Eric A. Sobie

Bio: Eric A. Sobie is an academic researcher from Icahn School of Medicine at Mount Sinai. The author has contributed to research in topics: Ryanodine receptor & Medicine. The author has an hindex of 35, co-authored 123 publications receiving 4291 citations. Previous affiliations of Eric A. Sobie include Johns Hopkins University & University of Maryland, Baltimore.

Orphaned ryanodine receptors in the failing heart

Abstract: Heart muscle is characterized by a regular array of proteins and structures that form a repeating functional unit identified as the sarcomere. This regular structure enables tight coupling between electrical activity and Ca2+ signaling. In heart failure, multiple cellular defects develop, including reduced contractility, altered Ca2+ signaling, and arrhythmias; however, the underlying causes of these defects are not well understood. Here, in ventricular myocytes from spontaneously hypertensive rats that develop heart failure, we identify fundamental changes in Ca2+ signaling that are related to restructuring of the spatial organization of the cells. Myocytes display both a reduced ability to trigger sarcoplasmic reticulum Ca2+ release and increased spatial dispersion of the transverse tubules (TTs). Remodeled TTs in cells from failing hearts no longer exist in the regularly organized structures found in normal heart cells, instead moving within the sarcomere away from the Z-line structures and leaving behind the sarcoplasmic reticulum Ca2+ release channels, the ryanodine receptors (RyRs). These orphaned RyRs appear to be responsible for the dyssynchronous Ca2+ sparks that have been linked to blunted contractility and, probably, Ca2+-dependent arrhythmias in diverse models of heart failure. We conclude that the increased spatial dispersion of the TTs and orphaned RyRs lead to the loss of local control and Ca2+ instability in heart failure.

An Introduction to Dynamical Systems

Abstract: This Teaching Resource provides lecture notes, slides, and a problem set that can assist in teaching concepts related to dynamical systems tools for the analysis of ordinary differential equation (ODE)-based models. The concepts are applied to familiar biological problems, and the material is appropriate for graduate students or advanced undergraduates. The lecture explains how equations describing biochemical signaling networks can be derived from diagrams that illustrate the reactions in graphical form. Because such reactions are most frequently described using systems of ODEs, the lecture discusses and illustrates the principles underlying the numerical solution of ODEs. Methods for determining the stability of steady-state solutions of one or two-dimensional ODE systems are covered and illustrated using standard graphical methods. The concept of a bifurcation, a condition at which a system's behavior changes qualitatively, is also introduced. A problem set is included that (i) requires students to implement an ODE model of biochemical reactions using MATLAB and (ii) allows them to explore dynamical systems concepts.

The Library of Integrated Network-Based Cellular Signatures NIH Program: System-Level Cataloging of Human Cells Response to Perturbations

Abstract: The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program that catalogs how human cells globally respond to chemical, genetic, and disease perturbations. Resources generated by LINCS include experimental and computational methods, visualization tools, molecular and imaging data, and signatures. By assembling an integrated picture of the range of responses of human cells exposed to many perturbations, the LINCS program aims to better understand human disease and to advance the development of new therapies. Perturbations under study include drugs, genetic perturbations, tissue micro-environments, antibodies, and disease-causing mutations. Responses to perturbations are measured by transcript profiling, mass spectrometry, cell imaging, and biochemical methods, among other assays. The LINCS program focuses on cellular physiology shared among tissues and cell types relevant to an array of diseases, including cancer, heart disease, and neurodegenerative disorders. This Perspective describes LINCS technologies, datasets, tools, and approaches to data accessibility and reusability.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Principles of Neural Science

Abstract: I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Reaction-diffusion model as a framework for understanding biological pattern formation

Abstract: The Turing, or reaction-diffusion (RD), model is one of the best-known theoretical models used to explain self-regulated pattern formation in the developing animal embryo. Although its real-world relevance was long debated, a number of compelling examples have gradually alleviated much of the skepticism surrounding the model. The RD model can generate a wide variety of spatial patterns, and mathematical studies have revealed the kinds of interactions required for each, giving this model the potential for application as an experimental working hypothesis in a wide variety of morphological phenomena. In this review, we describe the essence of this theory for experimental biologists unfamiliar with the model, using examples from experimental studies in which the RD model is effectively incorporated.

Physiology of cell volume regulation in vertebrates.

Abstract: The ability to control cell volume is pivotal for cell function. Cell volume perturbation elicits a wide array of signaling events, leading to protective (e.g., cytoskeletal rearrangement) and adap...

Microdomains of intracellular Ca2+: molecular determinants and functional consequences.

Abstract: Calcium ions are ubiquitous and versatile signaling molecules, capable of decoding a variety of extracellular stimuli (hormones, neurotransmitters, growth factors, etc.) into markedly different int...