Effects of the glutamic acid decarboxylase (GAD) inhibitor semicarbazide and anti-GAD autoantibodies-containing immunoglobulin G on neuronal network activity within the motor cortex

The electrical activity of the brain is the result of a complex interaction between excitation and inhibition mediated by several types of neurotransmitters. As the majority of neurons in the brain utilize either the inhibitory neurotransmitter γ-aminobutyric acid (GABA) or the excitatory neurotransmitter glutamate, the interplay of these two neurotransmitters principally controls brain excitability and, hence, imbalance between these two neurotransmitters may cause severe pathological conditions. Inhibition of glutamic acid decarboxylase (GAD), the rate-limiting enzyme of GABA synthesis, is believed to change neuronal network activity caused by impaired GABAergic inhibition. Recordings of intrinsic optical signals (IOSs) and whole-cell patch-clamp measurements of GABAA receptor-mediated miniature postsynaptic currents (GABAA Minis) and spontaneous excitatory postsynaptic currents (sEPSCs) were performed in the motor cortex in acute brain slices to unveil the effects of GAD inhibitors at the network level. The first project of this PhD thesis was to prove the IOS technique for its capability of monitoring neuronal network activity over several hours. Concurrently, new software for the analysis of IOS data was developed, which facilitates and significantly accelerates data analysis. Afterwards, changes in neuronal network activity after impairing GAD activity with the well-known GAD inhibitor semicarbazide (SMC) were observed with the IOS technique. If compared to the values of sham-drug application, a stable and reversible increase in both signal intensity and signal area was observed after 2 h of 2 mM SMC application. Consistent with these findings of IOS recordings, patch-clamp measurements of GABAA Minis revealed an SMC-induced reduction in the strength of GABAergic inhibition. The results are in line with the assumption that SMC impairs GABA synthesis by blocking GAD activity. SMC application, however, did not alter spontaneous excitatory neuronal network activity. The final aim of this study was to investigate potential effects of Anti-GAD autoantibodies-containing immunoglobulin G (IgG) derived from patients with stiff-person syndrome (SPS-IgG) on motor cortical neuronal network activity. IOS recordings do not reveal differences in neuronal network activity during SPS-IgG application and control IgG application. However, run-down of IOSs was significantly decelerated during IgG application, which possibly indicates a diminished neuronal cell death caused by an unspecific IgG effect. Compared to brain slices preincubated with IgG-free artificial cerebrospinal fluid, control IgG did not affect GABAA Mini amplitude and frequency as well as sEPSC amplitude. The sEPSC frequency, however, was significantly reduced under these conditions. This decreased excitatory transmitter release might explain the beneficial effect of immunoglobulin treatment in some forms of epilepsy. Similar to SMC, patch-clamp measurements of GABAA Minis revealed a reduction in the strength of GABAergic inhibition after preincubation with SPS-IgG. Consistent with this finding, application of SPS-IgG enhanced sEPSC frequency. This shows that IgG of SPS patients is indeed capable of altering GABAergic synaptic transmission, thus further supporting the hypothesis of an autoimmune origin of the stiff-person syndrome

Factionalism in the kirk during the Cromwellian invasion and occupation of Scotland 1650 to 1660

This Thesis is an examination into the origin and development of the Protester- Resolutioner controversy, the internecine feud which divided the hitherto unified Covenanting movement during the Cromwellian invasion and occupation of Scotland, 1650-60. During the English invasion of Scotland in 1650, incipient divisions within the kirk erupted as the moderate and radical Covenanters divided over the reception of Charles II as king and the passing of the Public Resolutions, which allowed "malignant" royalists into the army and state. When the 1651 General Assembly approved the Resolutions, the schism was institutionalized and the kirk divided into two factions: the Resolutioners, who supported the king and government, and the Protesters, who disavowed the authority of both. After the English conquest in late 1651, these divisions were internalized as both factions engaged in numerous (albeit unsuccessful) attempts to gain ascendancy in the kirk. In 1654, the Protester Patrick Gillespie attempted to break the resultant stalemate when he sought and obtained an ordinance from the English government establishing a system of "triers", which superseded the authority of the kirk's presbyterian courts. In doing this, Gillespie broke the factions' official policy of non-cooperation with the English and ushered in a period during which both factions courted the favour of the Cromwellian regime in an attempt to gain an advantage over their rival. From this point on, the fortunes of the factions became linked inextricably with the ebb and flow of English politics, the Protesters allying themselves with the radical officers of the English army and the Resolutioners with the conservative forces of parliament. The benefits of such alliances, however, proved transitory, serving only to intensify the factions' animosity. By the eve of the Restoration in 1660, the schism had not been remedied and the divided kirk proved an easy prey to its adversaries. This Thesis, in addition to providing the first detailed account of this controversy, will also seek to bridge an important gap in the history of the Covenanting movement by tracing the development and divergence of the Protesters' and Resolutioners' thought on certain key issues, including: the Covenants; the nature of presbyterian church government; the relationship between church and state; religious toleration; and the nature of true godliness. The way in which the factions handled these issues, all of which had their origins in the 1630s and 1640s, was to have a profound effect on the ideology of the presbyterian ministers and the way in which they interacted with the government during the period following the Restoratio

Personalized medicine : benefits and risks of personalized medicine in view of the patient

Die vorliegende Arbeit beschäftigt sich mit der personalisierten Medizin insbesondere in der Onkologie. Der Einsatz der personalisierten Medizin wird in Zukunft davon abhängen, welchen Nutzen die Patienten haben werden und ob sichergestellt werden kann, dass möglich Gefahren für den Patienten vermieden werden können. Außerdem wird herausgearbeitet, in welchen Bereichen die GKV bereits heute finanzierungspflichtig ist

Colorado Wetlands Mobile App: a user's guide

Prepared for: EPA Region 8 Wetlands Program.December 2015.The Colorado Wetlands Mobile App delivers information about Colorado's wetlands to users via smartphones or tablets. It was created by the Colorado Natural Heritage Program (CNHP) through a U.S. Environmental Protection Agency (EPA) Region 8 Wetland Program Development Grant (WPDG). The App is free and available to the public from the major App distribution points, including Apple App Store and Google Play Store. CNHP's main objective in creating the App was to provide wetland professionals and public citizens alike with information to guide conservation and appreciate of the state's value wetland resource

BAW-Brief Nr. 2 - November 2005

584-G, Geotechnik, Teil- und Vollverguss von Deckwerken - Herstellung und Qualitätssicherung583-G, Geotechnik, Zur Handhabung der neuen Norm DIN EN 13383 für Wasserbausteine und deren Umsetzung in einer Steinbemessun

Zum Geleit

Da kein Abstract des Artikels vorhanden ist, finden Sie hier den Beginn des Artikels: In einem zweisemestrigen Projektseminar beschäftigte sich im Frühjahrs- und Herbstsemester 2012 eine Gruppe Studierender unter der Leitung von Thomas Hengartner und Ute Holfelder mit dem audiovisuellen Artefakt Handyfilm. Diese Veranstaltung war Teil des vom Schweizerischen Nationalfonds geförderten Projekts «Handyfilme. Künstlerische und ethnografische Zugänge zu jugendlichen Alltagswelten»1. Den Interessen der Studierenden folgend, ist dabei eine breite Palette an Arbeiten in unterschiedlichen Formaten entstanden, die zum Teil in diesem «Werkstücke»-Band und zu einem anderen Teil auf der Homepage des Instituts für Populäre Kulturen der Universität Zürich präsentiert werden

BROWSING ACTIVITY SUPERVISION

A supervision system generates a user interface that summarizes user’s browsing trends based on user’s browsing activity. The system monitors browsing activity of a user. The system further determines browsing trends of the user based on user’s browsing activity for a predetermined time period. On determination of the browsing trends, the system generates the user interface that provides a summary of user’s browsing trends for the pre­determined time period

The influence of sex, stroke and distance on the lactate characteristics in high performance swimming

Background: In order to achieve world-class performances, regular performance diagnostics is required as an essential prerequisite for guiding high performance sport. In high performance swimming, the lactate performance diagnostic is an important instrument in testing the sport specific endurance capacity. Although the role of lactate as a signaling molecule, fuel and a gluconeogenic substrate is accepted, lactate parameters are discussed concerning stability, explanatory power and interpretability. Methods: We calculated the individual anaerobic threshold (IAT) of Bunc using the swimming-specific lactate threshold test by Pansold. Results: The cross-sectional analysis (ANOVA) of n = 398 high performance swimmers showed significant effects for sex, stroke and distance on the IAT, the percentage of personal best time on the IAT (% of PB on IAT) and maximal lactate values (max. bLA). For the freestyle events the IAT decreased, % of PB on IAT and max. bLA increased from 100 to 400 m significantly in men and women. Women showed significantly higher % of PB on IAT with descriptive lower IAT in 7 of 8 analyzed events. Men showed significantly higher max. bLA in 5 of 8 events. In the second step, the analysis of 1902 data sets of these 398 athletes with a multi-level analysis (MLA) showed also significant effects for sex, swimming distance and stroke. For initial status and development over time, the effect sizes for the variables distance and sex were medium to large, whereas for stroke there were no or small effect sizes. Discussion: These significant results suggest that lactate tests in swimming specifically have to consider the lactate affecting factors sex and distance under consideration of the time period between measurements. Anthropometrical factors and the physiology of women are possible explanations for the relative better performance for lower lactate concentrations compared to men