Effect of planting date on leaf number and total leaf area of hybrid grain sorghum (Sorghum bicolor (L.) Moench)

Call number: LD2668 .T4 1979 B85Master of Scienc

Behavioral phenotyping, gene expression profiles, and cognitive aspects in a mouse model of trait anxiety

Anxiety reflects a fundamental emotion, essential for survival. However, if it occurs unpredictably and exaggerated for a long period of time, it becomes pathological, confining a normal course of life. Anxiety disorders are among the most disabling psychiatric diseases, with increasing incidence. They are complex and occur as a combination of both, inherited and stress-related phenomena, whose origin and underlying mechanisms are still poorly understood. Besides clinical studies, extensive preclinical research is strongly focusing on the genetic, environmental, and developmental underpinnings of both, “physiological” and “pathological” anxiety. Thus, in the year 2000, two mouse lines were generated by bi-directional selective inbreeding, reflecting extremes in trait anxiety. These phenotypic extremes, independent of gender, display either high (HAB) or low (LAB) anxiety-related behavior as measured in the elevated plus-maze test and a variety of other paradigms. Since anxiety is not considered as a single entity, but covers multiple facets, the studies presented in this thesis address behavioral, neuroendocrine, genetic, developmental as well as cognitive aspects in this mouse model of trait anxiety. Comprehensive phenotyping confirmed the phenotypic divergence of the mouse lines. Although selection pressure was only exerted on anxiety-related behavior, the mouse lines exhibited comorbid depression-like and altered explorative behavior. Moreover, expression profiling of genes well described in the regulation of emotionality at the level of the hypothalamo-pituitary-adrenocortical axis and synaptic neurotransmission, as well as pharmacological intervention, highlighted arginine-vasopressin (AVP), corticotropin-releasing hormone (CRH), and synaptotagmin 4 (Syt4) as potential mediators contributing to the observed behavioral differences. AVP has been identified to be under-expressed in several brain regions of LAB mice associated with their non-anxious and non-depression-like behaviors. In addition, several genetic polymorphisms have been identified that are likely to play a critical role in the AVP under-expression of these animals. In contrast, the highly anxious HAB animals revealed a CRH over-expression in various brain areas. The significance of CRH over-expression in mediating the HAB-specific phenotype was pharmacologically validated via CRH receptor 1 antagonist administration. Synaptic release, indicated by Syt4 expression, was found to be altered in both inbred mouse lines in opposite directions, indicating a dysregulation in both extremes of trait anxiety. Furthermore, glyoxalase1 (Glx1), a cellular detoxification enzyme, has been identified to be differently expressed already at early postnatal developmental stages in association with the phenotypic divergence. Thus, Glx1 might act as a biomarker suitable for the early prediction of pathological anxiety. As anxiety disorders have often been described to be accompanied by alterations in cognitive abilities, this coherency was also addressed in the HAB/LAB model. Indeed, HAB mice showed a superior ability in a social learning paradigm and displayed delayed extinction in a classical fear-conditioning study, the latter being similarly observed in patients suffering from posttraumatic stress disorder. Taken together, the HAB/LAB mouse model covers many clinical core symptoms of anxiety disorders at different levels, including behavioral emotionality, gene expression, and cognitive alterations. Therefore, it provides a valuable and promising tool to elucidate the neurobiological basis of the continuum from vital to pathological anxiety

Model-Based Evaluation of Highly and Low Pathogenic Avian Influenza Dynamics in Wild Birds

There is growing interest in avian influenza (AI) epidemiology to predict disease risk in wild and domestic birds, and prevent transmission to humans. However, understanding the epidemic dynamics of highly pathogenic (HPAI) viruses remains challenging because they have rarely been detected in wild birds. We used modeling to integrate available scientific information from laboratory and field studies, evaluate AI dynamics in individual hosts and waterfowl populations, and identify key areas for future research. We developed a Susceptible-Exposed-Infectious-Recovered (SEIR) model and used published laboratory challenge studies to estimate epidemiological parameters (rate of infection, latency period, recovery and mortality rates), considering the importance of age classes, and virus pathogenicity. Infectious contact leads to infection and virus shedding within 1–2 days, followed by relatively slower period for recovery or mortality. We found a shorter infectious period for HPAI than low pathogenic (LP) AI, which may explain that HPAI has been much harder to detect than LPAI during surveillance programs. Our model predicted a rapid LPAI epidemic curve, with a median duration of infection of 50–60 days and no fatalities. In contrast, HPAI dynamics had lower prevalence and higher mortality, especially in young birds. Based on field data from LPAI studies, our model suggests to increase surveillance for HPAI in post-breeding areas, because the presence of immunologically naïve young birds is predicted to cause higher HPAI prevalence and bird losses during this season. Our results indicate a better understanding of the transmission, infection, and immunity-related processes is required to refine predictions of AI risk and spread, improve surveillance for HPAI in wild birds, and develop disease control strategies to reduce potential transmission to domestic birds and/or humans

Clinical effects of the GLP-1 receptor agonist exenatide in patients with type 2 diabetes

Diamant, M. [Promotor]Heine, R.J. [Promotor

Aktivität der sezernierten Sphingomyelinase bei akuter und chronischer systemischer Inflammation am Beispiel des SIRS, der Sepsis und der chronischen Herzinsuffizienz

Systemic inflammatory response syndrome (SIRS), Sepsis und chronische Herzinsuffizienz (CHF) sind gekennzeichnet durch eine generalisierte Inflammationsreaktion mit Hyperzytokinämie, vermehrtem oxidativen Stress, hämodynamischen und metabolischen Veränderungen. Erste Beobachtungen am Menschen haben gezeigt, dass sich generalisierte Entzündungsprozesse auch in systemischen Veränderungen des Sphingomyelinstoffwechsel niederschlagen. Metabolite des Sphingomyelinstoffwechsel sind an der zellulären Stressantwort beteiligt und greifen regulativ in die unterschiedlichsten Immunfunktionen ein. Daneben lassen sich kardiovaskuläre und metabolische Effekte beobachten. Sphingomyelinasen nehmen als Schrittmacherenzyme eine Schlüsselposition im Sphingomyelinstoffwechsel ein. Welche Rolle der sezernierten Sphingomyelinase (sSMPD1) in einer systemischen Aktivierung des Sphingomyelinstoffwechsels zukommt, ist bisher nur unzureichend untersucht. Ziele Wir gingen der Frage nach, inwieweit akute und chronische generalisierte Inflammationszustände beim Menschen mit einer veränderten Aktivität der sezernierten Sphingomyelinase einhergehen. Darüber hinaus sollte geklärt, ob ein Zusammenhang zwischen Krankheitsschwere und Ausmaß der sSMPD1 Aktivitätsänderung besteht. Dabei untersuchten wir auch mögliche Mechanismen der Aktivitätssteigerung. Schließlich untersuchten wir den Zusammenhang zwischen sSMPD1 Aktivität und verschiedenen Funktionsparametern der chronischen Herzinsuffizienz

Modulating the Folding Landscape of Superoxide Dismutase 1 with Targeted Molecular Binders

Amyotrophic lateral sclerosis, or Lou Gehrig's disease, is characterized by motor neuron death with average survival times of 2 ‐ 5 years. One cause of this disease is the misfolding of superoxide dismutase 1 (SOD1), a protein whose stability and aggregation propensity are affected by point mutations spanning the protein. Here, we use an epitope‐specific, high‐throughput screen to identify peptides that both stabilize the native conformation of SOD1 as well as accelerate its folding by 2.5‐fold. Ligands targeted to the electrostatic loop on the periphery of the protein tightened the non‐metalated structure and accelerated its folding. This strategy may be useful for fundamental studies of protein energy landscapes as well as designing new classes of therapeutics

Dual-Source CT Angiography of Peripheral Arterial Stents: In Vitro Evaluation of 22 Different Stent Types

Purpose. To test different peripheral arterial stents using four image reconstruction approaches with respect to lumen visualization, lumen attenuation and image noise in dual-source multidetector row CT (DSCT) in vitro. Methods and Materials. 22 stents (nitinol, steel, cobalt-alloy, tantalum, platinum alloy) were examined in a vessel phantom. All stents were imaged in axial orientation with standard parameters. Image reconstructions were obtained with four different convolution kernels. To evaluate visualization characteristics of the stent, the lumen diameter, intraluminal density and noise were measured. Results. The mean percentage of the visible stent lumen diameter from the nominal stent diameter was 74.5% ± 5.7 for the medium-sharp kernel, 72.8% ± 6.4 for the medium, 70.8% ± 6.4 for the medium-smooth and 67.6% ± 6.6 for the smooth kernel. Mean values of lumen attenuation were 299.7HU ± 127 (medium-sharp), 273.9HU ± 68 (medium), 270.7HU ± 53 (medium-smooth) and 265.8HU ± 43. Mean image noise was: 54.6 ± 6.3, 20.5 ± 1.7, 16.3 ± 1.7, 14.0 ± 2 respectively. Conclusion. Visible stent lumen diameter varies depending on stent type and scan parameters. Lumen diameter visibility increases with the sharpness of the reconstruction kernel. Smoother kernels provide more realistic density measurements inside the stent lumen and less image noise

Reproducibility of three different cardiac T2-mapping sequences at 1.5T and impact of cofactors on T2-relaxation times

Background: The high interindividual variability of myocardial T2 relaxation times appears to be one of the main challenges for the clinical application of cardiac T2-mapping. This study therefore aimed to evaluate potential underlying causes for this variability, analyzing the reproducibility of three different cardiac T2-mapping sequences and evaluating the influence of cofactors on T2 relaxation times. Methods: 30 healthy volunteers were examined three times on a clinical 1.5T scanner (scan 1: in the morning; scan 2: in the evening of the same day; scan 3: in the evening 2-3 weeks later). In each examination three different T2-mapping sequences were acquired at three slices in short axis view: Multi Echo Spin Echo (MESE), T2-prepared balanced Steady State Free Precession (T2prep; [1]) and Gradient Spin Echo (GraSE). Repeated measurements were performed for T2prep and GraSE. Segmented T2-maps were generated for each slice according to the AHA 17-segment model. Intra- and inter-observer reproducibility was tested in a subgroup of 10 randomly selected subjects, where manual ROIs were drawn independently to measure T2 values of each segment blinded to the other results. Results: Overall, we observed no systematic difference of T2 times due to diurnal effects and on long-term analysis. Differentiated analysis of variance components for all sequences, however, revealed a greater variance of T2 times over multiple time points than for repeated measurements within the same scan. Our study revealed a low intra-observer and inter-observer variability of manual ROI-definition and the acquired T2 times for each sequence. The coefficients of variation and intraclass correlation coefficients for intra-observer variability were: 1.3% and 0.89 for T2prep, 1.5% and 0.93 for GraSE, 3.1% and 0.83 for MESE; and for inter-observer variability: 3.3% and 0.66 for T2prep, 2.0% and 0.83 for GraSE, 3.6% and 0.77 for MESE. With respect to the influence of potential cofactors on T2 times, we observed a negative effect of the cofactor heart rate on mean T2 values, yet this effect proved to be not significant. Conversely, we found significant and positive relation between mean T2 times and the cofactors age, weight and height (p < 0.005, p < 0.05 and p < 0.05) in single linear regression models. Using multiple regression models, we observed significant relations between mean T2 times and age (p < 0.005), gender (p < 0.01), and either weight or height (p < 0.005), for given values of the remaining cofactors. Conclusions: Intra- and inter-observer reproducibility of all tested T2-mapping sequnces is high, thereby confirming previous studies. According to our study, the high interindividual variability of myocardial T2 relaxation times is most likely due to proband-related effects such as age, gender, weight and height and other cofactors intraindividually varying with time