75 research outputs found

    Amyotrophic lateral sclerosis-associated mutant VAPBP56S perturbs calcium homeostasis to disrupt axonal transport of mitochondria

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    A proline-to-serine substitution at position 56 in the gene encoding vesicle-associated membrane protein-associated protein B (VAPB; VAPBP56S) causes some dominantly inherited familial forms of motor neuron disease, including amyotrophic lateral sclerosis (ALS) type-8. Here, we show that expression of ALS mutant VAPBP56S but not wild-type VAPB in neurons selectively disrupts anterograde axonal transport of mitochondria. VAPBP56S-induced disruption of mitochondrial transport involved reductions in the frequency, velocity and persistence of anterograde mitochondrial movement. Anterograde axonal transport of mitochondria is mediated by the microtubule-based molecular motor kinesin-1. Attachment of kinesin-1 to mitochondria involves the outer mitochondrial membrane protein mitochondrial Rho GTPase-1 (Miro1) which acts as a sensor for cytosolic calcium levels ([Ca2+]c); elevated [Ca2+]c disrupts mitochondrial transport via an effect on Miro1. To gain insight into the mechanisms underlying the VAPBP56S effect on mitochondrial transport, we monitored [Ca2+]c levels in VAPBP56S-expressing neurons. Expression of VAPBP56S but not VAPB increased resting [Ca2+]c and this was associated with a reduction in the amounts of tubulin but not kinesin-1 that were associated with Miro1. Moreover, expression of a Ca2+ insensitive mutant of Miro1 rescued defective mitochondrial axonal transport and restored the amounts of tubulin associated with the Miro1/kinesin-1 complex to normal in VAPBP56S-expressing cells. Our results suggest that ALS mutant VAPBP56S perturbs anterograde mitochondrial axonal transport by disrupting Ca2+ homeostasis and effecting the Miro1/kinesin-1 interaction with tubulin

    Pore wall corrugation effect on the dynamics of adsorbed H 2 studied by in situ quasi elastic neutron scattering Observation of two timescaled diffusion

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    The self diffusion mechanisms for adsorbed H2 in different porous structures are investigated with in situ quasi elastic neutron scattering method at a temperature range from 50 K to 100 K and at various H2 loadings. The porous structures of the carbon materials have been characterized by sorption analysis with four different gases and the results are correlated with previous in depth analysis with small angle neutron scattering method. Thus, an investigation discussing the effect of pore shape and size on the nature of adsorbed H2 self diffusion is performed. It is shown that H2 adsorbed in nanometer scale pores is self diffusing in two distinguishable timescales. The effect of the pore, pore wall shape and corrugation on the fraction of confined and more mobile H2 is determined and analyzed. The increased corrugation of the pore walls is shown to have a stronger confining effect on the H2 motions. The difference of self diffusional properties of the two H2 components are shown to be smaller when adsorbed in smoother walled pores. This is attributed to the pore wall corrugation effect on the homogeneity of formed adsorbed layer

    Does urban sprawl increase the costs of providing local public services? Evidence from Spanish municipalities

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    This paper examines the impact of urban sprawl, a phenomenon of particular interest in Spain, which is currently experiencing this process of rapid, low-density urban expansion. Many adverse consequences are attributed to urban sprawl (e.g., traffic congestion, air pollution and social segregation), though here we are concerned primarily with the rising costs of providing local public services. Our initial aim is to develop an accurate measure of urban sprawl so that we might empirically test its impact on municipal budgets. Then, we undertake an empirical analysis using a cross-sectional data set of 2,500 Spanish municipalities for the year 2003 and a piecewise linear function to account for the potentially nonlinear relationship between sprawl and local costs. The estimations derived from the expenditure equations for both aggregate and six disaggregated spending categories indicate that low-density development patterns lead to greater provision costs of local public services

    Yardstick Competition in German Municipalities

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    Does increasing transparency improve fiscal policy behavior of local governments? One way this could take place is via Yardstick Competition between incumbents of neighboring municipalities. This paper contributes to the literature by introducing a simple model which employs probabilistic voting to show the effect of Yardstick Competition on the amount of political rents diverted from the tax revenue. Since additional rents lower the probability of being reelected, the incumbent will reduce equilibrium rents if voters use information on fiscal performance in similar municipalities to evaluate the incumbent's quality. I test this hypothesis on a panel dataset of municipal budget and electoral data in the german state of Northrine-Westphalia. I show evidence for Yardstick Competition in the local business and property tax rates.Kann zunehmende Transparenz im kommunalen Budgetprozess die fiskalpolitische Disziplin der politischen Entscheidungsträger verbessern? In dieser Arbeit wird ein positiver Modellrahmen entwickelt, anhand dessen die Wirkungsweise von steigen - der Transparenz auf das Entscheidungsverhalten von Kommunalpolitikern durch den Yardstick Competition Effekt dargestellt werden kann. Politiker reduzieren die Veruntreuung finanzieller Mittel, wenn ihr Verhalten von den Wählern relativ zur Leistung von Politikern in benachbarten Kommunen bewertet wird. Unter Anwendung von Methoden der räumlichen Ökonometrie auf kommunale Haushalts- und Wahldaten der Jahre 1989 bis 2004 wird gezeigt, dass die räumliche Korrelation in den Gewerbe- und Grundsteuerhebesätzen in Nordrhein-Westfalen auf die Existenz von Yardstick Competition zurückzuführen ist

    Does Corruption Erode Trust in Government? Evidence from a Recent Surge of Local Scandals in Spain

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    Tax Mimicking in the Short- and the Long-Run: Evidence from German Reunification

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    This paper uses the quasi-experiment of Germany's reunification to identify local tax mimicking by municipalities in Eastern-Germany. After reunification, East-German municipalities were allowed to independently set, for the first time in decades, local business and property tax rates. I explore whether the tax rates chosen by East-German border municipalities were influenced by the tax rates of adjacent West-German municipalities. To obtain causal estimates, I rely on instrumental variables regressions within the spatial lag framework, using West-German border municipalities' tax rates in 1989 as instruments for their post-reunification tax rates. The results suggest that East-German municipalities mimicked business tax rates immediately after reunification, but not in later years. I find no evidence of mimicking for property taxes. These results indicate that mimicking is not an important determinant of local tax policy

    Do Land Use Policies Follow Road Construction?

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    We study whether local land use policies are modified in response to enhanced demand for building generated by a new highway, and examine the extent to which this effect of land use regulations affects building activity. We focus on the case of Spain during the last housing boom (1995-2007). We assembled a new database with information about new highway segments and the modification of the land zoning status in nearby municipalities. The empirical strategy compares the variation in the amount of developable land before-after the construction of the highway in treated municipalities and in control municipalities with similar pre-treatment traits. Our results show that, following the construction of a highway, municipalities converted a huge amount of land from rural to urban uses. We also show that new highways have an impact on building activity
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