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Rich levitan

Katherine A O'Donnell, Hélène Gaudreau, Sara Colalillo, Meir Steiner, Leslie Atkinson, Ellen Moss, Susan Goldberg, Sherif Karama, Stephen G Matthews, John E Lydon, Patricia P Silveira, Ashley D Wazana, Robert D Levitan, Marla B Sokolowski, James L Kennedy, Alison Fleming, Michael J Meaney
OBJECTIVE: To describe the theory and methodology of the multi-wave, prospective Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) study. The goal of MAVAN is to examine the pre- and postnatal influences, and their interaction, in determining individual differences in mental health. METHOD: MAVAN is a community-based, birth cohort study of pregnant Canadian mothers and their offspring. Dyads are assessed longitudinally, with multiple assessments of both mother and child in home and laboratory across the child's development...
September 2014: Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie
Zhongkui Hong, Marius C Staiculescu, Paul Hampel, Irena Levitan, Gabor Forgacs
As endothelial cells form the barrier between blood flow and surrounding tissue, many of their functions depend on mechanical integrity, in particular those of the plasma membrane. As component and organizer of the plasma membrane, cholesterol is a regulator of cellular mechanical properties. Disruption of cholesterol balance leads to impairment of endothelial functions and eventually to disease. The mechanical properties of the membrane are strongly affected by the cytoskeleton. As Phosphatidylinositol-4,5-bisphosphate (PIP2) is a key mediator between the membrane and cytoskeleton, it also affects cellular biomechanical properties...
2012: Frontiers in Physiology
Cara L Ooi, James L Kennedy, Robert D Levitan
Increased food intake is a major contributor to the obesity epidemic in all age groups. Elucidating brain systems that drive overeating and that might serve as targets for novel prevention and treatment interventions is thus a high priority for obesity research. The authors consider 2 major pathways by which decreased activity of brain-derived neurotrophic factor (BDNF) may confer vulnerability to overeating and weight gain in an obesogenic environment. The first "direct" pathway focuses on the specific role of BDNF as a mediator of food intake control at brain areas rich in BDNF receptors, including the hypothalamus and hindbrain...
August 2012: Behavioral Neuroscience
Patrícia P Silveira, Marilyn Agranonik, Hadeel Faras, André K Portella, Michael J Meaney, Robert D Levitan
INTRODUCTION: Low birth weight is associated with obesity and an increased risk for metabolic/cardiovascular diseases in later life. RESULTS: The results of the snack delay test, which encompassed four distinct trials, indicated that the gender × intrauterine growth restriction (IUGR) × trial interaction was a predictor of the ability to delay the food reward (P = 0.002). Among children with normal birth weights, girls showed a greater ability to delay food rewards than did boys (P = 0...
March 2012: Pediatric Research
Irena Levitan, Tzu-Pin Shentu
Numerous studies have demonstrated that cholesterol-rich membrane rafts play critical roles in multiple cellular functions. However, the impact of the lipoproteins on the structure, integrity and cholesterol composition of these domains is not well understood. This paper focuses on oxidized low-density lipoproteins (oxLDLs) that are strongly implicated in the development of the cardiovascular disease and whose impact on membrane cholesterol and on membrane rafts has been highly controversial. More specifically, we discuss three major criteria for the impact of oxLDL on membrane rafts: distribution of different membrane raft markers, changes in membrane cholesterol composition, and changes in lipid packing of different membrane domains...
2011: Journal of Lipids
R K Grosberg, D R Levitan
When ecologists study organisms with multiphasic life cycles, they must often confront the problem of which phase to scrutinize. In principle, the dynamics and interactions of all stages could play a major role in the regulation of adult populations and species assemblages. In practice, however, the roles of larger and more sedentary phases - being easier to count and manipulate than motile propagules - have been emphasized. Nonetheless, several recent studies on the small, dispersing larval phase of marine invertebrate life cycles reach the conclusion that the spatial distribution and supply of propagules can control the distribution and abundance of populations of benthic adults...
April 1992: Trends in Ecology & Evolution
German V Kolmakov, Victor V Yashin, Steven P Levitan, Anna C Balazs
Using computational modeling, we design colonies of biomimetic microcapsules that exploit chemical mechanisms to communicate and alter their local environment. As a result, these synthetic objects can self-organize into various autonomously moving structures and exhibit ant-like tracking behavior. In the simulations, signaling microcapsules release agonist particles, whereas target microcapsules release antagonist particles and the permeabilities of both capsule types depend on the local particle concentration in the surrounding solution...
July 13, 2010: Proceedings of the National Academy of Sciences of the United States of America
Tzu Pin Shentu, Igor Titushkin, Dev K Singh, Keith J Gooch, Papasani V Subbaiah, Michael Cho, Irena Levitan
Oxidized low-density lipoprotein (oxLDL) is a major factor in development of atherosclerosis. Our earlier studies have shown that exposure of endothelial cells (EC) to oxLDL increases EC stiffness, facilitates the ability of the cells to generate force, and facilitates EC network formation in three-dimensional collagen gels. In this study, we show that oxLDL induces a decrease in lipid order of membrane domains and that this effect is inversely correlated with endothelial stiffness, contractility, and network formation...
August 2010: American Journal of Physiology. Cell Physiology
Irena Levitan, Yun Fang, Avia Rosenhouse-Dantsker, Victor Romanenko
A variety of ion channels, including members of all major ion channel families, have been shown to be regulated by changes in the level of membrane cholesterol and partition into cholesterol-rich membrane domains. In general, several types of cholesterol effects have been described. The most common effect is suppression of channel activity by an increase in membrane cholesterol, an effect that was described for several types of inwardly-rectifying K(+) channels, voltage-gated K(+) channels, Ca(+2) sensitive K(+) channels, voltage-gated Na(+) channels, N-type voltage-gated Ca(+2) channels and volume-regulated anion channels...
2010: Sub-cellular Biochemistry
Irena Levitan
To date, most of the major types of Kir channels, Kir2s, Kir3s, Kir4s, and Kir6s, have been found to partition into cholesterol-rich membrane domains and/or to be regulated by changes in the level of membrane cholesterol. Surprisingly, however, in spite of the structural similarities between different Kirs, effects of cholesterol on different types of Kir channels vary from cholesterol-induced decrease in the current density (Kir2 channels) to the loss of channel activity by cholesterol depletion (Kir4 channels) and loss of channel coupling by different mediators (Kir3 and Kir6 channels)...
August 2009: IUBMB Life
Inbal Dangoor, Hadas Peled-Zehavi, Alexander Levitan, Ohad Pasand, Avihai Danon
The reduction and the formation of regulatory disulfide bonds serve as a key signaling element in chloroplasts. Members of the thioredoxin (Trx) superfamily of oxidoreductases play a major role in these processes. We have characterized a small family of plant-specific Trxs in Arabidopsis (Arabidopsis thaliana) that are rich in cysteine and histidine residues and are typified by a variable noncanonical redox active site. We found that the redox midpoint potential of three selected family members is significantly less reducing than that of the classic Trxs...
March 2009: Plant Physiology
Chaoming Zhou, Chandra Z Vignere, Edwin S Levitan
Expression of cardiac myocyte Kv4 channels (Kv4.3 for human, Kv4.2 and Kv4.3 for rodents) is downregulated with hypertrophy in vivo leading to a decrease in the transient outward current (Ito). This effect is recapitulated in vitro with rat neonatal cardiac myocytes treated with angiotensin II (Ang II), which acts via AT(1) receptors, NADPH oxidase and p38 MAP kinase to destabilize the 3' untranslated region (3'UTR) of the Kv4.3 channel messenger RNA (mRNA). Here deletion analysis and mutagenesis identify an AU-rich element (ARE) in the Kv4...
December 2008: Journal of Molecular and Cellular Cardiology
Irena Levitan, Keith J Gooch
Membrane-cytoskeleton coupling is known to play major roles in a plethora of cellular responses, such as cell growth, differentiation, polarization, motility, and others. In this review, the authors discuss the growing amount of evidence indicating that membrane-cytoskeleton interactions are regulated by the lipid composition of the plasma membrane, suggesting that cholesterol-rich membrane domains (lipid rafts), including caveolae, are essential for membrane-cytoskeleton coupling. Several models for raft-cytoskeleton interactions are discussed...
September 2007: Antioxidants & Redox Signaling
Saloni Tikku, Yulia Epshtein, Heidi Collins, Alexander J Travis, George H Rothblat, Irena Levitan
Our earlier studies have shown that Kir2.x channels are suppressed by an increase in the level of cellular cholesterol, whereas cholesterol depletion enhances the activity of the channels. In this study, we show that Kir2.1 and Kir2.3 channels have double-peak distributions between cholesterol-rich (raft) and cholesterol-poor (non-raft) membrane fractions, indicating that the channels exist in two different types of lipid environment. We also show that whereas methyl-beta-cyclodextrin-induced cholesterol depletion removes cholesterol from both raft and non-raft membrane fractions, cholesterol enrichment results in cholesterol increase exclusively in the raft fractions...
July 2007: American Journal of Physiology. Cell Physiology
Jingmei Lin, Sanjeevkumar R Patel, Xu Cheng, Eun Ah Cho, Inna Levitan, Matthew Ullenbruch, Sem H Phan, John M Park, Gregory R Dressler
The bone morphogenetic proteins (BMPs) profoundly affect embryonic development, differentiation and disease. BMP signaling is suppressed by cysteine-rich domain proteins, such as chordin, that sequester ligands from the BMP receptor. We describe a novel protein, KCP, with 18 cysteine-rich domains. Unlike chordin, KCP enhances BMP signaling in a paracrine manner. Smad1-dependent transcription and phosphorylated Smad1 (P-Smad1) levels are increased, as KCP binds to BMP7 and enhances binding to the type I receptor...
April 2005: Nature Medicine
Victor G Romanenko, Yun Fang, Fitzroy Byfield, Alexander J Travis, Carol A Vandenberg, George H Rothblat, Irena Levitan
This study investigates how changes in the level of cellular cholesterol affect inwardly rectifying K+ channels belonging to a family of strong rectifiers (Kir2). In an earlier study we showed that an increase in cellular cholesterol suppresses endogenous K+ current in vascular endothelial cells, presumably due to effects on underlying Kir2.1 channels. Here we show that, indeed, cholesterol increase strongly suppressed whole-cell Kir2.1 current when the channels were expressed in a null cell line. However, cholesterol level had no effect on the unitary conductance and only little effect on the open probability of the channels...
December 2004: Biophysical Journal
E Meiri, A Levitan, F Guo, D A Christopher, D Schaefer, J-P Zrÿd, A Danon
Plant genomes typically contain several sequences homologous to protein disulfide isomerase (PDI). PDI was first identified as an abundant enzyme in the endoplasmic reticulum, where it catalyzes the formation, reduction, and isomerization of disulfide bonds during protein folding. PDI-like proteins have also been implicated in a variety of other functions, such as the regulation of cell adhesion, and may act as elicitors of the autoimmune response in mammals. A PDI-like protein (RB60) was recently shown to be imported into chloroplasts in the unicellular green alga Chlamydomonas reinhardtii and a higher plant, Pisum sativum, where it associates with thylakoid membranes...
April 2002: Molecular Genetics and Genomics: MGG
Claudette M St Croix, K J Wasserloos, K E Dineley, I J Reynolds, E S Levitan, B R Pitt
We hypothesized that metallothionein (MT), a cysteine-rich protein with a strong affinity for Zn(2+), plays a role in nitric oxide (NO) signaling events via sequestration or release of Zn(2+) by the unique thiolate clusters of the protein. Exposing mouse lung fibroblasts (MLF) to the NO donor S-nitrosocysteine resulted in 20-30% increases in fluorescence of the Zn(2+)-specific fluorophore Zinquin that were rapidly reversed by the Zn(2+) chelator N,N,N',N'-tetrakis-(2-pyridylmethyl)ethylenediamine. The absence of a NO-mediated increase in labile Zn(2+) in MLF from MT knockouts and its restoration after MT complementation by adenoviral gene transfer inferred a critical role for MT in the regulation of Zn(2+) homeostasis by NO...
February 2002: American Journal of Physiology. Lung Cellular and Molecular Physiology
L L Pearce, R E Gandley, W Han, K Wasserloos, M Stitt, A J Kanai, M K McLaughlin, B R Pitt, E S Levitan
Although the function of metallothionein (MT), a 6- to 7-kDa cysteine-rich metal binding protein, remains unclear, it has been suggested from in vitro studies that MT is an important component of intracellular redox signaling, including being a target for nitric oxide (NO). To directly study the interaction between MT and NO in live cells, we generated a fusion protein consisting of MT sandwiched between two mutant green fluorescent proteins (GFPs). In vitro studies with this chimera (FRET-MT) demonstrate that fluorescent resonance energy transfer (FRET) can be used to follow conformational changes indicative of metal release from MT...
January 4, 2000: Proceedings of the National Academy of Sciences of the United States of America
T C Holmes, D A Fadool, R Ren, I B Levitan
The human Kv1.5 potassium channel (hKv1.5) contains proline-rich sequences identical to those that bind to Src homology 3 (SH3) domains. Direct association of the Src tyrosine kinase with cloned hKv1.5 and native hKv1.5 in human myocardium was observed. This interaction was mediated by the proline-rich motif of hKv1.5 and the SH3 domain of Src. Furthermore, hKv1.5 was tyrosine phosphorylated, and the channel current was suppressed, in cells coexpressing v-Src. These results provide direct biochemical evidence for a signaling complex composed of a potassium channel and a protein tyrosine kinase...
December 20, 1996: Science
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