Receptor activator of NF-kappaB and podocytes: towards a function of a novel receptor-ligand pair in the survival response of podocyte injury

Background

Glomerulosclerosis correlates with reduction in podocyte number that occurs through mechanisms which include apoptosis. Podocyte injury or podocyte loss in the renal glomerulus has been proposed as the crucial mechanism in the development of glomerulosclerosis. However, the mechanism by which podocytes respond to injury is poorly understood. TNF and TNF receptor superfamilies are important in the pathogenesis of podocyte injury and apoptosis. The ligand of receptor activator of NF-kappaB (RANKL) and receptor activator of NF-kappaB (RANK) are members of the TNF and receptor superfamilies. We investigated whether RANK - RANKL is a receptor - ligand complex for podocytes responding to injury.

Methodology/Principal Findings

In this study, RANKL and RANK were examined in human podocyte diseases and a rat model of puromycin aminonucleoside nephrosis (PAN). Compared with controls, RANK and RANKL were increased in both human podocyte diseases and the rat PAN model; double immunofluorescence staining revealed that RANK protein expression was mainly attributed to podocytes. Immunoelectron microscopy showed that RANK was localized predominantly at the top of the foot process membrane and the cytoplasm of rat podocyte. In addition, RANK was upregulated in mouse podocytes in vitro after injury induced by puromycin aminonucleoside (PA). Knockdown of RANK expression by small interference RNA (siRNA) exacerbated podocyte apoptosis induced by PA. However, RANKL inhibited significantly the apoptosis of podocytes induced by PA.

Conclusions/Significance

These findings suggest the increase in RANK–RANKL expression is a response to podocyte injury, and RANK–RANKL may be a novel receptor–ligand complex for the survival response during podocyte injury.     

Proteomic analysis of effect of hyperthermia on spermatogenesis in adult male mice

We characterized cellular and molecular mechanisms involved in spermatogenesis following short-term heat exposure of murine testis. For these studies, we utilized a proteomic approach with two-dimensional gel electrophoresis (2DE) analyses and mass spectroscopic identification of proteins with altered expression in mouse testes at different times after heat shock. We established a proteome reference map from 7-wk-old mouse testis linked to a federated proteome database. We used these tools to analyze quantitative variations in the tissue over a time course of 0.5, 2, 6, and 12 h following heat exposure. We separated 108 protein spots expressed differentially between the heat shock tissues and the control mouse testes. Of these spots, we identified 36 by comparing with the control reference map. We then focused on the heterogeneous nuclear ribonucleoproteins (hnRNPs) and the chaperonins containing t-complex polypeptide-1 (CCT). Further analysis in this heat-shocked model suggests numerous potential mechanisms for heat shock-induced spermatogenic disorder.     

Effects of vessel compliance on flow pattern in porcine epicardial right coronary arterial tree

The compliance of the vessel wall affects hemodynamic parameters which may alter the permeability of the vessel wall. Based on experimental measurements, the present study established a finite element (FE) model in the proximal elastic vessel segments of epicardial right coronary arterial (RCA) tree obtained from computed tomography. The motion of elastic vessel wall was measured by an impedance catheter and the inlet boundary condition was measured by an ultrasound flow probe. The Galerkin FE method was used to solve the Navier–Stokes and Continuity equations, where the convective term in the Navier–Stokes equation was changed in the arbitrary Lagrangian–Eulerian (ALE) framework to incorporate the motion due to vessel compliance. Various hemodynamic parameters (e.g., wall shear stress—WSS, WSS spatial gradient—WSSG, oscillatory shear index—OSI) were analyzed in the model. The motion due to vessel compliance affects the time-averaged WSSG more strongly than WSS at bifurcations. The decrease of WSSG at flow divider in elastic bifurcations, as compared to rigid bifurcations, implies that the vessel compliance decreases the permeability of vessel wall and may be atheroprotective. The model can be used to predict coronary flow pattern in subject-specific anatomy as determined by noninvasive imaging.     

Detecting the Influence of Spreading in Social Networks with Excitable Sensor Networks

Detecting spreading outbreaks in social networks with sensors is of great significance in applications. Inspired by the formation mechanism of humans’ physical sensations to external stimuli, we propose a new method to detect the influence of spreading by constructing excitable sensor networks. Exploiting the amplifying effect of excitable sensor networks, our method can better detect small-scale spreading processes. At the same time, it can also distinguish large-scale diffusion instances due to the self-inhibition effect of excitable elements. Through simulations of diverse spreading dynamics on typical real-world social networks (Facebook, coauthor, and email social networks), we find that the excitable sensor networks are capable of detecting and ranking spreading processes in a much wider range of influence than other commonly used sensor placement methods, such as random, targeted, acquaintance and distance strategies. In addition, we validate the efficacy of our method with diffusion data from a real-world online social system, Twitter. We find that our method can detect more spreading topics in practice. Our approach provides a new direction in spreading detection and should be useful for designing effective detection methods.     

Label-free detection of nucleic acid and protein microarrays by scanning Kelvin nanoprobe

A high-resolution scanning Kelvin nanoprobe is introduced as an alternative technique to the conventional fluorescence and mass spectrometric detection methods currently employed in nucleic acid and protein microarray technology. The new instrument is capable of the highly sensitive discernment of surface biochemical events taking place at molecular level such as nucleic acid hybridization and antibody-antigen interaction. The method involves measurement of changes in work function and surface potential instigated by such interactions. Being a label-free and non-contact technique, the structure, spatial configuration, local properties or function of the molecular system under study are not affected, nor perturbed by intercalating dyes, a strong electric field or ionizing beam. Subsequent to scanning, the microarray can be examined by other alternative approaches. Nucleic acids and proteins have been printed in microarray format on slides with a gold film in place using gold-sulphur interactive chemistry. Hybridization of nucleic acids for complementary and mismatched configurations shows consistent and reproducible values of work function. Differentiation of single internal mismatches is demonstrated. Protein concentration and formation of antibody-antigen pairs can be visualized and examined with high sensitivity and good inter-spot reproducibility.