Abstract:
:We developed a multicellular model characterized by a high degree of heterogeneity to investigate possible mechanisms that underlie circadian network synchronization and rhythmicity in the suprachiasmatic nucleus (SCN). We populated a two-dimensional grid with 400 model neurons coupled via γ-aminobutyric acid (GABA) and vasoactive intestinal polypeptide (VIP) neurotransmitters through a putative Ca(2+) mediated signaling cascade to investigate their roles in gene expression and electrical firing activity of cell populations. As observed experimentally, our model predicted that GABA would affect the amplitude of circadian oscillations but not synchrony among individual oscillators. Our model recapitulated experimental findings of decreased synchrony and average periods, loss of rhythmicity, and reduced circadian amplitudes as VIP signaling was eliminated. In addition, simulated increases of VIP reduced periodicity and synchrony. We therefore postulated a physiological range of VIP within which the system is able to produce sustained and synchronized oscillations. Our model recapitulated experimental findings of diminished amplitudes and periodicity with decreasing intracellular Ca(2+) concentrations, suggesting that such behavior could be due to simultaneous decrease of individual oscillation amplitudes and population synchrony. Simulated increases in Cl(-) levels resulted in increased Cl(-) influx into the cytosol, a decrease of inhibitory postsynaptic currents, and ultimately a shift of GABA-elicited responses from inhibitory to excitatory. The simultaneous reduction of IPSCs and increase in membrane resting potential produced GABA dose-dependent increases in firing rates across the population, as has been observed experimentally. By integrating circadian gene regulation and electrophysiology with intracellular and intercellular signaling, we were able to develop the first (to our knowledge) multicellular model that allows the effects of clock genes, electrical firing, Ca(2+), GABA, and VIP on circadian system behavior to be predicted.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Vasalou C,Herzog ED,Henson MAdoi
10.1016/j.bpj.2011.04.051subject
Has Abstractpub_date
2011-07-06 00:00:00pages
12-20issue
1eissn
0006-3495issn
1542-0086pii
S0006-3495(11)00561-3journal_volume
101pub_type
杂志文章abstract::The shapes of fluorescence induction curves in spinach chloroplasts, measured using double-flash pump-probe techniques, are shown to depend on the duration of the actinic flashes. For flash durations tau(0) = 2 mus, the variable fluorescence F(nu) grows exponentially (or nearly so) with increasing fluence J of the a...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(91)82233-0
更新日期:1991-02-01 00:00:00
abstract::We report here several unusual features of inactivation of the rat Kv2.1 delayed rectifier potassium channel, expressed in Xenopus oocytes. The voltage dependence of inactivation was U-shaped, with maximum inactivation near 0 mV. During a maintained depolarization, development of inactivation was slow and only weakly ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(98)77888-9
更新日期:1998-04-01 00:00:00
abstract::Diluted bull semen samples were bombarded with a 24 Mev proton beam. Dose response curves for the fraction of cells which survived the bombardment and for the average velocity of the surviving cells were measured. Target theory indicated a cross section of the sensitive volume of 2.1 x 10(-10) cm(2). Respiration measu...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(69)86421-0
更新日期:1969-06-01 00:00:00
abstract::Glasses used to fabricate patch pipettes may release components which affect ion channels (Cota, G., and C.M. Armstrong. 1988. Biophys. J. 53:107-109; Furman, R.E., and J.C. Tanaka. 1988. Biophys. J. 53:287-292; Rojas, L., and C. Zuazaga. 1988. Neurosci. Lett. 88:39-44). The gating properties of maxi K+ channels from ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(91)82127-0
更新日期:1991-10-01 00:00:00
abstract::The giant protein titin is responsible for the elasticity of nonactivated muscle sarcomeres. Titin-based passive stiffness in myocardium is modulated by titin-isoform switching and protein-kinase (PK)A- or PKG-dependent titin phosphorylation. Additional modulatory effects on titin stiffness may arise from disulfide bo...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2009.05.037
更新日期:2009-08-05 00:00:00
abstract::It is shown that alpha-helical content of eleven proteins is well correlated with alanine plus leucine content. These residues, taken singly or together, are to a first approximation randomly distributed in the four proteins whose tertiary structures have been determined (i.e., myoglobin, lysozyme, ribonuclease, alpha...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(68)86553-1
更新日期:1968-11-01 00:00:00
abstract::Proteins are not rigid molecules, but exhibit internal motions on timescales ranging from femto- to milliseconds and beyond. In solution, proteins also experience global translational and rotational motions, sometimes on timescales comparable to those of the internal fluctuations. The possibility that internal and glo...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2011.05.041
更新日期:2011-07-06 00:00:00
abstract::RNA junctions are common secondary structural elements present in a wide range of RNA species. They play crucial roles in directing the overall folding of RNA molecules as well as in a variety of biological functions. In particular, there has been great interest in the dynamics of RNA junctions, including conformation...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2013.12.008
更新日期:2014-01-21 00:00:00
abstract::Cell motility is essential in a variety of biological phenomena ranging from early development to organ homeostasis and diseases. This phenomenon has mainly been studied and characterized on flat surfaces in vitro, whereas such conditions are rarely observed in vivo. Recently, cell motion in three-dimensional microfab...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2020.08.028
更新日期:2020-10-06 00:00:00
abstract::Nef is an HIV-1 accessory protein that directly contributes to AIDS progression. Nef is myristoylated on the N-terminus, associates with membranes, and may undergo a transition from a solution conformation to a membrane-associated conformation. It has been hypothesized that conformational rearrangement enables membran...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2010.07.016
更新日期:2010-09-22 00:00:00
abstract::The detection of the 1H NMR signal of myoglobin (Mb) in tissue opens an opportunity to examine its cellular diffusion property, which is central to its purported role in facilitating oxygen transport. In perfused myocardium the field-dependent transverse relaxation analysis of the deoxy Mb proximal histidyl NdeltaH in...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(97)78305-X
更新日期:1997-11-01 00:00:00
abstract::A detailed treatment is provided of the various free-energy terms that contribute to the transfer of a polyalanine alpha-helix from the aqueous phase into lipid bilayers. In agreement with previous work, the hydrophobic effect is found to provide the major driving force for helix insertion. However, an opposing effect...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(96)79744-8
更新日期:1996-04-01 00:00:00
abstract::Xenopus oocytes are widely employed for heterologous expression of cloned proteins, particularly electrogenic molecules such as ion channels and transporters. The high levels of expression readily obtained permit detailed investigations without interference from endogenous conductances. Injection of min K mRNA into Xe...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(95)79964-7
更新日期:1995-09-01 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::Chiral objects which scatter and absorb preferentially left versus right circularly polarized light give rise to bright-field circular dichroism (CD) images containing contributions from both these two phenomena. These contributions are separated and characterized mathematically, and the effect of the dimensions of th...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(91)82334-7
更新日期:1991-06-01 00:00:00
abstract::The cellular cytoplasm is a complex, heterogeneous environment (both spatially and temporally) that exhibits viscoelastic behavior. To further develop our quantitative insight into cellular transport, we analyze data sets of mRNA molecules fluorescently labeled with MS2-GFP tracked in real time in live Escherichia col...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2016.11.3208
更新日期:2017-02-07 00:00:00
abstract::The relative contributions of the allosteric and affinity factors toward the change in p50 have been calculated for a series of effectors of hemoglobin (Hb). Shifts in the ligand affinity of deoxy Hb and the values for 50% ligand saturation (p50) were obtained from oxygen equilibrium data. Because the high-affinity pa...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(90)82556-X
更新日期:1990-03-01 00:00:00
abstract::Deuterium nuclear magnetic resonance spectroscopy was used to study the thermotropic phase behavior of dilauroylphosphatidylcholine (DLPC) bilayers at pressures up to 221 MPa. Pressure was found to separate the liquid crystal to gel transition from the gel to ordered crystalline phase transition. The jump in chain ord...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(96)79842-9
更新日期:1996-06-01 00:00:00
abstract::The lateral mobility of the neural cell adhesion molecule (NCAM) was examined using single particle tracking (SPT). Various isoforms of human NCAM, differing in their ectodomain, their membrane anchorage mode, or the size of their cytoplasmic domain, were expressed in National Institutes of Health 3T3 cells and C2C12 ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(98)77787-2
更新日期:1998-01-01 00:00:00
abstract::We examined four cardiomyopathy-causing mutations of troponin I that appear to disturb function by altering the distribution of thin filament states. The R193H (mouse) troponin I mutant had greater than normal actin-activated myosin-S1 ATPase activity in both the presence and absence of calcium. The rate of ATPase act...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2008.12.3909
更新日期:2009-03-18 00:00:00
abstract::We propose an improved version of variable-angle total internal reflection fluorescence microscopy (vaTIRFM) adapted to modern TIRF setup. This technique involves the recording of a stack of TIRF images, by gradually increasing the incident angle of the light beam on the sample. A comprehensive theory was developed to...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2016.06.043
更新日期:2016-09-20 00:00:00
abstract::Cationic liposomes (CLs) are used worldwide as gene vectors (carriers) in nonviral clinical applications of gene delivery, albeit with unacceptably low transfection efficiencies (TE). We present three-dimensional laser scanning confocal microscopy studies revealing distinct interactions between CL-DNA complexes, for b...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(03)70055-1
更新日期:2003-05-01 00:00:00
abstract::The group-additive decomposition of the unfolding free energy of a protein in an osmolyte solution relative to that in water poses a fundamental paradox: whereas the decomposition describes the experimental results rather well, theory suggests that a group-additive decomposition of free energies is, in general, not va...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2013.08.011
更新日期:2013-09-17 00:00:00
abstract::For many cell types, growth, differentiation, and motility are dependent on receptor-mediated adhesion to ligand-coated surfaces. Focal contacts are strong, specialized, adhesive connections between cell and substrate in which receptors aggregate and connect extracellular ligand to intracellular cytoskeletal molecules...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(93)81456-5
更新日期:1993-03-01 00:00:00
abstract::To understand the thermodynamic exclusion of Na(+) relative to K(+) from the S(2) site of the selectivity filter, the distribution P(X)(epsilon) (X = K(+) or Na(+)) of the binding energy (epsilon) of the ion with the channel is analyzed using the potential distribution theorem. By expressing the excess chemical potent...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2008.12.3917
更新日期:2009-03-18 00:00:00
abstract::We studied the photocurrents of a cyanobacterial rhodopsin Gloeobacter violaceus (GR) in Xenopus laevis oocytes and HEK-293 cells. This protein is a light-driven proton pump with striking similarities to marine proteorhodopsins, including the D121-H87 cluster of the retinal Schiff base counterion and a glutamate at po...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2013.08.031
更新日期:2013-11-05 00:00:00
abstract::Secondary structure formation of nucleic acids strongly depends on salt concentration and temperature. We develop a theory for RNA folding that correctly accounts for sequence effects, the entropic contributions associated with loop formation, and salt effects. Using an iterative expression for the partition function ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2011.04.038
更新日期:2011-06-08 00:00:00
abstract::The structure of dynamic states in biological networks is of fundamental importance in understanding their function. Considering the elementary reaction structure of reconstructed metabolic networks, we show how appreciation of a gradient matrix, G =dv/dx (where v is the vector of fluxes and x is the vector of concent...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2009.06.049
更新日期:2009-09-02 00:00:00
abstract::There are several examples of membrane-associated protein domains that target curved membranes. This behavior is believed to have functional significance in a number of essential pathways, such as clathrin-mediated endocytosis, which involve dramatic membrane remodeling and require the recruitment of various cofactors...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2011.01.036
更新日期:2011-03-02 00:00:00
abstract::The retinal Na+:Ca2+, K+exchanger cDNA was transiently expressed in human embryonic kidney (HEK 293) cells by transfection with plasmid DNA. The correct targeting of the expressed protein to the plasma membrane was confirmed by immunocytochemistry. The reverse exchange offrent (Ca2+ imported per Na+ extruded) was meas...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(97)78046-9
更新日期:1997-07-01 00:00:00