1,721,185 research outputs found
The rediscovery of uromodulin (Tamm-Horsfall protein): from tubulointerstitial nephropathy to chronic kidney disease.
No full textAuthors' Reply: "On the Importance of Considering Glycosylation when Evaluating Biologic Therapies"
No full textAutosomal dominant polycystic kidney disease: clinical and genetic aspects
No full textAutosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disease caused by at least three different genes. The renal and extrarenal clinical manifestations, and the systemic complications due to cystic and non-cystic abnormalities in ADPKD patients have been widely investigated. Cellular and molecular aspects of cystogenetic mechanisms concern epithelial tubular cell proliferation, remodelling of extracellular matrix, fluid secretion and accumulation, and relations between cell proliferation and apoptosis. In vitro studies on cystogenesis suggest a key role of cell-to-cell or cell-to-matrix interactions. Surface proteins mediating cell-to-cell contact, such as E-cadherin (polycystin?), integrin interactions, growth factors, receptor expression, are involved in the process of differentiation of the cellular condition and of the extracellular matrix. Blocking any one of these complex mechanisms should influence the orientation and polarization of epithelial tubular cells and should mediate the inversion of fluid secretion which ends in renal cystogenesis. ADPKD comprises at least three phenotypically indistinguishable but genetically distinct entities, caused by mutations in three autosomal genes: PKD1 (chromosome 16p13.3) is present in about 85% of patients; PKD2 (chromosome 4q13q23) in 10%; PKD3 (unknown chromosome) in a few families. PCR-based mutation detection methods, automated DNA sequencing, and other "functional" methods are used to screen and analyse ADPKD patients. It is not yet known whether the mutations identified so far in PKD1 and PKD2 inactivate the genes or generate an aberrant product. The products of PKD1 and PKD2 genes have been called polycystin 1 and 2. Polycystins are members of a family of interactive proteins involved in complex adhesive cell-cell, cell-matrix, protein-protein, and protein-carbohydrate interactions in the extracellular compartment, and are involved in the same pathway (ion channel regulator? ion channel? pore?) where mutations in only one of the simple genes (PKD3 too?) may cause the ADPKD phenotype. Genotype-phenotype correlations, in terms of disease severity and/or progression to end-stage renal disease, probably depend on other factors, both genetic and environmental (for instance: DD genotype of the ACE gene in ADPKD hypertensive patients), that might influence the clinical course and progression of ADPKD. The hypothesis of the "two hits" has been proposed to explain at the molecular level the focal nature of cyst formation
2de maps in the discovery of human autoimmune kidney diseases: The case of membranous glomerulonephritis
No full textThe latest advancements in proteomic two-dimensional gel electrophoresis analysis applied to biological samples
No full textTranslational research methods: Basics of renal molecular biology
No full textMolecular biology has developed between years 1940s and 1960s as a branch of science that spans from genetics to cell biology and biochemistry with the goal of understanding the interactions by which DNA, RNA, and protein synthesis operate into cells [1]. Since then, numerous technological innovations pushed the field forward, allowing recombinant DNA technology to be applied to a wide variety of biologic problems and to enter the clinical practice. The discovery of restriction nucleases and DNA ligases, development of DNA libraries, DNA cloning procedures, nucleic acid hybridization techniques, and the polymerase chain reaction (PCR) together with transgenic animals have all represented successive steps for a successful delineation of the role of genes in cellular physiology and pathophysiology. This molecular revolution has affected all of the sciences, including medical and clinical research, and has culminated in the completion of the human genome project [2, 3]. In the past 15 years, we have witnessed tremendous technological advances for high-throughput analysis of DNA, RNA, and protein in a comprehensive and cost-effective manner, with great promises to translate the analysis of the central dogma of biology into precision diagnosis and treatment for both rare and common diseases (Fig. 1). The recent advances in RNA biology identified numerous noncoding functional regions of the genome, which “escape” the central dogma but that can be analyzed and studied using a similar framework
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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