Novel conditionally immortalized human proximal tubule cell line expressing functional influx and efflux transporters

Reabsorption of filtered solutes from the glomerular filtrate and excretion of waste products and xenobiotics are the main functions of the renal proximal tubular (PT) epithelium. A human PT cell line expressing a range of functional transporters would help to augment current knowledge in renal physiology and pharmacology. We have established and characterized a conditionally immortalized PT epithelial cell line (ciPTEC) obtained by transfecting and subcloning cells exfoliated in the urine of a healthy volunteer. The PT origin of this line has been confirmed morphologically and by the expression of aminopeptidase N, zona occludens 1, aquaporin 1, dipeptidyl peptidase IV and multidrug resistance protein 4 together with alkaline phosphatase activity. ciPTEC assembles in a tight monolayer with limited diffusion of inulin-fluorescein-isothiocyanate. Concentration and time-dependent reabsorption of albumin via endocytosis has been demonstrated, together with sodium-dependent phosphate uptake. The expression and activity of apical efflux transporter p-glycoprotein and of baso-lateral influx transporter organic cation transporter 2 have been shown in ciPTEC. This established human ciPTEC expressing multiple endogenous organic ion transporters mimicking renal reabsorption and excretion represents a powerful tool for future in vitro transport studies in pharmacology and physiology

Staying focused: A functional account of perceptual suppression during binocular rivalry

Presenting different images to either eye can induce perceptual switching, with alternating disappearances of each image—a phenomenon called binocular rivalry. We believe that disappearances during binocular rivalry can be driven by a process that facilitates visibility near the point of fixation. As the point of fixation is tied neither to a particular stimulus nor to a specific eye, indifference to both would be an essential characteristic for the process we envisage. Many factors that influence disappearances during binocular rivalry scale with distance in depth from fixation. Of these, here we use blur. We break the links between this cue and both eye of origin and stimulus type. We find that perceptual dominance can track a better focused image as it is swapped between the eyes and that perceptual switches can be driven by alternating the focus of images fixed in each eye. This implies that, as a determinant of suppression selectivity, blur is functionally independent from both eye of origin and stimulus type. Our data and theoretical account suggest that binocular rivalry is not an irrelevant laboratory curiosity but, rather, that it is a product of a functional adaptation that promotes visibility in cluttered environments

Analysis of extracellular mRNA in human urine reveals splice variant biomarkers of muscular dystrophies

Patients with myotonic dystrophy need to undergo invasive muscle biopsies to monitor disease progression and response to therapy. Here, the authors show that extracellular RNAs in human urine can be used as biomarkers to differentiate patients from unaffected controls, and to monitor exon skipping in patients with Duchenne muscular dystrophy taking the drug eteplirsen