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β-Phenylalanine Ester Synthesis from Stable β-Keto Ester Substrate Using Engineered ω-Transaminases
(2018)
Many intrastate conflicts see more than one mediation effort. As the sequencing of mediation efforts in intrastate conflicts is neglected in existing research, this project addresses the question how and why previous mediation outcomes have an impact on subsequent mediation onset and subsequent mediation success. Drawing on bargaining theory, it is argued that governments and rebel groups engaged in intrastate conflicts account for previous mediation outcomes in their cost-benefit calculations on subsequent mediation onset, and, should subsequent talks set on, their behaviour during subsequent mediation efforts, which influences subsequent mediation success.
If mediation did not produce an agreement, the persistence of the private information problem is noted by the conflict parties. Yet, no new costs of mediation are uncovered, and hence the conflict parties will agree to subsequent mediation onset. Being aware of the necessity to overcome the private information and the commitment problem, the mediator will seek to account for the concerns of the conflict parties, and thereby work towards subsequent mediation success. If mediation produced a partial agreement, the benefits of mediation are underlined. The private information and the commitment problem seem solved with the assistance of the mediator. Subsequent mediation onset and eventually subsequent mediation success are observed. If a mediated agreement was reneged on by the rebel group, the government will refrain from further talks, pointing out the rebel group’s illegitimacy. If the government reneged on the agreement itself, it will also decide against subsequent mediation, as the previous mediation effort produced an agreement which did not mirror the power distribution in the dyad. Costs of mediation, which outweigh the benefits of it, were highlighted. Rebel groups will opt for mediation regardless which side reneged on an agreement. As both governments and rebel groups have to agree to subsequent mediation for talks to set on, subsequent mediation onset is unlikely if a mediated agreement was reneged on. Given the onset of subsequent mediation after a mediated agreement was reneged on, subsequent mediation success is unlikely to be observed, due to the previously underlined hazards of sharing private information and the persistence of the commitment problem.
The theoretical argument is tested with a mixed-methods approach. The quantitative analysis accounts for mediation efforts in African intrastate conflicts between 1993 and 2007. The qualitative analysis scrutinises the mediation efforts between the Government of Uganda and the Lord’s Resistance Army. The results of both parts of analysis largely go hand-in-hand, and show that partial mediation success and mediation which did not produce an agreement have a positive impact on subsequent mediation onset in particular, but also on subsequent mediation success. Reneged on mediated agreements have a severe negative impact on subsequent mediation onset and subsequent mediation success though.
By addressing the question which impact previous mediation outcomes have on subsequent mediation efforts, this research shows that mediation which does not produce an agreement is not the mediation outcome which needs to be feared by the international community. Instead, the deteriorating impact of short-lived agreements, a mediation outcome which is unaccounted for in existing research as an explanatory variable, becomes apparent. This research has important policy implications, especially for mediators, as it suggests that accepting mediation efforts to end without an agreement is more conducive for subsequent mediation efforts. Moreover, this research points towards the necessity of including reneged on agreements in mediation research as an explanatory variable more extensively, thereby shedding more light onto the dynamics at play in consecutive mediation efforts.
Der Beitrag behandelt eine Problematik aus dem Bereich der
mittelbaren Täterschaft gem. § 25 I Alt. 2 StGB, die spätestens seit der berühmten Entscheidung des Bundesgerichtshofs im Mauerschützenfall (BGHSt 40, 218) zu den umstrittensten Fragen der deutschen Beteiligungsdogmatik zählt:
die Rechtsfigur der Organisationsherrschaft und ihre prinzipielle Übertragbarkeit auf Wirtschaftsunternehmen. Anliegen des Beitrags ist es, die Entwicklung der Organisationsherrschaft nachzuzeichnen, das kaum mehr überschaubaren
Meinungsspektrum zur Thematik in seinen wesentlichen
Leitlinien zusammenzufassen und so das nötige examensrelevante Wissen für das universitäre Schwerpunktstudium
zu vermitteln.
Three-year-olds and 4-year-olds have severe difficulties solving standard mental rotation tasks. Only 5-year-olds solve such tasks above chance reliably. In contrast studies relying on simplified mental rotation tasks indicate that infants discriminate between an object and its mirror image. Furthermore in another simplified mental rotation task with 3-year-olds, a linear relation between angular disparity and reaction time typical for mental rotation was revealed. Therefore it was assumed that 3-year-olds’ capabilities are underestimated. In the current study, 3-year-olds were trained in two isolated sessions to solve standard mental rotation tasks and were tested in a third session. Three-year-olds solved this test above chance as a group – a substantial number of them doing so on an individual level. However, a linear relation between angular disparity and reaction time, that would indicate an analog mental transformation, was not discernable. Nevertheless, these findings are in accordance with a continuous line describing mental rotation in infants and older children. And, these also indicate that children’s mental rotation capabilities might be underestimated.
Bacteria are exposed to oxidative stress as an unavoidable consequence of their aerobic lifestyle. Reactive oxygen species (ROS) are generated in the stepwise one-electron reduction of molecular oxygen during the respiration. Pathogens encounter ROS during the oxidative burst of macrophages as part of the host immune defense. Besides ROS, bacteria also have to cope with reactive chlorine, electrophilic and nitrogen species (RCS, RES, RNS). To cope with these reactive species, bacteria have evolved different defense and repair mechanisms. To maintain the reduced state of the cytoplasm, they utilize low molecular weight (LMW) thiols. LMW thiols are small thiol-containing compounds that can undergo post-translational thiolmodifications with protein thiols, termed as S-thiolations. S-thiolations function as major redox regulatory and thiol-protection mechanism under oxidative stress conditions. In eukaryotes and Gram-negative bacteria, the tripeptide glutathione (GSH) functions as major LMW thiol, which is present in millimolar concentrations. The Actinomycetes, such as Mycobacterium and Corynebacterium species do not produce GSH and utilize instead mycothiol (MSH) as their alternative LMW thiol. In Firmicutes, including Bacillus and Staphylococcus species, bacillithiol (BSH) functions as the major LMW thiol. LMW thiols protect protein thiols against the irreversible overoxidation of cystein residues to sulfinic and sulfonic acids. In addition, LMW thiols contribute to the virulence and survival of pathogens, function in metal homeostasis and serve as enzyme cofactors for detoxification of xenobiotics and antibiotics. In this doctoral thesis, we aimed to investigate the roles of MSH and BSH in redox regulation of main metabolic enzymes under oxidative stress in the pathogens Corynebacterium diphtheriae and Staphylococcus aureus. Previous redox proteomics studies identified the glyceraldehyde-3-phosphate dehydrogenase GapDH and the aldehyde dehydrogenase AldA as S-thiolated in S. aureus and C. diphtheriae. Thus, we aimed to study the redox regulation of the metabolic enzyme GapDH in C. diphtheriae in response to NaOCl and H2O2 stress by S-mycothiolation, which is described in chapter 1. Moreover, we studied the involvement of the mycoredoxin-1 (Mrx1) and thioredoxin (Trx) pathways in reactivation of S-mycothiolated GapDH in vitro. Using shotgun proteomics, 26 S-mycothiolated proteins were identified under NaOCl stress in C. diphtheriae. These are involved in energy metabolism (Ndh, GlpD) and in the biosynthesis of amino acids (ThrA, LeuB), purines (PurA) and cell wall metabolites (GlmS). The glycolytic GapDH was identified as conserved target for S-thiolation across Gram-positive bacteria. GapDH was the most abundant protein, contributing with 0.75 % to the total cystein proteome. Moreover, GapDH is a conserved target for redox regulation and S-glutathionylation in response to oxidative stress in several prokaryotic and eukaryotic organisms. Treatment of GapDH with NaOCl and H2O2 in the absence of MSH resulted in irreversible enzyme inactivation due to overoxidation. Pretreatment of GapDH with MSH prior to H2O2 or NaOCl exposure resulted in reversible inactivation due to S-mycothiolation of the active site Cys153. Since S-mycothiolation is faster compared to overoxidation, S-mycothiolation efficiently protects the GapDH active site against overoxidation. The activity of S-mycothiolated GapDH could be restored by both, the Mrx1 and Trx pathway in vitro. Interestingly, the recovery of Smycothiolated GapDH by Mrx1 was faster compared to its reduction by the Trx pathway. In previous studies, the reactivation of S-mycothiolated Mpx and MrsA by the mycoredoxin pathway occurred also faster compared to the Trx pathway, which is consistent with our results. We were further interested to analyze the redox regulation of the glyceraldehyde-3phosphate dehydrogenase Gap of S. aureus under NaOCl and H2O2 stress, which is described in chapter 2. Using the quantitative redox proteomic approach OxICAT, 58 NaOCl-sensitive cystein residues with >10% thiol oxidation under NaOCl stress were identified. Gap and AldA showed the highest oxidation increase of 29% under NaOCl stress at their active site cystein residues. Using shotgun proteomics, five S-bacillithiolated proteins were identified, including Gap, AldA, GuaB, RpmJ and PpaC. Gap contributed with 4 % as most abundant cystein protein to the total cystein proteome. Our activity assays demonstrated that Gap of S. aureus is highly sensitive to overoxidation by H2O2 and NaOCl in vitro in the absence of BSH. The active site Cys151 of Gap was oxidized to the BSH mixed disulfide under H2O2 and NaOCl stress in the presence of BSH in vitro, which resulted in the reversible Gap inactivation. Moreover, inactivation of Gap by NaOCl and H2O2 due to S-bacillithiolation was faster compared to overoxidation, indicating that S-bacillithiolation protects the Gap active site against overoxidation in vitro. We further showed that the bacilliredoxin Brx catalyzes the reduction of S-bacillithiolated Gap in vitro. Molecular docking of BSH into the Gap active site revealed that S-bacillithiolation does not require major structural changes. Apart from Gap, the aldehyde dehydrogenase AldA was identified as S-bacillithiolated at its active site Cys279 under NaOCl stress in S. aureus previously. Thus, the expression, function, redox regulation and structural changes of AldA were analysed under NaOCl and aldehyde stress in S. aureus as summarized in chapter 3. AldA was S-bacillithiolated in the presence of H2O2 and BSH as demonstrated in BSH-specific Western blots in vitro. The expression of aldA was previously shown to be regulated by the alternative sigma factor SigmaB in S. aureus. Transcription of aldA was strongly increased in a SigmaB-independent manner under formaldehyde, NaOCl and diamide stress in S. aureus. Using an aldA deletion mutant, we demonstrated that aldA is required for growth and survival under NaOCl stress in S. aureus. The purified AldA enzyme was shown to catalyze the oxidation of various aldehyde substrates, including formaldehyde, methylglyoxal, glycolaldehyde and acetaldehyde in vitro. In addition, the function of the conserved Cys279 for AldA activity was investigated in vivo and in vitro. The purified AldAC279S mutant was shown to be inactive for aldehyde oxidation in vitro. Moreover, the aldAC279S mutant was very sensitive under NaOCl stress in vivo, and this phenotype could be reversed using the aldA complemented strain. These experiments demonstrate the function of Cys279 for AldA activity both in vitro and in vivo. AldA activity assays showed that AldA is sensitive to overoxidation and irreversible inactivation by H2O2 alone in vitro. In the presence of BSH, AldA is protected against overoxidation by reversible Sbacillithiolation in vitro. Molecular docking and molecular dynamics simulations revealed that BSH occupies two different positions in the Cys279 active site, which depend on the NAD+ cofactor. In the apoenzyme, BSH forms the disulfide with Cys279 in the “resting” state position, while Cys279 is S-bacillithiolated in the “attacking” state position in the holoenzyme in the presence of the NAD+ cofactor.
As the tree of life is populated with sequenced genomes ever more densely, the new challenge is the accurate and consistent annotation of entire clades of genomes. In my dissertation, I address this problem with a new approach to comparative gene finding that takes a multiple genome alignment of closely related species and simultaneously predicts the location and structure of protein-coding genes in all input genomes, thereby exploiting negative selection and sequence conservation. The model prefers potential gene structures in the different genomes that are in agreement with each other, or—if not—where the exon gains and losses are plausible given the species tree. The multi-species gene finding problem is formulated as a binary labeling problem on a graph. The resulting optimization problem is NP hard, but can be efficiently approximated using a subgradient-based dual decomposition approach.
I tested the novel approach on whole-genome alignments of 12 vertebrate and 12 Drosophila species. The accuracy was evaluated for human, mouse and Drosophila melanogaster and compared to competing methods. Results suggest that the new method is well-suited for annotation of a large number of genomes of closely related species within a clade, in particular, when RNA-Seq data are available for many of the genomes. The transfer of existing annotations from one genome to another via the genome alignment is more accurate than previous approaches that are based on protein-spliced alignments, when the genomes are at close to medium distances. The method is implemented in C++ as part of the gene finder AUGUSTUS.
For the last two decades, heparins have been widely used as anticoagulants. Besides
numerous advantages, up to 5% patients with heparin administration suffer from a major adverse
drug effect known as heparin-induced thrombocytopenia (HIT). This typical HIT can result in deep
vein thrombosis, pulmonary embolism, occlusion of a limb artery, acute myocardial infarct, stroke, and
a systemic reaction or skin necrosis. The basis of HIT may lead to clinical insights. Recent studies using
single-molecule force spectroscopy (SMFS)-based atomic force microscopy revealed detailed binding
mechanisms of the interactions between platelet factor 4 (PF4) and heparins of different lengths in
typical HIT. Especially, SMFS results allowed identifying a new mechanism of the autoimmune HIT
caused by a subset of human-derived antibodies in patients without heparin exposure. The findings
proved that not only heparin but also a subset of antibodies induce thrombocytopenia. In this review,
the role of SMFS in unraveling a major adverse drug effect and insights into molecular mechanisms
inducing thrombocytopenia by both heparins and antibodies will be discussed.
The Flavivirus genus (Flaviviridae family) comprises the most important arboviruses in the world such as dengue virus, West Nile virus (WNV), Zika virus (ZIKV), Japanese encephalitis virus and yellow fever virus (YFV). Every year, several outbreaks caused by flaviviruses are reported worldwide (i.e.: ZIKV and YFV outbreaks in South America) with a huge impact on economy and public health. In the last few decades, many aspects of the flavivirus biology and the interaction of flaviviruses with host cells have been elucidated. However, many underlying mechanisms concerning receptor usage, entry process and viral interaction with host cell factors are still not completely understood. Integrins, the major class of cell adhesion molecules have been implicated in the infectious cycle of different viruses including flaviviruses. A previous report proposed that a particular integrin, the αVβ3 integrin, might act as a cellular receptor for WNV. However, this hypothesis was not confirmed by other groups. In the present study, murine cell lines lacking the expression of one or more integrin subunits were used to evaluate the involvement of different integrins in the flavivirus infection cycle. Mouse fibroblasts lacking the expression of β1 integrin (MKF-β1-/-) or β3 integrin (MEF-β3-/-) subunits or αVβ3 integrin (MEF-αVβ3-/-) as well as their corresponding wild-type cells were utilized. A second model using Chinese hamster ovary cells (CHO-K1), a cell line that has been described to be refractory to some flaviviruses, were modified to express either αV (CHO-αV+/+) or β3 (CHO-β3+/+) integrin subunits. All cell lines were first characterized by confocal laser microscopy, flow cytometry and functional assays prior to infection to assess their integrin expression. The cell lines were then inoculated with different flaviviruses of public health relevance: WNV, YFV-17D, Usutu virus (USUV), Langat virus (LGTV) and ZIKV. Infection assays were designed in order to evaluate whether integrins influence i) cell susceptibility; ii) binding; iii) internalization and iv) replication of the investigated flaviviruses. Our findings clearly demonstrate that β1, β3 and αVβ3 integrins do not act as flavivirus cellular receptor or attachment factor since their ablation does not completely abrogate flavivirus infection in the investigated cell lines. Flavivirus binding to the cell surface of MEFs, MKFs and CHO cells was not disturbed by the genomic deletion of the above-mentioned integrins. The deletion of β1 and β3 integrin subunit did not affect internalization of any of the flaviviruses tested. In contrast to that, loss of αVβ3 integrin in the MEF-αVβ3-/- cells showed a statistically significant decrease in WNV and USUV internalization while ZIKV, YFV-17D and LGTV internalization remained unaffected suggesting that αVβ3 integrin might be involved in the internalization process of at least some flaviviruses. On the other hand, flavivirus replication was substantially impaired in the integrin-deficient cell lines in comparison to their corresponding wild-type cells. Both, MEF-β3-/- and MKF-β1-/- cells showed a statistically significant reduction on viral load for all flaviviruses tested in comparison to their respective wild-type cells. The MEF-αVβ3-/- cells in particular, showed a strong inhibition of flavivirus replication with a reduction of up to 99% on viral loads for all flaviviruses tested. Levels of flavivirus negative-strand RNA were substantially decreased in MEF-αVβ3-/- cells indicating that integrins might influence flavivirus RNA replication. The ectopic expression of either αV or β3 integrin subunits in CHO cells slightly increased the replication of all flaviviruses tested. Taken together, this is the first report highlighting the involvement of integrins in ZIKV, USUV, LGTV and YFV infection. The results strongly indicate that the investigated integrins play an important role in flavivirus infection and might represent a novel host cell factor that enhances flavivirus replication. Although the exact mechanism of interaction between integrins and flaviviruses is currently unknown, the results provided in this study deepen our insight into flavivirus - host cell interactions and open doors for further investigations.
Platelets transfusion is a safe process, but during or after the process, the recipient may experience an adverse reaction and occasionally a serious adverse reaction (SAR). In this review, we focus on the inflammatory potential of platelet components (PCs) and their involvement in SARs. Recent evidence has highlighted a central role for platelets in the host inflammatory and immune responses. Blood platelets are involved in inflammation and various other aspects of innate immunity through the release of a plethora of immunomodulatory cytokines, chemokines, and associated molecules, collectively termed biological response modifiers that behave like ligands for endothelial and leukocyte receptors and for platelets themselves. The involvement of PCs in SARs—particularly on a critically ill patient’s context—could be related, at least in part, to the inflammatory functions of platelets, acquired during storage lesions. Moreover, we focus on causal link between platelet activation and immune-mediated disorders (transfusion-associated immunomodulation, platelets, polyanions, and bacterial defense and alloimmunization). This is linked to the platelets’ propensity to be activated even in the absence of deliberate stimuli and to the occurrence of time-dependent storage lesions.
Glacitectonic deformation in the Quaternary caused the tectonic framework of large-scale folds and displaced thrust sheets of Maastrichtian (Upper Cretaceous) chalk and Pleistocene glacial deposits in the southwestern Baltic Sea area.
A wide spectrum of methods has been compiled to unravel the structural evolution of the Jasmund Glacitectonic Complex. The analyses of digital elevation models (DEM) suggest a division into two structural sub-complexes – a northern part with morphological ridges striking NW–SE and a southern part with SW–NE trending ridges. Geological cross sections from the eastern coast (southern sub-complex) were constructed and restored using the software Move™ and the complementary module 2D Kinematic Modelling™.
The final geometric model of the southern sub-complex shows a small-scale fold-and-thrust belt. It includes three different orders of architectural surfaces (see PEDERSEN, 2014): erosional surfaces and the décollement (1st order), thrust faults (2nd order), and beds outlining hanging-wall anticlines as well as footwall synclines (3rd order). Thrust faults of the southern structural sub-complex are mainly inclined towards south, which indicates a local glacier push from the S/SE.
The glacitectonic structures have a surface expression in form of sub-parallel ridges and elongated valleys in between. Geomorphological mapping and detailed landform analyses together with the structural investigations provide an insight into the chronology of sub-complexes formation. The northern part of the glacitectonic complex is suggested to have been formed before the southern one, considering the partly truncated northerly ridges and their superimposition by the southern sub-complex.
Although there is a high number of scientific publications on the glacitectonic evolution of Jasmund, these presented models often lack a consistent theory for the development integrating all parts of the 100 km2 large complex. Therefore, the combination of all results leads to a more self-consistent genetic model for the entire Jasmund Glacitectonic Complex.
Background: Magnetic resonance imaging (MRI) techniques are rarely used in the context of abdominal sepsis and in sepsis research. This study investigates the impact of MRI for monitoring septic peritonitis in an animal model (colon ascendens stent-induced peritonitis, CASP). The CASP model closely mimics that of human disease and is highly standardized. The most frequently employed readout parameter in mouse CASP studies is prolonged or decreased rate of survival. Monitoring the progression of peritonitis via MRI could provide a helpful tool in the evaluation of severity. The use of alternative readout systems could very well reduce the number of research animals. Perspectively, clinical improvement after certain treatment could be classified. Methods: This study describes for the first time MRI findings following the induction of septic peritonitis in mice using the CASP model. Two sublethal groups of mice with septic peritonitis were investigated. Each had received one of two differing stent diameters in order to control the leakage of feces into the abdominal cavity. Each mouse served as its own control. Imaging and analyses were performed blinded. Gut diameters, stomach volume, abdominal organ wall diameters, and volume of the adrenal glands were measured. Serum corticosterone levels were detected using ELISA. Serum IL-6, TNF-α, IL-1β, and IL-10 levels were screened by cytometric bead array. Statistical analysis was performed using the Mann-Whitney U test for nonparametric probes and the Kruskal-Wallis and t tests. Results: Using a 7-tesla MRI scanner 24 and 48 h after induction of septic peritonitis, interenteric fluid, organ swelling of spleen and adrenal glands, as well as dilatation of the stomach were compared to nonseptic conditions. Swelling of adrenal glands resulted in an increased serum corticosterone level. In addition, the wall of the intestine bowel was thickened. Based upon these findings, an MRI score (MRI sepsis score, MSS) for abdominal sepsis in mice was established. Reduced stent sizes led to reduced severity of the abdominal sepsis, which could be reproduced in the MSS, which is described here for the first time. Conclusions: Intraabdominal variations during septic peritonitis are detectable by MRI techniques. MRI methods should become a more important tool for the evaluation of abdominal peritonitis. MSS could provide an interesting tool for the evaluation of therapeutic strategies.
Background: Magnetic resonance imaging (MRI) techniques are rarely used in the context of abdominal sepsis and in sepsis research. This study investigates the impact of MRI for monitoring septic peritonitis in an animal model (colon ascendens stent-induced peritonitis, CASP). The CASP model closely mimics that of human disease and is highly standardized. The most frequently employed readout parameter in mouse CASP studies is prolonged or decreased rate of survival. Monitoring the progression of peritonitis via MRI could provide a helpful tool in the evaluation of severity. The use of alternative readout systems could very well reduce the number of research animals. Perspectively, clinical improvement after certain treatment could be classified. Methods: This study describes for the first time MRI findings following the induction of septic peritonitis in mice using the CASP model. Two sublethal groups of mice with septic peritonitis were investigated. Each had received one of two differing stent diameters in order to control the leakage of feces into the abdominal cavity. Each mouse served as its own control. Imaging and analyses were performed blinded. Gut diameters, stomach volume, abdominal organ wall diameters, and volume of the adrenal glands were measured. Serum corticosterone levels were detected using ELISA. Serum IL-6, TNF-α, IL-1β, and IL-10 levels were screened by cytometric bead array. Statistical analysis was performed using the Mann-Whitney U test for nonparametric probes and the Kruskal-Wallis and t tests. Results: Using a 7-tesla MRI scanner 24 and 48 h after induction of septic peritonitis, interenteric fluid, organ swelling of spleen and adrenal glands, as well as dilatation of the stomach were compared to nonseptic conditions. Swelling of adrenal glands resulted in an increased serum corticosterone level. In addition, the wall of the intestine bowel was thickened. Based upon these findings, an MRI score (MRI sepsis score, MSS) for abdominal sepsis in mice was established. Reduced stent sizes led to reduced severity of the abdominal sepsis, which could be reproduced in the MSS, which is described here for the first time. Conclusions: Intraabdominal variations during septic peritonitis are detectable by MRI techniques. MRI methods should become a more important tool for the evaluation of abdominal peritonitis. MSS could provide an interesting tool for the evaluation of therapeutic strategies.
Aquaporins (AQPs) facilitate the transepithelial water flow involved in epithelial fluid secretion in numerous tissues; however, their function in the pancreas is less characterized. Acute pancreatitis (AP) is a serious disorder in which specific treatment is still not possible. Accumulating evidence indicate that decreased pancreatic ductal fluid secretion plays an essential role in AP; therefore, the aim of this study was to investigate the physiological and pathophysiological role of AQPs in the pancreas. Expression and localization of AQPs were investigated by real-time PCR and immunocytochemistry, whereas osmotic transmembrane water permeability was estimated by the dye dilution technique, in Capan-1 cells. The presence of AQP1 and CFTR in the mice and human pancreas were investigated by immunohistochemistry. Pancreatic ductal HCO3- and fluid secretion were studied on pancreatic ducts isolated from wild-type (WT) and AQP1 knock out (KO) mice using microfluorometry and videomicroscopy, respectively. In vivo pancreatic fluid secretion was estimated by magnetic resonance imaging. AP was induced by intraperitoneal injection of cerulein and disease severity was assessed by measuring biochemical and histological parameters. In the mice, the presence of AQP1 was detected throughout the whole plasma membrane of the ductal cells and its expression highly depends on the presence of CFTR Cl- channel. In contrast, the expression of AQP1 is mainly localized to the apical membrane of ductal cells in the human pancreas. Bile acid treatment dose- and time-dependently decreased mRNA and protein expression of AQP1 and reduced expression of this channel was also demonstrated in patients suffering from acute and chronic pancreatitis. HCO3- and fluid secretion significantly decreased in AQP1 KO versus WT mice and the absence of AQP1 also worsened the severity of pancreatitis. Our results suggest that AQP1 plays an essential role in pancreatic ductal fluid and HCO3- secretion and decreased expression of the channel alters fluid secretion which probably contribute to increased susceptibility of the pancreas to inflammation.
The Effect of the Patients Nutritional Status on Immune Alterations Induced by Ischemic Stroke
(2018)
Ischemic stroke is one of the leading causes of death and disability throughout the world.
One important aspect of stroke pathophysiology are immunological changes after stroke, especially a combination of post stroke immunodepression, leading to
infectious complications after stroke and an activation of the immune system, leading to cerebral injury. Adipose tissue has several immunological functions and obesity
leads to immunological complications and is accompanied by a chronic immune activation.
To study the effects of body weight and obesity on the immune system and measure weight and fat tissue changes after ischemic stroke we conducted the LIPS Trial and enrolled 50 stroke patients and 16 control subjects between July 2015 and July 2016. On the day of admission and on the days 1, 2, 3, 4, 5, 7, 30, 90 and 180 after admission stroke patients were weighed with an in-bed scale, body composition was measured with BIA, the triceps-skin fold thickness was measured, the NIHSS scale was obtained and blood was drawn. FACS-analysis was performed and triglycerides,cholesterol, CRP and PCT were measured at the central laboratory facility of the Universitätsmedizin Greifswald. Luminex-multiplex analysis for multiple cyto- and chemokines was performed at the Multiplex Facility at the University Leiden. A cerebral MRI and an abdominal MRI were performed shortly after admission and on days 5-7 for most patients and the infarct volume, abdominal fat and hepatic fat percentage were measured. On days 30, 90 and 180 after stroke Bartel Index and mRS were obtained.
After stroke our patients showed the typical immunological changes described previously as stroke induced immune alterations, namely a post stroke immunodepression as well as signs of an activated immune system and an acute
phase response. Our patients lost weight, but only 1.7 ± 0.5 kg. Skinfold thickness did not change during the course of our trial and abdominal fat measurement did not change in stroke patients. Immunological parameters (leukocytes, neutrophils,CRP, PCT, IL-6) did not differ between BMI subgroups (normal weight: BMI < 25,overweight: BMI ≥ 25, < 30, obese: BMI ≥ 30) and in this trial we could not detect a
difference in patients with normal weight, overweight or obesity in the post stroke periode. In an additional analysis we could show that rapid clinical improvement
did result in a rapid improvement of post stroke immune alterations, especially for leukocytes, neutrophils, IL-6 and CRP.
Rabies virus (RABV) is an ancient, highly neurotropic rhabdovirus that causes lethal encephalitis. Most RABV pathogenesis determinants have been identified with laboratory-adapted or attenuated RABVs, but details of natural RABV pathogenesis and attenuation mechanisms are still poorly understood. To provide a deeper insight in the cellular mechanism of pathogenies of field RABV, this work was performed to assess virus strain specific differences in intra-neuronal virus transport, to identify cell culture adaptive mutations in recombinant field viruses and to explore shRNA-expressing RABVs as research tools for targeted host manipulation in infected cells.
Comparison of chimeric RABVs with glycoprotein (G) ecto-domains of different lyssaviruses, together with field RABVs from dog and fox in dorsal root ganglion (DRG) neurons revealed no detectable differences in the axonal accumulation of the viruses. This indicates that previously described G-dependent transport of newly formed RABV in axons can occur both in laboratory-adapted and field RABV. Moreover, partial overlap of nucleoprotein (N) and G protein particles in field virus infected DRG axons supported the hypothesis of the “separate model” for anterograde RABV transport.
Serial passages of recombinant dog and fox field clones in different cell lines led to the identification of general (D266N) and cell line specific (K444N) adaptive mutations in the G ecto-domain of both viruses. In BHK cells, synergistic effects of D226N, K444N and A417T on field dog virus G protein surface localization led to the loss of endoplasmic reticulum (ER) retention of G and increased virus titers in the supernatant, indicating that limited virus release by ER retention is a major bottleneck in cell culture adaptation. In addition, selection of mutations within the C-terminus of the RABV phosphoprotein (P) (R293H and R293C in fox and dog viruses, respectively) led to the hypothesis of altered binding affinities to nucleoprotein and RNP complexes. Identification of the above mentioned amino acid substitutions together with alterations in a suboptimal transcription stop signal in the P/M gene border indicated that adaptation to cell culture replication occurs on both levels, RNA transcription/replication and virus release.
To evaluate the possibility of an expression of a functional microRNA-adapted short-hairpin RNAs (miR-shRNA) expressing RABV, recombinant RABVs encoding miR-shRNAs against cellular Dynein Light Chain 1 (DYNLL1) and Acidic Nuclear Phosphoprotein 32 family member B (ANP32B) were generated. In spite of cytoplasmic transcription of the respective mRNAs, downregulation of DYNLL1 and ANP32B mRNA and respective protein levels in infected cells revealed correct processing to functional shRNAs. Specific downregulation of the cellular genes at 2, 3 and 4 days post infection further demonstrated feasibility of the approach in standard cell lines. However, it remained open whether miR-shRNA expressing RABV can be used to study neuro-infection in vivo. Since first attempts in primary rat neuron cultures failed, it has to be clarified in further experiments whether this strategy can be used in mature, non-dividing neurons or whether breakdown of the nucleus in the course of cell division is a requirement for the processing of cytoplasmically expressed miR-RNA by nuclear RNases.
By providing novel insights in axonal RABV transport and cell culture adaptive mutations this work extends the current understanding of RABV pathogenesis in natural and non-natural cell environments. Moreover, it provides a basis for further pathogenicity studies in which the impact of cell culture adaptation through increased virus release on RABV virulence can be investigated. With successful expression of functional miR-shRNAs from RABV vectors, this work also provides a tool for RABV gene targeting in infected cell lines and thus may contribute to the further investigation of RABV-host-cell-interactions.
The social context plays a decisive role in the formation of the academic self-concept (ASC) and has been widely studied as the big-fish-little-pond-effect (BFLPE). This effect describes that comparable talented students in high-achieving school settings have a lower ASC compared to equally talented students attending low-achieving settings. Past research has focused on students’ domain-specific ASC, while little is known about the relation of achievement-related classroom compositions and the various facets of ASC. Additionally, BFLPE-research has been critiqued to build its theoretical frame on social comparison theory, without providing sufficient empirical support. To address this gap, we analyzed how the single student’s social, criterial, absolute, and individual ASC relate to class-level achievement of 8th graders. Applying Multilevel Structural Equation Modeling (MLSEM) we found that all facets of ASC were significantly related to average-class achievement, while student’s social ASC revealed the strongest associated. The results reveal explicitly that average-class achievement is strongly related to social comparison processes.
Objectives: We aimed to update the 2010 evidence- and consensus-based national clinical guideline on the diagnosis and management of uncomplicated urinary tract infections (UTIs) in adult patients. Materials and Methods: An interdisciplinary group consisting of 17 representatives of 12 medical societies and a patient representative was formed. Systematic literature searches were conducted in MEDLINE, EMBASE, and the Cochrane Library to identify literature published in 2010–2015. Results: We provide 75 recommendations and 68 statements in the updated evidence- and consensus-based national clinical guideline. The diagnostics part covers practical recommendations on cystitis and pyelonephritis for each defined patient group. Clinical examinations, as well as laboratory testing and microbiological pathogen assessment, are addressed. Conclusion: In accordance with the global antibiotic stewardship initiative and considering new insights in scientific research, we updated our German clinical UTI guideline to promote a responsible antibiotic use and to give clear hands-on recommendations for the diagnosis and management of UTIs in adults in Germany for healthcare providers and patients.
Background: We aimed to update the 2010 evidence- and consensus-based national clinical guideline on the diagnosis and management of uncomplicated urinary tract infections (UTIs) in adult patients. Results are published in 2 parts. Part 1 covers methods, the definition of patient groups, and diagnostics. This second publication focuses on treatment of acute episodes of cystitis and pyelonephritis as well as on prophylaxis of recurrent UTIs. Materials and Methods: An interdisciplinary group consisting of 17 representatives of 12 medical societies and a patient representative was formed. Systematic literature searches were conducted in MEDLINE, EMBASE, and the Cochrane Library to identify literature published in 2010–2015. Results: For the treatment of acute uncomplicated cystitis (AUC), fosfomycin-trometamol, nitrofurantoin, nitroxoline, pivmecillinam, and trimethoprim (depending on the local rate of resistance) are all equally recommended. Cotrimoxazole, fluoroquinolones, and cephalosporins are not recommended as antibiotics of first choice, for concern of an unfavorable impact on the microbiome. Mild to moderate uncomplicated pyelonephritis should be treated with oral cefpodoxime, ceftibuten, ciprofloxacin, or levofloxacin. For AUC with mild to moderate symptoms, instead of antibiotics symptomatic treatment alone may be considered depending on patient preference after discussing adverse events and outcomes. Primarily non-antibiotic options are recommended for prophylaxis of recurrent urinary tract infection. Conclusion: In accordance with the global antibiotic stewardship initiative and considering new insights in scientific research, we updated our German clinical UTI guideline to promote a responsible antibiotic use and to give clear hands-on recommendations for the diagnosis and management of UTIs in adults in Germany for healthcare providers and patients.
Abstract
Identifying materials with an efficient spin-to-charge conversion is crucial for future spintronic applications. In this respect, the spin Hall effect is a central mechanism as it allows for the interconversion of spin and charge currents. Spintronic material research aims at maximizing its efficiency, quantified by the spin Hall angle and the spin-current relaxation length . We develop an all-optical contact-free method with large sample throughput that allows us to extract and . Employing terahertz spectroscopy and an analytical model, magnetic metallic heterostructures involving Pt, W and Cu80Ir20 are characterized in terms of their optical and spintronic properties. The validity of our analytical model is confirmed by the good agreement with literature DC values. For the samples considered here, we find indications that the interface plays a minor role for the spin-current transmission. Our findings establish terahertz emission spectroscopy as a reliable tool complementing the spintronics workbench.
The rapid anthropogenic climate change that is projected for the 21st century is predicted to have severe impacts on ecosystems and on the provision of ecosystem services. With respect to the longevity of trees, forestry in particular has to adapt now to future climate change. This requires profound multidisciplinary knowledge on the direct and indirect climate sensitivity of forest ecosystems on various spatial scales. Predictions on growth declines due to increasing drought exposition during climate change are widely recognized for European beech (Fagus sylvatica L.), which is the major forest tree in European temperate deciduous forests. However, research from other continents or other biomes has shown that winter climate change may also affect forest growth dynamics due to declining snow cover and increased soil cooling. So far, this winter cold sensitivity is largely unexplored in Europe. Thus, particularly focussing on forest growth dynamics and winter cold sensitivity, the goal of this PhD-project was to explore how climate sensitivity of forest ecosystems differs regionally. By doing so, the project aimed to deliver insights about possibilities and limits of upscaling regional knowledge to a global understanding of climate sensitivity. To achieve these goals, this PhD-project integrated five studies (Manuscripts 1–5) that investigated the climate sensitivity of biogeochemical cycles, plant species composition in forests, and forest growth dynamics across spatial scales. In particular, a large-scale gradient-design field experiment simulated the influence of winter climate change on forest ecosystems by snow cover and soil temperature manipulations (Manuscript 1). This study indicated that soil cooling and decreased root nutrient uptake may indirectly reduce growth of adult forest trees. Moreover, this study indicated uniform ecological sensitivity to soil temperature changes across sites along a large winter temperature gradient (ΔT = 4 K across 500 km), irrespective of the site-specific history of snow cover conditions, which motivates upscaling from local winter climate change studies to the regional scale. Although regional climate drives growth of adult forest trees, local factors, such as site-specific edaphic conditions, might control plants in the forest understory. This assumption was tested by mapping the forest understory composition along the same winter temperature gradient as introduced above (Manuscript 2). Across sites, this study found that edaphic conditions explained the spatial turnover in the forest understory composition more than climate, which might moderate direct climate change impacts on the forest understory composition. However, edaphic conditions, forest structure, and climate are linked by triangular interactions. Thus, climate change might still indirectly affect the forest vegetation dynamics. Moreover, a dendroecological study focussed on the same winter temperature gradient from central to cold-marginal beech populations as above in order to identify gradual changes in summer drought and winter cold sensitivity in tree growth (Manuscript 3). Towards the cold distribution margin, the influence of drought on tree growth gradually decreased, while growth reductions were increasingly related to winter cold due to harsher winter climate. By a large-scale dendroecological network study assessed the relationship of growth dynamics to climate and reproductive effort in beech forests across Europe (Manuscript 4). Indeed, this study found the general pattern across the distribution range of beech that high temperature controlled growth indirectly via resource allocation to reproduction. However, the strong, direct drought signal that could be generally detected from dry-marginal to central populations vanished towards the cold-marginal populations, where the more focussed study of Manuscript 3 identified a stronger relationship of tree growth to winter cold. Further extending the scope of this PhD-thesis to global scales, litter decomposition rates were assessed across biomes (Manuscript 5). This study found a robust relationship between climate and decomposition rates, but it also demonstrated large within-biome variability on a local scale. These local scale differences might depend on habitat conditions that, in turn, could be modulated by climate change, which calls for a better exploration of indirect climate sensitivity. In conclusion, this PhD-thesis highlighted that multidisciplinary research can advance the understanding of ecological interactions in forest ecosystems under changing climate scenarios. In this PhD-project, a winter climate change experiment, where site-representative target trees were selected by means of dendroecology, contributed to a mechanistic understanding of winter cold sensitivity in forest growth dynamics. Dendroecological investigations then put the findings in a broader temporal and spatial context by describing local climate sensitivity of tree growth on different spatial scales. This thesis further shows that global generalizations about the relationship of climate and ecological processes in ecosystem models have to be critically reviewed for the need of local and regional adjustment because these processes might experience considerable regional- or local-scale variation. However, this thesis reports uniform sensitivity of ecological processes to altered winter soil temperature regimes across a large winter temperature gradient. Thus, upscaling from insights of previous winter climate change experiments to regional scales is encouraged.
Streptococcus pneumoniae is a commensal of the human upper respiratory tract and
the etiological agent of several life-threatening diseases. This pathogen is the model bacterium
for natural competence. Furthermore, the pneumococci played an important role in the
identification of DNA as the main molecule involved in bacterial transformation. As a result,
studies on the pneumococcal genome provided an initial overview of the genetic potential of
this pathogen. The pneumococcus is a highly versatile bacterium possessing a high rate of
uptake and recombination of exogenous DNA from neighboring bacteria. As such, a significant
diversity in the genome content among the different pneumococcal strains has been reported.
The capsular polysaccharide, an important pneumococcal virulence factor, is the best example
on the pneumococcal diversity. There are over 98 serotypes characterized to date presenting
differences in their capsule (cps) locus. Additional to the cps locus, the pneumococcus also
presents 13 genomic islets annotated as regions of diversity (RD) encoded in the auxiliary
genome. Remarkably, 8 of the pneumococcal RD studied so far have been associated with
virulence. Furthermore, the ongoing sequencing of over 4000 pneumococcal genomes have
shed light on the conservation level of well-known pneumococcal virulence factors.
Interestingly, important pneumococcal virulence determinants show variations in the gene and
protein sequence among the different strains. Prototypes are for example the pneumococcal
surface protein C (PspC) and pneumococcal adherence and virulence factor B (PavB).
Conversely, gene regulation in S. pneumoniae is carried out by highly conserved and genome-
wide distributed transcriptional factors. Overall, the pneumococci interplays with its
environment with 4 major regulatory systems: quorum sensing (QS), stand-alone
transcriptional regulators, small RNAs (sRNAs) and two-component regulatory systems (TCS).
Some of these systems are multifaceted and share more than one feature. Furthermore, there
is crosstalk among the different systems, requiring the activation of a signaling cascade to
function properly.
A comprehensive analysis of the distribution and conservation of pneumococcal
virulence factors and TCS was obtained in this study. The results are summarized as a
simplified variome in which 25 pneumococcal strains with a complete sequenced genome were
analyzed. Interestingly, the genes encoding the glycolytic protein enolase and the toxin
pneumolysin were the most conserved virulence determinants. Additionally, the high level of
conservation was confirmed for the pneumococcal TCS regulators, especially for WalKR,
CiaRH and TCS08.
The main focus of this study was on the regulatory functions of pneumococcal TCS.
With this in mind, an extensive and detailed systematic review of the 13 pneumococcal TCS
and its orphan RR was undertaken. For this purpose, every pneumococcal TCS was analyzed
for its reported functional and structural information along with its contribution to the main
pathophysiology of the pneumococci. In brief, S. pneumoniae can utilize its TCS for the
regulation of important cellular processes and the sensing of detectable signals in the
environment. Additionally, the role of TCS in pneumococcal processes and signal sensing can
be divided further. In the first place, pneumococcal TCS regulate competence and fratricide,
the production of bacteriocins and host-pathogen interaction processes, while the detectable
signals include cell-wall perturbations, environmental stress, and nutrients. As a conclusion
from this section, it is possible to analyze the pneumococcal TCS in a comprehensive manner.
There is a complex network among the different pneumococcal regulators and the TCS play
an important role. Moreover, these systems are highly conserved and essential for the proper
functioning of the pneumococcus as a pathogen.
Following up on pneumococcal TCS, this study focused especially on the TCS08.
Interestingly, the pneumococcal TCS08 has been previously associated with the regulation of the cellobiose metabolism. Furthermore, this system has also been reported to regulate the
expression of genes encoded in the RD4 (Pilus-1). Remarkably, the pneumococcal TCS08
was shown to be highly homologous to the SaeRS system of Staphylococcus aureus. Initially,
mutant strains lacking a single (Δrr08 or Δhk08) or both components (Δtcs08) of the TCS08
were generated in pneumococcal D39 and TIGR4 strains. Transcriptomics and functional
assays showed a downregulation of the PI-1 in the absence of the complete tcs08, while PavB
presented an upregulation in the Δhk08 knockout. Moreover, an important number of genes
coding for intermediary metabolism proteins were also found to be differentially expressed by
microarray analysis. As such, the TIGR4Δhk08 strain presented a downregulation for the
cellobiose operon (cel). In contrast, an upregulation was reported for the fatty acid biosynthesis
(fab) and arginine catabolism (arc) operons. Conversely, a decrease in gene expression was
seen in the TIGR4Δrr08 strain for the arc operon. Finally, in vivo murine pneumonia and sepsis
models highlighted an involvement of TCS08 in pneumococcal virulence. Remarkably, the
different TCS08 mutants presented a strain dependent effect on their virulence severity. The
TIGR4Δrr08, and all TCS08 mutants in D39 showed a decrease in virulence in the pneumonia
model, with no changes in sepsis. Conversely, the absence of HK08 in TIGR4 presented a
highly virulent phenotype in both pneumonia and sepsis models. To sum up, the pneumococcal
TCS08 influenced the expression of genes involved in fitness and colonization. Specifically,
those coding for the adhesins PavB and PI-1 and fitness proteins from the cel, arc and fab
operons. Remarkably, the highest changes in expression were observed in the strains lacking
the HK08. Additionally, TCS08 has a strain dependent impact on pneumococcal virulence as
showed by murine pneumonia and sepsis models when comparing the effects in D39 and
TIGR4.
This work study a monolayer of branched poly(ethyleneimine (PEI) adsorbed onto oppositely charged surfaces with iron chelates or iron ions in the absorption solution. The conformation of adsorbed PEI is explored in the dependence of the composition of the adsorption solution by measuring the surface forces using atomic force microscopy (AFM) with the colloidal probe (CP) at different ionic strengths (INaCl) in surrounding aqueous solution. The surface coverage of these layers is investigated using X-ray reflectivity.
PEI solutions show different pH values with iron chelates (pH = 3), iron ions (pH = 4.67) or pure water (pH = 9.3) at room temperature. Low surface coverage of PEI at pH = 3 adjusted by monovalent ions was also observed. However, adsorbing PEI with iron ions or iron chelates and washing with pure water shifts the pH, leading to an adsorbed PEI layer with high coverage. In our observation, the influence of iron ions and iron chelates on the surface coverage of PEI film is stronger than the pH effect. PEI adsorbed from a pure water solution shows flat conformation. Surface force measurements with CP show that PEI adsorbed from solutions containing iron chelates or iron ions cause almost identical steric forces. The thickness of the brush L is determined as a function of the ionic INaCl in the measuring solution. It scales as a polyelectrolyte brush.
The maximum number density of gold nanoparticles (AuNPs) adsorbed onto the PEI brushes was identical and larger than on flatly adsorbed PEI. On the PEI layer with the larger surface coverage, the AuNPs aggregate; on the PEI layer with the lower surface coverage they do not aggregate. Taken together, these results contribute to understanding the mechanisms determining surface coverage and conformation of PEI and demonstrate the possibility of controlling surface properties, which is highly desirable for potential future applications.
In this thesis, we also investigate the top layer (PSS and PDADMA) of polyelectrolyte multilayer (PEM) films. PEM films were prepared by sequential adsorption of oppositely charged PEs on solid substrates. PEM films consist of polydiallyldimethylammonium (PDADMA) as polycation and the polystyrene sulfonate (PSS) as polyanion. PDADMA has a smaller linear charge density than PSS. For this system, two different growth regimes are known: parabolic and linear. I studied the top layer (PSS and PDADMA) conformation of PEM films and how the structure of this top layer is affected by increasing the number of PDADMA/PSS layer pairs N and the addition of salt to the surrounding solution.
The INaCl was changed during the force-distance measurements. PSS terminated films always show electrostatic forces at INaCl < 0.1 M and flat conformation. The surface charge density is always negative at INaCl < 0.1 M. The surface charge of the PSS top layer starts to turn from negative to positive at N ≥ 14. At N between 13 and 15, adsorbed PSS cannot compensate all the excess PDADMA charge. This leads to an accumulation of the positive extrinsic sites within the PSS terminated film beyond a specific N. At INaCl ≈ 0.1 M, an exponential decaying force was measured. This is an indication of unusual long-ranged hydration force (decay length λ-1 ≈ 0.2-0.5 nm), and PSS terminated film shows zwitterionic or neutral surface. At INaCl > 0.1 M, a non-electrostatic action occurs and the PSS terminated film reswells in solution.
PDADMA terminated surface consisting of few layers show a flat conformation and the electrostatic forces were measured. For N ≥ 9 and INaCl ≤ 0.1 M, steric forces were measured. The force-distance profiles are well-explained by Alexander and de Gennes theory. PDADMA chains show a maximum L that is around 40-45 % of the contour length. For INaCl ≈ 0.1 M, and N > 9, a flat, neutral or zwitterionic surface is found (λ-1 ≈ 0.3-0.9 nm). For N = 9 and INaCl > 0.1 M, a strong screening of electrostatic interaction and attractive forces are observed. For N > 9 and INaCl > 0.1 M, the ion adsorption into the PE chains leads to an increase in the monomer size and as a result, the L increases and PDADMA brushes reswell again into the solution.
These data show that by varying N and INaCl, different surface forces can be obtained: Electrostatic forces (flat chains) both positive and negative, steric forces (brush), hydration force (flat, neutral or zwitterionic surface), and effects not yet explained (reswelling brush).
Growth corridors have been an instrument of
economic development for decades but have gained new
attention in regional economic development policies in recent years, e.g., in Sub-Saharan Africa or Southeast Asia.
They are seen by policy makers and private businesses as
catalysts of regional economic integration, pushing traditional businesses into increasingly complex international
value chains. However, the outcomes of such development
initiatives are still barely understood. Critics argue that development policies are based on simplified models that are
unable to sufficiently address the complexity of regional
development. Policies on value-chain development, for
example, can lead to conflicts, external dependencies,
land rush, and a polarization of wealth. Growth corridors
often go hand-in-hand with socio-economic transformations and land-use conflicts. This paper first discusses the
theoretically possible desired and undesired regional socio-economic effects of modern corridors. Second, we illustrate the potential and challenges to realize integrative
(or inclusive) development by contrasting three growth
corridors: the SAGCOT growth corridor in Tanzania, the
Walvis Bay-Ndola-Lubumbashi Development Corridor
(WBNLDC) in Namibia, Zambia and Zimbabwe, and the
growth corridors in the Greater Mekong Subregion (GMS)
In this thesis, size-sensitive phenomena of three-dimensional dust crystals emerged in a low temperature plasma are presented. Depending on the number of particles in the system phase transitions, collective vortex motions and large-scaled expansions can be observed. To investigate these fascinating effects an advanced experimental setup as well as new evaluation methods have been developed. This thesis will present these new techniques and the gained insights.
Significance of Hyperbaric Oxygenation in the Treatment of Fournier’s Gangrene: A Comparative Study
(2018)
Introduction: Hyperbaric oxygenation (HBO), in addition to anti-infective and surgical therapy, seems to be a key treatment point for Fournier’s gangrene. The aim of this study was to investigate the influence of HBO therapy on the outcome and prognosis of Fournier’s gangrene. Patients and Methods: In the present multicenter, retrospective observational study, we evaluated the data of approximately 62 patients diagnosed with Fournier’s gangrene between 2007 and 2017. For comparison, 2 groups were distinguished: patients without HBO therapy (group A, n = 45) and patients with HBO therapy (group B, n = 17). The analysis included sex, age, comorbidities, clinical symptoms, laboratory and microbiological data, debridement frequency, wound dressing, antibiotic use, outcome and prognosis. The statistical analysis was performed with GraphPad Prism 7® (GraphPad Software, Inc., La Jolla, USA). Results: Demographic data showed no significant differences. The laboratory parameters C-reactive protein and urea were significantly higher in group B (group B: 301.7 vs. 140.6 mg/dL; group A: 124.8 vs. 54.7 mg/dL). Sepsis criteria were fulfilled in 77.8 and 100% of the patients in groups A and B respectively. Treatment in the intensive care unit (ICU) was therefore indicated in 69% of the patients in group A and 100% of the patients in group B. The mean ICU stay was 9 and 32 days for patients in groups A and B respectively. The wound debridement frequency and hospitalization stay were significantly greater in group B (13 vs. 5 debridement and 40 vs. 22 days). Initial antibiosis was test validated in 80% of the patients in group A and 76.5% of the patients in group B. Mortality was 0% in group B and 4.4% in the group A. Conclusion: The positive influence of HBO on the treatment of Fournier’s gangrene can be estimated only from the available data. Despite poorer baseline findings with comparable risk factors, mortality was 0% in the HBO group. The analysis of a larger patient cohort is desirable to increase the significance of the results.
Significance of Hyperbaric Oxygenation in the Treatment of Fournier’s Gangrene: A Comparative Study
(2018)
Introduction: Hyperbaric oxygenation (HBO), in addition to anti-infective and surgical therapy, seems to be a key treatment point for Fournier’s gangrene. The aim of this study was to investigate the influence of HBO therapy on the outcome and prognosis of Fournier’s gangrene. Patients and Methods: In the present multicenter, retrospective observational study, we evaluated the data of approximately 62 patients diagnosed with Fournier’s gangrene between 2007 and 2017. For comparison, 2 groups were distinguished: patients without HBO therapy (group A, n = 45) and patients with HBO therapy (group B, n = 17). The analysis included sex, age, comorbidities, clinical symptoms, laboratory and microbiological data, debridement frequency, wound dressing, antibiotic use, outcome and prognosis. The statistical analysis was performed with GraphPad Prism 7® (GraphPad Software, Inc., La Jolla, USA). Results: Demographic data showed no significant differences. The laboratory parameters C-reactive protein and urea were significantly higher in group B (group B: 301.7 vs. 140.6 mg/dL; group A: 124.8 vs. 54.7 mg/dL). Sepsis criteria were fulfilled in 77.8 and 100% of the patients in groups A and B respectively. Treatment in the intensive care unit (ICU) was therefore indicated in 69% of the patients in group A and 100% of the patients in group B. The mean ICU stay was 9 and 32 days for patients in groups A and B respectively. The wound debridement frequency and hospitalization stay were significantly greater in group B (13 vs. 5 debridement and 40 vs. 22 days). Initial antibiosis was test validated in 80% of the patients in group A and 76.5% of the patients in group B. Mortality was 0% in group B and 4.4% in the group A. Conclusion: The positive influence of HBO on the treatment of Fournier’s gangrene can be estimated only from the available data. Despite poorer baseline findings with comparable risk factors, mortality was 0% in the HBO group. The analysis of a larger patient cohort is desirable to increase the significance of the results.
Human cytomegalovirus (HCMV) latency is typically harmless but reactivation can be largely detrimental to immune compromised hosts. We modeled latency and reactivation using a traceable HCMV laboratory strain expressing the Gaussia luciferase reporter gene (HCMV/GLuc) in order to interrogate the viral modulatory effects on the human adaptive immunity. Humanized mice with long-term (more than 17 weeks) steady human T and B cell immune reconstitutions were infected with HCMV/GLuc and 7 weeks later were further treated with granulocyte-colony stimulating factor (G-CSF) to induce viral reactivations. Whole body bio-luminescence imaging analyses clearly differentiated mice with latent viral infections vs. reactivations. Foci of vigorous viral reactivations were detectable in liver, lymph nodes and salivary glands. The number of viral genome copies in various tissues increased upon reactivations and were detectable in sorted human CD14+, CD169+, and CD34+ cells. Compared with non-infected controls, mice after infections and reactivations showed higher thymopoiesis, systemic expansion of Th, CTL, Treg, and Tfh cells and functional antiviral T cell responses. Latent infections promoted vast development of memory CD4+ T cells while reactivations triggered a shift toward effector T cells expressing PD-1. Further, reactivations prompted a marked development of B cells, maturation of IgG+ plasma cells, and HCMV-specific antibody responses. Multivariate statistical methods were employed using T and B cell immune phenotypic profiles obtained with cells from several tissues of individual mice. The data was used to identify combinations of markers that could predict an HCMV infection vs. reactivation status. In spleen, but not in lymph nodes, higher frequencies of effector CD4+ T cells expressing PD-1 were among the factors most suited to distinguish HCMV reactivations from infections. These results suggest a shift from a T cell dominated immune response during latent infections toward an exhausted T cell phenotype and active humoral immune response upon reactivations. In sum, this novel in vivo humanized model combined with advanced analyses highlights a dynamic system clearly specifying the immunological spatial signatures of HCMV latency and reactivations. These signatures can be merged as predictive biomarker clusters that can be applied in the clinical translation of new therapies for the control of HCMV reactivation.
Sphingosine-1-phosphate (S1P) regulates the migration of follicular B cells
(B2 cells) and directs the positioning of Marginal zone B cells (MZ B cells) within the spleen. The
function of S1P signalling in the third B cell lineage, B1 B cells, mainly present in the pleural and
peritoneal cavity, has not yet been determined. Methods: S1P receptor expression was analysed
in peritoneal B cells by real-time polymerase chain reaction (qPCR). The chemotactic response to
S1P was studied in vitro. The role of S1P signalling was further explored in a s1p4
−/− mouse
strain. Results: Peritoneal B cells expressed considerable amounts of the S1P receptors 1 and 4
(S1P1 and S1P4, respectively). S1P1 showed differential expression between the distinct peritoneal B
cell lineages. While B2 cells showed no chemotactic response to S1P, B1 B cells showed a migration
response to S1P. s1p4
−/− mice displayed significant alterations in the composition of peritoneal
B cell populations, as well as a significant reduction of mucosal immunoglobulin A (IgA) in the
gut. Discussion: S1P signalling influences peritoneal B1 B cell migration. S1P4 deficiency alters the
composition of peritoneal B cell populations and reduces secretory IgA levels. These findings suggest
that S1P signalling may be a target to modulate B cell function in inflammatory intestinal pathologies.
Quantitative reconstructions of past vegetation cover commonly require pollen productivity estimates (PPEs). PPEs are calibrated in extensive and rather cumbersome surface-sample studies, and are so far only available for selected regions. Moreover, it may be questioned whether present-day pollen-landcover relationships are valid for palaeo-situations. We here introduce the ROPES approach that simultaneously derives PPEs and mean plant abundances from single pollen records. ROPES requires pollen counts and pollen accumulation rates (PARs, grains cm−2 year−1). Pollen counts are used to reconstruct plant abundances following the REVEALS approach. The principle of ROPES is that changes in plant abundance are linearly represented in observed PAR values. For example, if the PAR of pine doubles, so should the REVEALS reconstructed abundance of pine. Consequently, if a REVEALS reconstruction is “correct” (i.e., “correct” PPEs are used) the ratio “PAR over REVEALS” is constant for each taxon along all samples of a record. With incorrect PPEs, the ratio will instead vary. ROPES starts from random (likely incorrect) PPEs, but then adjusts them using an optimization algorithm with the aim to minimize variation in the “PAR over REVEALS” ratio across the record. ROPES thus simultaneously calculates mean plant abundances and PPEs. We illustrate the approach with test applications on nine synthetic pollen records. The results show that good performance of ROPES requires data sets with high underlying variation, many samples and low noise in the PAR data. ROPES can deliver first landcover reconstructions in regions for which PPEs are not yet available. The PPEs provided by ROPES may then allow for further REVEALS-based reconstructions. Similarly, ROPES can provide insight in pollen productivity during distinct periods of the past such as the Lateglacial. We see a potential to study spatial and temporal variation in pollen productivity for example in relation to site parameters, climate and land use. It may even be possible to detect expansion of non-pollen producing areas in a landscape. Overall, ROPES will help produce more accurate landcover reconstructions and expand reconstructions into new study regions and non-analog situations of the past. ROPES is available within the R package DISQOVER.
Action comprehension that is related to language or gestural integration has been shown to engage the motor system in the brain, thus providing preliminary evidence for the gestural-verbal embodiment concept. Based on the involvement of the sensorimotor cortex (M1) in language processing, we aimed to further explore its role in the cognitive embodiment necessary for gestural-verbal integration. As such, we applied anodal (excitatory) and sham transcranial direct current stimulation (tDCS) over the left M1 (with reference electrode over the contralateral supraorbital region) during a gestural-verbal integration task where subjects had to make a decision about the semantic congruency of the gesture (prime) and the word (target). We used a cross-over within-subject design in young subjects. Attentional load and simple reaction time (RT) tasks served as control conditions, applied during stimulation (order of three tasks was counterbalanced). Our results showed that anodal (atDCS) compared to sham tDCS (stDCS) reduced RTs in the gestural-verbal integration task, specifically for incongruent pairs of gestures and verbal expressions, with no effect on control task performance. Our findings provide evidence for the involvement of the sensorimotor system in gestural-verbal integration performance. Further, our results suggest that functional modulation induced by sensorimotor tDCS may be specific to gestural-verbal integration. Future studies should now evaluate the modulatory effect of tDCS on semantic congruency by using tDCS over additional brain regions and include assessments of neural connectivity.
Humanity is constantly confronted with the emergence and reemergence of infectious diseases. Many of them produce large or devastating epidemics, like AIDS (HIV) and Ebola. Others have been long neglected, yet pose immediate threats to global public health as evidences the abrupt emergence of Zika virus in South America and its association with microcephaly in babies. The examples illustrate, that many of these diseases are provoked by RNA viruses. One of the first steps in understanding and eliminating those threats is the development of sensitive and rapid diagnostic methods. A general and relatively rapid method is the direct detection and examination of the agent’s genome. However, the nature of (re)emerging RNA viruses poses a series of very specific problems for the design of such methods. Therefore, a systematic approach was proposed for the design of DNA-hybridization-base methods to detect and characterize RNA viruses that will have both a high sensitivity and a specificity sufficiently broad to detect, per reaction, down to a single copy of any of the possible variants of the viral genome.
Following this approach a series of assays were designed, developed or adapted and put into use for detection and characterization of important RNA viruses. One of those viruses is West Nile virus (WNV), which after its explosive introduction into USA become the most widespread flavivirus throughout the world and, consequently, many countries began an intensive monitoring. While existing assay detected predominantly the Lineage 1, in Europa Lineage 2 was expected. Two new RT-qPCR for the detection of both lineages were developed, and reportedly used by independent laboratories. Due to more than 50000 associated deaths per year, the Hepatitis E virus also received an increasing attention to elucidate novel routes of transmission. This virus (especially genotype 3) has the zoonotic potential of transmission from pigs and wild boar to humans. RT-qPCR and nested qPCR for detection and characterization of this virus as well as a methodology for subtyping were developed and the first detected case of subtype 3b in a German wild animal was documented. In addition a novel assay for flaviviruses conformed by a RT-qPCR coupled with a low density DNA microarray was developed, which enabled the identification of WNV in mosquitoes from Greece. A RT-qPCR suitable for surveillance and diagnostic of all known variants of Venezuelan equine encephalitis virus was developed too. A causative agent of hemorrhagic infections, the Ngari virus, was detected and characterized in animal samples from Mauritania. These achievements were supported by the development of software applications for selection and visualization of primers and probes from aligned DNA sequences and for modeling of DNA hybridizations using unaligned sequences.
In conclusion a general methodology for rapid development of sensitive diagnostic methods based in DNA-hybridization technics (PCR, sequencing and microarray) was stablished and successful applications are reported.
Submerged macrophytes play a key role in north temperate shallow lakes by stabilizing clear-water conditions. Eutrophication has resulted in macrophyte loss and shifts to turbid conditions in many lakes. Considerable efforts have been devoted to shallow lake restoration in many countries, but long-term success depends on a stable recovery of submerged macrophytes. However, recovery patterns vary widely and remain to be fully understood. We hypothesize that reduced external nutrient loading leads to an intermediate recovery state with clear spring and turbid summer conditions similar to the pattern described for eutrophication. In contrast, lake internal restoration measures can result in transient clear-water conditions both in spring and summer and reversals to turbid conditions. Furthermore, we hypothesize that these contrasting restoration measures result in different macrophyte species composition, with added implications for seasonal dynamics due to differences in plant traits. To test these hypotheses, we analyzed data on water quality and submerged macrophytes from 49 north temperate shallow lakes that were in a turbid state and subjected to restoration measures. To study the dynamics of macrophytes during nutrient load reduction, we adapted the ecosystem model PCLake. Our survey and model simulations revealed the existence of an intermediate recovery state upon reduced external nutrient loading, characterized by spring clear-water phases and turbid summers, whereas internal lake restoration measures often resulted in clear-water conditions in spring and summer with returns to turbid conditions after some years. External and internal lake restoration measures resulted in different macrophyte communities. The intermediate recovery state following reduced nutrient loading is characterized by a few macrophyte species (mainly pondweeds) that can resist wave action allowing survival in shallow areas, germinate early in spring, have energy-rich vegetative propagules facilitating rapid initial growth and that can complete their life cycle by early summer. Later in the growing season these plants are, according to our simulations, outcompeted by periphyton, leading to late-summer phytoplankton blooms. Internal lake restoration measures often coincide with a rapid but transient colonization by hornworts, waterweeds or charophytes. Stable clear-water conditions and a diverse macrophyte flora only occurred decades after external nutrient load reduction or when measures were combined.
The highly oncogenic alphaherpesvirus Marek’s disease virus (MDV) causes immense economic losses in the poultry industry. The main targets of in vivo MDV infection are primary B and T lymphocytes. The cytolytic infection of B cells leads to depletion of lymphoid cells results in severe immunosuppression. Infected B cells recruit and activate T cells. The close interaction between B cells and T cells enables efficient intercellular transfer of MDV. During infection of T cells, the virus enters a latent state. Infection of T cells can lead to transformation of these cells and formation of lymphoma, which manifest in various visceral organs. This study aimed at the characterization of the proteomes of MDV-infected lymphocytes during the lytic and latent phases of infection.
Previous in vitro studies concerning the MDV pathogenesis and host-virus interactions have been mainly conducted with primary fibroblasts or kidney cells, due to the short lifespan of primary lymphocytes in cell culture. Recently, a cultivation system has been established that extents the lifespan of primary lymphocytes through the addition of cytokines to the growth medium. This allowed the infection of B cells in vitro and to conduct quantitative proteomic analysis of primary lymphocytes. Infection with GFP labelled virus recombinants allowed the isolation of infected cells by FACS for the proteome analysis of MDV infected B lymphocytes. An efficient quantitative proteomic workflow was developed, which consisted of a filter-aided (FASP) digest of the extracted proteins, followed by differential dimethyl chemical labeling of the peptides for quantitative evaluation prior to LC-MALDI TOF/TOF mass spectrometry. Only few alterations of the protein and transcript expression profiles were observed after infection of primary B cells with the very virulent RB-1B and the live-attenuated vaccine strain CVI988/Rispens. Relevant changes in relative protein levels were found for only twelve and six interesting host proteins after RB1B and CVI988 infection, respectively. However, the regulations were confirmed by inspection of the spectra from all experiments. The identified candidates play a role in immune response, translation and inflammatory response.
To confirm the potential infection markers, RNA-seq analysis of three biological replicates of each RB-1B -, CVI988- and mock-infected B cells was performed. Eighty expressed MDV transcripts could be identified, which were associated with lytic infection. The same MDV proteins were identified after infection with RB-1B or CVI988. However, transcriptome and proteome analysis of MDV-infected primary B cells showed only poor correlation. This indicates that the changes in protein expression profiles are mostly due to posttranscriptional events. Infection marker candidates were identified by the RNA-seq analysis, for which the gene expression was altered by MDV infection. Although almost 12,000 transcripts were identified, only few transcript levels changed markedly after MDV infection. The biological processes immune response, apoptotic process, signal transduction, cell migration and response to virus were enriched after MDV infection. The RNA-seq results confirm the observation that alterations of protein levels early after MDV infection are rare.
Most notably, MDV induces transformation of lymphocytes leading to malignant T-cell lymphomas in visceral organs with mortalities of up to 100 %. While several factors involved in MDV tumorigenesis have been identified, the transformation process is not fully understood. Therefore, we set out to fill this knowledge gap using proteome analysis of transformed T-cells ex vivo. In addition, the role of the viral telomerase RNA during transformation was assessed by comparison of tumors that had formed after infection with WT-virus or a telomerase RNA negative mutant. A major obstacle for tumor proteome analyses is the preparation of sufficient amounts of homogenous tumor tissue, as tumors appear with a dispersed morphology in the affected organs. The quantitation of cell types within the tumors indicated varying portions of hepatocytes, connective tissue, and CD3+ lymphocytes even with the same virus strain in different animals. However, the ∆vTR-induced tumors contained lower levels of hepatocytes and higher levels of CD3+ lymphocytes compared to WT tumors in all tested tumor samples. Thus, ∆vTR tumors were chosen for determination of differences in protein expression profiles of tumors and naïve T cells for their lower content of liver cells. We developed a workflow for the proteome analysis of T cell tumors from livers of MDV-infected chickens. Samples included laser capture micro-dissected tissue cuts from tumors and surrounding healthy liver tissue as well as naïve T-cells prepared from thymus. To enable quantitative proteome analysis, samples were digested using the FASP protocol and peptides were isotope-coded by differential dimethyl labeling. To improve proteome analysis peptides were fractionated by preparative isoelectric focusing prior to nano-HPLC MALDI/TOF-TOF mass- spectrometric analysis.
Proteomic analyses of LCM dissected ΔvTR tumor compared to naïve T cells, the main targets of transformation, identified nineteen potential transformation markers but again only minor changes in relative levels were observed. Several of the identified markers could also be verified by RT-qPCR on transcript level. The identified transformation candidates were associated with nucleosome assembly, regulation of transcription, inflammatory response, immune response and oxidation-reduction process.
However, further functional analyses are necessary to fully elucidate the role of the identified markers during MDV infection and transformation.
Background/Aim: Laparoscopic single-port surgery has emerged as a growing trend in minimally invasive surgery. Single-port access is preferred among women undergoing gynecologic surgery who have cosmetic concerns about scarring. Furthermore, this approach results in comparable clinical outcomes to standard laparoscopic surgery and perioperative morbidity rates have been reported to be low. The hypothesis is that a single-port technique might offer such advantages over the standard multi-port laparoscopy as less postoperative pain and better cosmetic results by decreasing abdominal wall tissue trauma. The potential disadvantages of single-port approaches are the larger umbilical incision and the technical difficulties. There are only a few randomized studies in the literature that investigate the value and safety of single-incision laparoscopic surgery in gynecological surgery. The aim of this study was to compare the safety and quality of life in patients who undergo single-incision laparoscopic assisted vaginal hysterectomy and those who undergo conventional laparoscopic assisted vaginal hysterectomy.
Methods: In a prospective randomized trial, 64 patients from three different centers in Germany were randomized (1:1) to conventional laparoscopic assisted vaginal hysterectomy (n=32) or single-incision laparoscopic assisted vaginal hysterectomy (n=30). Data was collected on 60 patients who fulfilled the criteria.
Results: The baseline characteristics of patients were similar in both groups. The mean operative time was comparable in both groups (68.2 vs 73.6 min., p = 0.409). Within the two groups, no differences were seen regarding estimated blood loss (p = 0.915), intra- and postoperative complications (p = 0.944), and wound infection rates (p = 0.944). Patients within the single-incision laparoscopic surgery group experienced significantly less pain in the first 24 hours postoperatively (p = 0.006), while pain scores at days 3, 5, 7 and 2 months postoperatively were comparable.
Conclusion: This study demonstrates that single-incision laparoscopic assisted vaginal hysterectomy is a reliable and safe setup in gynecologic surgery. Compared to conventional laparoscopic assisted vaginal hysterectomy, Notably, patients undergoing single-incision laparoscopic assisted vaginal hysterectomy experienced less pain postoperatively.
Production-Integrated Compensation in Environmental Offsets—A Review of a German Offset Practice
(2018)
Background: Biomarkers for gains of evidence based interventions for upper limb motor training in the subacute stage following stroke have rarely been described. Information about these parameters might help to identify patients who benefit from specific interventions and to determine individually expected behavioral gains for a certain period of therapy.
Objective: To evaluate predictors for hand motor outcome after arm ability training in the subacute stage after stroke selected from known potentially relevant parameters (initial motor strength, structural integrity of the pyramidal tract and functional motor cortex integrity).
Methods: We applied the arm ability training (AAT) over 3 weeks to a subpopulation of stroke patients with mild arm paresis, i.e., in 14 patients on average 4 weeks after stroke. The following biomarkers were measured before therapy onset: grip strength on the affected hand, transcranial magnetic stimulation recruitment curve steepness over the primary motor hand area [slope ratio between the ipsilesional hemisphere (IH) and contralesional hemisphere (CH)], and diffusion weighted MRI fractional anisotropy (FA) in the posterior limb of the internal capsule (PLIC; determined as a lateralization index between IH and CH). Outcome was assessed as the AATgain (percentage improvement over training). The “Test d'Evaluation des Membres Supérieurs de Personnes Âgées” (TEMPA) was assessed before and after training to test for possible associations of AAT with activity of daily living.
Results: A stepwise linear regression identified the lateralization index of PLIC FA as the only significant predictor for AAT-gain (R2 = 0.519; P = 0.029). AAT-gain was positively associated (r = 0.59; P = 0.028) with improvement in arm function during daily activities (TEMPA).
Conclusions: While all mildly affected patients achieved a clinically relevant therapeutic effect, pyramidal tract integrity nevertheless had a modifying role for clinical benefit.
Dendrochronology, the science of tree-rings is a tool which has been widely used for many years for understanding changes in the environment, as trees react to environmental changes over time. In the contemporary situation, where climate warming in the Arctic is unequivocal and its effects on the Alpine and tundra ecosystems are seen pronouncedly in the past decade, the role of dendro-studies and the use of trees and shrubs alike as proxies of change has become critical. Studies clearly indicate that warming in the Arctic and Alpine tundra has resulted in increased vegetation in recent years. Shrubs, in these sensitive ecosystems, have proven to be highly instrumental as they likely benefit from this warming and hence are good indicators and auditees of this change. Therefore, in this study, we investigate the potential of shrubs in the evolving field of dendro-ecology/climatology.
Studies from classical dendrochronology used annual rings from trees. Further, because of shrub sensitivity to contemporary change, shrub-based dendrochronological research has increased at a notable scale in the last decade and will likely continue. This is because shrubs grow even beyond the tree line and promise environmental records from areas where tree growth is very limited or absent. However, a common limitation noted by most shrub studies is the very hard cross-dating due to asynchronous growth patterns. This limitation poses a major hurdle in shrub-based dendrochronological studies, as it renders weak detection of common signals in growth patterns in population stands. This common signal is traced by using a ‘site-chronology’.
In this dissertation, I studied shrub growth through various resolutions, starting from understanding radial growth within individuals along the length of the stem, to comparison of radial growth responses among male and female shrubs, to comparing growth responses among trees and shrubs to investigation of biome-wide functional trait responses to current warming. Apart from Chapter 4 and Chapter 6, I largely used Juniperus communis sp. for investigations as it is the most widely distributed woody dioecious species often used in dendro-ecological investigations in the Northern Hemisphere.
Primarily, we investigated radial growth patterns within shrubs to better understand growth within individuals by comparing different stem-disks from different stem heights within individuals. We found significant differences in radial growth from different stem-disks with respect to stem heights from same individuals. Furthermore, we found that these differences depending on the choice of the stem-disk affect the resulting site-chronology and hence climate-sensitivity to a substantial extent and that the choice of a stem-disk is a crucial precursor which affects climate-growth relationships.
Secondly, we investigated if gender difference – often reported causing differential radial growth in dioecious trees – is an influential factor for heterogeneous growth. We found that at least in case of Juniperus communis. L and Juniperus communis ssp nana. WILLD there is no substantial gender biased difference in radial growth which might affect the site-chronology. We did find moderate differences between sexes in an overall analysis and attribute this to reproductive effort in females.
In our study to test the potential of shrubs for reconstruction, we used a test case of Alnus viridis ssp crispa. We found a strong correlation between ring-width indices and summer temperature. Initially, the model failed the stability tests when we tested the stability of this relation using a response function model. However, using wood-anatomical analysis we discovered that this was because of abnormal cell-wall formation resulting in very thin rings in the year 2004. Pointer year analysis revealed that the thin rings were caused because of a moth larval outbreak and when corrected for these rings the model passed all stability tests.
Furthermore, to see if trees and shrubs growing in same biomes react to environmental changes similarly, a network analysis with sites ranging from the Mediterranean biome to the Ural Mountains in Russia was carried out. We found that shrubs react better to the current climate warming and have a decoupled divergent temperature response as compared to coexisting trees. This outcome reiterated the importance of shrub studies in relation to contemporary climate change. Even though trees and shrubs are woody forms producing annual rings, they have very different growth patterns and need different methods for analysis and data treatment.
Finally, in a domain-wide network analysis from plant-community vegetation survey, we investigated functional relationships between plant traits (leaf area, plant height, leaf nitrogen content, specific leaf area (SLA), and leaf dry matter content (LDMC)) and abiotic factors viz. temperature and soil moisture. We found a strong relation between summer temperature and community height, SLA and LDMC on a spatial scale. Contrarily, the temporal-analysis revealed SLA and LDMC lagged and did not respond to temperature over the last decade. We realized that there are complex interactions between intra-specific and inter-specific plant traits which differ spatially and temporally impacting Arctic ecosystems in terms of carbon turn over, surface albedo, water balance and heat-energy fluxes. We found that ecosystem functions in the Arctic are closely linked with plant height and will be indicative of warming in the short term future becoming key factors in modelling ecosystem projections.
Planning Modes for Major Transportation Infrastructure Projects (MTIPs): Comparing China and Germany
(2018)
The present study seeks to determine potential associations between viral infections and neuropsychiatric diseases. To address this issue, we investigated the peptide commonalities between viruses that have been related to psychiatric and neurological disorders—such as rubella, human immunodeficiency virus, and herpesviruses—and human distal-less homeobox (DLX) proteins expressed in developing brain—namely, DLX1, DLX2, DLX5, and DLX6. Peptide matching analyses revealed a high degree of pentapeptide sharing. From an immunological perspective, this overlap is relevant because pentapeptides are endowed with immunogenicity and antigenicity—that is, they are immune determinants. Moreover, infection-induced immune cross-reactions might have functional, spatial, and temporal implications related to the functions and expression patterns of DLX1 and DLX5 in the fetal and adult human brain. In sum, our data support the hypothesis that viral infections may be linked to neuropsychiatric diseases through autoimmune cross-reactions caused by molecular mimicry between viral proteins and brain-specific DLX self-antigens.
Abstract
Background: Behavior management techniques (BMT) are essential in order to
achieve a successful dental treatment with a minimum amount of stress in paediatric
dentistry, but parents are not equally accepting different advanced BMT.
Purpose: To investigate the differences in parental acceptance of advanced
behavior management techniques between University of Greifswald/Germany and
Jordan University/Jordan.
Methods: Parents of the children treated in the pedodontic departments at the
University of Greifswald/Germany and Jordan University/Jordan rated their
acceptance level of four advanced behavior management techniques (passive
restraint, active restraint, nitrous oxide sedation and general anesthesia) for normal
treatment, and for urgent treatment using a five points Likert scale. 200 parents (100
in each university) completed the questionnaire forms for analysis.
Results: Nitrous oxide sedation was rated the most accepted technique in
Greifswald and Jordan (mean 3.78±1.34; 3.22±1.50, respectively). The least
acceptable technique in Greifswald was passive restraint (2.05±1.18) and in Jordan
general anesthesia (2.11±1.30). The parents in Greifswald are significantly more
accepting nitrous oxide sedation than parents in Jordan (p=0.010), while parents in
Jordan are significantly more willing to accept passive restraint (p=0.001). The
acceptance of all advanced behavior management techniques increased significantly
in both groups when the treatment is urgent (p≤0.05),
Conclusions: Parental culture and the urgency of the treatment affect the
acceptance to different behavior management techniques. Moreover, the parental
attitude to the pharmacological technique has changed, as nitrous oxide sedation
generally appears to be the most preferred advanced technique in both groups.
Unstable environments and habitats changing due to climate change force individuals to either respond by genetic adaptation, phenotypic plasticity or by dispersal to suitable environments. Theodoxus fluviatilis (Linneaus, 1758) is a good study organisms when researching phenotypic plasticity and genetic adaptation as it naturally appears in freshwater (FW) as well as brackish water (BW) and thus inhabits a wide range of environmental salinities (0-18‰). It is a euryhaline snail that can be found in shallow waters with stony ground or on Fucus spp. and has formed regional subgroups. The brackish water and the freshwater subgroups are spatially separated and the species cannot be found in areas inbetween, e.g. estuaries.
The species shows great variability in shell patterning and shell size and there is still debate whether the subgroups are distinguishable by these traits or not. The mitochdrial RNA marker cytochrome c subunit I did not show differences between the subgroups indicating that they must be closely related, but salinity tolerance has been observed to be higher in BW snails. This might be caused by the different protein expression patterns and osmolyte accumulation (measured as ninhydrin-positive substances) observed in this species in previous studies. The exact mechanisms regulating protein expression and osmolyte accumulation, however, are not fully understood yet.
Data collected for this thesis shows differences in shell size and suggests a less strict grouping of FW and BW individuals as shell sizes of one FW site are more similar to BW individuals than the other FW ones. A better salinity tolerance towards high salinities and a higher physiological salinity limit of BW snails was confirmed and extended by demonstrating an expanded tolerance range through slow acclimation to challenging salinities in snails from both subgroups. This was achieved by a shift in the slope of their reaction norms that was much more pronounced in BW snails than FW ones. S3 individuals showed a shift similar to that of BW individuals. The data for the salinity tolerance indicates that the underlying mechanism for these tolerances are a combination of phenotypic plasticity and genetic adaptation. Despite an acclimation and shift in the slope of the reaction norms and therefore an increased tolerance towards high salinities (plasticity) FW individuals from two collection sites were not able to cope with salinities as high as BW individuals (local adaptation). The general ability to mobilise free amino acids (FAA) as organic osmolytes was not the reason for this tolerance difference. Individuals from BW and FW sites were capable of accumulating quantities of FAAs equally well. Proline, alanine and urea were the most important components of the accumulated cocktail of organic osmolytes. Even though the total amount of FAAs accumulated under hyperosmotic conditions was the same in both subgroups, there were differences in the metabolic pathways involved in osmolyte accumulation in the foot muscle. The data indicates that the hydrolysis of storage proteins and the synthesis of proline and alanine are the main processes to avoid detrimental body volume shrinkage in T. fluviatilis. While FW individuals seemed to rely on the degradation of proteins and synthesis of alanine, BW individuals depended on newly synthesising proline and alanine and accumulating urea as a side product of transamination. The accumulation of urea is a new finding in aquatic living snails and has not been reported as a mechanism to avoid cell volume shrinkage in these animals.
Differing protein expression patterns were observed under control conditions across all collection sites. 9 spots showed volume changes in BW snails opposite to those of FW snails from collection sites S1 and S2. For 6 of those spots, S3 individuals showed patterns similar to those of BW individuals and for the remaining 3 they showed patterns similar to those of FW animals. The patterns observed when exposing snails to hypo- or hyperosmotic stress were not conclusive in relation to pinpointing individual spots that show the same pattern in all collection sites, but revealed the heterogeneity of protein expression in snails from the different collection sites and in the process of osmoregulation. It also showed the general tendency of protein reduction when snails where under osmotic stress of either kind (hypo- or hyperosmotic), which supports the hypothesis of storage protein degradation.
The investigation of an ANP-receptor showed two variations of the encoding sequence expressed in T. fluviatilis. S3 individuals as well as BW individuals were found to express one type, while FW individuals, with the exception of one sample expressed the other type. This showed that the FW subgroup of T. fluviatilis seems to be more heterogeneous than the BW subgroup, but also raises the question of the dispersal history of this species. The collected data indicates that T. fluviatilis individuals are firstly capable of surviving the acidity of a duck's gizzard and secondly can tolerate acute salinity changes to 16‰ when introduced into a new environment. Hence, if snails from the FW were to be transported to waters with a salinity of up to 16‰ by man, bird, drifting plants or some other means of transport, they would most likely survive and possibly be able to thrive and spread.
Cerebral palsy (CP) remains one of the most common debilitating diseases in the world.
Factors such as neuromuscular incoordination, use of soft diet and delayed oral
clearance of food make maintenance of optimum oral hygiene a challenging task in
these children. The compromised oral hygiene in turn make these children highly
vulnerable to dental disease. Maintaining optimal oral/dental health in CP children is of
utmost importance as these children usually suffer from several associated general
health problems in addition to their primary condition. Poor dental health further
compromises their general health. Nevertheless, CP children often suffer from dental
diseases including dental caries more than healthy children. This underscores the need
for improvement in oral health of the CP children. The CP children are dependent on
those around them for their oral hygiene maintenance and dietary intake. CP children
spend most of their time with health care workers in special centers for them or with
their parents/care takers at home. Therefore, the attitude of special health care workers
and parents towards their dental health is of prime importance. The purpose of this
project included to determine the attitude of special health care workers towards their
dental health and oral health comprehension by parents of CP children. In addition, a
study on caries experience of CP children and associated risk factors was also completed.
The final objective was to identify various potential areas of improvement with ultimate
goal of improving dental health of the CP children.
The study involving special health care workers in a Disabled Children’s Center revealed
that oral health knowledge and practices among the workers could generally be labeled
as satisfactory, however some weak areas (such as trend towards symptom-oriented
utilization of oral health care and lack of knowledge about fluoridated water) were
identified. There is a need to enhance the workers’ knowledge in these areas.
The study involving parents of the CP children showed mixed results. Some areas of
strong oral health comprehension (such as importance of good dental health, harmful
effects of sweetened foods), others satisfactory (such as need for routine dental visits,
use of fluoride) and some weak areas (use of flavored fizzy drinks, bottled/canned juices
and sweetened/flavored milks, seeking early treatment) were identified among parents
of CP children. The results strongly indicated a need for enhanced efforts towards
improvement of oral health comprehension in the parents of the CP children.
The study about caries experience and risk factors in CP children has provided useful
information in an area where literature has been scarce. Almost all the studied children
had clinical dental caries, and most of the caries were untreated. Very few children in
the present study had optimal oral hygiene. This study confirmed the strong correlation
between high dental caries experience and poor oral hygiene. Routine dental check-up
visits and topical fluoride application clearly resulted in lower caries experience. Bottled
juices and crispy potato chips were the two predictors for high caries experience.
As stated before, the goal of the project was to identify various potential areas of
improvement in oral health attitude of special health care workers, oral health
comprehension of the parents of CP children and risk factors for dental caries in CP
children. It is contemplated that by addressing the identified weak areas, an
improvement in dental health and care of the CP children is expected. It is also expected
that the collected information will help in improvement of clinical preventive as well as
restorative services for the CP children. CP children and their parents lead a challenging
life. This project was an effort to assist these children and their parents/care takers with
ultimate goal of improving their oral health and in turn their overall quality of life.