Biochemistry, Biophysics, and Structural Biology Commons^™

Mouse Embryonic Stem Cells Lacking P38Α And P38Δ Can Differentiate To Endothelial Cells, Smooth Muscle Cells, And Epithelial Cells, Samujjwal Chakraborty, Baobin Kang, Faqing Huang, Yan-Lin Guo

Faculty Publications

The p38 mitogen-activated protein (MAP) kinases (p38) are important signaling molecules that regulate various cellular processes. Four isoforms of p38 family, p38α, p38β, p38γ, and p38δ, have been identified in mammalian cells. Previous studies have shown that p38α knockout is embryonic lethal in mice. At the cellular level, p38α is abundantly expressed in mouse embryonic stem cells (ESCs), but p38α knockout (p38α-/-) ESCs can differentiate to endothelial cells (ECs), smooth muscle cells (SMCs), and neurons. We speculate that the lost function of p38α in p38α-/- ESCs may be compensated for by the redundant function of other isoforms. To test this …

Ionic Selectivity In L-Type Calcium Channels By Electrostatics And Hard-Core Repulsion, Dezso Boda, Douglas Henderson, Monika Valisko, Bob Eisenberg, Dirk Gillespie

Faculty Publications

A physical model of selective "ion binding" in the L-type calcium channel is constructed, and consequences of the model are compared with experimental data. This reduced model treats only ions and the carboxylate oxygens of the EEEE locus explicitly and restricts interactions to hard-core repulsion and ion–ion and ion–dielectric electrostatic forces. The structural atoms provide a flexible environment for passing cations, thus resulting in a self-organized induced-fit model of the selectivity filter. Experimental conditions involving binary mixtures of alkali and/or alkaline earth metal ions are computed using equilibrium Monte Carlo simulations in the grand canonical ensemble. The model pore rejects …

Ca2+ Extrusion By Ncx Is Compromised In Olfactory Sensory Neurons Of Omp-/- Mice, Hyun J. Kwon, Jae Hyung Koo, Frank Zufall, Trese Leinders-Zufall, Frank L. Margolis

Faculty Publications

Background: The role of olfactory marker protein (OMP), a hallmark of mature olfactory sensory neurons (OSNs), has been poorly understood since its discovery. The electrophysiological and behavioral phenotypes of OMP knockout mice indicated that OMP influences olfactory signal transduction. However, the mechanism by which this occurs remained unknown. Principal Findings: We used intact olfactory epithelium obtained from WT and OMP-/- mice to monitor the Ca2+ dynamics induced by the activation of cyclic nucleotide-gated channels, voltage-operated Ca2+ channels, or Ca2+ stores in single dendritic knobs of OSNs. Our data suggested that OMP could act to modulate the Ca2+-homeostasis in these neurons …

A Microrna Imparts Robustness Against Environmental Fluctuation During Development, Xin Li, Justin J. Cassidy, Catherine A. Reinke, Stephen Fischboeck, Richard W. Carthew

Faculty Publications

The microRNA miR-7 is perfectly conserved from annelids to humans, and yet some of the genes that it regulates in Drosophila are not regulated in mammals. We have explored the role of lineage restricted targets, using Drosophila , in order to better understand the evolutionary significance of microRNA-target relationships. From studies of two well characterized developmental regulatory networks, we find that miR-7 functions in several interlocking feedback and feedforward loops, and propose that its role in these networks is to buffer them against perturbation. To directly demonstrate this function for miR-7, we subjected the networks to temperature fluctuation and found …

The Metal Chelators, Trientine And Citrate, Inhibit The Development Of Cardiac Pathology In The Zucker Diabetic Rat, John W. Baynes, David B. Murray

Faculty Publications

Purpose. The objective of this study was to determine the efficacy of dietary supplementation with the metal chelators, trientine or citric acid, in preventing the development of cardiomyopathy in the Zucker diabetic rat.

Hypothesis. We hypothesized that dietary chelators would attenuate metal-catalyzed oxidative stress and damage in tissues and protect against pathological changes in ventricular structure and function in type II diabetes.

Methods. Animals (10 weeks old) included lean control (LC, fa/+), untreated Zucker diabetic fatty (ZDF, fa/fa), and ZDF rats treated with either trientine (triethylenetetramine) or citrate at 20 mg/d in drinking water, starting …