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bistability stochastic sensitivity

Ting Wang, Petr Plecháč
Stochastic reaction networks that exhibit bistable behavior are common in systems biology, materials science, and catalysis. Sampling of stationary distributions is crucial for understanding and characterizing the long-time dynamics of bistable stochastic dynamical systems. However, simulations are often hindered by the insufficient sampling of rare transitions between the two metastable regions. In this paper, we apply the parallel replica method for a continuous time Markov chain in order to improve sampling of the stationary distribution in bistable stochastic reaction networks...
December 21, 2017: Journal of Chemical Physics
Christian Cuba Samaniego, Elisa Franco
Life is sustained by a variety of cyclic processes such as cell division, muscle contraction, and neuron firing. The periodic signals powering these processes often direct a variety of other downstream systems, which operate at different time scales and must have the capacity to divide or multiply the period of the master clock. Period modulation is also an important challenge in synthetic molecular systems, where slow and fast components may have to be coordinated simultaneously by a single oscillator whose frequency is often difficult to tune...
January 19, 2018: ACS Synthetic Biology
Joanna Jaruszewicz-Błońska, Tomasz Lipniacki
BACKGROUND: In favorable conditions bacterial doubling time is less than 20 min, shorter than DNA replication time. In E. coli a single round of genome replication lasts about 40 min and it must be accomplished about 20 min before cell division. To achieve such fast growth rates bacteria perform multiple replication rounds simultaneously. As a result, when the division time is as short as 20 min E. coli has about 8 copies of origin of replication (ori) and the average copy number of the genes situated close to ori can be 4 times larger than those near the terminus of replication (ter)...
December 2, 2017: BMC Systems Biology
Anupam Dey, Debashis Barik
Cellular differentiations are often regulated by bistable switches resulting from specific arrangements of multiple positive feedback loops (PFL) fused to one another. Although bistability generates digital responses at the cellular level, stochasticity in chemical reactions causes population heterogeneity in terms of its differentiated states. We hypothesized that the specific arrangements of PFLs may have evolved to minimize the cellular heterogeneity in differentiation. In order to test this we investigated variability in cellular differentiation controlled either by parallel or serial arrangements of multiple PFLs having similar average properties under extrinsic and intrinsic noises...
2017: PloS One
Johannes Maier, Martti Pärs, Tina Weller, Mukundan Thelakkat, Jürgen Köhler
Photochromic molecules can be reversibly converted between two bistable conformations by light, and are considered as promising building blocks in novel macromolecular structures for sensing and imaging techniques. We have studied individual molecular triads consisting of two strong fluorophores (perylene bisimide) that are covalently linked via a photochromic unit (dithienylcyclopentene) and distinguished between deliberate switching and spontaneous blinking. It was verified that the probability for observing deliberate light-induced switching of a single triad (rather than stochastic blinking) amounts to 0...
January 31, 2017: Scientific Reports
Hinze Hogendoorn, Frans A J Verstraten, Hamish MacDougall, David Alais
Certain visual stimuli can have two possible interpretations. These perceptual interpretations may alternate stochastically, a phenomenon known as bistability. Some classes of bistable stimuli, including binocular rivalry, are sensitive to bias from input through other modalities, such as sound and touch. Here, we address the question whether bistable visual motion stimuli, known as plaids, are affected by vestibular input that is caused by self-motion. In Experiment 1, we show that a vestibular self-motion signal biases the interpretation of the bistable plaid, increasing or decreasing the likelihood of the plaid being perceived as globally coherent or transparently sliding depending on the relationship between self-motion and global visual motion directions...
January 2017: Vision Research
Andrew Leber, Vida Abedi, Raquel Hontecillas, Monica Viladomiu, Stefan Hoops, Stanca Ciupe, John Caughman, Tricity Andrew, Josep Bassaganya-Riera
T follicular helper (Tfh) cells are a highly plastic subset of CD4+ T cells specialized in providing B cell help and promoting inflammatory and effector responses during infectious and immune-mediate diseases. Helicobacter pylori is the dominant member of the gastric microbiota and exerts both beneficial and harmful effects on the host. Chronic inflammation in the context of H. pylori has been linked to an upregulation in T helper (Th)1 and Th17 CD4+ T cell phenotypes, controlled in part by the cytokine, interleukin-21...
June 7, 2016: Journal of Theoretical Biology
Lijie Hao, Zhuoqin Yang, Yuanhong Bi
The cyclic AMP (cAMP)-response element-binding protein (CREB) family of transcription factors is crucial in regulating gene expression required for long-term memory (LTM) formation. Upon exposure of sensory neurons to the neurotransmitter serotonin (5-HT), CREB1 is activated via activation of the protein kinase A (PKA) intracellular signaling pathways, and CREB2 as a transcriptional repressor is relieved possibly via phosphorylation of CREB2 by mitogen-activated protein kinase (MAPK). Song et al. [18] proposed a minimal model with only interlinked positive and negative feedback loops of transcriptional regulation by the activator CREB1 and the repressor CREB2...
April 2016: Mathematical Biosciences
Lei Yuan, Gary C Chan, David Beeler, Lauren Janes, Katherine C Spokes, Harita Dharaneeswaran, Anahita Mojiri, William J Adams, Tracey Sciuto, Guillermo Garcia-Cardeña, Grietje Molema, Peter M Kang, Nadia Jahroudi, Philip A Marsden, Ann Dvorak, Erzsébet Ravasz Regan, William C Aird
Previous studies have shown that biological noise may drive dynamic phenotypic mosaicism in isogenic unicellular organisms. However, there is no evidence for a similar mechanism operating in metazoans. Here we show that the endothelial-restricted gene, von Willebrand factor (VWF), is expressed in a mosaic pattern in the capillaries of many vascular beds and in the aorta. In capillaries, the mosaicism is dynamically regulated, with VWF switching between ON and OFF states during the lifetime of the animal. Clonal analysis of cultured endothelial cells reveals that dynamic mosaic heterogeneity is controlled by a low-barrier, noise-sensitive bistable switch that involves random transitions in the DNA methylation status of the VWF promoter...
January 8, 2016: Nature Communications
Zhongkui Sun, Jin Fu, Yuzhu Xiao, Wei Xu
In this paper, the effects of noise and time delay on stochastic bifurcations are investigated theoretically and numerically in a time-delayed Duffing-Van der Pol oscillator subjected to white noise. Due to the time delay, the random response is not Markovian. Thereby, approximate methods have been adopted to obtain the Fokker-Planck-Kolmogorov equation and the stationary probability density function for amplitude of the response. Based on the knowledge that stochastic bifurcation is characterized by the qualitative properties of the steady-state probability distribution, it is found that time delay and feedback intensity as well as noise intensity will induce the appearance of stochastic P-bifurcation...
August 2015: Chaos
Nicholas Peatfield, Nadia Mueller, Phillipp Ruhnau, Nathan Weisz
The Rubin's vase illusion evokes a bistable perception that alters between a pair of faces or a vase. In this study we looked at the oscillatory and network level effects that could differentiate between these two perceptions. Thus, tackling the issue of what leads to conscious access and, thus resulting in perceptual dominance between two competing signals. We conducted a study within the MEG, during which participants observed a brief presentation (150msec) of the Rubin's vase illusion, and subsequently reported the dominant percept...
2015: Journal of Vision
Marc Sturrock, Adriana T Dawes
Cell polarization is a ubiquitous process which results in cellular constituents being organized into discrete intracellular spatial domains. It occurs in a variety of cell types, including epithelial cells, immune system cells and neurons. A key player in this process is the Par protein family whose asymmetric localization to anterior and posterior parts of the cell is crucial for proper division and cell fate specification. In this paper, we explore a stochastic analogue of the temporal model of Par protein interactions first developed in Dawes & Munro (Dawes and Munro 2011 Biophys...
May 6, 2015: Journal of the Royal Society, Interface
Kim Sneppen, Ian B Dodd
How alternative chromatin-based regulatory states can be made stable and heritable in order to provide robust epigenetic memory is poorly understood. Here, we develop a stochastic model of the silencing system in Saccharomyces cerevisiae that incorporates cooperative binding of the repressive SIR complex and antisilencing histone modifications, in addition to positive feedback in Sir2 recruitment. The model was able to reproduce key features of SIR regulation of an HM locus, including heritable bistability, dependence on the silencer elements, and sensitivity to SIR dosage...
2015: Epigenetics: Official Journal of the DNA Methylation Society
Soledad Gonzalo Cogno, Susanne Schreiber, Ines Samengo
The reliability of a spiking neuron depends on the frequency content of the driving input signal. Previous studies have shown that well above threshold, regularly firing neurons generate reliable responses when the input signal resonates with the firing frequency of the cell. Instead, well below threshold, reliable responses are obtained when the input frequency resonates with the subthreshold oscillations of the neuron. Previous theories, however, provide no clear prediction for the input frequency giving rise to maximally reliable spiking at threshold, which is probably the most relevant firing regime in mammalian cortex under physiological conditions...
December 2014: Neural Computation
Jingchen Feng, David A Kessler, Eshel Ben-Jacob, Herbert Levine
A small fraction of cells in many bacterial populations, called persisters, are much less sensitive to antibiotic treatment than the majority. Persisters are in a dormant metabolic state, even while remaining genetically identical to the actively growing cells. Toxin and antitoxin modules in bacteria are believed to be one possible cause of persistence. A two-gene operon, HipBA, is one of many chromosomally encoded toxin and antitoxin modules in Escherichia coli and the HipA7 allelic variant was the first validated high-persistence mutant...
January 7, 2014: Proceedings of the National Academy of Sciences of the United States of America
Maier S Avendaño, Chad Leidy, Juan M Pedraza
Positive feedback loops can produce multistability, resulting in different phenotypic states. However, many transcription networks contain counteracting positive and negative feedbacks. Here we explore the dynamics of an interlinked positive and negative feedback motif based on the galactose-uptake control system of Saccharomyces cerevisiae modified to make the strength of each feedback externally controllable. Our results show that although the positive feedback loop determines the range of bistability and the width of the regions where intermediate activation is possible, the transition rates between states are mostly sensitive to the negative feedback strength...
2013: Nature Communications
Jason Lloyd-Price, Andre S Ribeiro
Small regulatory RNAs (srRNAs) are important regulators of gene expression in eukaryotes and prokaryotes. A common motif containing srRNA is a bistable two-gene motif where one gene codes for a transcription factor (TF) which represses the transcription of the second gene, whose transcript is a srRNA which targets the first gene's transcript. Here, we investigate the properties of this motif in a stochastic model which takes the low copy numbers of the RNA components into account. First, we examine the conditions for stability of the two "noisy attractors...
September 2013: Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics
Kyung Hyuk Kim, Hong Qian, Herbert M Sauro
Single-cell studies often show significant phenotypic variability due to the stochastic nature of intra-cellular biochemical reactions. When the numbers of molecules, e.g., transcription factors and regulatory enzymes, are in low abundance, fluctuations in biochemical activities become significant and such "noise" can propagate through regulatory cascades in terms of biochemical reaction networks. Here we develop an intuitive, yet fully quantitative method for analyzing how noise affects cellular phenotypes based on identifying a system's nonlinearities and noise propagations...
October 14, 2013: Journal of Chemical Physics
Edward M Nelson, Volker Kurz, Nicolas Perry, Douglas Kyrouac, Gregory Timp
Noise is inherent to single cell behavior. Its origins can be traced to the stochasticity associated with a few copies of genes and low concentrations of protein and ligands. We have studied the mechanisms by which the response of noisy elements can be entrained for biological signal processing. To elicit predictable biological function, we have engineered a gene environment that incorporates a gene regulatory network with the stringently controlled microenvironment found in a synthetic biofilm. The regulatory network leverages the positive feedback found in quorum-sensing regulatory components of the lux operon, which is used to coordinate cellular responses to environmental fluctuations...
May 16, 2014: ACS Synthetic Biology
Jaroslav Albert, Marianne Rooman
Turning genes on and off is a mechanism by which cells and tissues make phenotypic decisions. Gene network motifs capable of supporting two or more steady states and thereby providing cells with a plurality of possible phenotypes are referred to as genetic switches. Modeled on the bases of naturally occurring genetic networks, synthetic biologists have successfully constructed artificial switches, thus opening a door to new possibilities for improvement of the known, but also the design of new synthetic genetic circuits...
2012: PloS One
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