Metabolic rewiring of the hypertensive kidney
Hypertension is a persistent epidemic across the developed world that is closely associated with kidney disease. Here, we applied a metabolomic, phosphoproteomic, and proteomic strategy to analyze the effect of hypertensive insults on kidneys. Our data revealed the metabolic aspects of hypertension-induced glomerular sclerosis, including lipid breakdown at early disease stages and activation of anaplerotic pathways to regenerate energy equivalents to counter stress. For example, branched-chain amino acids and proline, required for collagen synthesis, were depleted in glomeruli at early time points. Furthermore, indicators ...
Source: Signal Transduction Knowledge Environment - December 10, 2019 Category: Science Authors: Rinschen, M. M., Palygin, O., Guijas, C., Palermo, A., Palacio-Escat, N., Domingo-Almenara, X., Montenegro-Burke, R., Saez-Rodriguez, J., Staruschenko, A., Siuzdak, G. Tags: STKE Research Resources Source Type: news
Structured spike series specify gene expression patterns for olfactory circuit formation
Neural circuits emerge through the interplay of genetic programming and activity-dependent processes. During the development of the mouse olfactory map, axons segregate into distinct glomeruli in an olfactory receptor (OR)–dependent manner. ORs generate a combinatorial code of axon-sorting molecules whose expression is regulated by neural activity. However, it remains unclear how neural activity induces OR-specific expression patterns of axon-sorting molecules. We found that the temporal patterns of spontaneous neuronal spikes were not spatially organized but were correlated with the OR types. Receptor substitution e...
Source: ScienceNOW - July 4, 2019 Category: Science Authors: Nakashima, A., Ihara, N., Shigeta, M., Kiyonari, H., Ikegaya, Y., Takeuchi, H. Tags: Development, Online Only r-articles Source Type: news
A small-molecule inhibitor of TRPC5 ion channels suppresses progressive kidney disease in animal models
Progressive kidney diseases are often associated with scarring of the kidney’s filtration unit, a condition called focal segmental glomerulosclerosis (FSGS). This scarring is due to loss of podocytes, cells critical for glomerular filtration, and leads to proteinuria and kidney failure. Inherited forms of FSGS are caused by Rac1-activating mutations, and Rac1 induces TRPC5 ion channel activity and cytoskeletal remodeling in podocytes. Whether TRPC5 activity mediates FSGS onset and progression is unknown. We identified a small molecule, AC1903, that specifically blocks TRPC5 channel activity in glomeruli of proteinuri...
Source: ScienceNOW - December 7, 2017 Category: Science Authors: Zhou, Y., Castonguay, P., Sidhom, E.-H., Clark, A. R., Dvela-Levitt, M., Kim, S., Sieber, J., Wieder, N., Jung, J. Y., Andreeva, S., Reichardt, J., Dubois, F., Hoffmann, S. C., Basgen, J. M., Montesinos, M. S., Weins, A., Johnson, A. C., Lander, E. S., Ga Tags: Medicine, Diseases reports Source Type: news
Multicluster Pcdh diversity is required for mouse olfactory neural circuit assembly
The vertebrate clustered protocadherin (Pcdh) cell surface proteins are encoded by three closely linked gene clusters (Pcdhα, Pcdhβ, and Pcdh). Here, we show that all three gene clusters functionally cooperate to provide individual mouse olfactory sensory neurons (OSNs) with the cell surface diversity required for their assembly into distinct glomeruli in the olfactory bulb. Although deletion of individual Pcdh clusters had subtle phenotypic consequences, the loss of all three clusters (tricluster deletion) led to a severe axonal arborization defect and loss of self-avoidance. By contrast, when endogenous Pcdh d...
Source: ScienceNOW - April 27, 2017 Category: Science Authors: Mountoufaris, G., Chen, W. V., Hirabayashi, Y., OKeeffe, S., Chevee, M., Nwakeze, C. L., Polleux, F., Maniatis, T. Tags: Neuroscience reports Source Type: news
YAP-mediated mechanotransduction determines the podocytes response to damage
Podocytes are terminally differentiated cells of the kidney filtration barrier. They are subjected to physiological filtration pressure and considerable mechanical strain, which can be further increased in various kidney diseases. When injury causes cytoskeletal reorganization and morphological alterations of these cells, the filtration barrier may become compromised and allow proteins to leak into the urine (a condition called proteinuria). Using time-resolved proteomics, we showed that podocyte injury stimulated the activity of the transcriptional coactivator YAP and the expression of YAP target genes in a rat model of g...
Source: Signal Transduction Knowledge Environment - April 11, 2017 Category: Science Authors: Rinschen, M. M., Grahammer, F., Hoppe, A.-K., Kohli, P., Hagmann, H., Kretz, O., Bertsch, S., Höhne, M., Göbel, H., Bartram, M. P., Gandhirajan, R. K., Krüger, M., Brinkkoetter, P.-T., Huber, T. B., Kann, M., Wickström, S. Tags: STKE Research Articles Source Type: news
Will blocking IL-17A help treat kidney disease?
(Bentham Science Publishers) Animal studies of diseases damaging glomeruli suggest that IL-17A/F and Th17 cells are involved in the initial inflammatory response within the kidney. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - January 22, 2016 Category: Global & Universal Source Type: news
Fluorescence-Activated Cell Sorting (FACS) Protocol for Podocyte Isolation in Adult Zebrafish
Zebrafish is becoming a very important model for studying human diseases. The conserved structure of the nephrons in the kidney allows the user to answer questions relating to study human kidney disorders. Wt1a-expressing podocytes are the most important cells within the glomeruli of adult zebrafish. In order to understand the molecular characteristics of these cells, within damage models, we have established a method for isolating them. (Source: Springer protocols feed by Cancer Research)
Source: Springer protocols feed by Cancer Research - January 1, 2016 Category: Cancer & Oncology Source Type: news
Laser Capture Microdissection of Archival Kidney Tissue for qRT-PCR
Whole-organ molecular analysis of the kidney potentially misses important factors involved in the pathogenesis of disease in glomeruli and tubules. Organ wide analysis can however be augmented by using laser capture microdissection (LCM) to isolate morphologically similar cells and nephron structures from a heterogeneous tissue section via direct visualization of the cells. The protocol here provides a practical approach utilizing LCM in combination with RNA isolation techniques for downstream analysis. This technique is readily applicable to study mRNA expression in isolated glomeruli and tubules in both experimental anim...
Source: Springer protocols feed by Molecular Medicine - December 22, 2015 Category: Molecular Biology Source Type: news
Microarray Technology for Analysis of MicroRNA Expression in Renal Biopsies of Lupus Nephritis Patients
This article offers a technological overview of microarray technology for analysis of microRNA gene expression in kidney biopsies from SLE patients. (Source: Springer protocols feed by Immunology)
Source: Springer protocols feed by Immunology - February 7, 2014 Category: Allergy & Immunology Source Type: news
How sights, sounds, and touch are mapped onto the brain
The body surface and certain features of external space are mapped onto the brain in a highly ordered mannerChapter 8 of my book, 50 Human Brain Ideas You Really Need to Know. Here's the introduction to the book, the chapter about mirror neurons, and my post about the most important idea in neuroscience.Summary: The body's surface and certain features of the external world are mapped onto the brain in a highly ordered fashion. these so-called 'topographic maps' exist in all of the brain's sensory systems, as well as in its motor system. they arise during brain development, and are vital for information processing.In the 19...
Source: Guardian Unlimited Science - September 3, 2013 Category: Science Tags: theguardian.com Blogposts Neuroscience Source Type: news
Nephrotic syndrome following mercury vapor exposure
3 out of 5 stars Mercury poisoning from home gold amalgam extraction. Saleem M et al. Med J Aust 2013;199:125-127. No abstract available This case report describes a 62-year-old man who presented with flu-like symptoms and increasing shortness of breath. History revealed that he had recently attempted to extract gold from mercury-containing amalgam by heating the amalgam in a pan. As a result, he had been exposed to mercury fumes for approximately 3 hours. Workup revealed pneumonitis, as well as elevated blood and urine mercury levels. The patient was treated with chelation (DMSA) and steroids. One month later...
Source: The Poison Review - July 24, 2013 Category: Toxicology Authors: Leon Tags: Medical mercury toxicity mercury vapor nephrotic syndrome pneumonitis renal toxicity Source Type: news