Doctoral Thesis
Refine
Year of publication
- 2012 (38) (remove)
Document Type
- Doctoral Thesis (38) (remove)
Language
- English (38) (remove)
Has Fulltext
- yes (38)
Is part of the Bibliography
- no (38)
Keywords
- Proteomanalyse (3)
- Atmosphärendruckplasma (2)
- Kaltes Plasma (2)
- Phylogenie (2)
- Streptococcus pneumoniae (2)
- Abregung (1)
- Adhäsine (1)
- Aeromonas salmonicida (1)
- Agoraphobie (1)
- Akupunktur (1)
- Altern (1)
- Aluminium (1)
- Aminoacylierung (1)
- Amperometric detection; EstraMonitor (1)
- Amperometrische Detektion; EstraMonitor (1)
- Angewandte Linguistik (1)
- Angst (1)
- Anion (1)
- Antibiotics (1)
- AnxA1 (1)
- Applied linguistics (1)
- Arrowworms (1)
- Atemwegsobstruktion (1)
- Attachmentverlust (1)
- Auftrittsgröße (1)
- Autophagie (1)
- Autophagy (1)
- Bacillus (1)
- Bacillus subtilis (1)
- Baeyer-Villiger monooxygenase (1)
- Baeyer-Villiger-Oxidation (1)
- Bakterielle Infektion (1)
- Bauchfellentzündung (1)
- Beam (1)
- Biokatalyse (1)
- Biosensor (1)
- Birds (1)
- Burkholderia pseudomallei (1)
- C. elegans (1)
- Caenorhabditis elegans (1)
- Campher (1)
- Chaetognatha (1)
- Clusterion (1)
- Clusterphysik (1)
- Cytometrie (1)
- DBD (1)
- DNA Triplex (1)
- DNA triplex (1)
- DNA-Wirkstoff-Interaktion (1)
- DNA-drug interaction (1)
- DNS (1)
- Darbellay-Vajda Partitionsregel (1)
- De-Excitation (1)
- Dekontamination (1)
- Dielectric Barrier Discharge (1)
- Dielektrische Entladung (1)
- Dilatative Kardiomyopathie (1)
- Dilated Cardiomyopathy (1)
- Duennschichten (1)
- EEG (1)
- Elastase inhibitor (1)
- Elastase inhibitoren (1)
- Elektronenbad (1)
- Elektrospray-Ionisation (1)
- Entzündung (1)
- Enzymkatalyse (1)
- Epidemiologie (1)
- Europa (1)
- Europe (1)
- FT-ICR-Spektroskopie (1)
- FT-IR-Spektroskopie (1)
- FTIR spectroscopy (1)
- FTIR-Spektrometrie (1)
- Flavine (1)
- Flow Cytometry (1)
- Flugzeitspektrometrie (1)
- Foraminiferen (1)
- Friedland clay (1)
- Friedland tons (1)
- Funktionalisierung <Chemie> (1)
- Furcht (1)
- Fusionsplasma (1)
- Ganzkörper-CT (1)
- Glomus irregulare (1)
- Glutathion (1)
- Green-Funktion (1)
- Grönland (1)
- HLW- Endlager (1)
- HLW- repository (1)
- Hanta-Virus (1)
- Hantavirus (1)
- Hearts (1)
- Hefeartige Pilze (1)
- Heißes Plasma (1)
- Herzen (1)
- Holozän (1)
- Host range (1)
- Hydrogen sulphide (1)
- Immuncytochemie (1)
- Impfstoff (1)
- Indolochinolin (1)
- Infektion (1)
- Informationsabhängigkeit (1)
- Infrarotspektroskopie (1)
- Ionenfalle (1)
- Kalziumsignale (1)
- Kinderheilkunde (1)
- Kongestive Herzmuskelkrankheit (1)
- LC-MS (1)
- Level-Set-Methode (1)
- Litauen (1)
- Lithuania (1)
- Low Temperature Plasma (1)
- Lungenfunktion (1)
- Lungenvolumen (1)
- MALDI-MS (1)
- MIR-Spektroskopie (1)
- MX80-bentonit (1)
- MX80-bentonite (1)
- Mass Specrtometry (1)
- Massenspektrometrie (1)
- Maßanalyse (1)
- Mehrsprachigkeit (1)
- Melioidosis (1)
- Metabolom (1)
- Metallcluster (1)
- Mice (1)
- Minkowski-Metrik (1)
- Mitteleuropa (1)
- Moldawien (1)
- Moldova (1)
- Monoklonaler Antikörper (1)
- Monooxygenasen (1)
- Monte-Carlo-Simulation (1)
- Morbidität (1)
- Mortalität (1)
- Mäuse (1)
- NADPH oxidase (1)
- Neutralisation (1)
- Neutralization (1)
- Nichtgleichgewicht (1)
- Oberflächenstöße (1)
- PCV7 (1)
- Paläoozeanographie (1)
- Pancreatitis (1)
- Panikstörung (1)
- Paniksyndrom (1)
- Pankreatitis (1)
- Parodontitis (1)
- Particle in Cell Simulation (1)
- PavB (1)
- Penning trap (1)
- Penningfalle (1)
- Peritonitis (1)
- Pfeilwürmer (1)
- Phylogenetische Systematik (1)
- Phylogeny (1)
- Pili (1)
- Pilus Islet-1 (1)
- Pilus Islet-2 (1)
- Plasma (1)
- Plasma Instability (1)
- Plasma dynamics (1)
- Plasma-Wand-Wechselwirkung (1)
- Plasmachemie (1)
- Plasmadynamik (1)
- Plasmainstabilität (1)
- Plasmaphysik (1)
- Plasmarandschicht (1)
- Plasmaschwingung (1)
- Plasmaspektroskopie (1)
- Pneumokokken (1)
- Polyanion (1)
- Polymere (1)
- Polytrauma (1)
- Proteom (1)
- Pseudomonas putida (1)
- PspC (1)
- PspC-hpIgR-vermittelten Endozytose (1)
- PsrP (1)
- Quasi-Pseudo-Metrik (1)
- RNS (1)
- Rainbow trout (1)
- Regenbogenforelle (1)
- Ribozym (1)
- Schadstoffabbau (1)
- Schmerz (1)
- Secondary Electrons (1)
- Segmentierung (1)
- Sekundärelektronen (1)
- Selective breeding (1)
- SigB (1)
- Sondierungstiefe (1)
- Spektroskopie (1)
- Spillover Infections (1)
- Spillover-Infektionen (1)
- Sporulation (1)
- Sprachlandschaften (1)
- Staphylococcus aureus (1)
- Stoffwandlung (1)
- Surface Collisions (1)
- Systematik (1)
- Thermodynamik (1)
- Thin films (1)
- Titan Tholins (1)
- Titan-Tholine (1)
- Ton-Eisen interaktion (1)
- Transporttheorie (1)
- Turbulenz (1)
- Unabhängigkeitanalyse (1)
- Variationsrechnung (1)
- Verhaltenstest (1)
- Vietnam (1)
- Virulenz (1)
- Vögel (1)
- Wasserstoffperoxid (1)
- Wirtsspektrum (1)
- Zahnmedizin (1)
- Zahnzahl (1)
- Zellkultur (1)
- acupuncture (1)
- aging (1)
- agoraphobia (1)
- airflow limitation (1)
- airway epithelial cells (1)
- appearance size (1)
- arbuscular mycorrhizal fungi (1)
- atmospheric pressure plasma (1)
- behavioral avoidance test (1)
- biological decontamination (1)
- children (1)
- clay-iron interaction (1)
- clinical attachment loss (1)
- culture based method (1)
- defensive Reaktivität (1)
- defensive reactivity (1)
- dentistry (1)
- diketocamphane monooxygenase (1)
- electron bath (1)
- extravasation (1)
- fear (1)
- flavin reductase (1)
- fumarate reductase (1)
- general stress response (1)
- generelle Stressantwort (1)
- genome size (1)
- gyrokinetic (1)
- gyrokinetisch (1)
- hydrogen peroxide (1)
- hypothermia (1)
- indoloquinoline (1)
- konsistente Schätzung (1)
- linguistic landscapes (1)
- lung function (1)
- lung volume (1)
- microinstabilities (1)
- microinstabilitäten (1)
- morbidity (1)
- mortality (1)
- multilingualism (1)
- natural analougs (1)
- natürliches Analogon (1)
- neoclassic (1)
- neoklassisch (1)
- neutrophil (1)
- non-thermal plasma (1)
- oxidative stress (1)
- pain (1)
- panic disorder (1)
- periodontal disease (1)
- phylogeny (1)
- plasma (1)
- plasma chemistry (1)
- plasma diagnostics (1)
- pollution control (1)
- polyanion (1)
- population-based study (1)
- populationsbasierte Studie (1)
- proteomics (1)
- qPCR (1)
- reactive oxygen species (ROS) (1)
- regulatorisches Netzwerk (1)
- regulatory network (1)
- species conversion (1)
- specific dissolution potential (1)
- spezifisches Auflösungspotential (1)
- sporulation (1)
- stellarator (1)
- stichprobenabhängige Partitionsregel (1)
- stroke (1)
- surface modification (1)
- whole body multislice CT (1)
- Östrogen-Rezeptor-Modulator (1)
- Östrogene (1)
Institute
- Institut für Physik (6)
- Institut für Mikrobiologie - Abteilung für Genetik & Biochemie (5)
- Abteilung für Mikrobiologie und Molekularbiologie (4)
- Institut für Biochemie (4)
- Institut für Mathematik und Informatik (3)
- Institut für Geographie und Geologie (2)
- Institut für Pharmazie (2)
- Zoologisches Institut und Museum (2)
- Friedrich-Loeffler-Institut für Medizinische Mikrobiologie (1)
- Institut für Anglistik/Amerikanistik (1)
Ribozymes for Aminoacylation
(2012)
Aminoacyl-tRNA synthetases (aaRS) are at the heart of modern translation, catalyzing the accurate biosynthesis of aminoacyl-tRNAs. According to the RNA world hypothesis, the early translation system should have aminoacylation ribozymes for RNA aminoacylation. For this, an aaRS ribozyme system, consisting of the KK13 ribozyme and the C3a ribozyme was successfully designed, which can perform both amino acid activation and aminoacyl transfer reaction. Generation of such aminoacylation ribozyme system would fill up the gap between the RNA world and the modern biological world. In addition, two types of diversified aminoacylation ribozymes, symmetrical ribozymes and self-assembling ribozymes were successfully developed, which may have great meaning in the origin of life.
Despite a plethora of therapeutic approaches, the injection of local anaesthetics itself remains one of the most painful and dreadful procedures among children. Stimulation of acupoint LI4 is associated with analgesic effects in dentistry. Goal of the study To investigate whether stimulation of LI4, added to standard therapy (ST), reduces pain and distress during injection of local anaesthetic (LA) in comparison with ST alone. Materials and Methods Children, scheduled for dental treatment in local anaesthesia on 2 separate days were enrolled in this trial, approved by local ethics commission. On one day each child received bilateral acupuncture of LI4 point, using indwelling fixed “New Pyonex” needles (0.2 x 1.5 mm; Seirin, Japan). The parents of the children were asked to stimulate the needles by massage. Standardized injection of LA was performed 5 min following acupuncture. The needles were withdrawn at the end of dental treatment. On the other day of treatment children received LA injection without acupuncture. The order of treatment days (acupuncture first or vice versa) was randomised. Primary endpoint was the pain intensity during LA injection reported by children on Visual Rating Scale from 0=no pain to 10=maximal pain imaginable (VRS-11). Secondary endpoints were parent- and dentist-assessed pain intensity (measured on Numeric Rating Scale 1-10), patients’ heart rate before and during dental treatment and satisfaction with received therapy (measured on Numerical Rating Scale 1-5.) Side effects of LI4 stimulation were also recorded. Results and Discussion The data of 49 children (22 females; age 10 ± 4 yrs; mean ± SD), who completed both visits, were analysed. Children reported less pain with than without acupuncture: 2.2 ± 2.5 vs. 3.9 ± 2.7; mean ± SD, p<0.001. Heart rate decreased after LI4 stimulation compared to ST alone throughout the dental treatment (p<0.05). LI4 stimulation was safe and raised better satisfaction with the treatment among children and parents, than ST alone (p<0.05). Other secondary endpoints were comparable between both sessions. Conclusion Stimulation of acupuncture point LI4 reduces pain and autonomous stress during injection of local anaesthetics in paediatric dentistry.
The worldwide distribution and prevalence of melioidosis, an infectious disease caused by the soil-dwelling Gram-negative bacterium Burkholderia pseudomallei, is unknown. In Vietnam, sporadic cases of melioidosis have been reported for decades, but clinical and epidemiological data for the indigenous population are still scarce. In this study, we reviewed clinical and demographic data of patients with culture-proven melioidosis diagnosed at a single large referral hospital in Hanoi between November 1997 and December 2005. The clinical manifestations of melioidosis with fatal septicaemia as the most common presentation, a high rate of underlying diseases and a peak of cases admitted during the wet season were similar to studies from other endemic areas. The geographical origin of melioidosis patients shows that melioidosis exists in at least 18 northern provinces. The characterization of clinical B. pseudomallei strains by multilocus sequence typing identified 17 different sequence types (STs), ten of which have (as yet) not been found outside Vietnam. Several of these STs presumably were generated through recent evolutionary events in this rapidly diversifying bacterial species, and thus restricted geographic distribution may be a consequence of limited time passed since emergence. In order to define the distribution of the bacterium in the environment, our study also aimed to develop a more sensitive culture method for the detection of B. pseudomallei from soil samples in endemic areas compared to the currently used culture method based on soil dispersion in water. Our newly developed protocol involving soil dispersion in a polyethylene glycol and sodium deoxycholate solution increased the yield of viable B. pseudomallei from soil samples. Comparative testing of soil samples from Northeast Thailand covering a wide range of B. pseudomallei concentrations demonstrated a significantly higher recovery (p < 0.0001) of B. pseudomallei colony forming units by the new method compared to the conventional method. Our data indicate that using the detergents polyethylene glycol and sodium deoxycholate not only results in a higher recovery of viable B. pseudomallei, but also results in a shift in the bacterial species recovered from soil samples. Molecular methods based on direct bacterial nucleic acid extraction from environmental samples and subsequent amplification have the potential to overcome many restrictions of traditional microbiological approaches. Moreover, culture-dependent methods require special expertise in recognizing B. pseudomallei colony morphologies. Thus, a highly sensitive culture-independent DNA-based method that allows direct quantification of B. pseudomallei from soil is needed, particularly in diagnostic laboratories outside endemic areas. We therefore aimed to establish a protocol for B. pseudomallei soil DNA isolation, purification and quantification by qPCR targeting a type three secretion system 1 single copy gene. This assay was validated using 40 soil samples from Northeast Thailand that underwent parallel bacteriological culture. All 26 samples that were B. pseudomallei-positive by direct culture were B. pseudomallei qPCR-positive, with a median of 1.84 x 104 genome equivalents (range 3.65 x 102 to 7.85 x 105) per gram of soil. This was 10.6 fold (geometric mean; range 1.1 to 151.3) higher than the bacterial count as defined by culture. Moreover, the qPCR detected B. pseudomallei in seven samples (median 36.9 genome equivalents per g soil; range 9.4 to 47.3), which were negative on direct culture. These seven positives were reproduced using a nested PCR targeting a second, independent B. pseudomallei-specific sequence. Two samples were direct culture and qPCR negative but nested PCR positive. Five samples were negative by both PCR methods and culture. In conclusion, this is the first report on a series of cases describing clinical and epidemiological features of melioidosis and corresponding Burkholderia pseudomallei strains from northern Vietnam. Moreover, our newly developed culture-based and PCR-based methods provide highly specific and sensitive tools for the quantitative environmental surveillance of B. pseudomallei.
I have investigated the role played by reactive oxygen species (ROS) generated by the phagocyte NADPH oxidase system in the innate immune response. I first looked at effector functions by asking whether ROS released from phagocytes might be effective in the killing of extracellular bacteria. Since bacteria can be killed in many other ways – for example by proteases or by cationic peptides – I made use of the recently demonstrated capacity of ROS to remove discontinuities from the surface of gold as the basis of an in vivo assay for extracellular ROS. Unlike bacterial killing, this readout system is not affected by enzymes, cationic peptides or other biological anti-bacterial agents. By this means I was able to use wild type mice and a congenic strain which lacks the gene coding for the gp91 subunit of the phagocyte NADPH oxidase to demonstrate that ROS generated by the NADPH oxidase system are indeed found outside the cells during an inflammation in vivo and that their principle source is neutrophil granulocytes rather than tissue macrophages. Since ROS released by these cells will be non-specific in its action it is to be expected that the releasing cell will itself suffer considerable damage. This fits well to the known short life of activated neutrophils and may explain the established fact that their death is dependent on the NADPH oxidase system. The long lived macrophages, in contrast, restrict their production of extracellular ROS. ROS are increasingly being found to be involved in both intra and intercellular signalling processes I looked for an involvement of NADPH oxidase derived ROS in the recruitment of neutrophils to sites of inflammation in vivo. Since the gene coding for the gp91 subunit of the NADPH oxidase is on the X chromosome I made use of a mosaic expression strategy based on X chromosomal inactivation. The results show that indeed ROS serves as a component of the neutrophil recruitment process in the critical early stages of an infection. Possible mechanisms are explored.
A molecular approach to characterize the arbuscular mycorrhizal fungus, Glomus sp. AMykor isolate
(2012)
The arbuscular mycorrhizal fungi (AMF) interaction with plants has a major impact on the soil ecosystem. However, so far, only a few studies on AMF genetics have been performed and molecular information on the genetic diversity of AMF is limited. In this study a fundamental genetic characterization of the industrial isolate, Glomus sp. AMykor (AMykor GmbH, Bitterfeld, Germany) has been undertaken to increase the understanding of AMF genetic diversity. Based on phylogenetic analysis of partial rDNA sequences, Glomus sp. AMykor isolate was proposed to belong to the G. irregulare species together with the reference isolate, DAOM197198. To investigate if both isolates differ in their ploidy level, fluorescence in situ hybridization (FISH) was performed and mainly one or two hybridization signals per nucleus were observed in both isolates. It is suggested that they harbour at least two major rDNA sites and possibly two minor sites. The DNA content was estimated by means of flow cytometry (FC) and confirmed by Feulgen densitometry (FD). The calculated average DNA content per nucleus is 153.0 ± 3.6 Mb for the G. irregulare AMykor isolate and 154.8 ± 6.2 Mb for the DAOM197198 isolate. Since there are plenty criticisms coming recently of using rDNA sequence for fungal barcoding there is necessity of development other system for the identification to species level of Glomeromycotan fungi. The focus of this part of the study was the GiFRD gene encoding fumarate reductase enzyme for use as a potential candidate for AMP species determination. Unfortunately, observed sequence variations do not allow the discrimination of Glomeromycotan species. However, further analysis of enzyme encoded by GiFRD showed a possible role of fumarate reductase in AMF redox balance maintaining under oxygen deficient conditions. Using a yeast expression system, it has been demonstrated that the protein encoded by GiFRD has fumarate reductase activity. The functional expression of GiFRD in the S. cerevisiae fumarate reductase deletion mutant restored the ability of growth under anaerobiosis which indicated that Gifrdp is able to functionally complement the S. cerevisiae missing genes. The fact that GiFRD expression was present only in the asymbiotic stage confirmed existence of at least one metabolic pathway involved in anaerobic metabolism and suggested that AMF behave as a facultative anaerobe in asymbiotic stage.
Hantaviruses (family Bunyaviridae) are enveloped viruses with a segmented RNA genome of negative polarity. They can cause two different diseases in humans, the hemorrhagic fever with renal syndrome in Europe and Asia and the hantavirus cardiopulmonary syndrome in America. The transmission to humans is mainly indirect by inhalation of aerosolized virus-contaminated rodent excreta. In contrast to the initial assumption that hantaviruses are mainly carried by rodents, during the last years many novel hantaviruses were detected in shrews, moles and recently in bats. These findings raise important questions about the evolutionary history of hantaviruses, their host association and adaptation, the role and frequency of spillover infections and host switch events. This study aims to prove the presence, geographical distribution and host association of the rodent-borne Tula virus (TULV) and the shrew-associated Seewis virus (SWSV) in Central Europe. For this purpose, novel laboratory techniques for molecular and serological hantavirus detection were developed. Initially, a broad-spectrum molecular assay to identify small mammal species from Central Europe was developed. This novel assay is based on PCR amplification using degenerated primers targeting the cytochrome b (cyt b) gene, nucleotide sequence analysis of the amplified cyt b gene portion and followed by pairwise sequence comparison to published sequences using the BLAST function of GenBank. Different small mammal species prevalent in Central Europe could be determined by this new approach, including not only representatives of various Rodentia and Soricomorpha, but also representatives of the orders Erinaceomorpha, Lagomorpha, Carnivora and Chiroptera. For characterization of insectivore-borne hantavirus Thottapalayam virus (TPMV), specific monoclonal antibodies were generated that detect native virus in infected mammalian cells. For the detection of TPMV-specific antibodies, Asian house shrew Suncus murinus immunoglobulin G (IgG)-specific antibodies were produced in laboratory mice and rabbit. Using this anti-shrew IgG and recombinant TPMV nucleocapsid (N) protein, an indirect enzyme-linked immunosorbent assay (ELISA) was developed allowing the detection of TPMV N protein-specific antibodies in immunized and experimentally TPMV infected shrews. A Pan-Hantavirus SYBR-Green RT-qPCR was developed for the search to novel hantaviruses. By this novel RT-qPCR and other conventional RT-PCR approaches, TULV infections were identified for the first time in the Eurasian water vole Arvicola amphibius from different regions in Germany and Switzerland. The phylogenetic analyses of the different partial TULV small (S)-, medium (M)- and large (L)-genome segment sequences from A. amphibius, with those of Microtus arvalis- and M. agrestis-derived TULV lineages, revealed a geographical, but host-independent clustering and may suggest multiple TULV spillover or a potential host switch from M. arvalis or M. agrestis to A. amphibius. In a further comprehensive study, different shrew species (Sorex araneus, S. minutus, S. coronatus, and S. alpinus) were collected in Germany, Czech Republic, and Slovakia and screened by another L-segment-targeting Pan-Hantavirus RT-PCR approach. This screening revealed hantavirus L-segment sequences in a large number of S. araneus and a few S. minutus indicating a broad geographical distribution of this hantavirus. For detailed analyses, S-segment sequences were obtained, from S. araneus and S. minutus. The sequences demonstrated their similarity to SWSV sequences from Hungary, Finland, Austria and Germany. A detailed phylogenetic analysis showed low intra-cluster sequence variability, but high inter-cluster divergence suggesting a long-term SWSV evolution in local shrew populations. In conclusion, the investigations demonstrated a broad geographical distribution and multiple spillover infections of rodent-borne TULV and shrew-borne SWSV in Europe. The finding of putative spillover transmissions described here and in other studies underline the current problem of the hantavirus reservoir host definition. In contrast to the hypothesis of a long-standing hantavirus–rodent (small mammal) host coevolution, the investigations support a more dynamic evolutionary history of hantavirus diversification including spillover infections and host-switch events. In future in vitro and in vivo infection studies as well as field studies has to define factors determining the host specificity of these hantaviruses.
Chaetognaths are a fascinating taxon with unique features and a great impact on marine food webs as primary predators of zooplankton. Their phylogenetic position has been subject to many speculations ever since their discovery and even contemporary phylogenomic methods have not yet been able to suggest a stable hypothesis on their phylogenetic position within the Bilateria. Neuroanatomical studies may contribute new aspects to this discussion. This study aims to provide new insights into the chaetognath nervous system using a fresh set of methods to determine characters for a phylogenetic discussion. The method of choice in this case was immunohistochemistry combined with confocal microscopy. Experiments were conducted with a host of antibodies. The most effective target antigenes were RFamides (a family of neuropeptides), synapsins (synaptic proteins), tyrosinated tubulin (a cytoskeletal element, especially in neurites) and BrdU (bromodeoxyuridin, a proliferation marker). Each of those markers was of great use in highlighting certain aspects of the nervous system. A fresh look at the development of juvenile chaetognaths shortly after hatching revealed that the ventral nerve center (VNC) is developing earlier than the brain and that the production of neurotransmitters has already started at hatching. Specifically, some neurons exhibit RFmide-like immunoreactivity (ir). Neurogenesis continues for about five days after hatching and the mode of division in the neuronal stemcells is asymmetrical. In adult chaetognaths, the brain is divided into a stomatogastric anterior and a sensory posterior neuropil domain. It contains a set of individually identifiable neurons that exhibit RFamide-like ir. The study highlights the interspecific variation of brain architecture between representatives of spadellids and sagittids. The VNC consists of two lateral bands of somata that flank a central neuropil. Within the VNC exists a serial arrangement of neurons with RFamide-like ir. A variety of other neurotransmitters and related substances are also present in both, the brain and the VNC. More interspecific differences and similarities were explored in another part of the study, comparing even more different chaetognath species and focusing on the VNC and its internal structure. The two species of Krohnitta have an unusual distribution of nuclei that is not clearly separated into two lateral bands like in other species. Many of the sagittid species exhibit a striation pattern of the neuropil that is mostly absent in other groups and some of their nerve nets show varying degrees of order as opposed to the rather disorganized nerve net in other groups. In addition, immunohistochemical methods were applied to several specimens of Gnathostomula sp. in order to test one of the many hypotheses about the chaetognaths phylogenetic position, a sister-group relationship to gnathostomulids. A comparison between the two taxa, taking into account also other gnathifera and platyhelminthes, makes a sistergroup relationship between chaetognaths and gnathostomulids very unlikely. In conclusion, chaetognaths remain in an enigmatic phylogenetic position and likely branched off close to the deuterostome/protostome split.
Indoloquinoline derivatives are very interesting compounds for pharmaceutical applications because of their broad spectrum of biological activity. However, phenyl-substituted indoloquinolines suffer from solubility problems in aqueous solution and require the synthesis of better soluble derivatives for their effective application. Therefore, the indoloquinoline derivatives were covalently attached to two different types of cationic aminoalkyl linkers. After having successfully established the synthesis and subsequent purification of the novel derivatives that could be isolated in excellent yields, these ligands were characterized in this thesis with regard to their spectral properties in different environments and their sequence specific binding to different types of nucleic acids with a variety of spectroscopic methods.
Chronic infections, including periodontal infections, may reduce lung function. To date, there are hardly any population-based studies evaluating the association between periodontitis and lung function. However, there are some studies that used variables associated with obstructive pulmonary diseases (FEV1, FEV1/FVC). Thus, we aimed to assess the potential association of periodontal diseases with lung volumes and airflow limitation in the population-based Study of Health in Pomerania (SHIP). Of 3300 participants aged 25-85 years of the 5-year follow-up (SHIP-1), 1809 subjects participated in lung function examinations. 1465 subjects were included in the analyses. Lung function was measured using spirometry, body plethysmography, helium dilution, and diffusing capacity for carbon monoxide. Periodontal status was assessed by clinical attachment loss, probing depth, and number of missing teeth. Linear regression models using fractional polynomials were used to assess linear and non-linear associations between periodontal disease and lung function adjusting for confounders. Adjusting for age, sex, waist circumference, physical activity, diabetes, asthma, and time between core and pulmonary examination, mean attachment loss was significantly associated with variables of dynamic and static lung volumes, airflow limitation and hyperinflation. Total lung capacity and diffusing capacity for carbon monoxide were not associated with mean attachment loss. Adjustment for smoking and height considerably changed coefficients indicating profound confounding. Including fibrinogen and high sensitive CRP into fully adjusted models did not change coefficients of mean attachment loss. Restricted to never smokers, mean attachment loss was significantly associated with FEV1, FVC, and RV/TLC. Relations with lung function were confirmed for mean probing depth, extent measures of attachment loss/probing depth, and number of missing teeth. Periodontal disease was significantly associated with decreased lung function. Systemic inflammation did not provide a mechanism linking both diseases. However, cohort studies evaluating lung function in the current manner are needed to confirm results from this study and to assess a causal relationship. Furthermore, it needs to be investigated with the help of randomized clinical trials whether prevention or treatment of periodontitis might have a beneficial impact on lung function.
The learning theory of panic disorder differs between panic attacks and anxious apprehension as distinct emotional states. Acute panic is accompanied by extreme fear, experience of strong body symptoms reflecting autonomic surge and flight tendencies. In contrast, anxious apprehension is associated with hypervigilance towards bodily sensations and increased distress when subtle somatic symptoms are identified. Following animal models, these clinical entities reflect different stages of defensive reactivity depending upon the imminence of interoceptive or exteroceptive threat cues with lowest distance to threat during panic attacks. We tested this model by investigating the dynamics of defensive reactivity in a large group of patients suffering from panic disorder and agoraphobia (PD/AG) prior to a multicenter controlled clinical trial. Three hundred forty-five patients participated in a standardized behavioral avoidance test (being entrapped in a small, dark chamber for 10 minutes). Defensive reactivity was assessed measuring avoidance and escape behavior, self reports of anxiety and panic symptoms, autonomic arousal (heart rate and skin conductance), and potentiation of the startle reflex before and during the exposure period of the behavioral avoidance test. While 125 patients showed strong anxious apprehension during the task (as indexed by increased reports of anxiety, elevated physiological arousal, and startle potentiation), 72 patients escaped from the test chamber. Active escape was initiated at the peak of the autonomic surge accompanied by an inhibition of the startle response as predicted by the animal model. These physiological responses were observed during 34 reported panic attacks as well. We found evidence that defensive reactivity in PD/AG patients is dynamically organized ranging from anxious apprehension to panic with increasing proximity of interoceptive threat. Importantly, the patients differed quite substantially according defensive reactivity during the behavioral avoidance test despite all patients received the same principal diagnosis. These differences can be explained in part by differences in the disposition according to two genetic variants previously associated with panic disorder. Patients carrying the risk variant of a polymorphism in the neuropeptide S receptor gene showed an overall increased heart rate during the whole behavioral avoidance test reflecting an enhanced sympathomimetic activation and consequently arousal level. During the entrapment situation in which heart rate further increased over an already elevated baseline level, risk variant carriers were prone to experience more panic symptoms. This is in line with the learning perspective of panic disorder, postulating that internal cues of elevated arousal increase the chance of experiencing another panic attack once they have been associated with aversive responses. Furthermore, the risk variant of a polymorphism in the monoamine oxidase A gene was observed to augment the occurrence of panic attacks and escape behavior preparation. In addition, we find evidence that suggest an enhanced resistance to corrective learning experiences as indicated by a lack of a reduction of avoiding and escaping behavior during repeated test chamber exposures in wait-list control patients carrying the risk gene variant. Both effects may strengthen the learning mechanism hypothesized to be involved in the pathogenesis of panic disorder. Exteroceptive and interoceptive cues previously associated with the initial panic attack might trigger subsequent attacks in risk allele carriers more rapidly while simultaneously the opportunity to dissolve once established associations due to contradictory experiences is limited. Now, differential dispositions regarding defensive reactivity in PD/AG patients has to be linked to mechanisms supposed to be involved in exposure based therapy. First outcome evaluations of the clinical trial indicated that a behavioral therapy variant suggested to be linked with higher fear activation during exposure exercises is more effective than another. Further analyses have to proof whether those patients showing a clear specific fear response during the behavioral avoidance test benefit more than others from exposure based therapy.