Autosomal dominant polycystic kidney disease(ADPKD) is the most common inherited monogenic kidney disease. Characterized by the development and growth of cysts that cause progressive kidney enlargement, it ultimately ...Autosomal dominant polycystic kidney disease(ADPKD) is the most common inherited monogenic kidney disease. Characterized by the development and growth of cysts that cause progressive kidney enlargement, it ultimately leads to end-stage renal disease. Approximately 85% of ADPKD cases are caused by mutations in the PKD1 gene, while mutations in the PKD2 gene account for the remaining 15% of cases. The PKD1 gene encodes for polycystin-1(PC1), a large multi-functional membrane receptor protein able to regulate ion channel complexes, whereas polycystin-2(PC2), encoded by the PKD2 gene, is an integral membrane protein that functions as a calcium-permeable cation channel, located mainly in the endoplasmic reticulum(ER). In the primary cilia of the epithelial cells, PC1 interacts with PC2 to form a polycystin complex that acts as a mechanosensor, regulating signaling pathways involved in the differentiation of kidney tubular epithelial cells. Despite progress in understanding the function of these proteins, the molecular mechanisms associated with the pathogenesis of ADPKD remain unclear. In this review we discuss how an imbalance between functional PC1 and PC2 proteins may disrupt calcium channel activities in the cilium, plasma membrane and ER, thereby altering intracellular calcium signaling and leading to the aberrant cell proliferation and apoptosis associated with the development and growth of renal cysts. Research in this field could lead to the discovery of new molecules able to rebalance intracellular calcium, thereby normalizing cell proliferation and reducing kidney cyst progression.展开更多
Amman,the capital of Jordan,has been subjected to incremental spatial transformation under the pressure of the emerging migration of various refugees since the beginning of the Syrian conflict(2011-present).Only 17%of...Amman,the capital of Jordan,has been subjected to incremental spatial transformation under the pressure of the emerging migration of various refugees since the beginning of the Syrian conflict(2011-present).Only 17%of the Syrian refugee influx to Jordan resides in camps.Amman hosts 28%of non-camp refugees(NCRs)who are living in urban areas and creating multiple forms of urban settlements.Diverse forms of NCR settlements are emerging extensively in Eastern Amman districts.These settlements are contributing to new morphological structures and leading to a gradual spatial change-socially and physically.This research intends to contribute to the increasing amount of available data by improving the understanding of the socio-spatial patterns of Syrian NCR settlements and providing insights,forecasts,and recommendations regarding this pressing issue on the basis of overall trends.Comprehensively contextualized areas in Amman were mapped,and after considering specific siteselection criteria,Jubilee Neighborhood was selected.Jubilee was built by the government in 1985 for low-income Jordanian families.This study aims to unravel one layer of the complex multilayered Amman City.It intends to explore and describe the urban forms of NCR settlements in Jubilee Neighborhood as a case study by interrelating spatial,social,and physical concepts.In addition,this study extensively uses rigorous qualitative and traditional methods.The outcome of this study is a comprehensive and descriptive spatial analysis that can provide socio-spatial interpretations and recommend urban response policies to cope with the future spatial transformation of urban forms.展开更多
基金Supported by University of Ferrara local funds:FAR 2012,2013,2014 and Regione Emilia Romagna grant(Ricerca Regione-Università)2007-2009
文摘Autosomal dominant polycystic kidney disease(ADPKD) is the most common inherited monogenic kidney disease. Characterized by the development and growth of cysts that cause progressive kidney enlargement, it ultimately leads to end-stage renal disease. Approximately 85% of ADPKD cases are caused by mutations in the PKD1 gene, while mutations in the PKD2 gene account for the remaining 15% of cases. The PKD1 gene encodes for polycystin-1(PC1), a large multi-functional membrane receptor protein able to regulate ion channel complexes, whereas polycystin-2(PC2), encoded by the PKD2 gene, is an integral membrane protein that functions as a calcium-permeable cation channel, located mainly in the endoplasmic reticulum(ER). In the primary cilia of the epithelial cells, PC1 interacts with PC2 to form a polycystin complex that acts as a mechanosensor, regulating signaling pathways involved in the differentiation of kidney tubular epithelial cells. Despite progress in understanding the function of these proteins, the molecular mechanisms associated with the pathogenesis of ADPKD remain unclear. In this review we discuss how an imbalance between functional PC1 and PC2 proteins may disrupt calcium channel activities in the cilium, plasma membrane and ER, thereby altering intracellular calcium signaling and leading to the aberrant cell proliferation and apoptosis associated with the development and growth of renal cysts. Research in this field could lead to the discovery of new molecules able to rebalance intracellular calcium, thereby normalizing cell proliferation and reducing kidney cyst progression.
文摘Amman,the capital of Jordan,has been subjected to incremental spatial transformation under the pressure of the emerging migration of various refugees since the beginning of the Syrian conflict(2011-present).Only 17%of the Syrian refugee influx to Jordan resides in camps.Amman hosts 28%of non-camp refugees(NCRs)who are living in urban areas and creating multiple forms of urban settlements.Diverse forms of NCR settlements are emerging extensively in Eastern Amman districts.These settlements are contributing to new morphological structures and leading to a gradual spatial change-socially and physically.This research intends to contribute to the increasing amount of available data by improving the understanding of the socio-spatial patterns of Syrian NCR settlements and providing insights,forecasts,and recommendations regarding this pressing issue on the basis of overall trends.Comprehensively contextualized areas in Amman were mapped,and after considering specific siteselection criteria,Jubilee Neighborhood was selected.Jubilee was built by the government in 1985 for low-income Jordanian families.This study aims to unravel one layer of the complex multilayered Amman City.It intends to explore and describe the urban forms of NCR settlements in Jubilee Neighborhood as a case study by interrelating spatial,social,and physical concepts.In addition,this study extensively uses rigorous qualitative and traditional methods.The outcome of this study is a comprehensive and descriptive spatial analysis that can provide socio-spatial interpretations and recommend urban response policies to cope with the future spatial transformation of urban forms.
