzung zur Verfügung stehender Ressourcen von invasiven Arten verdeutlicht. Ebenso wurden Unterschiede in der Parasitierung nachgewiesen, was die Notwendigkeit räumlicher und zeitlicher Analysen zur Erfassung der vollständigen Parasitenfauna einer invasiven Art, inklusive aller Variationen der Befallszahlen, unterstreicht. Beide Fischarten bilden zudem Zwischenwirte für heimische, als auch nicht-heimische Parasitenarten, wobei die direkte Einschleppung von nicht-heimischen Parasiten aus dem ursprünglichen Verbreitungsgebiet der Fische auszuschießen ist und somit die Enemy-Release-Hypothese (Verlust ursprünglicher Gegenspieler wie Prädatoren oder Parasiten) unterstützt. Dies könnte zusammen mit der opportunistischen Ernährungsweise ein Grund für die starke Ausbreitung sowie die anhaltend hohen Individuenzahlen dieser Arten im jeweils betrachteten Verbreitungsgebiet (Rhein, Main sowie Gillbach) sein.
Besonders hervorzuheben ist der Nachweis der nicht-heimischen Nematoden Anguillicoloides crassus und Camallanus cotti. Durch die Aufdeckung einer besonderen Form von Hyperparasitismus konnten erstmalig hohe Befallszahlen von A. crassus in N. melanostomus dokumentiert werden. Die hoch abundante Grundelart gilt somit potentiell als entscheidender Überträger des invasiven Parasiten auf den Europäischen Aal. Der durch seine hohe Virulenz in der Aquaristik bekannte C. cotti gelangte durch das Aussetzen von Zierfischen in den Gillbach und trat mit hohen Befallszahlen in A. nigrofasciata auf und wird bereits auf die heimische Fischfauna übertragen (z.B. auf den Gründling Gobio gobio und den Döbel Squalius cephalus). Ebenso ist der starke Befall der heimischen Parasiten Pomphorhynchus sp. (Acanthocephala) und Raphidascaris acus (Nematoda) bei N. melanostomus sowie A. anguillae (Acanthocephala) bei A. nigrofasciata zu nennen. Durch die zusätzliche Wirtfunktion der Neozoen und die hohen Befallsintensitäten ist mit einem verstärkten Spillback-Effekt (Rückinfizierung) auf heimische Fischarten zu rechnen.
Die stetig steigende Anzahl biologischer Invasionen führt zu immer weitreichenderen Veränderungen heimischer Ökosysteme. Für den Erhalt der Biodiversität sowie einhergehender Ökosystemfunktionen rückt auch die Forschung über Neobiota immer mehr in den Mittelpunkt. In diesem Zusammenhang gewinnen auch Pathogene wie Parasiten immer mehr an Bedeutung, welche durch gebietsfremde Arten eingeschleppt werden und die bestehende Biodiversität gefährden können. Die Ergebnisse der durchgeführten Studien haben gezeigt, dass die Verknüpfung von parasitologischen und nahrungsökologischen Untersuchungen Einblicke in die hoch dynamischen Prozesse der Invasionsbiologie geben können, was ein Vorantreiben der Forschung und Folgenabschätzungen auf diesem Gebiet ermöglicht.
Während in Deutschland in den letzten Jahren vermehrt wissenschaftliche Arbeiten zu literarischen Produktionen von eingewanderten AutorInnen vorliegen, die ihre Herkunftsländer verlassen und sich in weiterer Folge im deutschsprachigen Raum angesiedelt haben, gibt es in Österreich bislang wenig systematische Beschäftigung mit diesem Thema. Erst in den letzten Jahren hat sowohl die deutschsprachige als auch die internationale Germanistik begonnen, vermehrt österreichische AutorInnen, die zwischen verschiedenen Sprachen und Kulturen leben und arbeiten, in den Blick zu nehmen und damit zugleich ein Forschungsfeld zu eröffnen, das sich sowohl Fragen der Verortung und Positionierung der AutorInnen als auch den damit verknüpften literarischen Effekten widmet. Als ein weiterer Beitrag zu diesem Forschungsfeld liegt der Fokus der vorliegenden Nummer der Aussiger Beiträge auf der Literatur von eingewanderten AutorInnen aus mittel- und osteuropäischen Ländern in Österreich, wie etwa Jiří Gruša, Ivan Ivanji, Viktorija Kocman, Julya Rabinowich, Alja Rachmanowa, Michael Stavarič oder Fred Wander. Zudem wurde das Korpus um AutorInnen erweitert, die - wie etwa Semier Insayif - zwar in Österreich geboren sind, jedoch bi- oder multikulturellen Hintergrund haben, der in ihren Texten, bewusst oder unbewusst, literarisch reflektiert wird. Die vorliegende Nummer, in der entlang literarischer Texte sowohl theoretische Fragestellungen behandelt als auch die AutorInnen selbst und ihre Texte vorgestellt werden, verdeutlicht, dass es keine kulturell und sprachlich homogene 'österreichische Literatur' gibt, sondern viel mehr 'österreichische Literaturen', die als ein dynamischer Prozess von Bewegungen und Begegnungen zwischen verschiedenen Kulturen und Sprachen im gemeinsamen Kulturraum Österreich zu verstehen sind.
Ischemic injuries of the cardiovascular system are still the leading cause of death worldwide. They are often accompanied by loss of cardiomyocytes (CM) and their replacement by non-functional heart tissue. Cardiac fibroblasts (CF) play a major role in the recovery after ischemic injury and in the scar formation. In the last few years researchers were able to reprogram fibroblasts into CM in vitro and in murine models of myocardial infarction using various protocols including a cocktail of microRNAs (miRs). These miRs can target hundreds of messenger RNAs and inhibit their translation into proteins, potentially regulating multiple cellular signaling pathways. Because of this, there has been a rising interest in the use of miRs for therapeutic purposes. However, as different miRs have different effects in different cells, there is the danger of causing serious side effects. These could be alleviated by enacting a cell-specific transport of miRs, for example by using aptamers. Aptamers are usually short strands of DNA or RNA, which can fold into a specific three-dimensional confirmation which allows them to bind specifically to target molecules. Aptamers are commonly selected from a large library for their ability to bind to target molecules using a procedure called SELEX. Aptamers have already been used to transport miRs into cancer cells.
In this thesis, we first established the transport of miRs into cells of the cardiovascular system using aptamers. MiR-126 is an important part of the signaling in endothelial cells (EC), protects from atherosclerosis and supports angiogenesis, which is why we chose it as a candidate to transport into the vasculature. We first tested two aptamers for their ability to internalize into EC and fibroblasts. Both the aptamer for the ubiquitously expressed transferrin receptor (TRA) and a general internalizing RNA motif, but not a control construct, could internalize efficiently into all cell types tested. We then designed three chimeras (Ch) using different strategies to connect TRA to miR-126. While all chimeras could internalize efficiently, only Ch3, which connects TRA to Pre-miR-126 using a sticky bridge structure, had functional effects in EC. Ch3 reduced the protein expression of VCAM-1 in EC and increased the VEGF induced sprouting of EC in a spheroid-sprouting assay. Treatment of breast cancer cells with Ch3 emulated the effects of treatment with classical miR-126-3p and miR-126-5p mimics. In the SK-BR3 cell line Ch3 and miR-126-3p reduce the viability of the cells while they reduce recruitment of EC by the MCF7 cell line. miR-126-5p had no apparent effect in the SK-BR3 line, but increased viability of MCF7 cells, as did Ch3. This implies that Ch3 can be processed to both functional miR-126-3p and miR-126-5p in treated cells.
We were unable to achieve a reprogramming of adult murine cardiac fibroblasts into cells resembling CM using the cocktail of 4 miRs. This indicates that the miR-mediated transdifferentiation is only possible in neonatal fibroblasts. The effects in mice after an AMI might possibly be caused by an enhanced plasticity of fibroblasts in and close to the infarcted area.
We also screened to find aptamers specifically binding to cells of the cardiovascular system. We used two oligonucleotide libraries in a cell-SELEX to select candidates which bind to CF, but not EC. We observed that only the library which contains two randomized regions of 26 bases showed an enrichment of species binding to fibroblasts. We then sequenced rounds 5-7 of the SELEX and analyzed the data bioinfomatically to select 10 candidate aptamers. All candidates showed a strong binding not only to CF, but also EC. This indicates that the selection pressure against species binding to EC was not high enough and would have to be increased to find true CF-aptamers. Four promising candidates were also analyzed for their potential to be internalized and we surprisingly found that all of them were internalized by EC and CF more efficiently than TRA. The similar behavior of the candidates implies that they possibly share a ligand, which is expressed both by EC and CF, but more prominently by the latter.
This work demonstrates the possibility of using aptamers to transport miRs into cells of the cardiovascular system. It also shows that it is possible to select aptamers for non-cancerous mammalian cells, which has not been done before. It is reasonable to assume that a refinement of the cell-SELEX will allow selection of cell-specific aptamers. Due to the failure of reprogramming of adult fibroblasts into induced cardiomyocytes we were unable to test whether a miR-mediated reprogramming might be inducible using aptamer transported-miRs. Ultimately, aptamer mediated transport of miRs is a feasible and promising therapeutic option for the treatment of cardiovascular diseases and other disorders like cancer.
Ausdrucksphänomene fluktuieren zwischen den Sphären von Körperlichkeit und Bewegung sowie Sprachlichkeit und Kommunikation. Um Ausdruck in seiner eigentümlichen Mobilität und Wandlungsfähigkeit zu erfassen, erkunden die Beiträge des vorliegenden Bands seine ästhetischen, sozialen und (inter-)subjektiven Dimensionen und deren Überschneidungen sowohl im Rahmen historischer Entwicklungen als auch vor dem Hintergrund aktueller Erkenntnisse und Debatten der Psychologie, Philosophie, Hirnforschung und Linguistik. Aus den Themenbereichen Körper, Sprache und Künste, aber gleichfalls aus übergreifenden Fragestellungen der Anthropologie heraus werden kommunikative und körperliche Ausdrucksformen, auch in ihrem Zusammenspiel, in systematischer Weise analysiert und auf ihre situative und historische Spezifik hin untersucht. Nicht nur sprachliche Äußerungen, sondern ebenso Gesten und Gebärden, Tanz, Musik, Mienenspiel und Malerei stoßen dabei an Grenzen der Verständlichkeit und verweisen auf Ausdrucksqualitäten jenseits von Verbalität und Körperlichkeit.
The development of the atrioventricular (AV) canal and the cardiac valves is tightly linked and a critically regulated process. Anomalies in components of the involved pathways can lead to congenital valve malformations, a leading cause of morbidity and mortality in neonates. Myocardial Bmp as well as endocardial Notch and Wnt signaling have been identified as critical factors for the induction of EMT during the formation of the endocardial cushions and cardiac valves. Of these, canonical Wnt signaling positively regulates endocardial proliferation and EMT but negatively regulates endocardial differentiation. Further, elevated Wnt signaling leads to the ectopic expression of myocardial Bmp ligands suggesting a high level of integration of the involved pathways and crosstalk amongst the different cardiac tissues.
Here we have identified a novel role for Id4 as a mediator between Bmp and Wnt signaling. Id4 belongs to the Id family of proteins and is known to be involved in bone and nervous system development. We found that in zebrafish, id4 is expressed in the endocardium of the AV canal at embryonic stages and throughout the atrial chamber in addition to AV canal, in adults. Using transcription activator-like effector nucleases (TALENs) we established an id4 mutant allele. Our analysis shows that id4 mutant larvae are susceptible to retrograde blood flow, and show aberrant expression of developmental valvular markers. These include expanded expression domains of markers like bmp4, cspg2a and Alcam. In contrast, valve maturation as assessed by the expression of spp1 is considerably reduced in id4 mutants. Using conditional transgenic systems, along with elegant in vivo imaging of transgenic reporter lines, we further found that id4 is a transcriptional target of Bmp signaling, and it is capable of dose dependently restricting Wnt signaling in the endocardium of the Atrioventricular Canal.
Taken together, our data identifies Id4 as a novel player in Atrioventricular Canal and valve development. We show that Id4 function is important in valve development acting downstream of Bmp signaling by restricting endocardial Wnt to allow valve maturation
Purpose: To analyze the protein profile of human vitreous of untreated patients with retinal vein occlusion (RVO).
Methods: Sixty-eight vitreous humor (VH) samples (44 from patients with treatment naïve RVO, 24 controls with idiopathic floaters) were analyzed in this clinical-experimental study using capillary electrophoresis coupled to mass spectrometer and tandem mass spectrometry. To define potential candidate protein markers of RVO, proteomic analysis was performed on RVO patients (n = 30) and compared with controls (n = 16). To determine validity of potential biomarker candidates in RVO, receiver operating characteristic (ROC) was performed by using proteome data of independent RVO (n = 14) and control samples (n = 8).
Results: Ninety-four different proteins (736 tryptic peptides) could be identified. Sixteen proteins were found to be significant when comparing RVO and control samples (P = 1.43E-05 to 4.48E-02). Five proteins (Clusterin, Complement C3, Ig lambda-like polypeptide 5 (IGLL5), Opticin and Vitronectin), remained significant after using correction for multiple testing. These five proteins were also detected significant when comparing subgroups of RVO (central RVO, hemi-central RVO, branch RVO) to controls. Using independent samples ROC-Area under the curve was determined proving the validity of the results: Clusterin 0.884, Complement C3 0.955, IGLL5 1.000, Opticin 0.741, Vitronectin 0.786. In addition, validation through ELISA measurements was performed.
Conclusion: The results of the study reveal that the proteomic composition of VH differed significantly between the patients with RVO and the controls. The proteins identified may serve as potential biomarkers for pathogenesis induced by RVO.
Deciduous plants avoid the costs of maintaining leaves in the unfavourable season, but carry the costs of constructing new leaves every year. Deciduousness is therefore expected in ecological situations with pronounced seasonality and low costs of leaf construction. In our study system, a seasonally dry tropical savanna, many trees are deciduous, suggesting that leaf construction costs must be low. Previous studies have, however, shown that nitrogen is limiting in this system, suggesting that leaf construction costs are high. Here we examine this conundrum using a time series of soil moisture availability, leaf phenology and nitrogen distribution in the tree canopy to illustrate how trees resorb nitrogen before leaf abscission and use stored reserves of nitrogen and carbon to construct new leaves at the onset of the growing season. Our results show that trees deployed leaves shortly before and in anticipation of the first rains with its associated pulse of nitrogen mineralisation. Our results also show that trees rapidly constructed a full canopy of leaves within two weeks of the first rains. We detected an increase in leaf nitrogen content that corresponded with the first rains and with the movement of nitrogen to more distal branches, suggesting that stored nitrogen reserves are used to construct leaves. Furthermore the stable carbon isotope ratios (δ13C) of these leaves suggest the use of stored carbon for leaf construction. Our findings suggest that the early deployment of leaves using stored nitrogen and carbon reserves is a strategy that is integrally linked with the onset of the first rains. This strategy may confer a competitive advantage over species that deploy leaves at or after the onset of the rains.
Background: Hypothermia has been discussed as playing a role in improving the early phase of systemic inflammation. However, information on the impact of hypothermia on the local inflammatory response is sparse. We therefore investigated the kinetics of local and systemic inflammation in the late posttraumatic phase after induction of hypothermia in an established porcine long-term model of combined trauma.
Materials & Methods: Male pigs (35 ± 5kg) were mechanically ventilated and monitored over the study period of 48 h. Combined trauma included tibia fracture, lung contusion, liver laceration and pressure-controlled hemorrhagic shock (MAP < 30 ± 5 mmHg for 90 min). After resuscitation, hypothermia (33°C) was induced for a period of 12 h (HT-T group) with subsequent re-warming over a period of 10 h. The NT-T group was kept normothermic. Systemic and local (fracture hematoma) cytokine levels (IL-6, -8, -10) and alarmins (HMGB1, HSP70) were measured via ELISA.
Results: Severe signs of shock as well as systemic and local increases of pro-inflammatory mediators were observed in both trauma groups. In general the local increase of pro- and anti-inflammatory mediator levels was significantly higher and prolonged compared to systemic concentrations. Induction of hypothermia resulted in a significantly prolonged elevation of both systemic and local HMGB1 levels at 48 h compared to the NT-T group. Correspondingly, local IL-6 levels demonstrated a significantly prolonged increase in the HT-T group at 48 h.
Conclusion: A prolonged inflammatory response might reduce the well-described protective effects on organ and immune function observed in the early phase after hypothermia induction. Furthermore, local immune response also seems to be affected. Future studies should aim to investigate the use of therapeutic hypothermia at different degrees and duration of application.
Background: Common ECG criteria such as ST-segment changes are of limited value in patients with suspected acute myocardial infarction (AMI) and bundle branch block or wide QRS complex. A large proportion of these patients do not suffer from an AMI, whereas those with ST-elevation myocardial infarction (STEMI) equivalent AMI benefit from an aggressive treatment. Aim of the present study was to evaluate the diagnostic information of cardiac troponin I (cTnI) in hemodynamically stable patients with wide QRS complex and suspected AMI.
Methods: In 417 out of 1818 patients presenting consecutively between 01/2007 and 12/2008 in a prospective multicenter observational study with suspected AMI a prolonged QRS duration was observed. Of these, n = 117 showed significant obstructive coronary artery disease (CAD) used as diagnostic outcome variable. cTnI was determined at admission.
Results: Patients with significant CAD had higher cTnI levels compared to individuals without (median 250ng/L vs. 11ng/L; p<0.01). To identify patients needing a coronary intervention, cTnI yielded an area under the receiver operator characteristics curve of 0.849. Optimized cut-offs with respect to a sensitivity driven rule-out and specificity driven rule-in strategy were established (40ng/L/96ng/L). Application of the specificity optimized cut-off value led to a positive predictive value of 71% compared to 59% if using the 99th percentile cut-off. The sensitivity optimized cut-off value was associated with a negative predictive value of 93% compared to 89% provided by application of the 99th percentile threshold.
Conclusion: cTnI determined in hemodynamically stable patients with suspected AMI and wide QRS complex using optimized diagnostic thresholds improves rule-in and rule-out with respect to presence of a significant obstructive CAD.
Background: Advanced liver diseases are associated with profound alterations of the coagulation system increasing the risk not only of bleeding, but also of thromboembolic complications. A recent milestone study has shown that prophylactic anticoagulation in liver cirrhosis patients results in a reduced frequency of hepatic decompensation. Yet, INR measurement, one of the most widely applied tests to assess liver function, only inaccurately predicts the risk of hepatic decompensation related to alterations of the coagulation system. To assess the relationship between selected coagulation factors / natural anticoagulants with INR, MELD score, and hepatic decompensation, we performed the present pilot study. A total number of 92 patients with various stages of liver cirrhosis were included and prospectively followed for at least 6 months. We found that important natural anticoagulants, namely antithrombin and protein C, as well as factor XI (which may also serve as an anticoagulant) decreased earlier and by a larger magnitude than one would expect from classical coagulation test results. The correlation between these factors and INR was only moderate. Importantly, reduced plasma activities of natural anticoagulants but not INR or MELD score were independent predictors of hepatic encephalopathy (P = 0.013 and 0.003 for antithrombin and protein C, respectively).
Conclusion: In patients with liver cirrhosis plasma activities of several natural anticoagulants are earlier and stronger affected than routine coagulation tests. Reduced activities of natural anticoagulants may be predictive for the development of hepatic encephalopathy.
Thromboembolic events are one of the world’s leading causes of death among patients. Embolus or clot formations have several etiologies including paraneoplastic, post-surgery, cauterization, transplantation, or extracorporeal circuits. Despite its medical significance, little progress has been made in early embolus detection, screening and control. The aim of our study is to test the utility of the in vivo photoacoustic (PA) flow cytometry (PAFC) technique for non-invasive embolus detection in real-time. Using in vivo PAFC, emboli were non-invasively monitored in the bloodstream of two different mouse models. The tumor-free mouse model consisted of two groups, one in which the limbs were clamped to produce vessel stasis (7 procedures), and one where the mice underwent surgery (7 procedures). The melanoma-bearing mouse model also consisted of two groups, one in which the implanted tumor underwent compression (8 procedures), and one where a surgical excision of the implanted tumor was performed (8 procedures). We demonstrated that the PAFC can detect a single embolus, and has the ability to distinguish between erythrocyte–rich (red) and leukocyte/platelet-rich (white) emboli in small vessels. We show that, in tumor-bearing mice, the level of circulating emboli was increased compared to tumor-free mice (p = 0.0013). The number of circulating emboli temporarily increased in the tumor-free control mice during vessel stasis (p = 0.033) and after surgical excisions (signed-rank p = 0.031). Similar observations were noted during tumor compression (p = 0.013) and after tumor excisions (p = 0.012). For the first time, it was possible to detect unlabeled emboli in vivo non-invasively, and to confirm the presence of pigmented tumor cells within circulating emboli. The insight on embolus dynamics during cancer progression and medical procedures highlight the clinical potential of PAFC for early detection of cancer and surgery-induced emboli to prevent the fatal thromboembolic complications by well-timed therapy.
Leptomeningeal dissemination of a primary brain tumor is a condition which is challenging to treat, as it often occurs in rather late disease stages in highly pretreated patients. Its prognosis is dismal and there is still no accepted standard of care. We report here a good clinical effect with a partial response in three out of nine patients and a stable disease with improvement on symptoms in two more patients following systemic anti-angiogenic treatment with bevacizumab (BEV) alone or in combination with chemo- and/or radiotherapy in a series of patients with leptomeningeal dissemination from primary brain tumors (diffuse astrocytoma WHO°II, anaplastic astrocytoma WHO°III, anaplastic oligodendroglioma WHO°III, primitive neuroectodermal tumor and glioblastoma, both WHO°IV). This translated into effective symptom control in five out of nine patients, but only moderate progression-free and overall survival times were reached. Partial responses as assessed by RANO criteria were observed in three patients (each one with anaplastic oligodendroglioma, primitive neuroectodermal tumor and glioblastoma). In these patients progression-free survival (PFS) intervals of 17, 10 and 20 weeks were achieved. In three patients (each one with diffuse astrocytoma, anaplastic astrocytoma and primitive neuroectodermal tumor) stable disease was observed with PFS of 13, 30 and 8 weeks. Another three patients (all with glioblastoma) were primary non-responders and deteriorated rapidly with PFS of 3 to 4 weeks. No severe adverse events were seen. These experiences suggest that the combination of BEV with more conventional therapy schemes with chemo- and/or radiotherapy may be a palliative treatment option for patients with leptomeningeal dissemination of brain tumors.
Triple therapy of chronic hepatitis C virus (HCV) infection with boceprevir (BOC) or telaprevir (TVR) leads to virologic failure in many patients which is often associated with the selection of resistance-associated variants (RAVs). These resistance profiles are of importance for the selection of potential rescue treatment options. In this study, we sequenced baseline NS3 RAVs population-based and investigated the sensitivity of NS3 phenotypes in an HCV replicon assay together with clinical factors for a prediction of treatment response in a cohort of 165 German and Swiss patients treated with a BOC or TVR-based triple therapy. Overall, the prevalence of baseline RAVs was low, although the frequency of RAVs was higher in patients with virologic failure compared to those who achieved a sustained virologic response (SVR) (7% versus 1%, P = 0.06). The occurrence of RAVs was associated with a resistant NS3 quasispecies phenotype (P<0.001), but the sensitivity of phenotypes was not associated with treatment outcome (P = 0.2). The majority of single viral and host predictors of SVR was only weakly associated with treatment response. In multivariate analyses, low AST levels, female sex and an IFNL4 CC genotype were independently associated with SVR. However, a combined analysis of negative predictors revealed a significantly lower overall number of negative predictors in patients with SVR in comparison to individuals with virologic failure (P<0.0001) and the presence of 2 or less negative predictors was indicative for SVR. These results demonstrate that most single baseline viral and host parameters have a weak influence on the response to triple therapy, whereas the overall number of negative predictors has a high predictive value for SVR.
Background: Expected growth in the demand for health services has generated interest in the more effective deployment of health care assistants. Programs encouraging German general practitioners (GPs) to share responsibility for care with specially qualified health care assistants in the family practice (VERAHs) have existed for several years. But no studies have been conducted on the tasks German GPs are willing to rely on specially qualified personnel to perform, what they are prepared to delegate to all non-physician practice staff and what they prefer to do themselves.
Methods: As part of an evaluation study on the deployment of VERAHs in GP-centered health care, we used a questionnaire to ask about task delegation within the practice team. From a list of tasks that VERAHs are specifically trained to carry out, GPs were asked to indicate which they actually delegate. We also asked GPs why they had employed a VERAH in their practice and for their opinions on the benefits and limitations of assigning tasks to VERAHs. The aim of the study was to find out which tasks GPs delegate to their specially qualified personnel, which they permit all HCAs to carry out, and which tasks they do not delegate at all.
Results: The survey was filled in and returned by 245 GPs (83%). Some tasks were exclusively delegated to VERAHs (e.g. home visits), while others were delegated to all HCAs (e.g. vaccinations). About half the GPs rated the assessment of mental health, as part of the comprehensive assessment of a patient’s condition, as the sole responsibility of a GP.
The possibility to delegate more complex tasks was the main reason given for employing a VERAH. Doctors said the delegation of home visits provided them with the greatest relief.
Conclusions: In Germany, where GPs are solely accountable for the health care provided in their practices, experience with the transfer of responsibility to other non-physician health care personnel is still very limited. When HCAs have undergone special training, GPs seem to be prepared to delegate tasks that demand a substantial degree of know-how, such as home visits and case management. This “new” role allocation within the practice may signal a shift in the provision of health care by family practice teams in Germany.
Objective: Mucoactive drugs should increase the ability to expectorate sputum and, ideally, have anti-inflammatory properties. The aim of the study was to evaluate the mucolytic activity of Tyloxapol compared to saline (0.9%) in COPD.
Design: A randomized, placebo-controlled, double-blinded crossover, clinical trial was carried out. Patients were randomly assigned to either inhale 5 ml Tyloxapol 1% or saline 0.9% solution three times daily for 3 weeks and vice versa for another 3 weeks. 28 patients (18 male, 10 female, 47 to 73 years old, median age 63.50) were screened, 21 were treated and 19 patients completed the study per protocol.
Results: A comparison of the two treatment phases showed that the primary endpoint sputum weight was statistically significant higher when patients inhaled Tyloxapol (mean 4.03 g, 95% CI: 2.34–5.73 g at week 3) compared to saline (mean 2.63 g, 95% CI: 1.73–3.53 g at week 3). The p-value at three weeks of treatment was 0.041 between treatment arms. Sputum cells decreased during the Tyloxapol treatment after 3 weeks, indicating that Tyloxapol might have some anti-neutrophilic properties. Lung function parameters (FVC, FEV1, RV, and RV/TLC) remained stable during the study, and no treatment effect was shown. Interestingly, there was a mean increase in all inflammatory cytokines (IL-1β, IL-6, and IL-8) during the saline treatment from day 1 to week 3, whereas during the Tyloxapol treatment, all cytokines decreased. Due to the small sample size and the large individual variation in sputum cytokines, these differences were not significant. However, analyses confirmed that Tyloxapol has significant anti-inflammatory properties in vitro. Despite the high number of inhalations (more than 1000), only 27 adverse events (20 during the Tyloxapol and seven during saline) were recorded. Eleven patients experienced AEs under Tyloxapol and six under saline treatment, which indicates that inhalation of saline or Tyloxapol is a very safe procedure.
Conclusion: Our study demonstrated that inhalation of Tyloxapol by patients with COPD is safe and superior to saline and has some anti-inflammatory effects.
We integrated recent improvements within the floating catchment area (FCA) method family into an integrated ‘iFCA`method. Within this method we focused on the distance decay function and its parameter. So far only distance decay functions with constant parameters have been applied. Therefore, we developed a variable distance decay function to be used within the FCA method. We were able to replace the impedance coefficient β by readily available distribution parameter (i.e. median and standard deviation (SD)) within a logistic based distance decay function. Hence, the function is shaped individually for every single population location by the median and SD of all population-to-provider distances within a global catchment size. Theoretical application of the variable distance decay function showed conceptually sound results. Furthermore, the existence of effective variable catchment sizes defined by the asymptotic approach to zero of the distance decay function was revealed, satisfying the need for variable catchment sizes. The application of the iFCA method within an urban case study in Berlin (Germany) confirmed the theoretical fit of the suggested method. In summary, we introduced for the first time, a variable distance decay function within an integrated FCA method. This function accounts for individual travel behaviors determined by the distribution of providers. Additionally, the function inherits effective variable catchment sizes and therefore obviates the need for determining variable catchment sizes separately.
Background: Dengue virus infection is the most rapidly spreading vector-borne disease in the world. Essential research on dengue virus transmission and its prevention requires community participation. Therefore, it is crucial to understand the factors that are associated with the willingness of communities in high prevalence areas to participate in dengue research. The aim of this study was to explore factors associated with the willingness of healthy community members in Aceh province, Indonesia, to participate in dengue research that would require phlebotomy.
Methodology/Principal Findings: A community-based cross-sectional study was carried out in nine regencies and municipalities of Aceh from November 2014 to March 2015. Interviews using a set of validated questionnaires were conducted to collect data on demography, history of dengue infection, socioeconomic status, and knowledge, attitude and practice regarding dengue fever. Two-step logistic regression and Spearman’s rank correlation (rs) analysis were used to assess the influence of independent variables on dependent variables. Among 535 participants, less than 20% had a good willingness to participate in the dengue study. The factors associated with good willingness to participate were being female, working as a civil servant, private employee or entrepreneur, having a high socioeconomic status and good knowledge, attitude and practice regarding dengue. Good knowledge and attitude regarding dengue were positive independent predictors of willingness to participate (OR: 2.30 [95% CI: 1.36–3.90] and 3.73 [95% CI: 2.24–6.21], respectively).
Conclusion/Significance: The willingness to participate in dengue research is very low among community members in Aceh, and the two most important associated factors are knowledge and attitude regarding dengue. To increase participation rate, efforts to improve the knowledge and attitude of community members regarding dengue fever and dengue-related research is required before such studies are launched.
1. Objective: Chronic hepatitis C virus infections (HCV) cause a significant public health burden. Introduction of telaprevir (TVR) and boceprevir (BOC) has increased sustained virologic response rates (SVR) in genotype 1 patients but were accompanied by higher treatment costs and more side effects. Aim of the study was to assess outcomes and costs of treating HCV with TVR or BOC in routine care.
2. Material and Methods: Data was obtained from a non-interventional study. This analysis relates on a subset of 1,786 patients for whom resource utilisation was documented. Sociodemografic and clinical parameters as well as resource utilisation were collected using a web-based data recording system. Costs were calculated using official remuneration schemes.
3. Results: Mean age of patients was 49.2 years, 58.6% were male. In treatment-naive patients SVR-rates of 62.2% and 55.7% for TVR and BOC were observed (prior relapser: 68.5% for TVR and 63.5% for BOC; prior nonresponder: 45.6% for TVR and 39.1% for BOC). Treatment costs are dominated by costs for pharmaceuticals and range between €39,081 and €53,491. We calculated average costs per SVR of €81,347 (TVR) and €70,163 (BOC) in treatment-naive patients (prior relapser: 78,089 €/SVR for TVR and 82,077 €/SVR for BOC; prior non-responder: 116,509 €/SVR for TVR and 110,156 €/SVR for BOC). Quality of life data showed a considerable decrease during treatment.
4. Conclusion: Our study is one of few investigating both, outcomes and costs, of treating HCV in a real-life setting. Data can serve as a reference in the discussion of increasing costs in recently introduced agents
Mediation in der Türkei : Betrachtung ausgewählter Aspekte im Vergleich zur Mediation in Deutschland
(2016)
Angesichts der vergleichsweise noch sehr jungen Entwicklung der Mediation in der Türkei mag man es auf den ersten Blickerstaunlich finden, dass in der Türkei zeitgleich mit Deutschland ein Mediationsgesetz geschaffen wurde. Die Mediation als außergerichtliches Vermittlungsverfahren gründet darauf, dass Streitparteien freiwillig und selbstbestimmt ihren Konflikt mit Unterstützung eines Mediators einer gemeinsam entwickelten Lösung zuführen. Dies sind die Grundprinzipien der Mediation, die sowohl dem deutschen als auch dem türkischen Mediationsgesetz als Basis dienen.
Trotz vieler Ähnlichkeiten haben die kulturellen Besonderheiten beider Länder Einfluss auf die rechtliche Ausgestaltung dieses Einigungsverfahrens sowie dessen Umsetzung in der Praxis .Ziel des vorliegenden Arbeitspapiers ist es, dem Leser einen Einblick in die Unterschiede und Gemeinsamkeiten der Mediation in der Türkei und Deutschland zu vermitteln und dabei vergleichend zu untersuchen , ob und inwieweit landestypischen Spezifika in der Entstehungsgeschichte, den Grundlagen und der Praxis der Mediation erkennbar und durch gesellschaftliche und kulturelle Faktoren erklärbar sind.
Die vorliegende Studie vermittelt einen epidemiologischen Überblick über das mit Haut- und Nagelläsionen assoziierte Pilzspektrum im Westen Panamas. Hierzu wurden Proben von vermutlich durch Pilzinfektionen verursachten Haut- sowie Nagelläsionen gesammelt und zum Anlegen von Kulturen verwendet. Die isolierten Pilze wurden basierend auf dem D-H-S System (Rieth), anhand morphologischer Merkmale, rDNA Sequenzdaten sowie phylogenetischen Analysen klassifiziert und mit Hilfe von Literaturdaten sowie physiologischen Eigenschaften als saprotrophe, opportunistische oder pathogene Organismen beurteilt. In Panama wurden 52 Proben von 51 Personen gesammelt, wobei das Material von 42 Haut- und Nagelläsionen der Füße, vier Läsionen der Fingernägel, zwei Chromomykosen, einer Tinea nigra und drei sonstigen Hautläsionen stammt. Bei 75 Prozent (n = 39) der Proben konnten Pilze kultiviert und insgesamt 201 Pilzstämme isoliert und subkultiviert werden. Hiervon wurden 50 Isolate (24,9 %) als Dermatophyten, 24 Stämme (11,9 %) als Hefen und 127 Isolate (63,2 %) als Schimmelpilze klassifiziert. Bei 19 Probanden (48,7 %) konnten Dermatophyten isoliert werden, wobei aus dem Probenmaterial von 12 Personen (63,2 %) ebenfalls andere Pilzarten nachgewiesen wurden. Von zwei Läsionen (5,1 %) wurden nur Hefen isoliert, wobei einmal eine Schwarze Hefe kultiviert wurde. In dem Material acht weiterer Proben (20,5 %) wurden Schimmelpilze und Hefestämme nachgewiesen und bei zehn Probanden (25,6 %) konnten aus dem Probenmaterial nur Schimmelpilze kultiviert werden. 172 Isolate wurden taxonomisch klassifiziert und 44 Arten aus 25 Gattungen, 17 Familien, 15 Ordnungen, sechs Klassen sowie den Abteilungen Ascomycota oder Basidiomycota zugeordnet. Die Ascomyceten stellen mit 164 Stämmen 40 verschiedener Arten aus 23 Gattungen, 15 Familien, 11 Ordnungen und vier Klassen die am häufigsten isolierte und vielfältigste Gruppe dar, während die Basidiomycota nur mit acht Isolaten vier verschiedener Arten zwei unterschiedlicher Gattungen, Familien, Ordnungen und Klassen nachgewiesen wurden. Im Rahmen dieser Arbeit wurden in Panama die anthropophilen Dermatophyten Trichophyton rubrum und T. interdigitale dokumentiert, wobei T. rubrum die am häufigsten isolierte Art darstellt. Kultivierte Hefen waren Candida albicans, C. duobushaemulonii, C. tropicalis, Hortaea werneckii, Sporobolomyces sp., Trichosporon asahii, T. japonicum und T. montevideense. Die Schimmelpilze stellen die größte und ökologisch diverseste Organismengruppe der kultivierten Pilze dar. So wurden von den untersuchten Läsionen sowohl humanpathogene Erreger, als auch opportunistische Arten und rein saprotrophe Pilze sowie mehrere Vertreter wahrscheinlich bisher nicht wissenschaftlich beschriebener Arten bzw. Gattungen nachgewiesen. Aus dem Probenmaterial wurden die Pilze Acremonium collariferum, Aspergillus awamori, A. clavatus, A. flavus, A. giganteus, A. heteromorphus, A. niger, A. ochraceus, A. sclerotiorum, A. versicolor, Chaetomium globosum, Chrysosporium tuberculatum, Cladosporium sphaerospermum, C. tenuissimum, Curvularia geniculata, C. lunata, Fonsecaea pedrosoi, Fusarium oxysporum, F. solani, Lophotrichus bartlettii, Microascus cinereus, Neoscytalidium dimidiatum, Penicillium commune, Scolecobasidium sp., Scopulariopsis carbonaria, S. croci, Verticillium cf. epiphytum und Wardomycopsis litoralis isoliert. Zudem wurden vier Isolate von zwei vermutlich neuen Arten der Gattung Acremonium (Bionectriaceae, Hypocreales), zwei Stämme mit einer genetischen Affinität zu der Gattung Cryptendoxyla (Cephalothecaceae, Sordariales) und jeweils ein mit den Gattungen Fusicladium (Venturiaceae, Venturiales), Knufia (Trichomeriaceae, Chaetothyriales) bzw. Rhexothecium (Eremomycetaceae, Dothideomycetidae) assoziierter Stamm kultiviert. Im Rahmen dieser Studie wurden A. giganteus, C. tenuissimum, L. bartlettii, S. carbonaria, S. croci, V. epiphytum und W. litoralis erstmalig von Mykosen des Menschen dokumentiert und die in der Literatur als Verursacher sowie Besiedler von Haut- und Nagelläsionen beschriebenen Organismen A. clavatus, A. flavus, A. niger, A. ochraceus, C. tropicalis, C. globosum, C. sphaerospermum, C. lunata, F. oxysporum, M. cinereus, P. commune, T. asahii, T. japonicum und T. montevideense wurden das erste Mal in klinischem Probenmaterial aus Panama nachgewiesen. Die Arten A. awamori, A. heteromorphus, C. globosum, C. tenuissimum, L. bartlettii, M. cinereus, P. commune, S. croci, T. asahii, T. japonicum, T. montevideense, V. epiphytum, W. litoralis und die Gattung Scolecobasidium wurden zudem erstmalig für Panama dokumentiert. Die Isolation von W. litoralis ist ebenfalls der erste Nachweis dieses Pilzes außerhalb von Spanien und auf dem amerikanischen Kontinent. Die große Anzahl im Rahmen dieser Arbeit beschriebener, bisher für die Wissenschaft unbekannter bzw. nicht in Panama dokumentierter Pilzarten lässt auf eine große mykologische Biodiversität in Panama schließen und zeigt den Bedarf weiterer Forschung.
Structural characterization of stressosome complexes by single-particle cryo-electron microscopy
(2015)
The stressosome is a Mega Dalton macromolecular complex involved in stress adaptation in bacteria. Stressosomes are considered as stress signaling hubs. They are able to perceive a variety of different stress stimuli and transduce them into one single cellular answer, which is the initialization of a transcriptional up-regulation of hundreds of different genes encoding for universal but also very specific stress response proteins.
The stressosome of Bacillus subtilis became a prime example for this intriguing stress-triggered transcriptional regulation when its architecture was determined by Single-particle cryo-electron microscopy (cryo-EM) in 2008. In Gram-positive Bacillus species, the stressosome complex senses changes in salt concentration, ethanol content, blue-light, heat or acid stress contributing to the general stress response by activation of the alternative σB factor. σB is a transcriptional promoter that initiates the transcription of over 150 general stress genes, e.g., genes that encode osmolyte transporters to counteract osmotic and chill stress. The B. subtilis stressosome (stressosome_Bc) is composed of multiple copies of the 3 proteins: RsbR, RsbS and RsbT. These three Rsb proteins (Regulator of Sigma B) are found clustered in one operon forming the conserved RST module. RsbS and RsbR are scaffold proteins comprising a STAS domain, respectively. Because these domains are dominantly associated to sulfate transporters and anti-sigma antagonist they were named STAS domains, however, they were also identified in other sensor proteins. In the stressosome they form the internal ball-shaped core, while the N-terminal globin-fold sensor domain of RsbR, protruding to the outside, facilitates stress sensing. It is assumed that the stress signal is transduced to the stressosome core via the STAS domain resulting in conformational changes of the core. These changes affect the binding of the third protein, RsbT, a serin-threonine kinase. As a direct consequence of stress sensing the RsbT kinase is released from the complex to start an activation cascade involving the stepwise activation of RsbU, V, W, and X, which are all part of the same operon, and finally of σB. In Bacillus species, several RsbR orthologs were identified varying mainly in the sequence of the N-terminal sensor domains. It is assumed that the stressosome_Bc assembles with a still unknown combination of RsbR orthologs allowing for the broad spectrum of stress stimuli that can be processed in vivo. The pathogenic bacteria Listeria monocytogenes is a close relative of Bacillus. Its potent stress response allows Listeria to survive the harsh environmental conditions during host infection and therefore the stress regulation machinery is contributing heavily to the virulence of this pathogen. In Listeria the Rsb operon is conserved and highly homologous to the Bacillus one. In the frame of this thesis, the in vitro assembly of Listeria innocua stressosomes was shown for the first time by Single-particle (SP) negative stain EM. Moreover, binding of Listeria RsbT to the assembled RsbR-RsbS complex was demonstrated biochemically.
Despite the conservation of the RST-module the entire Rsb operon is not conserved in the bacterial kingdom suggesting that signal transduction and regulation of gene expression might occur by very different mechanisms in stressosomes of different species. We have focused here on a stressosome type from the Gram-negative pathogen Vibrio vulnificus that is quite distinct from the Bacillus ones with respect to (1) the missing conservation of the Rsb operon, (2) the role of RsbT, (3) the activation of a different transcriptional promoter, and (4) the absence of additional RsbR orthologs. Interestingly, there is only one RsbR protein encoded in the genome. This one contains a Haem-group in its N-terminal domain being oxygen sensitive. It is assumed that the Vibrio stressosome perceive only oxidative stress and that regulation occurs via a diguanylate cyclase with a GAF domain that synthesizes the second messenger c-di-GMP from GTP.
We have started a structure determination of the Vibrio vulnificus stressosome by SP cryo-EM to elucidate the differences in the molecular mechanism of stress sensing in divers stressosome types. A 3D map of the oxidized (activated) Vibrio vulnificus stressosome was determined to 7.6 Å resolution revealing an increased flexibility of both the core and the N-terminal sensor domains in comparison to the Bacillus stressosome suggesting that our structure has trapped for the first time an active state of a stressosome complex. A 3D map of the stressosome core to 7 Å resolution allowed fitting of a homology model of the Vibrio stressosome based on the Bacillus stressosome as template. The conformational changes could be attributed to the entire core, which was confirmed by MD simulations.
Mitochondrial cristae are connected to the inner boundary membrane via crista junctions which are implicated in the regulation of oxidative phosphorylation, apoptosis, and import of lipids and proteins. The MICOS complex determines formation of crista junctions. We performed complexome profiling and identified Mic13, also termed Qil1, as a subunit of the MICOS complex. We show that MIC13 is an inner membrane protein physically interacting with MIC60, a central subunit of the MICOS complex. Using the CRISPR/Cas method we generated the first cell line deleted for MIC13. These knockout cells show a complete loss of crista junctions demonstrating that MIC13 is strictly required for the formation of crista junctions. MIC13 is required for the assembly of MIC10, MIC26, and MIC27 into the MICOS complex. However, it is not needed for the formation of the MIC60/MIC19/MIC25 subcomplex suggesting that the latter is not sufficient for crista junction formation. MIC13 is also dispensable for assembly of respiratory chain complexes and for maintaining mitochondrial network morphology. Still, lack of MIC13 resulted in a moderate reduction of mitochondrial respiration. In summary, we show that MIC13 has a fundamental role in crista junction formation and that assembly of respiratory chain supercomplexes is independent of mitochondrial cristae shape.
Background & Aim: The resistance profile of anti-hepatitis C virus (HCV) agents used in combination is important to guide optimal treatment regimens. We evaluated baseline and treatment-emergent NS3/4A and NS5B amino-acid variants among HCV genotype (GT)-1a and -1b-infected patients treated with faldaprevir (HCV protease inhibitor), deleobuvir (HCV polymerase non-nucleoside inhibitor), and ribavirin in multiple clinical studies.
Methods: HCV NS3/4A and NS5B population sequencing (Sanger method) was performed on all baseline plasma samples (n = 1425 NS3; n = 1556 NS5B) and on post-baseline plasma samples from patients with virologic failure (n = 113 GT-1a; n = 221 GT-1b). Persistence and time to loss of resistance-associated variants (RAVs) was estimated using Kaplan–Meier analysis.
Results: Faldaprevir RAVs (NS3 R155 and D168) and deleobuvir RAVs (NS5B 495 and 496) were rare (<1%) at baseline. Virologic response to faldaprevir/deleobuvir/ribavirin was not compromised by common baseline NS3 polymorphisms (e.g. Q80K in 17.5% of GT-1a) or by NS5B A421V, present in 20% of GT-1a. In GT-1b, alanine at NS5B codon 499 (present in 15% of baseline sequences) was associated with reduced response. Treatment-emergent RAVs consolidated previous findings: NS3 R155 and D168 were key faldaprevir RAVs; NS5B A421 and P495 were key deleobuvir RAVs. Among on-treatment virologic breakthroughs, RAVs emerged in both NS3 and NS5B (>90%). Virologic relapse was associated with RAVs in both NS3 and NS5B (53% GT-1b; 52% GT-1b); some virologic relapses had NS3 RAVs only (47% GT-1a; 17% GT-1b). Median time to loss of GT-1b NS5B P495 RAVs post-treatment (5 months) was less than that of GT-1b NS3 D168 (8.5 months) and GT-1a R155 RAVs (11.5 months).
Conclusion: Faldaprevir and deleobuvir RAVs are more prevalent among virologic failures than at baseline. Treatment response was not compromised by common NS3 polymorphisms; however, alanine at NS5B amino acid 499 at baseline (wild-type in GT-1a, polymorphism in GT-1b) may reduce response to this deleobuvir-based regimen.
Introduction: Sepsis remains associated with a high mortality rate. Endotoxin has been shown to influence viscoelastic coagulation parameters, thus suggesting a link between endotoxin levels and the altered coagulation phenotype in septic patients. This study evaluated the effects of systemic polyspecific IgM-enriched immunoglobulin (IgM-IVIg) (Pentaglobin® [Biotest, Dreieich, Germany]) on endotoxin activity (EA), inflammatory markers, viscoelastic and conventional coagulation parameters.
Methods: Patients with severe sepsis were identified by daily screening in a tertiary, academic, surgical ICU. After the inclusion of 15 patients, the application of IgM-IVIg (5 mg/kg/d over three days) was integrated into the unit’s standard operation procedure (SOP) to treat patients with severe sepsis, thereby generating “control” and “IgM-IVIg” groups. EA assays, thrombelastometry (ROTEM®) and impedance aggregometry (Multiplate®) were performed on whole blood. Furthermore, routine laboratory parameters were determined according to unit’s standards.
Results: Data from 26 patients were included. On day 1, EA was significantly decreased in the IgM-IVIg group following 6 and 12 hours of treatment (0.51 ±0.06 vs. 0.26 ±0.07, p<0.05 and 0.51 ±0.06 vs. 0.25 ±0.04, p<0.05) and differed significantly compared with the control group following 6 hours of treatment (0.26 ±0.07 vs. 0.43 ±0.07, p<0.05). The platelet count was significantly higher in the IgM-IVIg group following four days of IgM-IVIg treatment (200/nl ±43 vs. 87/nl ±20, p<0.05). The fibrinogen concentration was significantly lower in the control group on day 2 (311 mg/dl ±37 vs. 475 mg/dl ±47 (p = 0.015)) and day 4 (307 mg/dl ±35 vs. 420 mg/dl ±16 (p = 0.017)). No differences in thrombelastometric or aggregometric measurements, or inflammatory markers (interleukin-6 (IL-6), leukocyte, lipopolysaccharide binding protein (LBP)) were observed.
Conclusion: Treatment with IgM-enriched immunoglobulin attenuates the EA levels in patients with severe sepsis and might have an effect on septic thrombocytopenia and fibrinogen depletion. Viscoelastic, aggregometric or inflammatory parameters were not influenced.
Abstract: Integration of synaptic currents across an extensive dendritic tree is a prerequisite for computation in the brain. Dendritic tapering away from the soma has been suggested to both equalise contributions from synapses at different locations and maximise the current transfer to the soma. To find out how this is achieved precisely, an analytical solution for the current transfer in dendrites with arbitrary taper is required. We derive here an asymptotic approximation that accurately matches results from numerical simulations. From this we then determine the diameter profile that maximises the current transfer to the soma. We find a simple quadratic form that matches diameters obtained experimentally, indicating a fundamental architectural principle of the brain that links dendritic diameters to signal transmission.
Author Summary: Neurons take a great variety of shapes that allow them to perform their different computational roles across the brain. The most distinctive visible feature of many neurons is the extensively branched network of cable-like projections that make up their dendritic tree. A neuron receives current-inducing synaptic contacts from other cells across its dendritic tree. As in the case of botanical trees, dendritic trees are strongly tapered towards their tips. This tapering has previously been shown to offer a number of advantages over a constant width, both in terms of reduced energy requirements and the robust integration of inputs at different locations. However, in order to predict the computations that neurons perform, analytical solutions for the flow of input currents tend to assume constant dendritic diameters. Here we introduce an asymptotic approximation that accurately models the current transfer in dendritic trees with arbitrary, continuously changing, diameters. When we then determine the diameter profiles that maximise current transfer towards the cell body we find diameters similar to those observed in real neurons. We conclude that the tapering in dendritic trees to optimise signal transmission is a fundamental architectural principle of the brain.
Optimizing spike-sorting algorithms is difficult because sorted clusters can rarely be checked against independently obtained “ground truth” data. In most spike-sorting algorithms in use today, the optimality of a clustering solution is assessed relative to some assumption on the distribution of the spike shapes associated with a particular single unit (e.g., Gaussianity) and by visual inspection of the clustering solution followed by manual validation. When the spatiotemporal waveforms of spikes from different cells overlap, the decision as to whether two spikes should be assigned to the same source can be quite subjective, if it is not based on reliable quantitative measures. We propose a new approach, whereby spike clusters are identified from the most consensual partition across an ensemble of clustering solutions. Using the variability of the clustering solutions across successive iterations of the same clustering algorithm (template matching based on K-means clusters), we estimate the probability of spikes being clustered together and identify groups of spikes that are not statistically distinguishable from one another. Thus, we identify spikes that are most likely to be clustered together and therefore correspond to consistent spike clusters. This method has the potential advantage that it does not rely on any model of the spike shapes. It also provides estimates of the proportion of misclassified spikes for each of the identified clusters. We tested our algorithm on several datasets for which there exists a ground truth (simultaneous intracellular data), and show that it performs close to the optimum reached by a support vector machine trained on the ground truth. We also show that the estimated rate of misclassification matches the proportion of misclassified spikes measured from the ground truth data.
Purpose: Quantitative T2'-mapping detects regional changes of the relation of oxygenated and deoxygenated hemoglobin (Hb) by using their different magnetic properties in gradient echo imaging and might therefore be a surrogate marker of increased oxygen extraction fraction (OEF) in cerebral hypoperfusion. Since elevations of cerebral blood volume (CBV) with consecutive accumulation of Hb might also increase the fraction of deoxygenated Hb and, through this, decrease the T2’-values in these patients we evaluated the relationship between T2’-values and CBV in patients with unilateral high-grade large-artery stenosis.
Materials and Methods Data from 16 patients (13 male, 3 female; mean age 53 years) with unilateral symptomatic or asymptomatic high-grade internal carotid artery (ICA) or middle cerebral artery (MCA) stenosis/occlusion were analyzed. MRI included perfusion-weighted imaging and high-resolution T2’-mapping. Representative relative (r)CBV-values were analyzed in areas of decreased T2’ with different degrees of perfusion delay and compared to corresponding contralateral areas.
Results: No significant elevations in cerebral rCBV were detected within areas with significantly decreased T2’-values. In contrast, rCBV was significantly decreased (p<0.05) in regions with severe perfusion delay and decreased T2’. Furthermore, no significant correlation between T2’- and rCBV-values was found. Conclusions rCBV is not significantly increased in areas of decreased T2’ and in areas of restricted perfusion in patients with unilateral high-grade stenosis. Therefore, T2’ should only be influenced by changes of oxygen metabolism, regarding our patient collective especially by an increase of the OEF. T2’-mapping is suitable to detect altered oxygen consumption in chronic cerebrovascular disease.
Flower color is an important characteristic that determines the commercial value of ornamental plants. Gentian flowers occur in a limited range of colors because this species is not widely cultivated as a cut flower. Gentiana lutea L. var. aurantiaca (abbr, aurantiaca) is characterized by its orange flowers, but the specific pigments responsible for this coloration are unknown. We therefore investigated the carotenoid and flavonoid composition of petals during flower development in the orange-flowered gentian variety of aurantiaca and the yellow-flowered variety of G. lutea L. var. lutea (abbr, lutea). We observed minor varietal differences in the concentration of carotenoids at the early and final stages, but only aurantiaca petals accumulated pelargonidin glycosides, whereas these compounds were not found in lutea petals. We cloned and sequenced the anthocyanin biosynthetic gene fragments from petals, and analyzed the expression of these genes in the petals of both varieties to determine the molecular mechanisms responsible for the differences in petal color. Comparisons of deduced amino acid sequences encoded by the isolated anthocyanin cDNA fragments indicated that chalcone synthase (CHS), chalcone isomerase (CHI), anthocyanidin synthase 1 (ANS1) and ANS2 are identical in both aurantiaca and lutea varieties whereas minor amino acid differences of the deduced flavonone 3-hydroxylase (F3H) and dihydroflavonol 4-reductase (DFR) between both varieties were observed. The aurantiaca petals expressed substantially higher levels of transcripts representing CHS, F3H, DFR, ANS and UDP-glucose:flavonoid-3-O-glucosyltransferase genes, compared to lutea petals. Pelargonidin glycoside synthesis in aurantiaca petals therefore appears to reflect the higher steady-state levels of pelargonidin synthesis transcripts. Moreover, possible changes in the substrate specificity of DFR enzymes may represent additional mechanisms for producing red pelargonidin glycosides in petals of aurantiaca. Our report describing the exclusive accumulation of pelargonidin glycosides in aurantiaca petals may facilitate the modification of gentian flower color by the production of red anthocyanins.
Magnetism is a beautiful example of a macroscopic quantum phenomenon. While known at least since the ancient Greeks, a microscopic theoretical explanation of magnetism could only be achieved with the advent of quantum mechanics at the beginning of the 20th century. Then it was understood that in a certain class of solids the famous Pauli exclusion principle leads to an effective interaction between the microscopic magnetic moments, i.e., the spins, which favors an ordered, and hence macroscopically magnetic, state. Nowadays, magnetic phenomena are used in a host of applications, and are especially relevant for information storage and processing technologies.
Despite the long history of the field, magnetic phenomena are still an active research topic. In particular, in the last decade the fields of spintronics and spin-caloritronics emerged, which manipulate the microscopic spins via charge and heat currents respectively. This opens new avenues to potential applications; including the possibility to use the magnetic spin degrees of freedom instead of charges as carriers of information, which could provide a number of advantages such as reduced losses and further miniaturization.
In this thesis we do not delve any further into the realm of possible applications. Instead we use sophisticated theories to explore the microscopic spin dynamics which is the basis of all such applications. We also focus on a particular compound: Yttrium-iron garnet (YIG), which is a ferrimagnetic insulator. This material has been widely used in experiments on magnetism over the last decades, and is a popular candidate for spintronic devices. Microscopically, the low-energy magnetic properties of YIG can be described by a ferromagnetic Heisenberg model. For spintronics and spin-caloritronics applications, it is however insufficient to only consider the magnetic degrees of freedom; one should also include the coupling of the spins to the elastic lattice vibrations, i.e., the phonons. Besides giving an overview on techniques used throughout the thesis, the introductory Ch. 1 provides a discussion of the microscopic Hamiltonian used to model the coupled spin-phonon system in the subsequent chapters.
The topic of Ch. 2 are the consequences of the magnetoelastic coupling on the low-energy magnon excitations in YIG. Starting from the microscopic spin-phonon Hamiltonian, we rigorously derive the magnon-phonon hybridization and scattering vertices in a controlled spin wave expansion. For the experimentally relevant case of thin YIG films at room temperature, these vertices are then used to compute the magnetoelastic modes as well as the magnon damping. In the course of this work, the damping of magnons in this system was also investigated experimentally using Brillouin light scattering spectroscopy. While comparison to the experimental data shows that the magnetoelastic interactions do not dominate the total magnon relaxation in the experimentally accessible regime, we are able to show that the spin-lattice relaxation time is strongly momentum dependent, thereby providing a microscopic explanation of a recent experiment.
In the final Ch. 3, we investigate a different phenomenon occurring in thin YIG films: Room temperature condensation of magnons. Prior work attributed this condensation process to quantum mechanics, i.e., it was interpreted as Bose-Einstein condensation. However, this is not satisfactory because at room temperature, the magnons in YIG behave as purely classical waves. In particular, the quantum Bose-Einstein distribution reduces to the classical Rayleigh-Jeans distribution in this case. In addition, the effective spin in YIG is very large. Therefore we start from the hypothesis that the room temperature magnon condensation is actually a new example of the kinetic condensation of classical waves, which has so far only been observed by imaging classical light in a photorefractive crystal. To distinguish this classical condensation from the quantum mechanical Bose-Einstein one, we refer to it as Rayleigh-Jeans condensation. To prove our claim, we consider the classical equations of motion of the coupled spin-phonon system. By eliminating the phonon degrees of freedom, we microscopically derive a non-Markovian stochastic Landau-Lifshitz-Gilbert equation (LLG) for the classical spin vectors. We then use this LLG to perform numerical simulations of the magnon dynamics, with all parameters fixed by experiments. These simulations accurately reproduce all stages of the magnon time evolution observed in experiments, including the appearance of the magnon condensate at the bottom of the magnon spectrum. In this way we confirm our initial hypothesis that the magnon condensation is a classical Rayleigh-Jeans condensation, which is unrelated to quantum mechanics.
Entwicklung und Test einer supraleitenden 217 MHz CH-Kavität für das Demonstrator-Projekt an der GSI
(2016)
In den letzten Jahrzehnten vergrößerten sich die Anwendungsgebiete von Linearbeschleunigern für Protonen und schwere Ionen, insbesondere im Nieder- und Mittelenergiebereich, stetig. Der überwiegende Teil dieser mittlerweile bewährten Anwendungen lag im Bereich der Synchrotroninjektion oder der Nachbeschleunigung von radioaktiven Ionenstrahlen. Darüber hinaus wird seit einiger Zeit die Entwicklung neuartiger, supraleitender Hochleistungslinearbeschleunigerkavitäten stark vorangetrieben, welche vor allem bei der Forschung an Spallationsneutronenquellen, in der Isotopenproduktion oder bei der Transmutation langlebiger Abfälle aus Spaltreaktoren Anwendung finden sollen. Die am Institut für Angewandte Physik der Goethe-Universität Frankfurt entwickelte CH-Kavität ist optimal für den Einsatz in derartigen Hochleistungsapplikationen geeignet. Sie ist die erste Vielzellenstruktur für den Nieder- und Mittelenergiebereich und kann sowohl normal- als auch supraleitend verwendet werden. Bislang konnten in der Vergangenheit ein supraleitender 360 MHz CH-Prototyp sowie eine für hohe Leistungen optimierte supraleitende 325 MHz CH-Struktur erfolgreich bei kryogenen Temperaturen ohne Strahl getestet werden. Um die Forschung im Bereich der Kernphysik, der Kernchemie und vor allem im Bereich der superschweren Elemente auch in Zukunft weiter fortzusetzen, ist der Bau eines neuen supraleitenden, dauerstrichbetriebenen Linearbeschleunigers an der GSI geplant. Das Kernstück des zukünftigen cw-LINAC basiert auf dem Einsatz supraleitender 217 MHz CH-Kavitäten, mit deren Hilfe ein adäquater Teilchenstrahl mit
maximal 7,5 MeV/u für die SHE-Synthese bereitgestellt werden soll. Auf dem Weg zur Realisierung des geplanten cw-LINACs wurde im Zuge des Demonstrator-Projektes die Umsetzung der ersten Sektion des gesamten Beschleunigers beschlossen. Der Fokus des Projektes liegt auf der Demonstration der Betriebstauglichkeit innerhalb einer realistischen Beschleunigerumgebung sowie insbesondere auf der erstmaligen Inbetriebnahme einer supraleitenden CH-Kavität mit Strahl. Im Rahmen der vorliegenden Arbeit wurde die erste supraleitende 217 MHz CH-Kavität für das Demonstrator-Projekt entwickelt, produziert und ihre Hochleistungseigenschaften in einem vertikalen Kryostaten bei 4,2 K getestet. Hierbei lag das Hauptaugenmerk auf der HF-Auslegung der Kavität, den begleitenden Tuningmaßnahmen während der Produktion sowie den ersten Leistungstests unter kryogenen Bedingungen. Weitere Schwerpunkte lagen auf der kompakten Bauweise, dem effektiven Tuning, der Oberflächenpräparation sowie auf dem Strahlbetrieb der Kavität mit einem dauerstrichfähigem 5 kW Hochleistungskoppler. Die Umsetzung
der Kavität beruhte auf dem geometrischen Konzept der supraleitenden, siebenzelligen 325 MHz CH-Struktur.
Ihre elektromagnetische und strukturmechanische Auslegung erfolgte mittels der Simulationsprogramme ANSYS Multiphysics und CST Studio Suite. Um während des Test- bzw. Strahlbetriebs mit der entsprechend notwendigen Kopplungsstärke die HF-Leistung in die Kavität einzuspeisen, wurden unterschiedliche Kopplerantennen für den jeweiligen Fall ausgelegt. Zum Erreichen der geforderten Zielfrequenz wurde ein Verfahren erarbeitet, welches die hierfür notwendigen Mess- und Arbeitsschritte während der einzelnen
Produktionsphasen beinhaltet. Diesbezüglich wurden während der Produktion der Kavität eine Reihe von Zwischenmessungen beim Hersteller durchgeführt, um den Frequenzverlauf innerhalb der jeweiligen Fertigungsschritte entsprechend beeinflussen zu können
und um vorangegangene Simulationswerte zu validieren. Alle untersuchten Parameter konnten während der Messungen in guter Übereinstimmung zu den Simulationen reproduziert und die Zielfrequenz der Kavität schließlich erreicht werden. Nach Abschluss der letzten Oberflächenpräparationen wurde die Kavität in einer neuen kryogenen Testumgebung innerhalb der Experimentierhalle des IAP für einen vertikalen Kalttest vorbereitet.
Daraufhin erfolgte das Evakuieren der Kavität, das Abkühlen auf 4,2 K sowie ihre Konditionierung. Anschließend erfolgte die Bestimmung der intrinsischen Güte der Kavität.
Sie betrug 1,44 x 10E9 und besitzt somit den bisher höchsten Gütewert, der jemals bei einer supraleitenden CH-Struktur erreicht wurde. Es konnte ein maximaler Beschleunigungsgradient von 7 MV/m im Dauerstrichbetrieb erreicht werden, was einer effektiven Spannung von 4,2 MV entspricht. Die zugehörigen magnetischen und elektrischen Oberflächenfelder lagen bei 39,3 mT bzw. 43,5 MV/m. Ein thermaler Zusammenbruch konnte während des gesamten Leistungstests nicht festgestellt werden, was auf eine gute thermische Eigenschaft der Kavität hindeutet. Allerdings zeigte der gemessene Verlauf ein frühes Abfallen der Güte ab 2,5 MV/m, was durch anormale Leistungsverluste aufgrund von Feldemission hervorgerufen wurde. Dies war aufgrund der unzureichenden Oberflächenbehandlung der Kavität zu erwarten, da die Hochdruckspülung aus technischen Gründen nur entlang der Strahlachse erfolgte. Dennoch konnte die Designvorgabe des geplanten cw-LINACs hinsichtlich der Güte bei 5,5 MV/m um einen Faktor 2 übertroffen werden.
Die positiven Ergebnisse der Simulationsrechnungen und der Messungen zeigen, dass die Anforderungen des Demonstrator-Projekts, insbesondere hinsichtlich des benötigten Beschleunigungsgradienten, mittels der entwickelten supraleitenden 217 MHz CH-Kavität erfüllt werden. Somit wurde im Rahmen dieser Arbeit maßgeblich an der Umsetzung des Demonstrator-Projekts bzw. an der Realisierung des geplanten cw-LINACs beigetragen und der Weg für einen Strahlbetrieb der Kavität vorbereitet.
The Asian tiger mosquito Aedes albopictus, native to South East Asia, is listed as one of the worst invasive vector species worldwide. In Europe the species is currently restricted to Southern Europe, but due to the ongoing climate change, Ae. albopictus is expected to expand its potential range further northwards. In addition to modelling the habitat suitability for Ae. albopictus under current and future climatic conditions in Europe by means of the maximum entropy approach, we here focused on the drivers of the habitat suitability prediction. We explored the most limiting factors for Aedes albopictus in Europe under current and future climatic conditions, a method which has been neglected in species distribution modelling so far. Ae. albopictus is one of the best-studied mosquito species, which allowed us to evaluate the applied Maxent approach for most limiting factor mapping. We identified three key limiting factors for Ae. albopictus in Europe under current climatic conditions: winter temperature in Eastern Europe, summer temperature in Southern Europe. Model findings were in good accordance with commonly known establishment thresholds in Europe based on climate chamber experiments and derived from the geographical distribution of the species. Under future climatic conditions low winter temperature were modelled to remain the most limiting factor in Eastern Europe, whereas in Central Europe annual mean temperature and summer temperatures were modelled to be replaced by summer precipitation, respectively, as most limiting factors. Changes in the climatic conditions in terms of the identified key limiting factors will be of great relevance regarding the invasive potential of the Ae. albopictus. Thus, our results may help to understand the key drivers of the suggested range expansion under climate change and may help to improve monitoring programmes. The applied approach of investigating limiting factors has proven to yield valuable results and may also provide valuable insights into the drivers of the prediction of current and future distribution of other species. This might be particularly interesting for other vector species that are of increasing public health concerns.
Panama, a small country between the major continents of North and South America, is one of the lesser studied regions in Central America, but is recognized for its mega-biodiversity. This is particularly true for Eastern Panama, which I am considering as the easternmost portion of the country, covering the area from the Chepo, which is also the beginning of the San Blas mountain range, towards east, up to the Darien Mountain range on the border with its neighboring country Colombia. In the lowland region I visited two physiographic areas: the Isthmian-Atlantic Moist Forests (IAMF) and the Chocó-Darién Moist Forests (CDMF). In the IAMF I worked at the localities of Río Mono, Wacuco, La Moneda, Arretí, Metetí, Filo del Tallo, and Laguna de Matusagaratí. In the CDMF I visited the localities of Cruce de Mono, Cana, Garachiné, Sambú, and Pavarandó. And I have worked in the highlands of Darién (DM), Majé (MM), Jingurudó-Sapo (JSM), Pirre (PM) and San Blas (SSM) in the highlands.
Before my research, 138 reptile and 104 amphibian species had been reported for EP. From 2008 to 2013, I collected specimens to evaluate the diversity of amphibians and reptiles for this region. I applied an integrative approach to evaluate the taxonomy, diversity, biogeography, and conservation of the herpetofauna of EP. I included analyses of morphometrics, molecular genetics (e.g. barcoding), biogeography, bioacoustics (in anurans), hemipenial morphology (in squamates), and ecology. This is the first regional evaluation of the biodiversity in EP applying integrative taxonomy. Aside from morphological and bioacoustic data, my work is based on the barcoding of 608 specimens, from which I obtained 16S mtDNA for 486 specimens and COI mtDNA for 455. In total I have got sequences for 69.2 %of the amphibian and 48.6 % of the reptile species present in EP. For the morphological analyses, I compared 1597 specimens, including my samples complemented by specimens obtained from various museums. The bioacoustic data were obtained from the analysis of 1504 calls of 27 species of frogs. Based on specimens collected in EP and according to external morphology, I could identify 65 species of amphibians and 72 reptiles, but after applying an integrative approach these numbers increased to 79 amphibians and 88 reptiles described species within my collected specimens. Additionally, I uncovered 33 taxonomic units that could not be assigned to any described species until now, 22 of them represent confirmed candidate species (CCS), and 11 were classified as Unconfirmed candidate species (UCS). Thus, increasing the known species of amphibian by 19.4 % and of reptiles by 4.8 %. Currently, there are 145 reptiles and 129 amphibians known to occur in EP. Based on my results, I have initiated several projects to solve taxonomic uncertanties, including the species of the genera Bolitoglossa, Diasporus, Dactyloa, Ecnomiohyla, Lepidoblepharis, and the taxonomic status of the species Pristimantis caryophyllaceus and Norops tropidogaster.
Out of the 22 CCS I found, I described nine species new to science with type locality in EP, six amphibians and four reptiles. Among these is a new species of Bolitoglossa described from Cerro Chucantí, Cordillera de Majé, Provincia de Darién, Panama. Additionally, I include comments on the other species of congeneric salamanders known to occur in the region. Among the tink frogs, only Diasporus quidditus was known to occur in EP. During my field work I collected six additional species of this genus, four of which are new to science, plus two species new for this region.
I also described one new species of Dactyloa (giant anole lizards) related to the former D. chocorum. I synonymized D. chocorum with D. purpurescens, and included information about the other species of the group from EP. The new species of Dactyloa resembles D. ibanezi, D. limon, and D. purpurescens in external morphology but differs from these species in dewlap coloration, dorsal color pattern, morphometrics, and scalation. I discovered one species of the genus Ecnomiohyla, which exhibits significant genetic distances (16S mtDNA gene) and morphological differences to all known Ecnomiohyla species. Along with the description of the new Ecnomiohyla species, I provide detailed comparisons of morphological and molecular characters of almost all members of the genus in Lower Central America, as well as an identification key for the entire genus. Two new species of the genus Lepidoblepharis from EP were described. In the corresponding work, I include an analysis of Lepidoblepharis spp. in the region, including phylogeography and taxonomy. One of the new species, Lepidoblepharis emberawoundule, can be differentiated from most species in the genus by its small size and its low number of lamellae under the fourth toe and finger. The other species described from EP, Lepidoblepharis rufigularis, can be differentiated from all species in the genus by its small size and the reddish throat in males.
Background: Astrocytomas are the most common primary brain tumors distinguished into four histological grades. Molecular analyses of individual astrocytoma grades have revealed detailed insights into genetic, transcriptomic andepigenetic alterations. This provides an excellent basis to identify similarities and differences between astrocytoma grades. Methods: We utilized public omics data of all four astrocytoma grades focusing on pilocytic astrocytomas (PA I), diffuse astrocytomas (AS II), anaplastic astrocytomas (AS III) and glioblastomas (GBM IV) to identify similarities and differences using well-established bioinformatics and systems biology approaches. We further validated the expression and localization of Ang2 involved in angiogenesis using immunohistochemistry. Results: Our analyses show similarities and differences between astrocytoma grades at the level of individual genes, signaling pathways and regulatory networks. We identified many differentially expressed genes that were either exclusively observed in a specific astrocytoma grade or commonly affected in specific subsets of astrocytoma grades in comparison to normal brain. Further, the number of differentially expressed genes generally increased with the astrocytoma grade with one major exception. The cytokine receptor pathway showed nearly the same number of differentially expressed genes in PA I and GBM IV and was further characterized by a significant overlap of commonly altered genes and an exclusive enrichment of overexpressed cancer genes in GBM IV. Additional analyses revealed a strong exclusive overexpression of CX3CL1 (fractalkine) and its receptor CX3CR1 in PA I possibly contributing to the absence of invasive growth. We further found that PA I was significantly associated with the mesenchymal subtype typically observed for very aggressive GBM IV. Expression of endothelial and mesenchymal markers (ANGPT2, CHI3L1) indicated a stronger contribution of the micro-environment to the manifestation of the mesenchymal subtype than the tumor biology itself. We further inferred a transcriptional regulatory network associated with specific expression differences distinguishing PA I from AS II, AS III and GBM IV. Major central transcriptional regulators were involved in brain development, cell cycle control, proliferation, apoptosis, chromatin remodeling or DNA methylation. Many of these regulators showed directly underlying DNA methylation changes in PA I or gene copy number mutations in AS II, AS III and GBM IV. Conclusions: This computational study characterizes similarities and differences between all four astrocytoma grades confirming known and revealing novel insights into astrocytoma biology. Our findings represent a valuable resource for future computational and experimental studies.
Background & Aims: Simeprevir is an oral, once-daily inhibitor of hepatitis c virus (HCV) protease NS3/4A. We investigated the safety and efficacy of simeprevir with peg-interferon α-2a and ribavirin (PR) in a randomized, double-blind, placebo-controlled, phase 3 trial of patients with HCV genotype 1 infection who relapsed after previous interferon-based therapy.
Methods: Patients were assigned randomly (2:1) to groups given simeprevir (150 mg, once daily) and PR (n = 260) or placebo and PR (n = 133) for 12 weeks. Patients then were given PR alone for 12 or 36 weeks (simeprevir group, based on response-guided therapy criteria) or 36 weeks (placebo group).
Results: Simeprevir and PR was significantly superior to placebo and PR; rates of sustained virologic response 12 weeks after planned end of treatment (SVR12) were 79.2% vs 36.1%, respectively (43.8% difference; 95% confidence interval, 34.6–53.0; P < .001). Among patients given simeprevir, 92.7% met the response-guided therapy criteria and were eligible to complete PR at week 24; of these, 83.0% achieved SVR12. HCV RNA was undetectable at week 4 in 77.2% of patients given simeprevir and 3.1% given placebo. On-treatment failure and relapse rates were lower among patients given simeprevir and PR than those given placebo and PR (3.1% vs 27.1%, and 18.5% vs 48.4%, respectively). Patients given simeprevir did not have adverse events beyond those that occurred in patients given PR alone. Most adverse events were grades 1/2; the prevalence of anemia and rash was similar in both groups. Patients in both groups reported similar severity of fatigue and functional impairments during the study, but duration was reduced among patients given simeprevir.
Conclusions: In a phase 3 trial of patients who had relapsed after interferon-based therapy, the addition of simeprevir to PR was generally well tolerated, with an SVR12 rate of 79.2%. Most patients (92.7%) receiving simeprevir were able to shorten therapy to 24 weeks. ClinicalTrials.gov number: NCT01281839.
Als Hinführung zum Phänomen der Gesichtsauflösungen sollen schlagwortartig zwei hinlänglich bekannte Diskurse gegenübergestellt werden, die einander mehr als 200 Jahre trennen und konträre epistemische sowie ästhetische Programme repräsentieren. Dieser kurze Rekurs wird unternommen, weil beide Aussagewelten symptomatisch für zwei Haltungen zum Gesicht sind, aus denen Fragen zur Darstellbarkeit bzw. Wahrnehmbarkeit und schlussendlich zu Konzepten des Subjekts folgen. Auch wenn beide Diskurse die Male ihrer historischen Entstehungskontexte aufweisen, so sprechen sie in gleichem Maße von Gegebenheiten, die noch heute die mediale und ästhetische Wirklichkeit betreffen. Das Ziel dieses Vorgehens ist es, in der Zusammenfassung beider Haltungen eine Blindstelle aufscheinen zu lassen, die die Frage der Interpretation von Gesichtsrepräsentationen berührt. Die Gegenstände der Untersuchung entstammen der Performance- und Medienkunst.
Ich möchte kurz voranstellen, dass ich als Umweltwissenschaftlerin ausgebildet bin, in der Epidemiologie promoviert und mich daraufhin der Wissensgeschichte und -soziologie und insbesondere den Science & Technology Studies zugewandt habe. Mein Interesse an den alltäglichen Praktiken der Wissensbildung und technischen Formalisierungsprozessen in der Ernährungsepidemiologie ist zum einen inspiriert durch den practice turn und den material turn in der Wissenschaftsforschung, zum andern aber auch durch meine eigene Forschungserfahrung in der Epidemiologie. Im Hinblick auf Epigenetik und Ernährung als Medium der Übertragung frage ich nach so banalen Dingen wie: "Wie werden Äpfel in Experimenten formalisiert?", um einigen konkreten Arbeitsweisen der Postgenomik innerhalb des Feldes Nahrung - Ernährung - Stoffwechsel nachzugehen. Im Sinne der bereits erwähnten Unterscheidung zwischen intra- und intergenerationaler Bedeutung des Begriffs Epigenetik von Testa und Boniolo geht es in den folgenden Beispielen primär um intragenerationale Epigenetik. Allerdings gibt es auch in der Ernährungsepidemiologie durchaus Forschung zu inter- oder transgenerationalen Effekten, hier werden oft die Langzeitstudien genannt, in denen die Folgen des niederländischen Hungerwinters 1944, während der deutschen Besatzung, als die Wehrmacht die Versorgungswege der Bevölkerung blockierte, über mehrere Generationen untersucht wurden (vgl. auch den Beitrag von Guy Vergères).
I would like to start off my cultural-historical intervention with a trouvaille from the 'Denktagebuch', a sort of intellectual notebook, of Hannah Arendt, the famous German-Jewish philosopher (1906–1975). Arendt's publications include a most profound book on the 'Human Condition' (1958, in German 'Vita activa', 1960) in which she develops the idea of 'acting / Handlung' as the crucial realm of intersubjectivity and humanity. This realm is based in the space between human beings, a literal 'inter-est' of togetherness. It is only in this space, only in the relationship to others, that the full sense of the Self, including the involuntary expressions of the person, manifests itself. It is the same realm in which the moral, social and political life is created. In the notebook of the 44-year-old Arendt one comes across the following entry: "In nichts offenbart sich die eigentümliche Vieldeutigkeit der Sprache [...] deutlicher als in der Metapher. So habe ich zum Beispiel ein Leben lang die Metapher 'es öffnet sich mir das Herz' benutzt, ohne je die dazu gehörende physische Sensation erfahren zu haben. Erst seit ich die physische Sensation kenne, weiss ich, wie oft ich gelogen habe [...]. Wie aber hätte ich je die Wahrheit der physischen Sensation erfahren, wenn die Sprache mit ihrer Metapher mir nicht bereits eine Ahnung von der Bedeutsamkeit des Vorgangs gegeben hätte?" (Notebook II, 22 December 1950, Arendt 2002, 46) The entry discusses the mutual transferral between mind and body by reflecting the role of language as a mediator for minding the body and the embodiment of the mind. Since the phrase of the 'open heart' belongs to a register of long-established metaphors, these reflections concern the comprehension of body-metaphors and their role for a 'shared meaningful space of experiences' (Gallese 2009a, 527), i.e. language as transmitter of experiences and memory in cultural history.
The dualism of movements and institutions. A structurational approach towards the two concepts
(2016)
In studies of social mobilization, the distinction between institutions and organizations is often as blurry as the instant of time from which on we can actually speak of a proper movement. Using the idea of a `duality of structure’ as a starting point, this article suggests a way of fixing the boundaries: a brief analysis of the South African Landless People’s Movement demonstrates the merit of conceiving of movements as aggregate actors with shared common objectives and common norms, which institutionalize particular modes of cooperation by purposefully drawing on existing institutions in order to shape functioning internal structures.
Eine besondere Affinität zwischen dem Gesicht als Eindrucks- und Ausdrucksfläche für Emotionen und dem Film ist in filmtheorischen Schriften häufig festgestellt worden. Namentlich Béla Balázs hat sich in seiner 1924 erschienenen Abhandlung ‚Der sichtbare Mensch oder die Kultur des Films‘ ausgiebig mit der filmischen Gestaltung der natürlichen Physiognomie von Menschen und Dingen beschäftigt. Sein besonderes Interesse galt dabei den Affektpotentialen des menschlichen Gesichts. Wie bereits Hugo Münsterberg in seiner 1916 erschienenen Schrift ‚The Photoplay‘ bemerkt hat, rückt der Film vor allem durch die Technik der Großaufnahme Gesichter wie Dinge ins Zentrum der Aufmerksamkeit von Zuschauern. Die Vergrößerung stellt sie nicht nur von ihrer räumlichen Umgebung frei, sondern hebt auch mimische Details hervor, die sonst meist übersehen werden. Deshalb spielt die Großaufnahme eine wichtige Rolle in der filmischen Montage.
Gesichter und Gesichte, im Sinne von Visionen des Gewesenen oder Möglichen, sind in epischen, dramatischen und den filmischen Arbeiten von Samuel Beckett eng miteinander verknüpft. Becketts Arbeiten im Sektor der bewegten Bilder, um die es mir hier geht, umfassen einen Zeitraum von gut 20 Jahren, beginnend mit dem 1963 konzipierten "Film" und endend mit "Was wo" im Jahr 1986, einem Fernsehspiel, das Beckett zusammen mit dem SDR in Stuttgart produzierte. Sehen, Gesehenwerden, Gesicht und Gesichtetwerden, das Auflösen und Auslöschen des Gesichts im dreifachen Wortsinn, nämlich der physischen Erscheinung, des geschauten Bewusstseinsinhalts und des Gesichtssinns sind zentrale Themen der Arbeit auch in diesem Feld.
In der Moderne wird das Menschengesicht, das lange Zeit Sinnbild für die Ebenbildlichkeit Gottes und somit für menschliche Ganzheitlichkeit war, radikalen Auflösungsprozessen unterzogen. Zugleich scheinen immer wieder Erlösungsutopien durch, die eine neue Suche nach dem verlorenen oder erst noch zu schauenden Gesicht initiieren. Dieser Doppelstrebigkeit wird im Folgenden unter dem Leitbegriff des Rätsels nachgegangen. Letzterer lässt sich hierbei auf seinen zweifachen altgriechischen Ursprung zurückführen, auf 'griphos' ('Fischernetz, Schlinge': Ratespiel) und 'ainigma' ('dunkle Andeutung': das Rätselhafte). Das Rätsel wird in der Theologie seit jeher - in der Philosophie vermehrt in der Moderne – mit dem Gesicht (in seiner Doppeldeutigkeit von gesehenem und sehendem Gesicht) assoziiert, dessen Les- und Lösbarkeit es einer hermeneutischen Bewährungsprobe unterzieht. An zwei philosophischen Werken soll in einem ersten Schritt dieses Junktim von Rätsel und Gesicht(e) im Diagramm der beiden Lösungsbewegungen von Auflösung und Erlösung nachgezeichnet werden: an Friedrich Nietzsches 'Also sprach Zarathustra' (1883–1885) und Franz Rosenzweigs 'Stern der Erlösung' (1921) sowie seinen "nachträgliche[n] Bemerkungen" hierzu in "Das neue Denken" (1925).
Gesichter in Lyrik und Prosa verweisen auf vielfältige Techniken ihrer verbalen Kreation - und ihrer Auflösung. Anders als die Bildkunst, die Gesichter simultan evident macht, konstituiert sich das Verbalporträt (in der Regel) linear-sukzessiv. Es ist medial zur Fragmentierung des Motivs und zur Anordnung der semiotischen Einheiten in einer eindimensionalen Abfolge gezwungen: das heißt, die Zerlegung des darzustellenden Gesichts ist zwingend notwendig, ein Moment der Auflösung ist ihm seit jeher eingeschrieben. Daher experimentiert es aber auch seit jeher mit den Verfahren der Zusammenfügung (Re-Komposition) der Einzelteile. Diesbezüglich verzeichnet das poetische Porträt schon in der Renaissance erste spielerische Höhepunkte, die frappierende Ähnlichkeiten aufweisen mit den ungewöhnlichen, heute sehr bekannten Porträts des manieristischen Malers Giuseppe Arcimboldo, dessen Gesichter sich aus Blumen, Früchten, Büchern u.a. zusammensetzen und Kippfiguren zwischen Menschenähnlichkeit und Realitätsferne bilden, indem sie ihren Komposit-Charakter ostentativ zur Schau stellen. Die punktuelle Feststellung vergleichbarer Darstellungsprinzipien wirft notwendig die Frage auf, ob und inwiefern sich Auflösungserscheinungen in verbalen und pikturalen Porträts trotz ihrer Mediendifferenz stilhistorisch parallelisieren lassen – so lautet die Rahmenfrage, die erneut aufzugreifen ist nach einer Betrachtung verschiedener in Auflösung befindlicher Verbalporträts. Die einzelnen Werkanalysen sind konzise, zugunsten eines möglichst breiten Spektrums fazialer De-Kompositionen.
Sozusagen als Motto meiner Ausführungen zur Gattung des Porträts bzw. zur Porträtkunst habe ich eine Arbeit von Robert Rauschenberg gewählt. 1961 plante die Pariser Galeristin Iris Clert eine Porträt-Ausstellung und lud Robert Rauschenberg, den amerikanischen Pop-Künstler, zu einem Beitrag ein. Dieser reagierte mit einem aus Stockholm geschickten Telegramm mit dem Inhalt: 'This is a portrait of Iris Clert if I say so – Robert Rauschenberg'. Als Motto zeige ich die Arbeit deshalb, weil das Porträt im Laufe der Moderne und insbesondere im 20. Jahrhundert zu einer umstrittenen, ja in gewisser Hinsicht unmöglichen Gattung wird, und Rauschenbergs Telegramm nun zeigen kann, dass dieses Umstrittene zwei unterschiedliche Dimensionen hat: zum einen ist es der Streit über das, was als legitimes Porträt eines Menschen angesehen werden kann; zum anderen ist es der Streit darüber, was legitimerweise als ein Kunstwerk angesehen werden kann.
Ausgangspunkt der folgenden Überlegungen ist meine Dissertation mit dem Thema "Porträt – Ikone - Kunst. Methodische Studien zum Porträt in der Kunstliteratur. Zu einer Bildtheorie der Kunst", aus deren Breite ich mich für das Bildparadigma Kunst auf Francis Bacon (mit einem Ausblick auf Alberto Giacometti) beschränke. Das Porträt, in dem Sinne, wie es die Neuzeit versteht, mit all den Implikationen an Authentizität und Ähnlichkeit und unmittelbarer Wiedergabe einer gesehenen Wirklichkeit, hat es in der europäischen Bilderkultur nicht immer gegeben. Auch vorneuzeitliche Bilder, wie eben die Ikone, hatten als besonders wichtige, ihnen übertragene Aufgabe die Vergegenwärtigung einer bestimmten Person, ohne dass man sie deshalb als Bildnisse oder Porträts bezeichnen kann. Sie werden auf diese Vergegenwärtigung sehr wohl verpflichtet, also zu garantieren, dass die gemeinte Person in ihnen wirklich getroffen ist, aber durch signifikant andere bildliche Strategien als dies bei Porträts beschrieben werden kann. Das war für mich der Grund von unterschiedlichen „Bildparadigmen“, dem der Ikone und dem des Kunstwerks zu sprechen. Bilder zu machen und zu betrachten dürfen wir wohl als Grundkonstante menschlicher Kultur seit ihren allerersten Anfängen ansehen. Wie aber Bilder hergestellt und verstanden werden ist bildhistorisch zu beschreiben, das heißt es gibt Perioden der kulturellen Geltung und Dominanz eines Bildverständnisses und Zeiten des Umbruchs und des Wechsels im Verständnis, der Entstehung, der Betrachtung und des Sprechens über Bilder.
Gesichter sind in der modernen Gesellschaft zwiespältig geworden: Einerseits ist von einer "facialen Gesellschaft" die Rede, entsprechend der Leitfunktion, welche Gesichter als Vorbilder in der Medienkultur einnehmen, ob nun bei Stars, Politikern, Sportlern, Promis - Berufsgruppen für die face lifting selbstverständlich zur Vorbildfunktion mit Nachahmungseffekten hinzugehört. Fernsehformate wie Casting- Shows beruhen auch darauf, dass Gesichter zur Nachahmung vorgegeben werden. Selbstverständlich sind diese Gesichter nie natürlich oder wahrhaft, wie dies die Anthropologie seit dem 18. Jahrhundert behauptet hatte, sondern künstlich und verstellt. Aber der Topos des natürlichen Ausdrucks wird gleichwohl aufrecht erhalten und rhetorisch angewendet. Die biopolitische Diskursmacht führt dazu, dass trotz der maskenhaften Verstellung der Mediengesichter der empathisch-emotive Effekt eintritt. Es handelt sich um eine bemerkenswerte Leistung von Medienkultur, Indikator einer anthropologischen Macht der Medien. Michael Taussig spricht unter Berufung auf Benjamin vom mimetischen Vermögen, das durch Medien zustande kommt und Fremdheit durch Nachahmung minimiert, entsprechend dem antirassistischen Leitmotiv von Kafkas "Wunsch, Indianer zu werden". Insbesondere Gefühle wie Liebe oder Angst werden dabei im Gesichtsausdruck der Medienbilder präsentiert und unter Zuhilfenahme der anthropologischen Topik einer Entsprechung des Äußeren im Inneren vom Zuschauer mimetisch hervorgebracht oder ihm zur Nachahmung angeboten.
Gesichtsauflösung und Biometrie sind zunächst nur schwer zusammenzubringen. Beschäftigt man sich jedoch ein wenig mit der Informationstechnologie, so kommt man schnell darauf, dass Auflösung bei Bildern eine eklatante Rolle spielt, allerdings nicht im Sinne von wegbrechen, verschwinden sondern ganz im Gegenteil; hier meint man eher einen Detaillierungsgrad. Je höher die Auflösung eines Bildes, desto mehr kann man erkennen, desto mehr kann man aus dem Bild auslesen.
In unserem visuell geprägten Kulturkreis bestimmt das Gesicht die Identität eines Menschen - doch ab wann kann von einer Gesichtsauflösung gesprochen werden? Deutliche Abweichungen von der in der Gesellschaft bekannten und deshalb akzeptierten Norm lassen sich als Gesichtsdefekte, Gesichtsdeformitäten oder eben als Gesichtsauflösung betrachten. Ursächlich können beispielsweise Unfälle, Infektionen, Tumorerkrankungen oder angeborene Fehlbildungen sein. Der Alterungsprozess sollte hingegen nicht als Gesichtsauflösung interpretiert werden. Hier handelt es sich um eine Strukturanpassung des Gewebes. Aufgabe der Medizin bzw. in diesem Falle der gesichtschirurgischen Profession ist es, dem Vorgang der Gesichtsauflösung entgegen zu wirken. Sie bietet die Möglichkeit, durch rekonstruktive Verfahren das Gesicht in seiner Ursprünglichkeit zu erhalten bzw. wieder herzustellen. Besteht im Falle von Gesichtsdefekten keine Möglichkeit mehr, durch operative Techniken eine adäquate Wiederherstellung zu gewährleisten, so kann auf die Versorgung mit künstlichen Gesichtsteilen zurück gegriffen werden. Ziel ist es, ein dysmorphes (fehlgestaltetes) Gesicht in ein wieder erkennbares, also in dem soziokulturellen Umfeld des Betroffenen akzeptiertes Gesicht umzuwandeln. Angestrebt wird, das durch die unterschiedlichen Ursachen geschädigte Gesicht im Rahmen ästhetischer Aspekte wieder herzustellen. Dadurch soll dem Betroffenen die problemlose Integration in sein soziales Umfeld ermöglicht werden. Für den Betroffenen kann dadurch ein Teil der bekannten Normalität wieder hergestellt sowie ein akzeptables Dasein vermittelt werden.
Gesichtsauflösungen
(2013)
Zu Beginn des 18. Jahrhunderts wird aus einem wiedergeöffneten Stollen der Bergwerke von Falun in Schweden der nahezu unversehrte Leib eines verschütteten Mannes geborgen. Die verblüfften Bergleute blicken in ein frisches Gesicht, in "die noch unveränderten Gesichtszüge eines verunglückten Jünglings" – wie es in der Quelle, in Gotthilf Heinrich von Schuberts Ansichten von der Nachtseite der Naturwissenschaften (1808) heißt. Gleichsam eingelegt in Kupfervitriolwasser hat das Gesicht in 300 Ellen Tiefe überdauert, doch kann dessen Konservierung der Berührung mit Luft und Licht und mithin dem Auge der Umstehenden nicht standhalten. Gesicht und Körper lösen sich auf, zerfallen zu Staub, doch erst, nachdem ein altes Mütterchen "an Krücken und mit grauem Haar" den Konservierten erkennt und an ihre Brust drücken kann: Nicht die Mutter, nein sie ist die Braut des Jünglings von vor fünfzig Jahren, und ihr eingefallenes, "verwelktes" Gesicht kontrastiert der Wirkung des seinen. Die Geschichte vom konservierten Bergmanngesicht ist eine der bekanntesten Kombinationen von Literatur und anorganischer Chemie. Johann Peter Hebel und E.T.A. Hoffmann haben diese Geschichte der Flüssigkeiten als eine Art Antidoton gegen die Auflösungserscheinungen des Gesichts erzählt, die zumindest bei Hebel von einer Verwirrung der Chemikalien und ihrer Wirkungen geprägt ist. Denn die schnelle Auflösung, freilich nach vollzogener Identifikation durch die alte Braut, widerspricht dem chemischen Prozess, durch die jedoch deutlich werden soll, dass der unversehrte Kopf in Vitriol, seine Erkennbarkeit und Präsenz nur um den Preis der Sichtbarkeit zu haben ist: Allein als ein den Blicken und Interaktionen mit den Menschen entzogener Kopf bleibt er sich gleich, ist er intakt, unvergänglich. Damit wird gleichsam auf dem Haupt des aus der Zeitlichkeit herausgefallenen Bergmanns ein Spiel um natürliche und erworbene Konservierungsmodalitäten durch das Vitriol des Berges einerseits und das Gedächtnis der ergrauten Braut andererseits ausgetragen. Als Garanten gegen die Auflösung buhlen sie um die Haltbarkeit und physische Integrität des Menschen, genauer um das Bild von ihm. Durch eine "Verwirrung der Chemikalien", die im Übertrag von der Quelle zur Prosaerzählung erfolgte, wird der Konservierungsstoff Kupfervitriol oft als Eisenvitriol oder folgenreicher und entgegen der Nomenklatur gar als Schwefelsäure überliefert. In dieser starken Säure allerdings hätten sich nicht nur Gesicht und Körper des Bergmanns in maximal zwei Stunden, sondern auch das ganze Bergwerk zersetzt. Im konservierten Bergmann als der Geschichte einer aufgeschobenen Auflösung konvergieren einige Themenfelder der folgenden Beiträge: Neben dem Entzug und der Bergung eines unversehrten Antlitzes, dem eine Art facelifting zuteil wurde, sind es die Umstände seiner Erinnerung und die Bedingungen zu seiner Wiedererkennung, seine Fragilität und sein Zerfall. Themen, in die an dieser Stelle ein wenig eingeführt werden soll.
Nach 1989 ist Europa – wieder einmal – in Bewegung geraten und die Mitte des Kontinents hat sich "ostwärts" verlagert. Diese Verschiebung Europas, die Frage nach neuen und alten Grenzen und Zentren, ist Anlass, sich mit jener vergessenen Himmelsrichtung und ihren Gebieten zu befassen, die 'plötzlich' wieder auf der Landkarte und in den Köpfen aufgetaucht sind. Wird der Osten zum Standort gemacht, von dem aus Europa zu konturieren ist, so erschließt sich dieser Osten in seinen unterschiedlichen geographischen, historischen und imaginären Mehrdeutigkeiten. Europa wird dabei zu einem dezentralen Gebilde, für dessen kulturelle Semantiken gerade die Peripherien von entscheidender Bedeutung sind.
In den Beiträgen des Bandes werden diese "schmerzenden Nähte" (Jurij Andruchowitsch) aufgesucht: von Vilnius über den Balkan, den Kaukasus, die Schwarzmerregion bis nach Istanbul, Alexandria oder Beirut. Es eröffnen sich plurale Kulturen, deren Umgang mit Sprachen, Religionen, Bild- und Zeichensystemen in vielem quer zu westlich-europäischen Ordnungskonzepten liegen. Zugleich liegt die Brisanz dieser Kulturen darin, dass sie auf vielfältige Weise mit modernen kulturellen Homogenisierungsstrategien verbunden sind und immer wieder auf die auch diesen inhärenten, verdeckten oder getilgten Pluralitäten verweisen. Die Beiträge zeigen, wie die Vermessung dieser Orte zu allen Zeiten zu einem beträchtlichen Teil in Literatur und Kunst stattfindet. Hier werden territorial-kulturelle Zugehörigkeiten verhandelt, wird ein nuanciertes Spiel mit geopolitischen Verschiebungen, Verwerfungen und Umkodierungen von Topographien, mit ironischen oder melancholischen Wahrnehmungen "fremder" Räume und Gepflogenheiten betrieben.
Wir alle wissen ungefähr, was Epigenetik heute ist. Wir haben das Gefühl, dass wir über die gleiche Sache reden und dies auch aus ähnlichen Gründen tun. Die Frage, was epigenetische Vererbung ist, zielt also nicht so sehr darauf, was diese Klasse von Phänomenen, über die wir reden (epigenetische Vererbung, transgenerationelle epigenetische Effekte etc.) ist, sondern darauf, warum wir über sie reden. Die Antwort lautet wahrscheinlich: Weil es in den letzten zehn, zwanzig Jahren zu einem Umbruch gekommen ist, der mit Stichworten wie "New Genetics", "postgenomische Ära" usw. beschrieben wird. Irgendetwas Dramatisches ist passiert, und im Zentrum des zu beobachtenden Umbruchs steht die epigenetische Vererbung - was auch immer das eigentlich ist. Diese mehr oder weniger intuitive Antwort möchte ich infrage stellen: Gibt es überhaupt so etwas wie "epigenetische" Vererbung?
Für die stabile Weitergabe von phänotypischen Merkmalen an nachfolgende Generationen über die Keimbahn ist in der Biologie der Begriff der Vererbung reserviert. In diesem ist die Transgenerationalität immer schon mitgemeint, sie muss nicht gesondert angezeigt werden. Dies ist anders im Forschungsfeld der "Epigenetik". Hier werden seit einigen Jahren molekularbiologische Übertragungsprozesse mit dem Wort "transgenerationell" bezeichnet. Das Wort wird sowohl im Zusammenhang mit Übertragung ("transmission") als auch mit Vererbung ("inheritance") verwendet. "Transgenerational epigenetic inheritance" bezeichnet dabei die Weitergabe von epigenetischen Modifikationen von einer Organismen-Generation auf nachfolgende Generationen. Die Bezeichnung wird in Abgrenzung zur Weitergabe epigenetischer Modifikationen von einer Zelle an eine andere Zelle innerhalb somatischer Zellteilung (cell-cell inheritance) verwendet. Transgenerationelle epigenetische Vererbung meint also letztlich die über mehrere Generationen stabile Weitergabe epigenetischer Modifikationen in mehrzelligen Organismen. Dass der biologische Vererbungsbegriff im Zusammenklang mit "epigenetisch" den Zusatz "transgenerationell" benötigt, ist klärungsbedürftig. Hierin zeigt sich, so die These dieses Beitrags, dass der angenommene Übertragungsprozess instabil oder dessen Nachweis prekär ist. Im Folgenden werde ich zunächst drei historische Einschnitte skizzieren, die für diese Konnotation transgenerationeller Vererbung als "prekäre" Übertragung prägend waren: 1. die Verengung des biologischen Vererbungsbegriffs auf die Weitergabe über die Keimbahn und die Theorie der Konstanz des Keimplasmas von August Weismann; 2. die Unterscheidung zwischen Vererbung und kultureller oder psychosozialer Übertragung von Phänotypen in der frühen Entwicklungspsychologie; und 3. die familiale Übertragung psychischer Traumata von Holocaust-Überlebenden. Abschließend werde ich darstellen, wie in epigenetischer Forschung Transgenerationalität modelliert wird, und hieran die Prekarität der Übertragungsannahme diskutieren.
Die Interaktionen von DNA mit Umwelt, die Kopplungen zwischen biologischen Prozessen und mentaler Erfahrung, deren mögliche Vererbbarkeit sowie das Aufzeigen der potentiellen Reversibilität von "krankhaften" Entwicklungen innerhalb solcher Wechselspiele bilden Faszinationen, die jenseits der molekularbiologischen Labore das öffentliche Interesse entzündet haben. Diese Faszinationen sollen hier im Mittelpunkt stehen. Denn fast unvermeidlich verfallen die Forschungsbefunde einem Deutungsanspruch auf Humankultur, auf einen Bereich, der zunächst einmal jenseits der konkreten Forschung liegt und weit über diesen hinaus zeigt. Die folgende Mischung aus Glosse und Essay zur epigenetischen Weltbildproduktion – höher kann der Anspruch angesichts einer unabgeschlossenen, derzeit noch emergierenden Publizistik nicht sein – hat mehrere Teile. Die beiden ersten sind dem Auftritt der Epigenetik in der Öffentlichkeit gewidmet: Zuerst in einer impressionistischen Bestandsaufnahme der diesbezüglichen Publizistik, danach, um einen prominenten Bildbereich festzuhalten, wie er sich in der öffentlichen Diskussion der Epigenetik sedimentiert hat. Die darauf folgenden Teile widmen sich dem Emporkommen einer molekularen Vergemeinschaftungsrhetorik. Abschließend soll kurz die soteriologische Hoffnung erörtert werden, mit welcher der epigenetischen Forschung zumindest in ausgewählten theologischen Diskursen begegnet wird.
Die zwei folgenden Vortragsskripte sowie die Transkripte von Kommentar und Diskussion entstammen einem Workshop, auf dem die "Verfahren" der Epigenetik im Fokus der Diskussion standen. Darin wurden die Technologien der Epigenetik innerhalb der Forschung und an ihren Schnittstellen mit anderen Disziplinen und der Öffentlichkeit beobachtet. Leitend war die Frage, wie das Wissen um epigenetische Prozesse in Forschungslabor und Öffentlichkeit zwischen 'techne' und 'logos' greifbar wird, wie es dargestellt, modelliert, angewendet wird. Das schließt ausdrücklich sowohl die geschichtliche Herkunft dieser Verfahren ein, als auch die Art und Weise, wie Epigenetik als Wissenschaft und wie ihre Befunde kulturell verankert und zur Darstellung gebracht werden. Die hier aus diesem Diskussionszusammenhang ausgekoppelten Beiträge werfen einen Blick auf die Konstruktionen von Übertragungsphänomenen in Forschung und Öffentlichkeit. Der Beitrag von Jörg Thomas Richter unternimmt eine kurze Medienschau, die skizziert, welche Relevanz den Befunden dieser Forschung in der breiteren Publizistik beigemessen wird. Vanessa Lux eruiert die konzeptionellen Interferenzen, auf die die Forschung trifft, wenn sie transgenerationelle Übertragung als Vererbung modelliert. Ohad Parnes geht in seinem Kommentar sowohl auf historische als auch systematische Probleme des Vererbungsbegriffs ein, wie er aus der Genetik in die Epigenetik übertragen wird. Dem beigeordnet sind Auszüge aus der Abschlussdiskussion. Sie belegen ihrerseits das faszinierende Schillern, das die Epigenetik umgibt, aber sie suchen darüber hinaus die Spiegel und Splitter zu orten, von denen es möglicherweise ausgeht.
Die dreibändige Sammlung der Fragmente der römischen Historiker bildet den Abschluss eines langjährigen Unternehmens (vii). Bereits 1996 fand ein Zusammenschluss verschiedener Wissenschaftler statt, die den Nutzen einer derartigen Kollektion erkannten und die ersten Planungsschritte vollzogen. Es folgten mehrere weitere Treffen, die der Konzeption des Corpus und der Vergrößerung des Autorenkreises gewidmet waren. Nach vielen Jahren der Zusammenarbeit und Diskussion der Ergebnisse liegt nunmehr ein beeindruckendes Ergebnis vor: 1203 Fragmente, die in jeder nur wünschenswerter Weise dokumentiert und kommentiert werden...
Zur großen Ausstellung „Imperium der Götter“ des Badischen Landesmuseums Karlsruhe, die vom 16. November 2013 bis zum 18. Mai 2014 die Vielfalt und Bedeutung der Kulte und Religionen im römischen Reich mit einer Fülle an beeindruckenden Exponaten vor Augen führte, ist ein Ausstellungsband erschienen, in dem nicht nur die ausgestellten Objekte präsentiert, sondern auch die im Blickfeld stehenden Kulte, die „orientalischen“ Kulte einschließlich des frühen Christentums und Judentums, durch zahlreiche, kurze Beiträge näher beleuchtet werden...
Gedenkrituale für Kriegsgefallene ebenso wie die Erinnerung an vergangene Kriege befinden sich in einem Zustand fortwährenden Wandels und passen sich an die jeweiligen sozialen und politischen Begebenheiten an. Dies gilt besonders für jene Gedenkrituale, mit denen an die Gefallenen in Grenzkonflikten erinnert wird: Da es derartige Situationen immer wieder gibt, werden die Gedenkrituale dazu genutzt, um im Hinblick auf neuere Konflikte die Erinnerung zu bewahren. Dies wird im Folgenden am repräsentativen Beispiel Spartas untersucht. In der ersten Hälfte des 7. Jh.s. v. Chr. wurde dort das Gymnopaidiai-Fest eingeführt, das in Verbindung zu den argivisch-spartanischen Feindseligkeiten stand. Dabei lassen sich drei Ereignisse in den Auseinandersetzungen zwischen Argos und Sparta ausmachen, die sich auf die Rituale in den Gymnopaidiai ausgewirkt haben – alle drei betreffen Thyrea. Der erste Fall greift die spartanisch-argivischen Zusammenstöße im 8. bzw. 7. Jh. v. Chr. auf, die in Thyrea stattgefunden haben dürften. Die zweite Auseinandersetzung, etwa in der Mitte des 6. Jh.s. v. Chr., war der Kampf der Dreihundert. Der dritte Konflikt lässt sich auf den Anfang des zweiten Viertels des 4. Jh.s. v. Chr. datieren, als Argos der Überlieferung nach wieder die Kontrolle über die Thyreatis erlangte. In den Quellen lassen sich hingegen keine Belege für die Einführung der Gymnopaidiai finden, die auf einen Kampf zwischen Sparta und Argos, sei es in der Thyreatis oder in Hysiai, hinweisen.