The Physarum polycephalum Genome Reveals Extensive Use of Prokaryotic Two-Component and Metazoan-Type Tyrosine Kinase Signaling.

Physarum polycephalum is a well-studied microbial eukaryote with unique experimental attributes relative to other experimental model organisms. It has a sophisticated life cycle with several distinct stages including amoebal, flagellated, and plasmodial cells. It is unusual in switching between open and closed mitosis according to specific life-cycle stages. Here we present the analysis of the genome of this enigmatic and important model organism and compare it with closely related species. The genome is littered with simple and complex repeats and the coding regions are frequently interrupted by introns with a mean size of 100 bases. Complemented with extensive transcriptome data, we define approximately 31,000 gene loci, providing unexpected insights into early eukaryote evolution. We describe extensive use of histidine kinase-based two-component systems and tyrosine kinase signaling, the presence of bacterial and plant type photoreceptors (phytochromes, cryptochrome, and phototropin) and of plant-type pentatricopeptide repeat proteins, as well as metabolic pathways, and a cell cycle control system typically found in more complex eukaryotes. Our analysis characterizes P. polycephalum as a prototypical eukaryote with features attributed to the last common ancestor of Amorphea, that is, the Amoebozoa and Opisthokonts. Specifically, the presence of tyrosine kinases in Acanthamoeba and Physarum as representatives of two distantly related subdivisions of Amoebozoa argues against the later emergence of tyrosine kinase signaling in the opisthokont lineage and also against the acquisition by horizontal gene transfer.

Study of uremic toxin fluxes across nanofabricated hemodialysis membranes using irreversible thermodynamics.

INTRODUCTION: The flux of uremic toxin middle molecules through currently used hemodialysis membranes is suboptimal, mainly because of the membranes' pore architecture. AIM: Identifying the modifiable sieving parameters that can be improved by nanotechnology to enhance fluxes of uremic toxins across the walls of dialyzers' capillaries. METHODS: We determined the maximal dimensions of endothelin, cystatin C, and interleukin - 6 using the macromolecular modeling software, COOT. We also applied the expanded Nernst-Plank equation to calculate the changes in the overall flux as a function of increased electro-migration and pH of the respective molecules. RESULTS: In a high flux hemodialyzer, the effective diffusivities of endothelin, cystatin C, and interleukin - 6 are 15.00 x 10(-10) cm(2)/s, 7.7 x 10(-10) cm(2)/s, and 5.4 x 10(-10) cm(2)/s, respectively, through the capillaries' walls. In a nanofabricated membrane, the effective diffusivities of endothelin, cystatin C, and interleukin - 6 are 13.87 x 10(-7) cm(2)/s, 5.73 x 10(-7) cm(2)/s, and 3.45 x 10(-7) cm(2)/s, respectively, through a nanofabricated membrane. Theoretical modeling showed that a 96% reduction in the membrane's thickness and the application of an electric potential of 10 mV across the membrane could enhance the flux of endothelin, cystatin C, and interleukin - 6 by a factor of 25. A ΔpH of 0.07 altered the fluxes minimally. CONCLUSIONS: Nanofabricated hemodialysis membranes with a reduced thickness and an applied electric potential can enhance the effective diffusivity and electro-migration flux of the respective uremic toxins by 3 orders of magnitude as compared to those passing through the high flux hemodialyzer.