Nicotinic receptor channelopathies and epilepsy

Characterized by sudden episodes called seizures, epilepsy was recognized long ago as a neurological disorder that can have multiple forms ranging from benign to life threatening depending upon its severity. Although several evidences indicated that genes play an important role in at least half of the patients, it is only with the advances in molecular biology and genetics that the puzzle about oligogenic and monogenic epilepsies slowly starts to unfold. The finding of an association between a monogenic form of epilepsy and a mutation in the gene encoding the neuronal nicotinic acetylcholine receptor subunit CHRNA4 marked, in 1995, a turning point in our understanding of epilepsy. It also marked the first step towards the today widely acknowledged concept of epilepsies as channelopathies. Several mutations in nicotinic acetylcholine receptor genes have, since then, been identified, and the functional properties of these mutated receptors were characterized. In this work, we review, in the light of the latest discoveries, the effects caused by the mutations on the physiological properties of the receptors and the impact of such mutations on neuronal network function

Development of a decision support app for short term production control to improve the adherence to delivery dates

In manufacturing, adherence to delivery dates is one of the main logistic goals. The production control department has to cope with short-term deviations from the planned route sheets. Because of unforeseen disruptions, e.g. machine breakdowns or shortage of material or personnel, in some situations, the promised delivery date to the customer is at stake. In practice, a fast and reasonable decision on how to deal with the delayed order is required. This decision process is often based on a qualitative analysis relying on the planner’s subjective assessment of a complex situation. To improve the quality of possible countermeasures this paper presents an application, which supports the decision process through a quantified analysis using real-time data from business application systems in combination with a simulation of the value stream. The developed app is part of the decision process and estimates the effect of selected countermeasures to accelerate a delayed order. Performance indicators illustrate the effect of the countermeasures on the specific order as well as the whole system. This approach empowers the planner to assess unforeseen situations and aims to improve the quality of the decision-making process. This paper describes the architecture of the application, its simulation ecosystem, the relevant data and the decision process to select the most effective countermeasures

Melanocortin-3-receptor promoter polymorphism associated with tuberculosis susceptibility does not influence protein expression.

Background: The melanocortin-3-receptor (MC3R) is a member of the G-protein coupled receptor family that mediate cellular response through the cyclic adenosine monophosphate signalling pathway. In the promoter region of MC3R the polymorphism rs6127698 has previously been shown to be strongly associated with tuberculosis susceptibility. It is predicted to generate an alternative transcription factor binding site. Findings: We investigated the functional impact of rs6127698 by luciferase assay to assess if this polymorphism is capable of altering protein expression. Our results did not show any significant protein expression changes when comparing the two alleles of rs6127698. Conclusions: Our experiments demonstrate that the rs6127698 polymorphism does not influence protein translation. A functional role of the predicted alternative transcription factor binding site could therefore not be confirmed. These results suggest rs6127698 has no direct role in tuberculosis susceptibility. The possibility remains that this polymorphism is linked to an adjacent functional genetic variant, acting as a surrogate marker for disease risk

Conspicuous Anti-Consumption? The Motives of Anti-Consumption and their Connection to Conspicuous Consumption

The conscious renunciation of different types of consumption is justified by various motives, such as the sustainability aspect. This fact suggests that motives are very different from the ones of conspicuous consumption. But is that true? The aim of the study is to examine whether the motives for anti-consumption can be found in the motives for conspicuous consumption. The research question therefore is: What motives lie behind anti-consumption, and can these motives be found in classical conspicuous consumption? As part of a qualitative study, eight in-depth interviews were conducted in order to generate a broad range of motives for different anti-consumption behaviors. In addition to previously deductively determined motives for the renunciation, the motives obtained from these interviews were then inductively summarized in a motive scheme and subsequently compared to the motives of classical conspicuous consumption. As a result, there is a connection between the motives of anti-consumption and the motives of conspicuous consumption. While the primary motives for anti-consumption are not related to conspicuous consumption motives, there are secondary motives (supporting the primary motives) for anti-consumption that can also be assigned to conspicuous consumption. This implies that some kind of “conspicuous anti-consumption” is part of today's consumer culture

Märchen als poetische Erziehungsform : zum kinderliterarischen Status der Grimmschen "Kinder- und Hausmärchen" ; Antrittsvorlesung, 16. Juni 1993, Humboldt-Universität zu Berlin, Fachbereich Germanistik

Es gehört zu den bleibenden Leistungen der "Kinder- und Hausmärchen", daß sie die fiktionalisierte Moralförmigkeit älterer Kinder- und Jugendliteratur in eine poetisierende Märchenförmigkeit überführen - auf diesem Wege das kollektive Imaginäre ihrer Epoche als Ermöglichungsgrund jeglichen Bilderbewußtseins neu besetzend und umformulierend. Anders gesagt: die "Kinder- und Hausmärchen" öffnen – wiewohl sie sich nicht allein für die intentionale Kinderliteratur reklamieren lassen - deren Bereich nachdrücklich der Geltung der sog. “Ästhetik-Konvention”, die sich im Literatursystem um 1800 allgemein durchgesetzt hat. Sie bewirken damit eine folgenreiche Lockerung der für die Kinderliteratur immer noch verbindlichen Pädagogik-Konvention

Cytogenetic Characterization of the TM4 Mouse Sertoli Cell Line. II. Chromosome Microdissection, FISH, Scanning Electron Microscopy, and Confocal Laser Scanning Microscopy

The chromosomes and interphase cell nuclei of the permanent mouse Sertoli cell line TM4 were examined by chromosome microdissection, FISH, scanning electron microscopy, and confocal laser scanning microscopy. The already known marker chromosomes m1-m5 were confirmed, and 2 new large marker chromosomes m6 and m7 were characterized. The minute heterochromatic marker chromosomes m4 and m5 were microdissected and their DNA amplified by DOP-PCR. FISH of this DNA probe on TM4 metaphase chromosomes demonstrated that the m4 and m5 marker chromosomes have derived from the centromeric regions of normal telocentric mouse chromosomes. Ectopic pairing of the m4 and m5 marker chromosomes with the centromeric region of any of the other chromosomes (centromeric associations) was apparent in ∼60% of the metaphases. Scanning electron microscopy revealed DNA-protein bridges connecting the centromeric regions of normal chromosomes and the associated m4 and m5 marker chromosomes. Interphase cell nuclei of TM4 Sertoli cells did not exhibit the characteristic morphology of Sertoli cells in the testes of adult mice as shown by fluorescence microscopy and confocal laser scanning microscopy