Three-Dimensional architecture and biogenesis of membrane structures associated with hepatitis C virus replication
- All positive strand RNA viruses are known to replicate their genomes in close association with intracellular membranes. In case of the hepatitis C virus (HCV), a member of the family Flaviviridae, infected cells contain accumulations of vesicles forming a membranous web (MW) that is thought to be the site of viral RNA replication. However, little is known about the biogenesis and three-dimensional structure of the MW. In this study we used a combination of immunofluorescence- and electron microscopy (EM)-based methods to analyze the membranous structures induced by HCV in infected cells. We found that the MW is derived primarily from the endoplasmic reticulum (ER) and contains markers of rough ER as well as markers of early and late endosomes, COP vesicles, mitochondria and lipid droplets (LDs). The main constituents of the MW are single and double membrane vesicles (DMVs). The latter predominate and the kinetic of their appearance correlates with kinetics of viral RNA replication. DMVs are induced primarily by NS5A whereas NS4B induces single membrane vesicles arguing that MW formation requires the concerted action of several HCV replicase proteins. Three-dimensional reconstructions identify DMVs as protrusions from the ER membrane into the cytosol, frequently connected to the ER membrane via a neck-like structure. In addition, late in infection multi-membrane vesicles become evident, presumably as a result of a stress-induced reaction. Thus, the morphology of the membranous rearrangements induced in HCV-infected cells resemble those of the unrelated picorna-, corona- and arteriviruses, but are clearly distinct from those of the closely related flaviviruses. These results reveal unexpected similarities between HCV and distantly related positive-strand RNA viruses presumably reflecting similarities in cellular pathways exploited by these viruses to establish their membranous replication factories.
Strange and charm meson masses from twisted mass lattice QCD
- We present first results of a 2+1+1 flavor twisted mass lattice QCD computation of strange and charm meson masses. We focus on D and D_s mesons with spin J = 0,1 and parity P = -,+.
Definitions of a static SU(2) color triplet potential
- We discuss possibilities and problems to non-perturbatively define and compute a static color triplet potential in SU(2) gauge theory. Numerical lattice results are presented and compared to analytical perturbative results.
Scalar mesons and tetraquarks by means of lattice QCD
Jan Oliver Daldrop
Mattia Dalla Brida
- We study the light scalar mesons a_0(980) and kappa using N_f = 2+1+1 flavor lattice QCD. In order to probe the internal structure of these scalar mesons, and in particular to identify, whether a sizeable tetraquark component is present, we use a large set of operators, including diquark-antidiquark, mesonic molecule and two-meson operators. The inclusion of disconnected diagrams, which are technically rather challenging, but which would allow us to extend our work to e.g. the f_0(980) meson, is introduced and discussed.
The mitochondrial genome of the venomous cone snail conus consors
- Cone snails are venomous predatory marine neogastropods that belong to the species-rich superfamily of the Conoidea. So far, the mitochondrial genomes of two cone snail species (Conus textile and Conus borgesi) have been described, and these feed on snails and worms, respectively. Here, we report the mitochondrial genome sequence of the fish-hunting cone snail Conus consors and describe a novel putative control region (CR) which seems to be absent in the mitochondrial DNA (mtDNA) of other cone snail species. This possible CR spans about 700 base pairs (bp) and is located between the genes encoding the transfer RNA for phenylalanine (tRNA-Phe, trnF) and cytochrome c oxidase subunit III (cox3). The novel putative CR contains several sequence motifs that suggest a role in mitochondrial replication and transcription.
Genetic Basis of Self-Incompatibility in the Lichen-Forming Fungus Lobaria pulmonaria and Skewed Frequency Distribution of Mating-Type Idiomorphs: Implications for Conservation
Francesco Dal Grande
- Fungal populations that reproduce sexually are likely to be genetically more diverse and have a higher adaptive potential than asexually reproducing populations. Mating systems of fungal species can be self-incompatible, requiring the presence of isolates of different mating-type genes for sexual reproduction to occur, or self-compatible, requiring only one. Understanding the distribution of mating-type genes in populations can help to assess the potential of self-incompatible species to reproduce sexually. In the locally threatened epiphytic lichen-forming fungus Lobaria pulmonaria (L.) Hoffm., low frequency of sexual reproduction is likely to limit the potential of populations to adapt to changing environmental conditions. Our study provides direct evidence of self-incompatibility (heterothallism) in L. pulmonaria. It can thus be hypothesized that sexual reproduction in small populations might be limited by an unbalanced distribution of mating-type genes. We therefore assessed neutral genetic diversity (using microsatellites) and mating-type ratio in 27 lichen populations (933 individuals). We found significant differences in the frequency of the two mating types in 13 populations, indicating a lower likelihood of sexual reproduction in these populations. This suggests that conservation translocation activities aiming at maximizing genetic heterogeneity in threatened and declining populations should take into account not only presence of fruiting bodies in transplanted individuals, but also the identity and balanced representation of mating-type genes.
Entwicklung einer digitalen Korpusanwendung zur türkeitürkischen Dialektologie
- Inhalt dieser Arbeit ist die Entwicklung einer digitalen Korpusanwendung zur türkeitürkischen Dialektologie, in welcher der Inhalt des in Kapitel 3.1 beschriebenen Wörterbuchs komplett enthalten und umfangreich durchsuchbar sein soll. Da das Dialektwörterbuch insgesamt 126.468 Einträge enthält, ist eine manuelle Recherche darin äußerst zeitintensiv und unkomfortabel. Selbst die Suche innerhalb einer digitalen Version, die z. B. in einer Word-Datei gespeichert sein kann, ist nicht komfortabel möglich, sobald Optionen bzw. Einschränkungen getätigt werden sollen, wie z. B. die Beschränkung der Ergebnisse auf das Vorkommen in einer bestimmten Provinz. Daher ist es das Ziel der Entwicklung, den Anwendern folgende Suchmöglichkeiten zu bieten: Das Wörterbuch soll entweder komplett im Volltext durchsucht werden können, oder nur innerhalb des Lemmas1. Dabei soll jeweils die Angabe einer oder mehrerer Provinzen möglich sein, sodass die Suchergebnisse nur jene Einträge beinhalten, in denen Suchbegriff und Provinz in der gleichen Zeile enthalten sind. Die Treffer der Suche sollen farbig hervorgehoben sein, damit insbesondere bei großen Wörterbucheinträgen nicht manuell nach den darin enthaltenen Suchbegriffen gesucht werden muss, sondern diese dem Anwender direkt auffallen. Außerdem ist es wünschenswert, mittels Platzhaltern und sogenannten Coversymbolen nach Wortformen und phonetisch bedingten Allomorphen suchen zu können. Letzteres ist für Linguisten, die sich mit dem Türkischen beschäftigen, bei der Eingabe der Suchbegriffe äußerst praktisch, da das Türkische eine vokalharmonische Sprache ist, in der phonetisch bedingte Varianten üblicherweise durch die Schreibung mit Coversymbolen dargestellt werden: z. B. -lAr für die Pluralallomorphe -lar und -ler...
A comparison of third-generation semi-invasive arterial waveform analysis with thermodilution in patients undergoing coronary surgery
Matthias Lars Grünewald
- Uncalibrated semi-invasive continous monitoring of cardiac index (CI) has recently gained increasing interest. The aim of the present study was to compare the accuracy of CI determination based on arterial waveform analysis with transpulmonary thermodilution. Fifty patients scheduled for elective coronary surgery were studied after induction of anaesthesia and before and after cardiopulmonary bypass (CPB), respectively. Each patient was monitored with a central venous line, the PiCCO system, and the FloTrac/Vigileo-system. Measurements included CI derived by transpulmonary thermodilution and uncalibrated semi-invasive pulse contour analysis. Percentage changes of CI were calculated. There was a moderate, but significant correlation between pulse contour CI and thermodilution CI both before (r(2) = 0.72, P < 0.0001) and after (r(2) = 0.62, P < 0.0001) CPB, with a percentage error of 31% and 25%, respectively. Changes in pulse contour CI showed a significant correlation with changes in thermodilution CI both before (r(2) = 0.52, P < 0.0001) and after (r(2) = 0.67, P < 0.0001) CPB. Our findings demonstrated that uncalibrated semi-invasive monitoring system was able to reliably measure CI compared with transpulmonary thermodilution in patients undergoing elective coronary surgery. Furthermore, the semi-invasive monitoring device was able to track haemodynamic changes and trends.
Species distribution modelling of stream macroinvertebrates under climate change scenarios
- There is increasing evidence that climate change will have a severe impact on species’ distributions by altering the climatic conditions within their present ranges. Especially species inhabiting stream ecosystems are expected to be strongly affected due to warming temperatures and changes in precipitation patterns. The aim of this thesis was to
investigate how distributions of aquatic insects, i.e., benthic stream macroinvertebrates would be impacted by warming climates. The methods comprised of an ensemble forecasting technique based on species distribution models (SDMs) and climate change scenarios of the Intergovernmental Panel on Climate Change of the year 2080. Future model projections were generated for a wide variety of species from a number of taxonomic orders for two spatial scales: a stream network within the lower mountain ranges of Germany, and the entire territory across Europe. In addition, the effect of the modelling technique on habitat suitability projections was investigated by modifying the choice of study area (continuous area vs. stream network) and the choice of predictors (standard vs. corrected set).
Projections of future habitat suitability showed that potential climate-change impacts would be dependent on species’ thermal preferences, and with a similar pattern for both spatial scales. Future habitat suitability was projected to remain for most or all of the modelled species, and species were projected to track their climatically suitable conditions by shifting uphill along the river continuum within the lower mountain ranges, and into a north-easterly direction across Europe. Cold-adapted headwater and high-latitude species were projected to lose suitable habitats, whereas gains would be expected for warm-adapted river and low-latitude species along the river continuum and across Europe, respectively. Additionally, habitat specialist species in terms of endemics of the Iberian Peninsula were identified as potential climate-change losers, highlighting their restricted habitat availability and therefore vulnerability to warming climates.
The main findings of this thesis underline the high susceptibility of stream macroinvertebrates to ongoing climate change, and give insights into patterns of possible consequences due to changes in species’ habitat suitability. Concerning the methodology, a clear recommendation can be given for future modelling approaches of stream macroinvertebrates by building models within a stream network and with a careful choice of environmental predictors, to reduce uncertainties and thus to improve model projections.
Nanolesions induced by heavy ions in human tissues: experimental and theoretical studies
- The biological effects of energetic heavy ions are attracting increasing interest for their applications in cancer therapy and protection against space radiation. The cascade of events leading to cell death or late effects starts from stochastic energy deposition on the nanometer scale and the corresponding lesions in biological molecules, primarily DNA. We have developed experimental techniques to visualize DNA nanolesions induced by heavy ions. Nanolesions appear in cells as “streaks” which can be visualized by using different DNA repair markers. We have studied the kinetics of repair of these “streaks” also with respect to the chromatin conformation. Initial steps in the modeling of the energy deposition patterns at the micrometer and nanometer scale were made with MCHIT and TRAX models, respectively.