The Effect of Agglomeration Size on Local Taxes

Standard tax competition models predict a ‘race-to-the-bottom’ of corporate tax rates when firms are mobile. Recent theoretical literature has qualified this view by offering a theoretical explanation why this extreme prediction need not occur: central regions with large clusters of economic activity are able to set positive tax rates without fearing to lose firms to peripheral regions as the firms would forego ‘rents’ from agglomeration economies. In this paper, we study whether local policy makers effectively tax such agglomeration rents. We test this with panel data from Swiss municipalities between 1985 and 2005. We find that large urban areas set indeed higher tax rates than small ones. This is consistent with the theoretical prediction. Within urban areas, however, municipal tax rates are unrelated to the size of economic activity in and around municipalities while they are positively related to the size of the political jurisdiction. We see this result as evidence that the standard tax competition model for asymmetric jurisdictions is at work in the competition of municipalities within an urban area. Both results are robust to controlling for reverse causality by using instrumental variables. Controlling for fixed effects in a 20 year panel is non-informative and neither supports nor contradicts these findings. As a robustness check we introduce an new measure of cluster intensity which considers the varying intensities in agglomeration economies across sectors.agglomeration, local taxation, corporate taxes, tax competition

HTT-lowering reverses Huntington's disease immune dysfunction caused by NFκB pathway dysregulation

The peripheral immune response is altered in Huntington's disease, but the underlying mechanisms are unclear. Using RNA interference to lower huntingtin levels in leucocytes from patients, Träger et al. reverse disease-associated phenotypes including cytokine elevation and transcriptional dysregulation, and argue for a direct effect of mutant huntingtin on NFκΒ signallin

Tax competition: dynamic policy and empirical evidence

This thesis studies tax competition from both a theoretical and an empirical point of view. In chapter 1 we develop a dynamic two-country optimal taxation model to study tax competition. We find that tax competition is costly and that the equilibrium with tax competition differs remarkably from the first-best outcome in a fiscal union, both during transition and in the long run. In chapter 2 we empirically test the relationship between taxation and agglomeration economies. In the presence of agglomeration economies firms are less sensitive to changes in tax rates, and therefore capital tax competition has a smaller effect on investment. We find some evidence that municipalities in large agglomerations set higher tax rates than municipalities in smaller ones.Esta tesis estudia la competencia impositiva tanto desde el punto de vista teórico como empírico. En el capítulo 1, desarrollamos un modelo dinámico de imposición óptima en dos países con el objetivo de estudiar la competencia impositiva. Encontramos que la competencia impositiva es costosa y que el equilibrio con competencia impositiva difiere significativamente del mejor resultado en una unión fiscal, tanto durante la transición como en el largo plazo. En el capítulo 2, analizamos empíricamente la relación entre imposición y economías de aglomeración. En presencia de economías de aglomeración, las empresas son menos sensibles a cambios en los tipos impositivos y, por tanto, la competencia impositiva para atraer capital tiene efectos menores en la inversión. Encontramos evidencia a favor de que los municipios en grandes aglomeraciones establecen tipos impositivos más altos que los que están en pequeñas aglomeraciones

The Effect of Agglomeration Size on Local Taxes

Standard tax competition models predict a ‘race-to-the-bottom’ of corporate tax rates when firms are mobile. Recent theoretical literature shows that central regions with large clusters of economic activity are able to set positive tax rates without fear of losing firms to peripheral regions as the firms would forego ‘rents’ from agglomeration economies. We study whether local policy makers effectively tax such agglomeration rents. We test this with data from Swiss municipalities. We find that municipalities in large urban areas indeed set higher tax rates than those in small ones. Within urban areas, however, municipal tax rates are unrelated to the size of economic activity in and around municipalities while they are positively related to the size of the political jurisdiction. We see this result as evidence that the standard tax competition model for asymmetric jurisdictions is at work in the competition of municipalities within an urban area

Genome-Wide Histone Acetylation Is Altered in a Transgenic Mouse Model of Huntington's Disease

In Huntington's disease (HD; MIM ID # 143100), a fatal neurodegenerative disorder, transcriptional dysregulation is a key pathogenic feature. Histone modifications are altered in multiple cellular and animal models of HD suggesting a potential mechanism for the observed changes in transcriptional levels. In particular, previous work has suggested an important link between decreased histone acetylation, particularly acetylated histone H3 (AcH3; H3K9K14ac), and downregulated gene expression. However, the question remains whether changes in histone modifications correlate with transcriptional abnormalities across the entire transcriptome. Using chromatin immunoprecipitation paired with microarray hybridization (ChIP-chip), we interrogated AcH3-gene interactions genome-wide in striata of 12-week old wild-type (WT) and transgenic (TG) R6/2 mice, an HD mouse model, and correlated these interactions with gene expression levels. At the level of the individual gene, we found decreases in the number of sites occupied by AcH3 in the TG striatum. In addition, the total number of genes bound by AcH3 was decreased. Surprisingly, the loss of AcH3 binding sites occurred within the coding regions of the genes rather than at the promoter region. We also found that the presence of AcH3 at any location within a gene strongly correlated with the presence of its transcript in both WT and TG striatum. In the TG striatum, treatment with histone deacetylase (HDAC) inhibitors increased global AcH3 levels with concomitant increases in transcript levels; however, AcH3 binding at select gene loci increased only slightly. This study demonstrates that histone H3 acetylation at lysine residues 9 and 14 and active gene expression are intimately tied in the rodent brain, and that this fundamental relationship remains unchanged in an HD mouse model despite genome-wide decreases in histone H3 acetylation

HTT-lowering reverses Huntington's disease immune dysfunction caused by NF kappa B pathway dysregulation

Huntington's disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system contributes to Huntington's disease pathogenesis and has been targeted successfully to modulate disease progression, but mechanistic understanding relating this to mutant huntingtin expression in immune cells has been lacking. Here we demonstrate that human Huntington's disease myeloid cells produce excessive inflammatory cytokines as a result of the cell-intrinsic effects of mutant huntingtin expression. A direct effect of mutant huntingtin on the NF kappa B pathway, whereby it interacts with IKK gamma, leads to increased degradation of I kappa B and subsequent nuclear translocation of RelA. Transcriptional alterations in intracellular immune signalling pathways are also observed. Using a novel method of small interfering RNA delivery to lower huntingtin expression, we show reversal of disease-associated alterations in cellular function-the first time this has been demonstrated in primary human cells. Glucan-encapsulated small interfering RNA particles were used to lower huntingtin levels in human Huntington's disease monocytes/macrophages, resulting in a reversal of huntingtin-induced elevated cytokine production and transcriptional changes. These findings improve our understanding of the role of innate immunity in neurodegeneration, introduce glucan-encapsulated small interfering RNA particles as tool for studying cellular pathogenesis ex vivo in human cells and raise the prospect of immune cell-directed HTT-lowering as a therapeutic in Huntington's disease

HTT-lowering reverses Huntington\u27s disease immune dysfunction caused by NFkappaB pathway dysregulation

Huntington\u27s disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system contributes to Huntington\u27s disease pathogenesis and has been targeted successfully to modulate disease progression, but mechanistic understanding relating this to mutant huntingtin expression in immune cells has been lacking. Here we demonstrate that human Huntington\u27s disease myeloid cells produce excessive inflammatory cytokines as a result of the cell-intrinsic effects of mutant huntingtin expression. A direct effect of mutant huntingtin on the NFkappaB pathway, whereby it interacts with IKKgamma, leads to increased degradation of IkappaB and subsequent nuclear translocation of RelA. Transcriptional alterations in intracellular immune signalling pathways are also observed. Using a novel method of small interfering RNA delivery to lower huntingtin expression, we show reversal of disease-associated alterations in cellular function-the first time this has been demonstrated in primary human cells. Glucan-encapsulated small interfering RNA particles were used to lower huntingtin levels in human Huntington\u27s disease monocytes/macrophages, resulting in a reversal of huntingtin-induced elevated cytokine production and transcriptional changes. These findings improve our understanding of the role of innate immunity in neurodegeneration, introduce glucan-encapsulated small interfering RNA particles as tool for studying cellular pathogenesis ex vivo in human cells and raise the prospect of immune cell-directed HTT-lowering as a therapeutic in Huntington\u27s disease

AcH3 localization is found downstream of transcriptional start sites within the gene.

<p>(A) Schematic indicating the location of probes as defined by Agilent annotation. Promoter = upstream of transcriptional start site; Inside = within coding region of gene; Downstream = downstream of coding region; Divergent promoter = located within the upstream region of two genes transcribed in opposite directions; Unknown = unannotated. (B) Locations of probes within the gene expressed as percent bound of total probe type within the microarray. (C) Numbers of genes bound as expressed by AcH3-bound locationsWhite bars, WT; black bars, TG.</p

Histone H3 acetylation and gene expression in TG striata.

<p>Histone H3 acetylation and gene expression in TG striata.</p