Synapse Dysfunctions in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system (CNS) affecting nearly three million humans worldwide. In MS, cells of an auto-reactive immune system invade the brain and cause neuroinflammation. Neuroinflammation triggers a complex, multi-faceted harmful process not only in the white matter but also in the grey matter of the brain. In the grey matter, neuroinflammation causes synapse dysfunctions. Synapse dysfunctions in MS occur early and independent from white matter demyelination and are likely correlates of cognitive and mental symptoms in MS. Disturbed synapse/glia interactions and elevated neuroinflammatory signals play a central role. Glutamatergic excitotoxic synapse damage emerges as a major mechanism. We review synapse/glia communication under normal conditions and summarize how this communication becomes malfunctional during neuroinflammation in MS. We discuss mechanisms of how disturbed glia/synapse communication can lead to synapse dysfunctions, signaling dysbalance, and neurodegeneration in MS

Modelling the Effect of Process Parameters on the Wet Extrusion and Spheronisation of High-Loaded Nicotinamide Pellets Using a Quality by Design Approach

Open access articleThe aim of the present study was to develop an alternative process to spray granulation in order to prepare high loaded spherical nicotinamide (NAM) pellets by wet extrusion and spheronisation. Therefore, a quality by design approach was implemented to model the effect of the process parameters of the extrusion-spheronisation process on the roundness, roughness and useable yield of the obtained pellets. The obtained results were compared to spray granulated NAM particles regarding their characteristics and their release profile in vitro after the application of an ileocolon targeted shellac coating. The wet extrusion-spheronisation process was able to form highly loaded NAM pellets (80%) with a spherical shape and a high useable yield of about 90%. However, the water content range was rather narrow between 24.7% and 21.3%. The design of experiments (DoE), showed that the spheronisation conditions speed, time and load had a greater impact on the quality attributes of the pellets than the extrusion conditions screw design, screw speed and solid feed rate (hopper speed). The best results were obtained using a low load (15 g) combined with a high rotation speed (900 m/min) and a low time (3–3.5 min). In comparison to spray granulated NAM pellets, the extruded NAM pellets resulted in a higher roughness and a higher useable yield (63% vs. 92%). Finally, the coating and dissolution test showed that the extruded and spheronised pellets are also suitable for a protective coating with an ileocolonic release profile. Due to its lower specific surface area, the required shellac concentration could be reduced while maintaining the release profil

Gender, Regional and Social Differences at the Transition from Lower to Upper Secondary Education: An Analysis in the Context of FAMSIM+ Family Microsimulation Model for Austria

Die Entwicklung von Simulationsmodellen nimmt in der sozioökonomischen Abteilung einen zentralen Forschungsschwerpunkt ein, dies einerseits in der Form von Hochrechnungsmodellen zur Berechnung von Kosten und Verteilungswirkungen familienpolitischer Maßnahmen (Förderungen) - hierzu wurden insbesondere Modelle und Softwarepakete für die Bundesländer Niederösterreich und Wien entwickelt - und andererseits in der Form des dynamischen Mikrosimulationsmodells FAMSIM. Dynamische Mikrosimulation erlaubt es, die Individuen einer Bevölkerung über ihren ganzen Lebenslauf im Computer zu simulieren, was insbesondere zur Erforschung demographischer Prozesse dient bzw. die Erforschung der Auswirkungen dieser Prozesse auf andere Systeme - wie etwa Pensionssysteme. Statische "cell-based" Modelle zur Berechnung der Kosten von Familienförderungen in der Form frei parametrisierbarer Simulationsmodelle auf Basis von realen Antragsdaten zu Förderungen: Anwendungen in Wien und Niederösterreich. Modellierung, Programmierung und ökonometrische Schätzung des dynamischen FAMSIM Modells für 5 Europäische Länder; Internationale Vergleichsstudien zu typischen "Risikomustern" betreffend dem Beginn und Ende von Partnerschaften, Erwerbstätigkeit, Ausbildungen sowie Schwangerschaften/Geburten. Zusammenführung der statischen und dynamischen Modelle zu einem dynamischen Familien - Mikrosimulationsmodell FAMSIM+ zur Erforschung demographischer Prozesse (wie sich verändernder Familienstrukturen) sowie der Evaluierung der Kosten und Wirkung familienrelevanter Maßnahmen im Quer- und Längsschnitt. Dieser Ansatz erlaubt zum Beispiel die Erforschung der Auswirkungen von Erwerbsunterbrechungen zur Kinderbetreuung auf die gesamte weitere Erwerbskarriere einschließlich Pensionsansprüche. Nationale und internationale Kooperationen für verschiedene Anwendungsgebiete, wie derzeit für Bildungsprognosen (Kooperation mit dem Institut für Bildungsforschung der Wirtschaft) sowie im Bereich Altenpflege (Netzwerkpartner im International Network for the Research on Elderly Care INREC).The central aim of this paper is to reveal differences in educational placement at the transition from lower to upper secondary education, such as gender differences, differences caused by the education of parents, the place of living (rural vs. urban areas) as well as by the type of school attended in lower secondary education ('Hauptschule' vs. 'AHS'). Beside a descriptive analysis, this paper develops a model of the second educational choice in the form of a logistic regression model with multiple outcome that can be directly employed in the FAMSIM+ microsimulation project, currently developed at the Austrian Institute for Family Studies

University Education: An Analysis in the Context of the FAMSIM+ Microsimulation Model for Austria

Das ÖIF betreibt zum Thema Bildungsentscheidung aktuelle Forschungen, u.a. werden Mikroanalysen als Basis eines Simulationsmodells verwendet, welches die zukünftige Zusammensetzung der österreichischen Bevölkerung nach Bildungsschicht untersucht. Diese Modelle schließen zusätzlich das unterschiedliche Fertilitätsverhalten (Anzahl, Zeitpunkt von Geburten) und Partnerschaftsverhalten (etwa Bildungsunterschiede in Partnerschaften) unterschiedlicher Bildungsgruppen ein. Datenbasis für diese Mikrosimulationsmodelle ist das Sonderprogramm des Mikrozensus 2/1996.This working paper on university education analyzes the influencing factors on university enrollment rates, graduation vs. dropout rates as well as study durations in Austria. The analysis is based on the special program of the 1996 micro census that includes detailed educational histories. On the macro level, a considerable increase of enrollment rates can be observed that more than doubled in the second half of the last century. Female enrollment rates that were only one third of the male rates for the 1935-39 birth cohort, have already drawn level with the male rates. Changes on the macro level are the outcome of decisions taken by the individual agents on the micro level. Moving from the macro to a micro analysis of university enrollments and graduations, a very stable relation between parents’ educational attainments and the university graduation rates of their offspring can be found, besides the diminishing gender differences in educational behavior. For given educational levels of the parents, enrollment rates almost remained constant or even slightly decreased over time for the males, while female rates moderately increased and eventually met the male rates in the last decades. Given the marked differences in enrollment rates according to parents’ education - for the last birth cohort 1965-69 the rates range from around 4% to nearly 60% for the lowest and the highest (of the five) educational groups - a considerable part of the changes on the macro level can therefore be attributed to the changing educational composition of the parents’ generation. This result is consistent with the findings regarding prior educational transitions as studied in two previous papers. Being written in the framework of the FAMSIM+ microsimulation model currently under development at the Austrian Institute for Family Studies, various regression models regarding university education will be developed in this paper, besides providing a descriptive analysis. These models will serve as basis of the behavioral modules of the FAMSIM+ model that consists of three sub modules regarding university enrollments and graduations: First, it is determined whether a person enrolls at university. Second, it is decided if an enrolled person will graduate from university or drop out. Third, the individual enrollment duration is determined by means of a survival analysis

Minireview and case report: Duplication of the portal vein and combinations

This is a minireview and case report on a concurrent duplication of the portal vein and a duplication of the left renal vein. The portal vein system supplies about seventy five percent of the blood for the liver and is involved in the manifestation of several liver diseases such as portal hypertension and portosystemic shunts. The vitelline veins and their anastomoses are involved in this anatomical variation during development. Similar to that also variations or malformations of the renal veins resulted from early primitive structures and their obliteration or non obliteration, respectively. Two rather rare anomalies of two venous systems might have been a coincidence or a common cause

Development and characterization of solid lipid nanoparticles (SLNs) made of cocoa butter: a factorial design study

The present study is motivated by the development of solid lipid nanoparticles (SLNs) for food applications. A focus of the study is the use of a factorial design to optimize the preparation variables. SLNs were prepared by hot homogenization at 60 °C. Cocoa butter was used to form the lipid core and the surfactant blend used to emulsify and stabilize the system was a mixture of sodium stearoyl-2-lactylate (SSL) and mono- and diglycerides of fatty acids (MDG). The particle characteristics and stability of obtained SLN-suspensions were investigated. Moreover, the effect of various cooling conditions on the properties of SLNs and the storage stability during a period of three months were examined. Results proved that cocoa butter is suitable to prepare SLNs with a food-grade quality where the optimized preparation variables resulted in a particle size of 112.7 nm

The multiple faces of collective responses to organizational change: Taking stock and moving forward

This special issue focuses on collective responses to organizational change with a goal of enhancing knowledge on the emergence of these higher-level responses to change. While researchers acknowledge that organizational change inherently involves processes at multiple levels (individual, team, organization), scholars have only recently begun to increasingly promote models of collective responses to change. Spotlighting this gap, in this paper, we explore the dynamic character of collective responses to change, note the multiple ways in which these may develop,and identify theoretical frames rooted in psychology and sociology. This approach contributes to the growing field of responses beyond the individual. Through the papers in the special issue, we offer a framework based on Bourdieu's theory of practice as a platform for bringing together perspectives on agency and structuralism on how responses to change are shaped in the collective. With this framing, we provide direction for future research on successful organizational change through the interrelations between individuals and collectives undergoing change

Unlocking CO Depletion in Protoplanetary Disks II. Primordial C/H Predictions Inside the CO Snowline

CO is thought to be the main reservoir of volatile carbon in protoplanetary disks, and thus the primary initial source of carbon in the atmospheres of forming giant planets. However, recent observations of protoplanetary disks point towards low volatile carbon abundances in many systems, including at radii interior to the CO snowline. One potential explanation is that gas phase carbon is chemically reprocessed into less volatile species, which are frozen on dust grain surfaces as ice. This mechanism has the potential to change the primordial C/H ratio in the gas. However, current observations primarily probe the upper layers of the disk. It is not clear if the low volatile carbon abundances extend to the midplane, where planets form. We have run a grid of 198 chemical models, exploring how the chemical reprocessing of CO depends on disk mass, dust grain size distribution, temperature, cosmic ray and X-ray ionization rate, and initial water abundance. Building on our previous work focusing on the warm molecular layer, here we analyze the results for our grid of models in the disk midplane at 12 au. We find that either an ISM level cosmic ray ionization rate or the presence of UV photons due to a low dust surface density are needed to chemically reduce the midplane CO gas abundance by at least an order of magnitude within 1 Myr. In the majority of our models CO does not undergo substantial reprocessing by in situ chemistry and there is little change in the gas phase C/H and C/O ratios over the lifetime of the typical disk. However, in the small sub-set of disks where the disk midplane is subject to a source of ionization or photolysis, the gas phase C/O ratio increases by up to nearly 9 orders of magnitude due to conversion of CO into volatile hydrocarbons.Comment: Accepted for publication in ApJ, 15 pages, 10 figures, 3 table

Early Changes in Exo- and Endocytosis in the EAE Mouse Model of Multiple Sclerosis Correlate with Decreased Synaptic Ribbon Size and Reduced Ribbon-Associated Vesicle Pools in Rod Photoreceptor Synapses

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system that finally leads to demyelination. Demyelinating optic neuritis is a frequent symptom in MS. Recent studies also revealed synapse dysfunctions in MS patients and MS mouse models. We previously reported alterations of photoreceptor ribbon synapses in the experimental auto-immune encephalomyelitis (EAE) mouse model of MS. In the present study, we found that the previously observed decreased imunosignals of photoreceptor ribbons in early EAE resulted from a decrease in synaptic ribbon size, whereas the number/density of ribbons in photoreceptor synapses remained unchanged. Smaller photoreceptor ribbons are associated with fewer docked and ribbon-associated vesicles. At a functional level, depolarization-evoked exocytosis as monitored by optical recording was diminished even as early as on day 7 after EAE induction. Moreover compensatory, post-depolarization endocytosis was decreased. Decreased post-depolarization endocytosis in early EAE correlated with diminished synaptic enrichment of dynamin3. In contrast, basal endocytosis in photoreceptor synapses of resting non-depolarized retinal slices was increased in early EAE. Increased basal endocytosis correlated with increased de-phosphorylation of dynamin1. Thus, multiple endocytic pathways in photoreceptor synapse are differentially affected in early EAE and likely contribute to the observed synapse pathology in early EAE