Aspartame and Its Metabolites Cause Oxidative Stress and Mitochondrial and Lipid Alterations in SH-SY5Y Cells

Due to a worldwide increase in obesity and metabolic disorders such as type 2 diabetes, synthetic sweeteners such as aspartame are frequently used to substitute sugar in the diet. Possible uncertainties regarding aspartame’s ability to induce oxidative stress, amongst others, has led to the recommendation of a daily maximum dose of 40 to 50 mg per kg. To date, little is known about the effects of this non-nutritive sweetener on cellular lipid homeostasis, which, besides elevated oxidative stress, plays an important role in the pathogenesis of various diseases, including neurodegenerative diseases such as Alzheimer’s disease. In the present study, treatment of the human neuroblastoma cell line SH-SY5Y with aspartame (271.7 µM) or its three metabolites (aspartic acid, phenylalanine, and methanol (271.7 µM)), generated after digestion of aspartame in the human intestinal tract, resulted in significantly elevated oxidative stress associated with mitochondrial damage, which was illustrated with reduced cardiolipin levels, increased gene expression of SOD1/2, PINK1, and FIS1, and an increase in APF fluorescence. In addition, treatment of SH-SY5Y cells with aspartame or aspartame metabolites led to a significant increase in triacylglycerides and phospholipids, especially phosphatidylcholines and phosphatidylethanolamines, accompanied by an accumulation of lipid droplets inside neuronal cells. Due to these lipid-mediating properties, the use of aspartame as a sugar substitute should be reconsidered and the effects of aspartame on the brain metabolism should be addressed in vivo

Characterization of Ku702–NLS as Bipartite Nuclear Localization Sequence for Non-Viral Gene Delivery

Several barriers have to be overcome in order to achieve gene expression in target cells, e.g. cellular uptake, endosomal release and translocation to the nucleus. Nuclear localization sequences (NLS) enhance gene delivery by increasing the uptake of plasmid DNA (pDNA) to the nucleus. So far, only monopartite NLS were analysed for non-viral gene delivery. In this study, we examined the characteristics of a novel bipartite NLS like construct, namely NLS Ku70. We synthesized a dimeric structure of a modified NLS from the Ku70 protein (Ku702-NLS), a nuclear transport active mutant of Ku702-NLS (s1Ku702-NLS) and a nuclear transport deficient mutant of Ku702-NLS (s2Ku702). We examined the transfection efficiency of binary Ku702-NLS/DNA and ternary Ku702-NLS/PEI/DNA gene vector complexes in vitro by using standard transfection protocols as well as the magnetofection method. The application of Ku702-NLS and s1Ku702-NLS increased gene transfer efficiency in vitro and in vivo. This study shows for the first time that the use of bipartite NLS compounds alone or in combination with cationic polymers is a promising strategy to enhance the efficiency of non-viral gene transfer

The Impact of Performance Payments on Job Satisfaction - Studied Over Time

By establishing an ordered probit regression model and using data from the British Household Panel Survey, I investigate whether the increasing amount of workplaces related to individual performance payments can be attributed to a positive trend in the impact of performance payments on overall job satisfaction over time from 2001 until 2009. The Agency Theory predicts that implementing performance-related payments should lead to higher risk exposure and an increased effort, i.e. a higher productivity. In return, workers receive a higher wage. My findings cannot confirm a trend, but can confirm the previous literature by finding an insignificant impact of performance payments on job satisfaction, while the Agency Theory would predict a negative relationship as the wage is held constant. My research also provides information about other determinants of overall job satisfaction. According to the data, the most important factor is the worker`s age. Job satisfaction decreases until the mid-forties and then increases, confirming the presence of a midlife crisis. Also important is whether one has a job in the private sector or not. Working for a private firm decreases overall job satisfaction, maybe because of a higher risk exposure of the employees and/or less beneficial business objectives in comparison to public firms or charity organizations. I further find support for the common assumption that women and married couples are more satisfied with work

Essays On International Finance And Prudential Regulation

Financial markets have been central to academic and policy debates for decades and are crucial to the functioning of economies. However they occasionally lead to financial crises, which have been associated with several and severe downturns in economic activity. Particularly since the 2008 Financial Crisis, a lively literature on appropriate financial regulation emerged. At the forefront of regulatory interventions are macroprudential policies. Macroprudential policies are implemented ex-ante and are supposed to reduce the likelihood and costs of a potential future crisis. Common macroprudential policies resort to countercyclical equity buffers or leverage and liquidity constraints. More recently, a new literature emerged that justifies capital controls from a macroprudential perspective. All of these policies are appealing, because they are incentive compatible and do not require a large fiscal or monetary stimulus. This dissertation evaluates macroprudential policies in an international context both from a theoretical and applied perspective. The international context is important since financial markets are global, yet little is known about the effects of financial interlinkages on financial regulation. A specific focus of this dissertation is on capital controls, which received renewed interest in the policy debate to limit external overborrowing. In my first chapter I study the strategic interactions between national regulators in a model of international prudential liquidity regulation. The model justifies coordinated liquidity regulation due to an international fire-sale externality. However, I theoretically and empirically argue that domestically oriented regulators from countries with a smaller banking sector do not internalize the global benefits of regulation and therefore do not adhere to international standards. In terms of policy recommendations, the model justifies capital controls if countries do not cooperate. Though capital controls improve the welfare of regulating economies, they also align the interest of free-riding countries with international regulation.The second chapter (joint work with Florian Loipersberger) empirically analyzes financial spillovers from advanced economies towards emerging markets. The comovement of financial markets has raised concerns about the ability of emerging market economies to insulate their economy from international financial shocks. We empirically show that capital controls are as potent as floating exchange rates in dampening the response of international financial shocks on domestic financial variables and the real economy. We relate this finding to muted boom-bust cycles in short-term non-resident capital flows. However, the benefits of floats or capital controls are reaped in isolation, i.e. either tool is enough. We argue that these patterns can be explained by nominal frictions in labor markets and provide empirical support for this claim. In the third chapter, I ask a very simple question: How should countries balance macroprudential capital controls and pure domestic or international prudential policies. I introduce a domestic financial market into an otherwise standard small open economy model with an occasionally binding international borrowing constraint. The key result is that capital controls or international macroprudential policies should be accompanied by purely domestic macroprudential instruments even when domestic markets are frictionless. Intuitively, domestic regulation is welfare enhancing because it shifts resources towards agents who are not able to borrow internationally and as a consequence have a higher propensity to consume. I provide a simple formula that links the degree of domestic regulation to the level of international regulation, the cost of regulation, the investment profitability and the underlying inefficiency in the international financial market

The Impact of Group Membership on Collaborative Learning with Wikis

The social web stimulates learning through collaboration. However, information in the social web is often associated with information about its author. Based on previous evidence that ingroup information is preferred to outgroup information, the current research investigates whether group memberships of wiki authors affect learning. In an experimental study, we manipulated the group memberships (ingroup vs. outgroup) of wiki authors by using nicknames. The designated group memberships (being fans of a soccer team or not) were completely irrelevant for the domain of the wiki (the medical disorder fibromyalgia). Nevertheless, wiki information from the ingroup led to more integration of information into prior knowledge as well as more increase of factual knowledge than information from the outgroup. The results demonstrate that individuals apply social selection strategies when considering information from wikis, which may foster, but also hinder, learning and collaboration. Practical implications for collaborative learning in the social web are discussed

Analysing luciferase expression in lung homogenisates after nasal instillation of gene transfer agents.

<p>1, Ku70₂-NLS/PEI/DNA; 2, s1Ku70₂-NLS/PEI/DNA; 3, s2Ku70₂/PEI/DNA; 4, PEI/DNA. Gene vector complexes were formulated as follows: 30 µg DNA; NLS: ± ratio = 5; PEI: N/P ratio = 10. Luciferase activity was measured in lung homogenisates 24 h after application of gene vectors. Values between Ku70₂-NLS/PEI and PEI significantly different (<i>p</i>≤0.043; n = 4). Statistical analysis was performed using the Mann-Whithney-U test.</p