47 research outputs found
Compressed Stabilized Earthen Blocks and Their Use in Low-Cost Social Housing
No full textEarthen techniques have been historically used in construction of housing in Africa, Asia and Latin America. In the past two decades the interest in earthen material has grown considerably, leading to the development of sustainable materials such as compressed earth blocks (CEB), compressed stabilized earth blocks (CSEB) and interlocking stabilized soil blocks (ISSB). Scientific publications from various countries and context have examined the physical aspects of these earthen building materials, but so far, the results are not well connected to housing practices for and by low-income households with their self-organizing skills. This research sought to close this gap by documenting the housing projects where earth blocks are applied in participatory social housing. The study provides an overview of relevant practical examples from the three world regions (Africa, Asia and Latin America), with their cultural and climatic differences, and an analysis of similarities and possibilities. Based on the lessons learned from these examples, recommendations are made on further research on sustainable building materials within social housing practices, which can benefit the scientific community. We propose to set up a worldwide database of housing projects where earthen techniques have been applied responsibly. We conclude and recommend that more high-quality pilot projects with CSEB and ISSB are needed to get a broader picture on the potential of these materials for social housing, and the necessary support for local communities wishing to be involved in these sustainable housing practices
Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome
No full textGenetics; Minimal change disease; Paediatric kidney diseaseGenética; Enfermedad de cambios mínimos; Enfermedad renal pediátricaGenètica; Malaltia de canvis mínims; Malaltia renal pediàtricaPediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. Here, we conduct a multi-population GWAS meta-analysis in 38,463 participants (2440 cases). We then conduct conditional analyses and population specific GWAS. We discover twelve significant associations-eight from the multi-population meta-analysis (four novel), two from the multi-population conditional analysis (one novel), and two additional novel loci from the European meta-analysis. Fine-mapping implicates specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk locus. Non-HLA loci colocalize with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs is lacking but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associates with earlier disease onset. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cell-specific insights into its molecular drivers. Evaluating these associations in additional cohorts will refine our understanding of population specificity, heterogeneity, and clinical and molecular associations.K.I., K.N., and K.T. were supported by the Japan Agency for Medical Research and Development (AMED) under grant number JP17km0405108h0005. K.T. was supported by the Japan Agency for Medical Research and Development (AMED) under grants JP17km0405205h0002 and 18km0405205h0003. K.I., T.H., C.N., and K.N. were supported by the Japan Society for the Promotion of Science (JSPS) under Grant-in-Aid for Scientific Research fostering Joint International Research (B) 18KK0244. K.I., X.J., T.H., C.N., and K.N. were supported by the Japan Society for the Promotion of Science (JSPS) under Grant-in-Aid for Scientific Research fostering Joint International Research (B) 21KK0147. This work is supported by the Department of Defense (PR190746, PR212415) to S.S-C., by the National Center for Advancing Translational Sciences, National Institutes of Health (Grant Number UL1TR001873) to S.S-C., and by the National Institute of Health Grant RC2DK122397, M.Sam, S.S-C., M.R.P., and F.H. A.M. received support from the American Society of Nephrology KidneyCure Ben J. Lipps Research Fellowship. Y.G. received support from the NEPTUNE Career Development Award. P.R. and H.D. were funded by European Research Council grant ERC-2012- ADG_20120314 (grant agreement 322947) and Agence Nationale pour la Recherche “Genetransnephrose” grant ANR-16-CE17-004-01. M.Sam. was supported by NIH grants R01DK119380, 2U54DK083912, and a gift from The Pura Vida Kidney Foundation. The Nephrotic Syndrome Study Network (NEPTUNE) is part of the Rare Diseases Clinical Research Network (RDCRN), which is funded by the National Institutes of Health (NIH) and led by the National Center for Advancing Translational Sciences (NCATS) through its Division of Rare Diseases Research Innovation (DRDRI). NEPTUNE is funded under grant number U54DK083912 as a collaboration between NCATS and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Additional funding and/or programmatic support is provided by the University of Michigan, NephCure Kidney International, and the Halpin Foundation. RDCRN consortia are supported by the RDCRN Data Management and Coordinating Center (DMCC), funded by NCATS and the National Institute of Neurological Disorders and Stroke (NINDS) under U2CTR002818. The authors wish to thank Seong Kyu Han, Ph.D. (Boston Children’s Hospital and Harvard Medical School) for his assistance in creating figures
Gene Expression Analysis Reveals Novel Shared Gene Signatures and Candidate Molecular Mechanisms between Pemphigus and Systemic Lupus Erythematosus in CD4+ T Cells
No full textGene Expression Analysis Reveals Novel Shared Gene Signatures and Candidate Molecular Mechanisms between Pemphigus and Systemic Lupus Erythematosus in CD4+ T Cells
No full textGenetic control of psoriasis is relatively distinct from that of metabolic syndrome and coronary artery disease
No full textGene Expression Analysis Reveals Novel Shared Gene Signatures and Candidate Molecular Mechanisms between Pemphigus and Systemic Lupus Erythematosus in CD4+ T Cells
No full textPemphigus and systemic lupus erythematosus (SLE) are severe potentially life-threatening autoimmune diseases. They are classified as B-cell-mediated autoimmune diseases, both depending on autoreactive CD4+ T lymphocytes to modulate the autoimmune B-cell response. Despite the reported association of pemphigus and SLE, the molecular mechanisms underlying their comorbidity remain unknown. Weighted gene co-expression network analysis (WGCNA) of publicly available microarray datasets of CD4+ T cells was performed, to identify shared gene expression signatures and putative overlapping biological molecular mechanisms between pemphigus and SLE. Using WGCNA, we identified 3,280 genes co-expressed genes and 14 co-expressed gene clusters, from which one was significantly upregulated for both diseases. The pathways associated with this module include type-1 interferon gamma and defense response to viruses. Network-based meta-analysis identified RSAD2 to be the most highly ranked hub gene. By associating the modular genes with genome-wide association studies (GWASs) for pemphigus and SLE, we characterized IRF8 and STAT1 as key regulatory genes. Collectively, in this in silico study, we identify novel candidate genetic markers and pathways in CD4+ T cells that are shared between pemphigus and SLE, which in turn may facilitate the identification of novel therapeutic targets in these diseases
Genetic control of spontaneous arthritis in a four-way advanced intercross line.
No full textIdentifying the genetic basis of complex diseases, such as rheumatoid arthritis, remains a challenge that requires experimental models to reduce the genetic and environmental variability. Numerous loci for arthritis have been identified in induced animal models; however, few spontaneous models have been genetically studied. Therefore, we generated a four-way advanced intercross line (AIL) from four inbred strains, including BXD2/TyJ which spontaneously develops autoimmune arthritis. A genome-wide scan for spontaneous arthritis was performed in a cohort of 366 mice of the fourth generation (G4) of this cross. Five loci contributing to clinical phenotypes were identified in chromosomes 3, 7, 13, 18, and X. Three of the loci found in this study, confirm previously identified loci; whereas two of them are novel loci. Interesting candidate genes for the loci are highlighted. This study provides a genetic overview of spontaneous arthritis in mice and aids to solve the genetic etiology of rheumatoid arthritis and to gain a better understanding of the disease
Phenotypic characteristics of spontaneous arthritis in G4 mice from the four-way autoimmune-prone AIL.
No full text<p>a. Onset measured in weeks. Mean ± standard error of the mean; only disease mice were included in the calculation.</p><p>b. Mean ± standard error of the mean; all mice were included in the calculation.</p
Whole-genome association map for spontaneous arthritis traits.
No full text<p>Phenotypes are (A) susceptibility to disease, and (B) disease severity, measured as maximum score. Each graph represents the strength of association between phenotype and marker, using HAPPY (linear plot) or EMMAX (Manhattan plot), for the whole set of 366 G4 mice tested. Gender and ColVII immunization were used as covariates. The x-axis indicates the SNP's chromosomal position, and the y-axis shows the -log <i>P</i> value of association.</p
