scholarly journals Mechanical challenges and cytoskeletal impairments in focal segmental glomerulosclerosis

2018 ◽  
Vol 314 (5) ◽  
pp. F921-F925 ◽  
Author(s):  
Di Feng ◽  
Clark DuMontier ◽  
Martin R. Pollak
Keyword(s):  
Blood Flow ◽  
Focal Segmental Glomerulosclerosis ◽  
Kidney Injury ◽  
Future Research ◽  
Disease States ◽  
Filtration Barrier ◽  
Segmental Glomerulosclerosis ◽  
The Face ◽  
Foot Process ◽  
Future Research Directions

Focal segmental glomerulosclerosis (FSGS) is a histologically defined form of kidney injury typically mediated by podocyte dysfunction. Podocytes rely on their intricate actin-based cytoskeleton to maintain the glomerular filtration barrier in the face of mechanical challenges resulting from pulsatile blood flow and filtration of this blood flow. This review summarizes the mechanical challenges faced by podocytes in the form of stretch and shear stress, both of which may play a role in the progression of podocyte dysfunction and detachment. It also reviews how podocytes respond to these mechanical challenges in dynamic fashion through rearranging their cytoskeleton, triggering various biochemical pathways, and, in some disease states, altering their morphology in the form of foot process effacement. Furthermore, this review highlights the growing body of evidence identifying several mutations of important cytoskeleton proteins as causes of FSGS. Lastly, it synthesizes the above evidence to show that a better understanding of how these mutations leave podocytes vulnerable to the mechanical challenges they face is essential to better understanding the mechanisms by which they lead to disease. The review concludes with future research directions to fill this gap and some novel techniques with which to pursue these directions.

scholarly journals Kidney Injury by Variants in the COL4A5 Gene Aggravated by Polymorphisms in Slit Diaphragm Genes Causes Focal Segmental Glomerulosclerosis

2019 ◽  
Vol 20 (3) ◽  
pp. 519 ◽  
Author(s):  
Jenny Frese ◽  
Matthias Kettwig ◽  
Hildegard Zappel ◽  
Johannes Hofer ◽  
Hermann-Josef Gröne ◽  
...  
Keyword(s):  
Renal Failure ◽  
Basement Membrane ◽  
Focal Segmental Glomerulosclerosis ◽  
Glomerular Basement Membrane ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Slit Diaphragm ◽  
Filtration Barrier ◽  
Segmental Glomerulosclerosis ◽  
Case Series Study

Kidney injury due to focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular disorder causing end-stage renal disease. Homozygous mutations in either glomerular basement membrane or slit diaphragm genes cause early renal failure. Heterozygous carriers develop renal symptoms late, if at all. In contrast to mutations in slit diaphragm genes, hetero- or hemizygous mutations in the X-chromosomal COL4A5 Alport gene have not yet been recognized as a major cause of kidney injury by FSGS. We identified cases of FSGS that were unexpectedly diagnosed: In addition to mutations in the X-chromosomal COL4A5 type IV collagen gene, nephrin and podocin polymorphisms aggravated kidney damage, leading to FSGS with ruptures of the basement membrane in a toddler and early renal failure in heterozygous girls. The results of our case series study suggest a synergistic role for genes encoding basement membrane and slit diaphragm proteins as a cause of kidney injury due to FSGS. Our results demonstrate that the molecular genetics of different players in the glomerular filtration barrier can be used to evaluate causes of kidney injury. Given the high frequency of X-chromosomal carriers of Alport genes, the analysis of genes involved in the organization of podocyte architecture, the glomerular basement membrane, and the slit diaphragm will further improve our understanding of the pathogenesis of FSGS and guide prognosis of and therapy for hereditary glomerular kidney diseases.

scholarly journals Novel diagnostic and therapeutic techniques reveal changed metabolic profiles in recurrent focal segmental glomerulosclerosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Janina Müller-Deile ◽  
George Sarau ◽  
Ahmed M. Kotb ◽  
Christian Jaremenko ◽  
Ulrike E. Rolle-Kampczyk ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Raman Spectra ◽  
Focal Segmental Glomerulosclerosis ◽  
Disease Recurrence ◽  
Early Recurrence ◽  
Metabolome Analysis ◽  
Novel Technologies ◽  
Filtration Barrier ◽  
Segmental Glomerulosclerosis ◽  
Living Related

AbstractIdiopathic forms of Focal Segmental Glomerulosclerosis (FSGS) are caused by circulating permeability factors, which can lead to early recurrence of FSGS and kidney failure after kidney transplantation. In the past three decades, many research endeavors were undertaken to identify these unknown factors. Even though some potential candidates have been recently discussed in the literature, “the” actual factor remains elusive. Therefore, there is an increased demand in FSGS research for the use of novel technologies that allow us to study FSGS from a yet unexplored angle. Here, we report the successful treatment of recurrent FSGS in a patient after living-related kidney transplantation by removal of circulating factors with CytoSorb apheresis. Interestingly, the classical published circulating factors were all in normal range in this patient but early disease recurrence in the transplant kidney and immediate response to CytoSorb apheresis were still suggestive for pathogenic circulating factors. To proof the functional effects of the patient’s serum on podocytes and the glomerular filtration barrier we used a podocyte cell culture model and a proteinuria model in zebrafish to detect pathogenic effects on the podocytes actin cytoskeleton inducing a functional phenotype and podocyte effacement. We then performed Raman spectroscopy in the < 50 kDa serum fraction, on cultured podocytes treated with the FSGS serum and in kidney biopsies of the same patient at the time of transplantation and at the time of disease recurrence. The analysis revealed changes in podocyte metabolome induced by the FSGS serum as well as in focal glomerular and parietal epithelial cell regions in the FSGS biopsy. Several altered Raman spectra were identified in the fractionated serum and metabolome analysis by mass spectrometry detected lipid profiles in the FSGS serum, which were supported by disturbances in the Raman spectra. Our novel innovative analysis reveals changed lipid metabolome profiles associated with idiopathic FSGS that might reflect a new subtype of the disease.

Cross-cultural testing of face threats to predict apology and thanks intentions

2017 ◽  
Vol 45 (10) ◽  
pp. 1643-1654
Author(s):  
Hye Eun Lee ◽  
Hyunjin Park
Keyword(s):  
Future Research ◽  
North Americans ◽  
Face Threats ◽  
The Face ◽  
Future Research Directions ◽  
Face Threat ◽  
Korean College Students ◽  
Favor Asking ◽  
Negative Face

We examined whether Koreans intended to make an apology and North Americans intended to express thanks in a message asking for a favor. Because one reason for apologizing or thanking is to lessen the face threat occurred by favor asking, four face threats were empirically measured to predict participants' intentions. Participants were 104 North American and 90 Korean college students who took the role of an email sender making a favor request and selected from options for apologizing or thanking the receiver to lessen the four types of face threat. Results showed that North Americans intended to express thanks, and both North Americans and Koreans intended to make an apology when asking a favor; further, for Koreans, a speaker's positive face threat triggered intention to make an apology and, for North Americans, a receiver's negative face threat triggered an intention to express thanks. Implications and future research directions are discussed.

Decision Making Under Uncertainty and Risks in the Face of Rapidly Advancing Technologies

2019 ◽  
pp. 38-56
Author(s):  
Vicente González-Prida Díaz ◽  
Jesus Pedro Zamora Bonilla ◽  
Pablo Viveros Gunckel
Keyword(s):  
Decision Making ◽  
Social Perception ◽  
Industry 4.0 ◽  
Future Research ◽  
Risk And Uncertainty ◽  
Research Directions ◽  
The Face ◽  
Future Research Directions ◽  
Key Aspects ◽  
Reduction Of Uncertainty

This chapter aims to consider the effects of the new concept Industry 4.0 on decision making, particularly on the reduction of uncertainty and the risk associated with any choice between alternatives. For this purpose, this chapter begins by dealing with the concepts of risk and uncertainty and their epistemological evolution. After observing certain trends and recent studies in this regard, the authors address a more philosophical perception of risk, mainly on aspects related to engineering and social perception. The concept of human reliability will also be reviewed and how it can be improved with the application of emerging technologies, considering some methodological proposals to improve the decision making. After that, some of the possible future research directions will be briefly discussed. Finally, the chapter concludes by highlighting key aspects of the chapter as a context for other chapters in the book.

Directions in the Field of Technology Innovation Management

2010 ◽  
pp. 281-300
Author(s):  
Robert S. Friedman ◽  
Desiree M. Roberts ◽  
Jonathan D. Linton
Keyword(s):  
Economic Theory ◽  
Technology Innovation ◽  
Innovation Management ◽  
Future Research ◽  
Research Directions ◽  
The Past ◽  
The Face ◽  
Future Research Directions ◽  
Business And Management ◽  
Underlying Theme

Although the goal of this book is to provide foundational knowledge through indepth consideration of the seminal literature in the technology innovation management field, we now offer some thoughts on integrating the past, present, and future research directions in this field. The underlying theme that holds together the research considered in this book is the tension between the old (current routine) and the new (innovation). Mainstream business and management theory, like economic theory, focuses on the assumption of equilibrium. The study of technology innovation management at its core considers how to manage in the face of dynamics caused by the novelty and uncertainty associated with innovation. The nature of these dynamics can differ depending on a variety of factors. In some cases, the innovation causes smaller disruptions, due either to the magnitude or the nature of its effects. Such changes are often associated with terminology such as continuous, evolutionary, incremental, or sustaining. At other times, the disruptions are quite large, either due to a greater magnitude of change or a substantial difference in the change. These changes are often associated with terms such as discontinuous, disruptive, radical, or revolutionary. A major challenge to technology innovation management research is that the assumption of equilibrium is needed in many cases to allow for sufficient simplification of phenomena to produce generalizable theory and solutions that are tractable and close formed.

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