Preferential binding to elk-1 by sle-associated il10 risk allele upregulates il10 expression

Immunoregulatory cytokine interleukin-10 (IL-10) is elevated in sera from patients with systemic lupus erythematosus (SLE) correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s) and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA) (P = 2.7×10−8, OR = 1.30), but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively), and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G) allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1) detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele upregulates IL10 expression and confers increased risk for SLE in European Americans.

Spatial Inequalities and Social Utility: Mobility Efforts and Accessibility in Greater Santiago

Emergent phenomena such as urban sprawl, travel intensification and loss of cohesion in contemporary metropolises, impose stronger constraints on its inhabitants. Among them, travel and location capabilities become a fundamental factor of social integration and a multiplier of income inequalities. The simultaneous analysis of housing-travel efforts and accessibility to urban opportunities in Greater Santiago shows that these dimensions are closely related and exert an important influence on spatial mobility and inequalities among its inhabitants. Furthermore, a theoretical model of displacements, considering income and location, confirms the importance of proximity and non-motorized transport in order to optimize daily mobility strategies of households. Overall, the empirical and theoretical results presented show the need to implement coordinated planning strategies between the housing and transport sectors, addressing not only travel acceleration, but mainly the consistency between accommodation and opportu  ties location. The creation of such planning tools could be a more sustainable alternative than current growth trends in Greater Santiago.

Resources for an Intersectorial Management of Public Policies: Mobility and Access

The objective of this paper is to integrate mobility as across component of the management of specific public actions. The case of study concerns the public health services in Argentina, and mother’s mobility conditions in the suburban of the Buenos Aires Metropolitan Area. In terms of methodology, the paper working on the concept of access trying to identify, measure and evaluate the relationship between mobility conditions and maternal health care. Access is weighted according to the realization of health services, and not according to the arrival at the places where they are offers. The result is innovative empirical evidence, useful as an indicator to make more relevant the role of mobility within the public agenda of transport and others specific sectors, asa basic social right behind the access that requires coordinated actions and cross-sectoral approaches.

Entropic system of daily mobility in a Metropolitan Area of Bogota, Colombia.

The fundamental diseconomy in the large metropolitan areas is the significant and sustained increase in travel time incurred by its inhabitants daily. Since a portion of the energy consumed in the daily mobility does not necessarily translate into individual and collective wealth, entropic systems have a feature which, as discussed for the case of Bogotá, does not have metropolitan institutions with the ability to redirect.

Residential Mobility: a Sociological Concern

The aim of this paper is to present a theoretical-conceptual approach to residential mobility, in general, and residential trajectories, in particular. It seeks to understand how from the unequal distribution and appropriation of social resources —both material and symbolic— different trajectories are developed and how socio-territorial structures constrain, shape and enable interactions between families, their members and the various contexts of action towards meeting their housing needs. From sociological contributions of different traditions, we present a scheme that pays attention to articulating the relationship between structural factors, position in social structure and decisions elating to changes of residence. We conclude that mobility patterns are relational patterns that are defined in dialogue with the opportunities and limitations that are set up around the housing stock and new or vacant land, the land market dynamics and housing, the labor market, the provision of nfrastructure services and social facilities, etc.