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

Evaluation Of Feed Intake, Growth, And Reproduction In The Zebrafish, Danio Rerio, Fed A Gel-Based Diet

EVALUATION OF FEED INTAKE, GROWTH, AND REPRODUCTION IN THE ZEBRAFISH, DANIO RERIO, FED A GEL-BASED DIET THOMAS LOGAN HOLFELDER BIOLOGY ABSTRACT The zebrafish, Danio rerio, is a valuable pre-clinical model, aiding human health understanding and translational aquaculture. Comprehensive documentation of the culture of this model exists, with ongoing efforts to optimize husbandry requirements, particularly in the areas of diet and nutrition. Labor or mechanical costs related to feeding are high in most laboratories and alternative protocols to reduce feed handling would be beneficial and could allow the capability to monitor feed consumption. A commercially produced gel-based diet has a high moisture content, mimicking natural live prey. This diet maintains its physical integrity in the water, and one daily ration can be consumed over 24 hours. The present study goal was to evaluate D. rerio fed gel-based diets relative to (1) feed intake parameters, (2) long term growth, survival, reproductive success, and (3) efficacy when fed during larval development. We found that adult D. rerio readily accommodate to the gel diet. In addition, feed intake is highest in the morning after lights-on, although they continue to feed during the dark period. Feed intake was density dependent, with higher levels of feed intake observed at the highest densities tested (5 individuals/L). Juvenile D. rerio were fed one of three diets over a 12-week period, including a dry granulated reference diet, a commercial gel diet, and a dry granulated form (dehydrated and ground to the same physical form of the reference diet) of the gel diet. Survival was \u3e 95.8% in all diets and supported growth and reproductive success. Terminal measures of weight and length in females fed the reference diet or gel-based diet did not differ significantly, whereas males fed the reference diet had the highest terminal weight and length measures. Reproductive success was similar among treatments, with all treatments exhibiting substantial egg production and embryo viability. Early replacement (at 6dpf) of a live diet for a gel-based diet negatively impacted survival and final weights. However, the gel diet supported survival and growth when fed at 12dpf or higher. Our study supports the use of a gel-based diet in daily D. rerio colony maintenance, but further nutritional assessments are necessary

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

Prospective association between objective measures of childhood motor coordination and sedentary behaviour in adolescence and adulthood

BACKGROUND: Higher levels of gross motor coordination are positively associated with physical activity in childhood, but little is known about how they relate to sedentary behaviour. The aim of this study was to investigate the longitudinal association between gross motor coordination at childhood and sedentary behaviour in adolescence and adulthood. METHODS: Data were from the 1970 British Cohort Study (the age 10, 16, and 42-year surveys). At age 10 the participant's mother provided information on how often participants watched TV and played sports and a health visitor administered several tests to assess gross motor coordination. At aged 16 and 42-years participants reported their daily screen and TV time, respectively, and physical activity status. We examined associations between gross motor coordination at age 10 with sedentary behaviour and physical activity at age 16 and 42, using logistic regression. RESULTS: In multivariable models, higher levels of gross motor coordination were associated with lower odds of high screen time (n = 3073; OR 0.79, 95% CI 0.64, 0.98) at 16-years although no associations with physical activity were observed (OR 1.16, 95% CI 0.93, 1.44). Similar associations were observed with TV time in adulthood when participants were aged 42, and in addition high gross motor coordination was also associated with physical activity participation (n = 4879; OR 1.18, 95 % CI 1.02, 1.36). CONCLUSIONS: Intervention efforts to increase physical activity participation and reduce sedentary behaviour over the life course may be best targeted towards children with low gross motor coordination

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

Estimating physical activity in children aged 8-11 years using accelerometry: contributions from fundamental movement skills and different accelerometer placements.

Accelerometers are widely used to assess physical activity, but it is unclear how effective accelerometers are in capturing fundamental movement skills in children. This study examined the energy expenditure during different physical activities (PA) and calibrated triaxial accelerometry, worn at the wrist, waist and ankle, during children’s PA with attention to object control movement skills and cycling. Thirty children (14 girls) aged 8 to 11 years wore a GENEActiv accelerometer on their non-dominant wrist, dominant wrist, waist and ankle. Children undertook eight, 5-min bouts of activity comprising being lay supine, playing with Lego, slow walking, medium walking, medium paced running, overarm throwing and catching, instep passing a football and cycling at 35 W. VO2 was assessed concurrently using indirect calorimetry. Indirect calorimetry indicated that being lay supine and playing with Lego were classified as sedentary in nature (3 METs). ROC curve analysis indicated that discrimination of sedentary activity was excellent for all placements although the ankle performed better than other locations. This pattern was replicated for moderate physical activity (MPA) where the ankle performed better than other locations. Data were reanalyzed removing cycling from the data set. When this analysis was undertaken discrimination of sedentary activity remained excellent for all locations. For MPA discrimination of activity was considered good for waist and ankle placement and fair for placement on either wrist. The current study is the first to quantify energy expenditure in object control fundamental movement skills via indirect calorimetry in children aged 8–11 years whilst also calibrating GENEActiv accelerometers worn at four body locations. Results suggest throwing and catching is categorized as light intensity and instep kicking a football moderate intensity, resulting in energy expenditure equivalent to slow or medium paced walking or cycling and running, respectively. Ankle worn accelerometry appears to provide the most suitable wear location to quantify MPA including ambulatory activity, object control skills and cycling, in children aged 8–11 years.N/

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

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