Microarray analysis of peripheral blood lymphocytes from ALS patients and the SAFE detection of the KEGG ALS pathway

<p>Abstract</p> <p>Background</p> <p>Sporadic amyotrophic lateral sclerosis (sALS) is a motor neuron disease with poorly understood etiology. Results of gene expression profiling studies of whole blood from ALS patients have not been validated and are difficult to relate to ALS pathogenesis because gene expression profiles depend on the relative abundance of the different cell types present in whole blood. We conducted microarray analyses using Agilent Human Whole Genome 4 × 44k Arrays on a more homogeneous cell population, namely purified peripheral blood lymphocytes (PBLs), from ALS patients and healthy controls to identify molecular signatures possibly relevant to ALS pathogenesis.</p> <p>Methods</p> <p>Differentially expressed genes were determined by LIMMA (Linear Models for MicroArray) and SAM (Significance Analysis of Microarrays) analyses. The SAFE (Significance Analysis of Function and Expression) procedure was used to identify molecular pathway perturbations. Proteasome inhibition assays were conducted on cultured peripheral blood mononuclear cells (PBMCs) from ALS patients to confirm alteration of the Ubiquitin/Proteasome System (UPS).</p> <p>Results</p> <p>For the first time, using SAFE in a global gene ontology analysis (gene set size 5-100), we show significant perturbation of the KEGG (Kyoto Encyclopedia of Genes and Genomes) ALS pathway of motor neuron degeneration in PBLs from ALS patients. This was the only KEGG disease pathway significantly upregulated among 25, and contributing genes, including <it>SOD1</it>, represented 54% of the encoded proteins or protein complexes of the KEGG ALS pathway. Further SAFE analysis, including gene set sizes >100, showed that only neurodegenerative diseases (4 out of 34 disease pathways) including ALS were significantly upregulated. Changes in <it>UBR2 </it>expression correlated inversely with time since onset of disease and directly with ALSFRS-R, implying that <it>UBR2 </it>was increased early in the course of ALS. Cultured PBMCs from ALS patients accumulated more ubiquitinated proteins than PBMCs from healthy controls in a serum-dependent manner confirming changes in this pathway.</p> <p>Conclusions</p> <p>Our study indicates that PBLs from sALS patients are strong responders to systemic signals or local signals acquired by cell trafficking, representing changes in gene expression similar to those present in brain and spinal cord of sALS patients. PBLs may provide a useful means to study ALS pathogenesis.</p

De la marginalité à l'intégration: les migrants du bidonville Siloe, Cali, Colombie

Abstract not available

On the Past and the Future of the Urban Agriculture Movement: Reflections in Tribute to Jac Smit

First paragraph: In the second half of the 19th century and early 20th century, a number of reformers responded to the horrific conditions of life in the expanding industrial cities of Europe and North America by calling for the transformation of modern cities through a rationalized system for producing built environments that can accommodate growing populations while improving living conditions. As Carolyn Steel has rightly pointed out, food has long shaped our cities (Steel, 2008), and food did hold a central place in the theories of many of the key early thinkers about cities and land.[1] These theories were intimately connected to urban reforms through a range of progressive but paternalistic urban design interventions that consciously sought to weave the green shade and restfulness of the countryside into city parks, street tree plantings, urban allotment gardens, and green river and canal banks. On a darker note, the healthy relaxation touted by garden enthusiasts also served to shift the burden of sustenance away from industrialists and fair-wage policies and onto the shoulders of urbanizing families, especially the women in them (cf. Bellows, 2004). But on balance, garden spaces in densely populated cities and factory settlements offered valuable  nourishment and quiet retreats from the chaos of work and cycles of economic instability and war. [1] Just to cite some key theorists who gave a central place to the food system in their thinking about urban settlements: Henry George, von Thünen, Ebenezer Howard, Patrick Geddes, Frank Lloyd Wright