Characterising Tenebrio molitor, mealworm, as a host for studying Aspergillus fumigatus pathogenesis

Aspergillus fumigatus is an opportunistic fungal pathogen that is the leading cause of Invasive Aspergillosis (IA). Despite the availability of diagnostics and treatments, IA has high morbidity and mortality ranging from 30-95%. This is due to the complexity of infection as virulence depends on interactions that occur between fungal traits and host immunity. Model organisms can be utilised to investigate these interactions including invertebrates as they utilise innate immunity, which when impaired in humans represents an important IA risk factor. In this project, Tenebrio molitor larvae were explored as an alternative invertebrate to study A. fumigatus pathogenesis. Several methods were utilised to characterise infection. This includes colony forming unit (CFU) counts and quantitative polymerase chain reaction (qPCR) to quantify infection over time. To visualise infection, histological examination and magnetic resonance imaging (MRI) were utilised, and haemocyte interaction assays to examine haemocyte-fungal interactions in detail. Inoculation of T. molitor larvae with A. fumigatus was observed to decrease survival over time, increase the fungal burden, and cause the presence of nodules within larval tissue. These nodules were accompanied by cells suspected to be haemocytes, which during interaction assays became activated upon exposure to A. fumigatus conidia. Similar observations have been observed in other invertebrates including Galleria mellonella. T. molitor larvae may thus be useful to study A. fumigatus pathogenesis, however further optimisations of these methods are necessary to confirm these findings and characterise infection, such as utilisation of fungal specific stains and additional methodologies including confocal microscopy and flow cytometry to assess phagocytosis

Genetic determinants of the metabolic syndrome

Das Ziel dieser Diplomarbeit war es, die genetischen Determinanten des MetSyn durch ein Literaturreview der betreffenden genomweiten Assoziationsstudien (GWASs) zu bestimmen. Weiters wurden die wichtigsten Definitionen des MetSyn, die Prävalenzraten, die klinische Relevanz (dazu wurde das MetSyn mit bestehenden Prognosemodellen für kardiovaskulare Erkrankungen oder Diabetes verglichen), die zu Grunde liegenden Faktoren und die Heretabilität diskutiert sowie die Grundlagen einer GWAS beschrieben. Zur Bestimmung der involvierten Gene bzw. Genvarianten wurden GWAS herangezogen, die Genassoziationen mit Komponenten des MetSyn sowie mit C-reaktiven Protein und Folgeerkrankungen, wie z.B. Diabetes mellitus untersuchten. Dieser Ansatz begründet sich dadurch, dass noch keine GWAS publiziert wurde, die das MetSyn als solches untersucht hat sowie durch die Annahme, dass die Interaktion verschiedener Genvarianten assoziiert mit den Komponenten des MetSyn zur Entwicklung des MetSyn beitragen kann. Der Vergleich der durch die GWASs als assoziiert identifizierten Gene zeigte, dass neun Gene sich auf verschiedene MetSyn Komponenten gleichzeitig auswirken. Ein zehntes Gen wird dadurch interessant, da dessen Identifikation anhand einer an MetSyn erkrankten Gruppe erfolgte. Die Evidenz aller zehn Gene wird zusammengefasst dargestellt und diskutiert. Zu den Genen mit der besten Evidenz zählen APOE, FTO, GCKR, MC4R und PPARG. Varianten dieser Gene wurden mindestes mit zwei Komponenten des MetSyn assoziiert, mit einer den genomweiten Assoziationsstudien entsprechenden Signifikanz. Eine Ausnahme bildet PPARG. Bei diesem Gen wurde nur eine grenzwertige Signifikanz festgestellt. Interessanterweise wurden vorwiegend SNPs als assoziiert identifiziert, die keine Evidenz aus Kandidatengenstudien mitbrachten. Ein Beispiel ist hierfür die Genvariante Val103Ile des MC4R Genes. Alle der bisherigen assoziierten Genvarianten zeigen relativ moderate Effektwerte und können somit die beobachtbaren Variationen nicht erklären. Ebenso kann die Summation der Effektwerte die Variationen nicht vollständig, bei den Plasmalipiden sind es z.B. 5-8%, erklären. Daraus lässt sich schließen, dass es noch eine Vielzahl an assoziierten Genvarianten zu identifizieren gibt bzw. Umweltfaktoren einen großen Teil zur Variation beitragen. Zusammenfassend kann man sagen, dass Genvariationen die Entwicklung der MetSyn Komponenten sowie des MetSyn beeinflussen. Es ist allerdings noch unklar zu welchem Anteil dies geschieht. GWAS sind jedenfalls eine erfolgreiche Methode, um die Beteiligung der Gene bzw. die genetischen Determinanten des MetSyn und seiner Komponenten weiter zu untersuchen.This thesis mainly intended to investigate the genetic determinants of the MetSyn and its components by reviewing gene-wide association studies (GWASs). Furthermore the most important definitions, the prevalence rates, the clinical relevance (a brief comparison of the MetSyn with established risk predicting models for CVD and T2DM is given), the underlying factors and the heritability estimates were discussed as well as the basic principles of a GWAS described. To determine which genes or gene variants are involved in the development of the MetSyn GWASs were reviewed that investigated gene associations with components of the MetSyn, C-reactive protein or with known outcomes, like T2DM. This approach was due to the reason that no GWAS was published so far that investigated the MetSyn directly and the assumption that the interaction of gene variants associated with MetSyn components leads to the development of the MetSyn. The results of the reviewed GWASs were then compared and the ten genes or gene regions with overlapping or particular evidence (genome scan was conducted in individuals affected by the MetSyn) were discussed briefly to summarize the evidence. The most important genes implicated in the development of the MetSyn seem to be APOE, FTO, GCKR, MC4R, and PPARG. SNPs of these genes are associated with at least two MetSyn components with genome-wide significance except of PPARG, which significance was borderline. Interestingly, those SNPs found formally in candidate gene studies to be associated, mostly were not identified by GWASs; for instance the variant of MC4R Val103Ile. All of the so far associated SNPs account only for modest effect sizes; therefore, they cannot explain the observed trait variations. Even the summation of effect sizes could not explain, for instance, more then 5-8% of the variation seen in blood lipids. It follows that many more implicated gene variants or other contributors to the observed trait variation, as environmental factors, have to be identified. In conclusion, genetic variations influence the development of MetSyn components and the MetSyn itself, but to what extent remains unanswered. However, the GWAS is a powerful method to further investigate the genetic contribution and the genetic determinants of the MetSyn and its components

Appetitively motivated tasks in the IntelliCage reveal a higher motivational cost of spatial learning in male than female mice

The IntelliCage (IC) permits the assessment of the behavior and learning abilities of mice in a social home cage context. To overcome water deprivation as an aversive driver of learning, we developed protocols in which spatial learning is motivated appetitively by the preference of mice for sweetened over plain water. While plain water is available at all times, only correct task responses give access to sweetened water rewards. Under these conditions, C57BL/6J mice successfully mastered a corner preference task with the reversal and also learned a more difficult time-place task with reversal. However, the rate of responding to sweetened water decreased strongly with increasing task difficulty, indicating that learning challenges and reduced success in obtaining rewards decreased the motivation of the animals to seek sweetened water. While C57BL/6J mice of both sexes showed similar initial taste preferences and learned similarly well in simple learning tasks, the rate of responding to sweetened water and performance dropped more rapidly in male than in female mice in response to increasing learning challenges. Taken together, our data indicate that male mice can have a disadvantage relative to females in mastering difficult, appetitively motivated learning tasks, likely due to sex differences in value-based decision-making

The accuracy and annual rank-order stability of elementary school children's self-monitoring judgments

The present study investigated age-related development in children's metacognitive self-monitoring skills; eight-year-olds (N = 140) and ten-year-olds (N = 164) were compared. Children learned paired associates and completed a recognition test. Two types of monitoring judgments were compared: predictions and postdictions of performance. To investigate the rank-order stability of monitoring judgments, the task was repeated one year later. Prediction accuracy was low for both age groups and did not improve over time. Postdictions were more accurate than predictions; this indicates that self-test experiences support children to take actual performance into account when monitoring learning. For the second graders, postdiction accuracy improved over one year. Annual rank-order stability was found for predictions and postdictions, suggesting that habitual judgment tendencies affect children's monitoring judgments and judgment accuracy

Detection and localisation of unilateral hindlimb pathologies in cattle using the cow pedogram.

ISSN:0042-490

Connecting teachers’ classroom instructions with children’s metacognition and learning in elementary school

Many children have difficulties with accurate self-monitoring and effective regulation of study, and this may cause them to miss learning opportunities. In the classroom, teachers play a key role in supporting children with metacognition and learning. The present study aimed to acquire insights into how teachers’ cognitive and metacognitive strategy instruction, as well as teacher-directed and child-centered instructional practices are related to children’s self-monitoring accuracy, regulation of study, and learning performance. Twenty-one teachers and 308 children (2nd and 4th grade elementary school) participated. Teachers instructed a secret code task, children had to learn the match between letters of the alphabet and corresponding symbols. Teachers were observed and audio-recordings were made of their instructions. Then, children were asked to (a) make restudy selections, (b) complete a test, and (c) self-monitor test performance. Although teachers both addressed cognitive and metacognitive strategies, they more often instructed children about cognitive strategies. Further, teaching practices were more often teacher-directed than child-centered. Although there were no relations between teachers’ instructions for metacognitive strategies and children’s outcome measures, teaching cognitive strategies was positively associated with children’s performance and selfmonitoring accuracy. However, teaching cognitive strategies did not predict effective restudy selections. Rather, child-centered instructions (i.e., giving children autonomy to regulate their own learning) positively predicted children’s restudy, and further, children’s self-monitoring was more accurate in classrooms where teachers more often used childcentered instructional practices. This seems to imply that not only the content of the instructions itself, but particularly the way these are given, affects children’s metacognition

Diode Effects in Current-Biased Josephson Junctions

Current-biased Josephson junctions exhibit hysteretic transitions between dissipative and superconducting states as characterized by switching and retrapping currents. Here, we develop a theory for diodelike effects in the switching and retrapping currents of weakly damped Josephson junctions. We find that while the diodelike behavior of switching currents is rooted in asymmetric current-phase relations, nonreciprocal retrapping currents originate in asymmetric quasiparticle currents. These different origins also imply distinctly different symmetry requirements. We illustrate our results by a microscopic model for junctions involving a single magnetic atom. Our theory provides significant guidance in identifying the microscopic origin of nonreciprocities in Josephson junctions

Moderne Public Affairs versus traditionelle Interessenvertretung? Agenturen, Unternehmen und Verbände in der politischen Kommunikation

'Die Bedingungen und Merkmale der politischen Vertretung gesellschaftlicher Interessen verändern sich: Die Zahl und Vielfalt von Akteuren nimmt zu, Einflussnahme erfolgt zielgerichtet und punktuell, die Relevanz institutionalisierter Zugänge zu Entscheidungssystemen nimmt ab und es ist eine Informalisierung wie auch Medialisierung politischer Interessenvertretung zu beobachten. Vor diesem Hintergrund will der Beitrag die Frage beantworten, wie sich Agenturen, Unternehmen und Verbände als AkteurInnen politischer Kommunikation unterscheiden. Empirische Grundlage ist eine sekundäranalytische Auswertung zweier Befragungen von Verantwortlichen für politische Interessenvertretung in der Schweiz, deren Organisationen primär Interessen aus dem Bereich Wirtschaft vertreten. Die Befunde zeigen, dass vor allem Agenturen und mit Abstrichen Unternehmen als Promotoren einer 'modernen' Public Affairs gelten können, während sich Verbände eher an 'traditionellen' Formen der politischen Interessenvertretung orientieren.' (Autorenreferat)'The representation of political interests is changing: more and more actors are involved, the diversity of interests is increasing, institutionalized structures of corporatism are in decline. Instead, strategies become more tightly and short term focused on the exertion of political influence. This comes along with an 'informalization' and 'mediatization' of interest representation. Against this background, the article is analyzing, how consultancies, business organizations and associations differ in their ways of influencing politics in economic fields. The empirical data come from two Swiss surveys. The results show that especially consultancies and to a less extent business organizations reflect changing conditions of interest representation. They can be regarded as promoters of 'modern' public affairs, whereas associations prefer 'traditional' ways of influencing political decision making.' (author's abstract)