Abstract:
:It is now known that the flexibility of the troponin T (TnT) tail determines thin filament conformation and hence cross-bridge cycling properties, expanding the classic structural role of TnT to a dynamic role regulating sarcomere function. Here, using transgenic mice bearing R-92W and R-92L missense mutations in cardiac TnT known to alter the flexibility of the TnT tropomyosin-binding domain, we found mutation-specific differences in the cost of contraction at the whole heart level. Compared to age- and gender-matched sibling hearts, mutant hearts demonstrate greater ATP utilization measured using (31)P NMR spectroscopy as decreases in [ATP] and [PCr] and |DeltaG(~ATP)| at all workloads and profound systolic and diastolic dysfunction at all energetic states. R-92W hearts showed more severe energetic abnormalities and greater contractile dysfunction than R-92L hearts. The cost of increasing contraction was abnormally high when [Ca(2+)] was used to increase work in mutant hearts but was normalized with supply of the beta-adrenergic agonist dobutamine. These results show that R-92L and R-92W mutations in the TM-binding domain of cardiac TnT alter thin filament structure and flexibility sufficiently to cause severe defects in both whole heart energetics and contractile performance, and that the magnitude of these changes is mutation specific.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
He H,Javadpour MM,Latif F,Tardiff JC,Ingwall JSdoi
10.1529/biophysj.107.107557subject
Has Abstractpub_date
2007-09-01 00:00:00pages
1834-44issue
5eissn
0006-3495issn
1542-0086pii
S0006-3495(07)71438-8journal_volume
93pub_type
杂志文章abstract::To give a realistic representation of the pulse propagation in arteries a theoretical analysis of the wave propagation through a viscous incompressible fluid contained in an initially stressed elastic tube is considered. The tube is assumed to be orthotropic and its longitudinal motion is constrained by a uniformly di...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/s0006-3495(68)86512-9
更新日期:1968-05-01 00:00:00
abstract::Nuclear transport receptors (NTRs) mediate nucleocytoplasmic transport via their affinity for unstructured proteins (polymers) in the nuclear pore complex (NPC). Here, we have modeled the effect of NTRs on polymeric structure in the nanopore confinement of the NPC central conduit. The model explicitly takes into accou...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2013.11.013
更新日期:2013-12-17 00:00:00
abstract::A brief summary of the major results in enhanced wound healing by electrolysis in animals and humans is presented along with the results of enhanced growth by electrolysis in plants. Hypotheses of normal and enhanced wound healing in animal and plants are reviewed. A comparison of the experimental results indicates st...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(79)85230-3
更新日期:1979-09-01 00:00:00
abstract::Membrane proteins diffuse within the membrane, form oligomers and supramolecular assemblies. Using high-speed atomic force microscopy, we present direct experimental measure of an in-membrane-plane interaction potential between membrane proteins. In purple membranes, ATP-synthase c-rings formed dimers that temporarily...
journal_title:Biophysical journal
pub_type: 信件
doi:10.1016/j.bpj.2010.07.028
更新日期:2010-10-06 00:00:00
abstract::Although the structure, function, conformational dynamics, and controlled thermodynamics of proteins are manifested by their corresponding amino acid sequences, the natural rules for molecular design and their corresponding interplay remain obscure. In this study, we focused on the role of internal cavities of protein...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2014.11.012
更新日期:2015-01-06 00:00:00
abstract::The most probable source of force generation in muscle fibers in the rotation of the myosin head when bound to actin. This laboratory has demonstrated that ATP induces microsecond rotational motions of spin-labeled myosin heads bound to actin (Berger, C. L. E. C. Svensson, and D. D. Thomas. 1989. Proc. Natl. Acad. Sci...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(91)82338-4
更新日期:1991-06-01 00:00:00
abstract::The dependence of the fluorescence of catalase upon the concentration of added superoxide dismutase (SOD) indicates that SOD binds to saturable sites on catalase. The affinity of SOD for these sites varies with temperature, and with the concentration of each of three nominally inert polymeric additives--dextran 70, Fi...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2010.05.013
更新日期:2010-08-04 00:00:00
abstract::Ras is a membrane-anchored signaling protein that serves as a hub for many signaling pathways and also plays a prominent role in cancer. The intrinsic behavior of Ras on the membrane has captivated the biophysics community in recent years, especially the possibility that it may form dimers. In this article, we describ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2017.10.042
更新日期:2018-01-09 00:00:00
abstract::The nucleus has a smooth, regular appearance in normal cells, and its shape is greatly altered in human pathologies. Yet, how the cell establishes nuclear shape is not well understood. We imaged the dynamics of nuclear shaping in NIH3T3 fibroblasts. Nuclei translated toward the substratum and began flattening during t...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2015.07.006
更新日期:2015-08-18 00:00:00
abstract::We present a two-component coarse-grained molecular-dynamics model for simulating the erythrocyte membrane. The proposed model possesses the key feature of combing the lipid bilayer and the erythrocyte cytoskeleton, thus showing both the fluidic behavior of the lipid bilayer and the elastic properties of the erythrocy...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2011.11.4012
更新日期:2012-01-04 00:00:00
abstract::The mathematical model of steady-state iron kinetics in the human presented here extends the use of radioactive tracer observations in the determination of erythron maturative and proliferative behavior. Functions descriptive of that behavior appear explicitly in the model together with functions customarily measured ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(65)86750-9
更新日期:1965-11-01 00:00:00
abstract::The accurate prediction of membrane-insertion probability for arbitrary protein sequences is a critical challenge to identifying membrane proteins and determining their folded structures. Although algorithms based on sequence statistics have had moderate success, a complete understanding of the energetic factors that ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2012.01.021
更新日期:2012-02-22 00:00:00
abstract::The investigation of the mechanism of protein folding is complicated by the context dependence of the rates of intramolecular contact formation. Methods based on site-specific labeling and ultrafast spectroscopic detection of fluorescence signals were developed for monitoring the rates of individual subdomain folding ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2017.01.037
更新日期:2017-05-09 00:00:00
abstract::Protein splicing is an autocatalytic reaction where an intervening element (intein) is excised and the remaining two flanking sequences (exteins) are joined. The reaction requires specific conserved residues, and activity may be affected by both the intein and the extein sequence. Predicting how sequence will affect a...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2011.02.037
更新日期:2011-05-04 00:00:00
abstract::Proton permeation rates across membranes of a synthetic branch-chained glycolipid, 1,3-di-O-phytanyl-2-O-(beta-D-maltotriosyl)glycerol (Mal3(Phyt)2) as well as a branch-chained phospholipid, diphytanoylphosphatidylcholine (DPhPC) were lower than those of straight-chained lipids such as egg yolk phosphatidylcholine (EP...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(01)75970-X
更新日期:2001-12-01 00:00:00
abstract::We study a Brownian dynamics simulation model of a biopolymeric shell deformed by axial forces exerted at opposing poles. The model exhibits two distinct, linear force-extension regimes, with the response to small tensions governed by linear elasticity and the response to large tensions governed by an effective spring...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2017.08.034
更新日期:2017-10-17 00:00:00
abstract::It has been previously demonstrated that the Stepanov equation provides a rather good description of the absorption/fluorescence spectra in Photosystem I, even though excited state equilibration is not rapid with respect to the excited state decay. In the present article this apparent contradiction is examined analyti...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(03)74805-X
更新日期:2003-12-01 00:00:00
abstract::Platinum-containing molecules are widely used as anticancer drugs. These molecules exert cytotoxic effects by binding to DNA through various mechanisms. The binding between DNA and platinum-based drugs hinders the opening of DNA, and therefore, DNA duplication and transcription are severely hampered. Overall, impeding...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2016.02.030
更新日期:2016-05-24 00:00:00
abstract::A recently completed model of Ca concentration and movements in the cardiac cell diadic cleft space predicts that removal or neutralization of inner sarcolemmal (SL) leaflet anionic Ca-binding sites at the sarcolemmal border of this space will greatly diminish Na/Ca exchange-mediated Ca efflux. The present study tests...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(96)79792-8
更新日期:1996-05-01 00:00:00
abstract::Neurons communicate by releasing neurotransmitters that are stored in intracellular vesicular compartments. PC12 cells are frequently used as a model secretory cell line that is described to have two subpools of vesicles: small clear vesicles and dense core vesicles. We measured transmitter molecules released from ves...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2014.10.060
更新日期:2014-12-16 00:00:00
abstract::A kinetic analysis of membrane conductance under conditions of stationary flow is presented. The semipermeable membrane is idealized as a homogeneous laminar phase separating ionic solutions on either side. It is assumed, without consideration of the mechanisms involved, that some ion species permeate the membrane whi...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(65)86757-1
更新日期:1965-11-01 00:00:00
abstract::Verapamil and amlodipine are calcium ion influx inhibitors of wide clinical use. They are partially charged at neutral pH and exhibit amphiphilic properties. The noncharged species can easily cross the lipid membrane. We have measured with solid-state NMR the structural changes induced by verapamil upon incorporation ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.106.089581
更新日期:2006-10-15 00:00:00
abstract::The barbiturate pentobarbital binds to gamma-aminobutyric acid type A (GABA(A)) receptors, and this interaction plays an important role in the anesthetic action of this drug. Depending on its concentration, pentobarbital can potentiate (approximately 10-100 microM), activate (approximately 100-800 microM), or block (a...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2008.09.037
更新日期:2009-01-01 00:00:00
abstract::Neal and Cunningham (Neal, M. J., and J. R. Cunningham. 1995. J. Physiol. (Lond.). 482:363-372) showed that GABA(B) agonists and glycinergic antagonists enhance the light-evoked release of retinal acetylcholine. They proposed that glycinergic cells inhibit the cholinergic Starburst amacrine cells and are in turn inhib...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.105.072256
更新日期:2006-07-15 00:00:00
abstract::The infrared spectra of tripalmitoyl glyceride confirm the tuning fork configuration previously attributed to trilauroyl glyceride (Small, D. M. 1986. Handbook of Lipid Research. Vol. 4). The acyl chains in solid tripalmitoyl glycerol, either within each molecule or between neighboring molecules, are oriented parallel...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(89)82730-4
更新日期:1989-11-01 00:00:00
abstract::The effects of Mg++ on the spatial organization of nuclei from rat hepatocytes are analyzed in the range 0-60 mM, in the presence of suitable concentrations of KCl to reproduce physiological conditions. It is shown that the scatter-signal distribution measured by means of a flow microfluorimeter is greatly affected by...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(85)83938-2
更新日期:1985-04-01 00:00:00
abstract::Sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA) and phospholamban (PLB) are essential for intracellular Ca2+ transport in myocytes. Ca2+-dependent activation of SERCA-PLB provides a control function that regulates cytosolic and SR Ca2+ levels. Although experimental and computational studies alone have led to a greater...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2020.09.014
更新日期:2020-11-03 00:00:00
abstract::Many experiments have measured the effect of force on the dissociation of single selectin bonds, but it is not yet clear how the force dependence of molecular dissociation can influence the rolling of cells expressing selectin molecules. Recent experiments using constant-force atomic force microscopy or high-resolutio...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.106.082321
更新日期:2007-02-01 00:00:00
abstract::Helix-coil transitions in polyalanine molecules of length 10 are studied by multi-canonical Monte Carlo simulations. The solvation effects are included by either a distance-dependent dielectric permittivity or by a term that is proportional to the solvent-accessible surface area of the peptide. We found a strong depen...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(02)75668-3
更新日期:2002-06-01 00:00:00
abstract::Coarse-grained molecular dynamics simulations are applied to explore the experimentally observed ability of the liquid-ordered (lo)/liquid-disordered (ld) phase boundary to facilitate viral membrane fusion. Surprisingly, a formed fusion stalk can be both attracted (i.e., stalkophilic) and repelled (i.e., stalkophobic)...
journal_title:Biophysical journal
pub_type: 信件
doi:10.1016/j.bpj.2017.04.031
更新日期:2017-06-20 00:00:00