Absence of p300 induces cellular phenotypic changes characteristic of epithelial to mesenchyme transition

p300 is a transcriptional cofactor and prototype histone acetyltransferase involved in regulating multiple cellular processes. We generated p300 deficient (p300−) cells from the colon carcinoma cell line HCT116 by gene targeting. Comparison of epithelial and mesenchymal proteins in p300− with parental HCT116 cells showed that a number of genes involved in cell and extracellular matrix interactions, typical of ‘epithelial to mesenchyme transition' were differentially regulated at both the RNA and protein level. p300− cells were found to have aggressive ‘cancer' phenotypes, with loss of cell–cell adhesion, defects in cell–matrix adhesion and increased migration through collagen and matrigel. Although migration was shown to be metalloproteinase mediated, these cells actually showed a downregulation or no change in the level of key metalloproteinases, indicating that changes in cellular adhesion properties can be critical for cellular mobility

Whose Sense of Place? A Political Ecology of Amenity Development

Using a political ecology framework, this chapter examines the ways in which sense of place and amenity migration contribute to alternative residential development, which relies on uneven use of conservation subdivision features in the American West. Using case studies from Central Oregon, this chapter demonstrates how senses of place and developer decision-making are tied to wider political economic changes. It highlights the roles that amenity migrants and developers, two groups that are sometimes identical, play in landscape transformations that simultaneously draw on a particular sense of place and commodify landscapes in new ways

Genome-Wide Analyses of Nkx2-1 Binding to Transcriptional Target Genes Uncover Novel Regulatory Patterns Conserved in Lung Development and Tumors

The homeodomain transcription factor Nkx2-1 is essential for normal lung development and homeostasis. In lung tumors, it is considered a lineage survival oncogene and prognostic factor depending on its expression levels. The target genes directly bound by Nkx2-1, that could be the primary effectors of its functions in the different cellular contexts where it is expressed, are mostly unknown. In embryonic day 11.5 (E11.5) mouse lung, epithelial cells expressing Nkx2-1 are predominantly expanding, and in E19.5 prenatal lungs, Nkx2-1-expressing cells are predominantly differentiating in preparation for birth. To evaluate Nkx2-1 regulated networks in these two cell contexts, we analyzed genome-wide binding of Nkx2-1 to DNA regulatory regions by chromatin immunoprecipitation followed by tiling array analysis, and intersected these data to expression data sets. We further determined expression patterns of Nkx2-1 developmental target genes in human lung tumors and correlated their expression levels to that of endogenous NKX2-1. In these studies we uncovered differential Nkx2-1 regulated networks in early and late lung development, and a direct function of Nkx2-1 in regulation of the cell cycle by controlling the expression of proliferation-related genes. New targets, validated in Nkx2-1 shRNA transduced cell lines, include E2f3, Cyclin B1, Cyclin B2, and c-Met. Expression levels of Nkx2-1 direct target genes identified in mouse development significantly correlate or anti-correlate to the levels of endogenous NKX2-1 in a dosage-dependent manner in multiple human lung tumor expression data sets, supporting alternative roles for Nkx2-1 as a transcriptional activator or repressor, and direct regulator of cell cycle progression in development and tumors

Disaggregate economic base multipliers in small communities

Economic base analysis is frequently used to describe employment profiles and to predict project-related impacts in small communities. Considerable evidence suggests, however, that economic base multipliers should be estimated from survey data and not from shortcut methods. In this paper two competing versions of the economic base model are developed and then these two models are estimated by use of the Arizona community data set. In both cases, marginal multiplier estimates, controlled for transfer payments, are generated for ten individual sectors in five different types of communities. Results from these two disaggregate economic base models are assessed and then compared with results provided earlier by more aggregate models. The better of these two new models closely resembles the popular input - output model.

Initial diagnostics of a regional adjustment model

Adjustment models are used increasingly to analyze population and employment changes inregional economies. However, questions remain about the most appropriate geographic scales and time lags for these models. In this paper we estimate a well-known adjustment model for a recent 25-year period in the USA. Regional population and employment changes (levels and densities) are examined at three scales (states, Bureau of Economic Analysis regions, counties) using various time lags (one to ten years). Two-stage least squares regression estimates, based on Regional Economic Information System data running between 1969 and 1994, are generated and discussed. Analysis is restricted to the core relationships between population and employment; the roles of other exogenous variables, normally included in adjustment models, are not considered. Instead, concern is focused on issues such as stability and directional causality of the interacting population - employment systems. Some brief suggestions regarding future research conclude the paper.

Milk Collection and Distribution Networks in African Sudano-Sahelian Cities

In secondary African Sudano-Sahelian cities, proximity to rural areas still allows milk collection from producers in periurban zones and its distribution to urban consumers. Many actors transport and trade small quantities. Small dairy farms sometimes play a major role as intermediaries. On the other hand, the gap is widening in capitals as the collection and distribution network is not adapting to market needs. Although small dairy farms are dynamic, they only bring partial answers to the need to adapt. The population growth, the urban expansion at the periphery of cities to the detriment of pastures or the increasing distance between production and consumption make obsolete the traditional system of transportation. For milk production, to keep a significant role in the potential urban market, “industrial” collection in production zones should be promoted in spite of the distance as in the case of Tiviski in Mauritania. But industrialization conditions are not easily met. In addition, the distribution of imported powder milk and its derived products respond efficiently to recent transformations in urban markets (multiplication of shops, product diversification, increase of cold chains, attractive prices, good sanitary quality…) making competitiveness harder or even elusive. Public policy should take into account this situation. Supporting local milk collection and distribution is a priority with the reservation that local production development must also be a priority of decision makers