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The pathogenesis of Huntington's disease (HD) remains elusive. The identification of increasingly early pathophysiological abnormalities in HD suggests the possibility that impairments of striatal medium spiny neuron (MSN) specification and maturation may underlie the etiology of HD. In fact, we demonstrate that HD knock-in (Hdh-Q111) mice exhibited delayed acquisition of early striatal cytoarchitecture with aberrant expression of progressive markers of MSN neurogenesis (Islet1, DARPP-32, mGluR1, and NeuN). Hdh-Q111 striatal progenitors also displayed delayed cell cycle exit between E13.5-15.5 (BrdU birth-dating) and an enhanced fraction of abnormal cycling cells in association with expansion of the pool of intermediate progenitors and over expression of the core pluripotency (PP) factor, Sox2. Clonal analysis further revealed that Hdh-Q111 neural stem cells (NSCs) displayed: impaired lineage restriction, reduced proliferative potential, enhanced late-stage self-renewal, and deregulated MSN subtype specification. Further, our analysis revealed that in addition to Sox2, the core PP factor, Nanog is expressed within the striatal generative and mantle regions, and in Hdh-Q111 embryos the fraction of Nanog-expressing MSN precursors was substantially increased. Moreover, compared to Hdh-Q18 embryos, the Hdh-Q111 striatal anlagen exhibited significantly higher levels of the essential PP cofactor, Stat3. These findings suggest that Sox2 and Nanog may play roles during a selective window of embryonic brain maturation, and alterations of these factors may, in part, be responsible for mediating the aberrant program of Hdh-Q111 striatal MSN specification and maturation. We propose that these HD-associated developmental abnormalities might compromise neuronal homeostasis and subsequently render MSNs more vulnerable to late life stressors. development | huntingtin | medium spiny neurons | neurodegeneration doi/10.1073/pnas.0912171106

Notch has been linked to [beta]-catenin-dependent tumorigenesis; however, the mechanisms leading to Notch activation and the contribution of the Notch pathway to colorectal cancer is not yet understood. By microarray analysis, we have identified a group of genes downstream of Wnt/[beta]-catenin (down-regulated when blocking Wnt/beta]-catenin) that are directly regulated by Notch (repressed by [gamma]-secretase inhibitors and up-regulated by active Notch1 in the absence of [beta]-catenin signaling). We demonstrate that Notch is downstream of Wnt in colorectal cancer cells through [beta]-catenin-mediated transcriptional activation of the Notch-ligand Jagged1. Consistently, expression of activated Notch1 partially reverts the effects of blocking Wnt/[beta]-catenin pathway in tumors implanted s.c. in nude mice. Crossing [APC.sup.MinI+] with [Jagged.sup.1+/[DELTA] mice is sufficient to significantly reduce the size of the polyps arising in the APC mutant background indicating that Notch is an essential modulator of tumorigenesis induced by nuclear [beta]-catenin. We show that this mechanism is operating in human tumors from Familial Adenomatous Polyposis patients. We conclude that Notch activation, accomplished by [beta]-catenin-mediated up-regulation of Jagged1, is required for tumorigenesis in the intestine. The Notch-specific genetic signature is sufficient to block differentiation and promote vasculogenesis in tumors whereas proliferation depends on both pathways. beta-catenin | APC | intestine | crosstalk

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1468-2427.2006.00693.x Byline: SARA GONZALEZ (1) Abstract: Abstract In this article I explore how theoretical metaphors about the contemporary rescaling of the capitalist economy are used by local policy actors to justify an entrepreneurial urban policy. I develop a new theoretical concept (scalar narrative), suggest an analytical approach (cultural politics of scales) and give evidence of a particular case (Bilbao). The article is structured in the following way. First, I briefly review the literature on politics of scales and contribute to the debate with an approach that incorporates elements from cultural political economy and interpretative policy analysis. Within this approach I mobilize the concept of 'scalar narrative' that has already been suggested in the literature but not fully explored. I then put this approach into practice with a particular case study, Bilbao, a city in the north of Spain, which has recently gone through extensive urban regeneration, where I describe the appropriation of three scalar narratives by the policymakers. To show this I draw from empirical work done in Bilbao that looks at statutory and strategic planning documents as well as urban marketing literature and interviews with key informants. Author Affiliation: (1)School of Geography, University of Leeds, Woodhouse Lane, UK Article note: Sara Gonzalez (s.gonzalez@leeds.ac.uk), School of Geography, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK.

Angela Cavender Wilson's 2004 essay 'Reclaiming Our Humanity: Decolonization and the Recovery of Indigenous Knowledge' provides a useful starting point for considering the role of decolonization in both the academy [...]

Study is conducted which focuses on institutionalist approaches as developed in the fields of policy analysis and planning, to develop a methodological approach for assessing how the governance capacity for socially innovative action might emerge. The power dynamics of episodes of socially innovative governance arising from within civil society and their potential to transform wider governance processes and cultures are considered.

Study is conducted which introduces the social innovation in the governance of urban communities. It also seeks to widen the debate on the meaning of social innovation both in social science theory and as a tool for empirical research on socioeconomic development and governance at the local level.

The dependence of the neuromagnetic source localization accuracy on the volume conductor model was studied by the analysis of measured magnetic fields generated by tangentially oriented dipoles in a realistically shaped skull phantom. When using a homogeneous sphere model in the localization procedure, the errors were found to increase from about 3 mm to about 9 mm when the distance between the dipoles and the inner surface of the skull increased from 1 cm to 3 cm, whereas when using a true, realistic model in the inverse procedure the localization errors were only about 2-3 mm, independent of dipole depth. To account for the realistic geometry of the inner surface of the skull, the Boundary Element Method, based on a surface discretization in terms of about 300 triangles, proved to be sufficient. In addition to these analyses of experimental data, simulations were carried out to study the localization errors in the case of the spherical approximation for a dipole orientation changing from tangential to radial. For the latter orientation, errors of up to a few centimeters were found.

Restriction analysis of five nuclear genes located in different chromosomes, 5.8S-ITS rDNA region and the mitochondrial COX2 gene was carried out to genetically characterize the wine Saccharomyces cerevisiae and Saccharomyces kudriavzevii hybrids. The results from analysis confirmed the presence of three different genome types among wine hybrids that contain putative chimeric chromosomes that probably generated by a recombination between homeologous chromosomes of different parental origins.

A PCR-restriction fragment length polymorphism (PCR-RFLP) analysis was used characterize and compare the genomic diversity between beer and wine Saccharomyces kudriavzevii x S. cerevisiae hybrid strains. The results confirmed the presence of new kind of Saccharomyces hybrid among brewing strains originally classified as S. cerevisiae and their contribution to the properties of the final product.