Publish in OALib Journal

ISSN: 2333-9721

APC: Only $99


Any time

2019 ( 144 )

2018 ( 365 )

2017 ( 381 )

2016 ( 417 )

Custom range...

Search Results: 1 - 10 of 208851 matches for " Lori L. Isom "
All listed articles are free for downloading (OA Articles)
Page 1 /208851
Display every page Item
Na+ Channel β Subunits: Overachievers of the Ion Channel Family
William J. Brackenbury,Lori L. Isom
Frontiers in Pharmacology , 2011, DOI: 10.3389/fphar.2011.00053
Abstract: Voltage-gated Na+ channels (VGSCs) in mammals contain a pore-forming α subunit and one or more β subunits. There are five mammalian β subunits in total: β1, β1B, β2, β3, and β4, encoded by four genes: SCN1B–SCN4B. With the exception of the SCN1B splice variant, β1B, the β subunits are type I topology transmembrane proteins. In contrast, β1B lacks a transmembrane domain and is a secreted protein. A growing body of work shows that VGSC β subunits are multifunctional. While they do not form the ion channel pore, β subunits alter gating, voltage-dependence, and kinetics of VGSCα subunits and thus regulate cellular excitability in vivo. In addition to their roles in channel modulation, β subunits are members of the immunoglobulin superfamily of cell adhesion molecules and regulate cell adhesion and migration. β subunits are also substrates for sequential proteolytic cleavage by secretases. An example of the multifunctional nature of β subunits is β1, encoded by SCN1B, that plays a critical role in neuronal migration and pathfinding during brain development, and whose function is dependent on Na+ current and γ-secretase activity. Functional deletion of SCN1B results in Dravet Syndrome, a severe and intractable pediatric epileptic encephalopathy. β subunits are emerging as key players in a wide variety of physiopathologies, including epilepsy, cardiac arrhythmia, multiple sclerosis, Huntington’s disease, neuropsychiatric disorders, neuropathic and inflammatory pain, and cancer. β subunits mediate multiple signaling pathways on different timescales, regulating electrical excitability, adhesion, migration, pathfinding, and transcription. Importantly, some β subunit functions may operate independently of α subunits. Thus, β subunits perform critical roles during development and disease. As such, they may prove useful in disease diagnosis and therapy.
Cloning and expression of a zebrafish SCN1B ortholog and identification of a species-specific splice variant
Amanda J Fein, Laurence S Meadows, Chunling Chen, Emily A Slat, Lori L Isom
BMC Genomics , 2007, DOI: 10.1186/1471-2164-8-226
Abstract: Two β1-like subunit mRNAs from zebrafish, scn1ba_tv1 and scn1ba_tv2, arise from alternative splicing of scn1ba. The deduced amino acid sequences of Scn1ba_tv1 and Scn1ba_tv2 are identical except for their C-terminal domains. The C-terminus of Scn1ba_tv1 contains a tyrosine residue similar to that found to be critical for ankyrin association and Na+ channel modulation in mammalian β1. In contrast, Scn1ba_tv2 contains a unique, species-specific C-terminal domain that does not contain a tyrosine. Immunohistochemical analysis shows that, while the expression patterns of Scn1ba_tv1 and Scn1ba_tv2 overlap in some areas of the brain, retina, spinal cord, and skeletal muscle, only Scn1ba_tv1 is expressed in optic nerve where its staining pattern suggests nodal expression. Both scn1ba splice forms modulate Na+ currents expressed by zebrafish scn8aa, resulting in shifts in channel gating mode, increased current amplitude, negative shifts in the voltage dependence of current activation and inactivation, and increases in the rate of recovery from inactivation, similar to the function of mammalian β1 subunits. In contrast to mammalian β1, however, neither zebrafish subunit produces a complete shift to the fast gating mode and neither subunit produces complete channel inactivation or recovery from inactivation.These data add to our understanding of structure-function relationships in Na+ channel β1 subunits and establish zebrafish as an ideal system in which to determine the contribution of scn1ba to electrical excitability in vivo.Voltage gated Na+ channel β1 (Scn1b) subunits are multi-functional proteins that participate in inter- and intra-cellular communication on multiple time scales via modulation of electrical signal transduction and cell adhesion [1,2]. β1 subunits modulate Na+ currents [3], regulate the level of Na+ channel cell surface expression [4], and participate in cell adhesive interactions that lead to changes in cell migration [5], cellular aggregation [6], cyto
Ordered Assembly of the Adhesive and Electrochemical Connections within Newly Formed Intercalated Disks in Primary Cultures of Adult Rat Cardiomyocytes
Sarah B. Geisler,Kathleen J. Green,Lori L. Isom,Sasha Meshinchi,Jeffrey R. Martens,Mario Delmar,Mark W. Russell
Journal of Biomedicine and Biotechnology , 2010, DOI: 10.1155/2010/624719
Abstract: The intercalated disk (ID) is a complex structure that electromechanically couples adjoining cardiac myocytes into a functional syncitium. The integrity of the disk is essential for normal cardiac function, but how the diverse elements are assembled into a fully integrated structure is not well understood. In this study, we examined the assembly of new IDs in primary cultures of adult rat cardiac myocytes. From 2 to 5 days after dissociation, the cells flatten and spread, establishing new cell-cell contacts in a manner that recapitulates the in vivo processes that occur during heart development and myocardial remodeling. As cells make contact with their neighbors, transmembrane adhesion proteins localize along the line of apposition, concentrating at the sites of membrane attachment of the terminal sarcomeres. Cx43 gap junctions and ankyrin-G, an essential cytoskeletal component of voltage gated sodium channel complexes, were secondarily recruited to membrane domains involved in cell-cell contacts. The consistent order of the assembly process suggests that there are specific scaffolding requirements for integration of the mechanical and electrochemical elements of the disk. Defining the relationships that are the foundation of disk assembly has important implications for understanding the mechanical dysfunction and cardiac arrhythmias that accompany alterations of ID architecture.
Altered Cardiac Electrophysiology and SUDEP in a Model of Dravet Syndrome
David S. Auerbach, Julie Jones, Brittany C. Clawson, James Offord, Guy M. Lenk, Ikuo Ogiwara, Kazuhiro Yamakawa, Miriam H. Meisler, Jack M. Parent, Lori L. Isom
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0077843
Abstract: Objective Dravet syndrome is a severe form of intractable pediatric epilepsy with a high incidence of SUDEP: Sudden Unexpected Death in epilepsy. Cardiac arrhythmias are a proposed cause for some cases of SUDEP, yet the susceptibility and potential mechanism of arrhythmogenesis in Dravet syndrome remain unknown. The majority of Dravet syndrome patients have de novo mutations in SCN1A, resulting in haploinsufficiency. We propose that, in addition to neuronal hyperexcitability, SCN1A haploinsufficiency alters cardiac electrical function and produces arrhythmias, providing a potential mechanism for SUDEP. Methods Postnatal day 15-21 heterozygous SCN1A-R1407X knock-in mice, expressing a human Dravet syndrome mutation, were used to investigate a possible cardiac phenotype. A combination of single cell electrophysiology and in vivo electrocardiogram (ECG) recordings were performed. Results We observed a 2-fold increase in both transient and persistent Na+ current density in isolated Dravet syndrome ventricular myocytes that resulted from increased activity of a tetrodotoxin-resistant Na+ current, likely Nav1.5. Dravet syndrome myocytes exhibited increased excitability, action potential duration prolongation, and triggered activity. Continuous radiotelemetric ECG recordings showed QT prolongation, ventricular ectopic foci, idioventricular rhythms, beat-to-beat variability, ventricular fibrillation, and focal bradycardia. Spontaneous deaths were recorded in 2 DS mice, and a third became moribund and required euthanasia. Interpretation These data from single cell and whole animal experiments suggest that altered cardiac electrical function in Dravet syndrome may contribute to the susceptibility for arrhythmogenesis and SUDEP. These mechanistic insights may lead to critical risk assessment and intervention in human patients.
Cations Form Sequence Selective Motifs within DNA Grooves via a Combination of Cation-Pi and Ion-Dipole/Hydrogen Bond Interactions
Mikaela Stewart, Tori Dunlap, Elizabeth Dourlain, Bryce Grant, Lori McFail-Isom
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0071420
Abstract: The fine conformational subtleties of DNA structure modulate many fundamental cellular processes including gene activation/repression, cellular division, and DNA repair. Most of these cellular processes rely on the conformational heterogeneity of specific DNA sequences. Factors including those structural characteristics inherent in the particular base sequence as well as those induced through interaction with solvent components combine to produce fine DNA structural variation including helical flexibility and conformation. Cation-pi interactions between solvent cations or their first hydration shell waters and the faces of DNA bases form sequence selectively and contribute to DNA structural heterogeneity. In this paper, we detect and characterize the binding patterns found in cation-pi interactions between solvent cations and DNA bases in a set of high resolution x-ray crystal structures. Specifically, we found that monovalent cations (Tl+) and the polarized first hydration shell waters of divalent cations (Mg2+, Ca2+) form cation-pi interactions with DNA bases stabilizing unstacked conformations. When these cation-pi interactions are combined with electrostatic interactions a pattern of specific binding motifs is formed within the grooves.
Osteoporosis knowledge, beliefs, and calcium intake of college students: Utilization of the health belief model  [PDF]
Ellen Edmonds, Lori W. Turner, Stuart L. Usdan
Open Journal of Preventive Medicine (OJPM) , 2012, DOI: 10.4236/ojpm.2012.21005
Abstract: Objective: The purpose of this study was to examine the relationships between osteoporosis knowledge, beliefs and calcium intake among college students. This study also examined perceived susceptibility, severity, benefits, barriers and self-efficacy related to osteoporosis prevention. Participants: Seven hundred and ninety two (n = 792) men and women ages 17 - 31 of all ethnicities at a mid-western regional university in the US participated in the study. Methods: The Osteoporosis Knowledge Test, Osteoporosis Health Belief Scale, and Osteoporosis Preventing Behaviors Survey were utilized. Each of these tools were previously validated and found reliable. Correlation and multiple regression analyses were completed. Results: Participants did not perceive themselves as susceptible to osteoporosis and perceived minimal barriers to calcium intake. Their knowledge was minimal concerning alternate sources of calcium. Conclusions: Prevention programs should aim to increase osteoporosis knowledge of risk factors and osteoprotective behaviors and to decrease high-risk behaviors during college years when behavior changes can have the strongest impact on bone health.
Compassionate Care: Can it be Defined and Measured? The Development of the Compassionate Care Assessment Tool
Lori Burnell,Donna L. Agan
International Journal of Caring Sciences , 2013,
Abstract: Background: Compassion has not been universally defined or understood, nonetheless is recognized as a component of nursing excellence. If compassionate care is routine in health care delivery models, nursing behaviors and actions that exemplify compassion ought to be easily identifiable to patients. However, a standardized scale measuring compassionate care attributes has been notably absent.Objective: To address this gap and ascertain the importance of compassionate care to patients, a Compassionate Care Assessment Tool (CCAT) was formulated. This new tool, derived from a pilot study of two published surveys, combined the constructs of compassion and caring to generate 28 elements of compassionate care.Methodology: The CCAT was administered to 250 hospitalized patients. Patients were asked to rate (a) the importance of these items to compassionate care and (b) the extent to which nurses made this type of care apparent to them.Results: Four categorical segments illustrated compassion from the patients’ perspective: the ability to establish meaningful connections, meet expectations, exhibit caring attributes, and function as a capable practitioner.Conclusions: The provision of compassionate care requires a holistic approach. Patients value nurses forming personal connections, serving as their advocates, and responding to their individual needs.
American Society for Clinical Oncology 40th Annual Meeting, New Orleans, LA, 5–8 June 2004: breast cancer highlights
Mark L Sundermeyer, Lori J Goldstein
Breast Cancer Research , 2004, DOI: 10.1186/bcr944
Abstract: Emerging diagnostic tools in breast cancer include magnetic resonance imaging (MRI) and positron emission tomography evaluation. Data presented this year add to the growing understanding of how these modalities can be applied to patient management.The use of MRI in evaluation of the breast remains a controversial topic. In an abstract presented by Dr Schnall on behalf of the International Breast MRI Consortium, the value of MRI in multifocal disease was assessed [1]. This multicenter prospective trial enrolled 1004 women with suspicious mammograms and/or clinical findings. Prior to undergoing biopsy, these women received mammograms and underwent MRI of the breast. Biopsy of the index lesion was malignant in 428 women. Of these, 103 women had a second area of suspicion indicated by MRI compared with 36 women by mammogram alone. Biopsy confirmed multifocal disease in 56 of 78 MRI-detected abnormalities and in 17 of 20 mammogram-detected abnormalities. This study confirms the higher yield of MRI for detecting multifocal disease than the mammogram. It has yet to be shown that this higher yield will translate into clinical benefit for patients. Randomized trials to assess this benefit are warranted.One of the biggest concerns expressed by breast cancer patients prior to surgical intervention is the effect of axillary evaluation on mobility, pain symptoms and risk of lymphedema. Studies presented this year address the optimal approach to axillary evaluation in terms of morbidity, and address whether certain subgroups of women do not require an axillary evaluation.Two randomized trials were presented that address the role of axillary evaluation in clinically node-negative breast cancer patients. The initial results of the ALMANAC study were presented by Dr Mansel [2]. This study compared sentinel lymph node biopsy with axillary dissection, with regards to primary outcomes of arm and axillary morbidity, the quality of life and costs in terms of resources. A total of 1031 pa
Demand-driven Inlining in a Region-based Optimizer for ILP Architectures
Thomas P. Way,Lori L. Pollock
Computer Science , 2006,
Abstract: Region-based compilation repartitions a program into more desirable compilation units using profiling information and procedure inlining to enable region formation analysis. Heuristics play a key role in determining when it is most beneficial to inline procedures during region formation. An ILP optimizing compiler using a region-based approach restructures a program to better reflect dynamic behavior and increase interprocedural optimization and scheduling opportunities. This paper presents an interprocedural compilation technique which performs procedure inlining on-demand, rather than as a separate phase, to improve the ability of a region-based optimizer to control code growth, compilation time and memory usage while improving performance. The interprocedural region formation algorithm utilizes a demand-driven, heuristics-guided approach to inlining, restructuring an input program into interprocedural regions. Experimental results are presented to demonstrate the impact of the algorithm and several inlining heuristics upon a number of traditional and novel compilation characteristics within a region-based ILP compiler and simulator.
A Hypomethylating Variant of MTHFR, 677C>T, Blunts the Neural Response to Errors in Patients with Schizophrenia and Healthy Individuals
Joshua L. Roffman,Adam Z. Nitenson,Yigal Agam,Marlisa Isom,Jesse S. Friedman,Kara A. Dyckman,David G. Brohawn,Jordan W. Smoller,Donald C. Goff,Dara S. Manoach
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0025253
Abstract: Responding to errors is a critical first step in learning from mistakes, a process that is abnormal in schizophrenia. To gain insight into the neural and molecular mechanisms of error processing, we used functional MRI to examine effects of a genetic variant in methylenetetrahydrofolate reductase (MTHFR 677C>T, rs1801133) that increases risk for schizophrenia and that has been specifically associated with increased perseverative errors among patients. MTHFR is a key regulator of the intracellular one-carbon milieu, including DNA methylation, and each copy of the 677T allele reduces MTHFR activity by 35%.
Page 1 /208851
Display every page Item

Copyright © 2008-2017 Open Access Library. All rights reserved.