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Bistable networks

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...
December 11, 2017: ACS Synthetic Biology
Shyam Srinivasan, William R Cluett, Radhakrishnan Mahadevan
Motivation: Metabolism can exhibit dynamic phenomena like bistability due to the presence of regulatory motifs like the positive feedback loop. As cell factories, microorganisms with bistable metabolism can have a high and a low product flux at the two stable steady states, respectively. The exclusion of metabolic regulation and network dynamics limits the ability of pseudo-steady state stoichiometric models to detect the presence of bistability, and reliably assess the outcomes of design perturbations to metabolic networks...
December 6, 2017: Bioinformatics
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
Bashar Ibrahim
The precise regulation of cell life division is indispensable to the reliable inheritance of genetic material, i.e. DNA, in successive generations of cells. This is governed by dedicated biochemical networks which ensure that all requirements are met before transition from one phase to the next. The Spindle Assembly Checkpoint (SAC) is an evolutionarily mechanism that delays mitotic progression until all chromosomes are properly linked to the mitotic spindle. During some asymmetric cell divisions, such as those observed in budding yeast, an additional mechanism, the Spindle Position Checkpoint (SPOC), is required to delay exit from mitosis until the mitotic spindle is correctly aligned...
April 1, 2018: Mathematical Biosciences and Engineering: MBE
Giacomo Mariani, Antoine Goujon, Emilie Moulin, Michel Rawiso, Nicolas Giuseppone, Eric Buhler
In this article, the dynamic structure of complex supramolecular polymers composed of bistable [c2]daisy chain rotaxanes as molecular machines that are linked by ureidopyrimidinones (Upy) as recognition moieties was studied. pH actuation of the integrated mechanically active rotaxanes controls the contraction/extension of the polymer chains as well as their physical reticulation. Small-angle neutron and X-ray scattering were used to study in-depth the nanostructure of the contracted and extended polymer aggregates in toluene solution...
November 21, 2017: Nanoscale
Jean-Baptiste Lugagne, Sebastián Sosa Carrillo, Melanie Kirch, Agnes Köhler, Gregory Batt, Pascal Hersen
Cybergenetics is a novel field of research aiming at remotely pilot cellular processes in real-time with to leverage the biotechnological potential of synthetic biology. Yet, the control of only a small number of genetic circuits has been tested so far. Here we investigate the control of multistable gene regulatory networks, which are ubiquitously found in nature and play critical roles in cell differentiation and decision-making. Using an in silico feedback control loop, we demonstrate that a bistable genetic toggle switch can be dynamically maintained near its unstable equilibrium position for extended periods of time...
November 17, 2017: Nature Communications
Antonio A García-Valdivia, Jose M Seco, Javier Cepeda, Antonio Rodríguez-Diéguez
Detailed structural, magnetic, and photoluminescence (PL) characterization of four new compounds based on 1-methylimidazole-5-carboxylate (mimc) ligand and transition metal ions, namely [Ni(mimc)2(H2O)4] (1), [Co(μ-mimc)2]n (2), {[Cu2(μ-mimc)4(H2O)]·2H2O}n (3), and [Cd(μ-mimc)2(H2O)]n (4) is reported. The structural diversity found in the family of compounds derives from the coordination versatility of the ligand, which coordinates as a terminal ligand to give a supramolecular network of monomeric entities in 1 or acts as a bridging linker to build isoreticular 2D coordination polymers (CPs) in 2-4...
November 9, 2017: Inorganic Chemistry
Gang Zhao, Dagmar Wirth, Ingo Schmitz, Michael Meyer-Hermann
Physiological insulin secretion exhibits various temporal patterns, the dysregulation of which is involved in diabetes development. We analyzed the impact of first-phase and pulsatile insulin release on glucose and lipid control with various hepatic insulin signaling networks. The mathematical model suggests that atypical protein kinase C (aPKC) undergoes a bistable switch-on and switch-off, under the control of insulin receptor substrate 2 (IRS2). The activation of IRS1 and IRS2 is temporally separated due to the inhibition of IRS1 by aPKC...
November 8, 2017: Nature Communications
Augustine Kshetrimayum, Hendrik Weimer, Román Orús
Understanding dissipation in 2D quantum many-body systems is an open challenge which has proven remarkably difficult. Here we show how numerical simulations for this problem are possible by means of a tensor network algorithm that approximates steady states of 2D quantum lattice dissipative systems in the thermodynamic limit. Our method is based on the intuition that strong dissipation kills quantum entanglement before it gets too large to handle. We test its validity by simulating a dissipative quantum Ising model, relevant for dissipative systems of interacting Rydberg atoms, and benchmark our simulations with a variational algorithm based on product and correlated states...
November 3, 2017: Nature Communications
Mar Martinez-Pastor, W Andrew Lancaster, Peter D Tonner, Michael W W Adams, Amy K Schmid
Iron is required for key metabolic processes but is toxic in excess. This circumstance forces organisms across the tree of life to tightly regulate iron homeostasis. In hypersaline lakes dominated by archaeal species, iron levels are extremely low and subject to environmental change; however, mechanisms regulating iron homeostasis in archaea remain unclear. In previous work, we demonstrated that two transcription factors (TFs), Idr1 and Idr2, collaboratively regulate aspects of iron homeostasis in the model species Halobacterium salinarum...
September 29, 2017: Nucleic Acids Research
V I Ponomarenko, D D Kulminskiy, M D Prokhorov
We study the collective dynamics of oscillators in a network of identical bistable time-delayed feedback systems globally coupled via the mean field. The influence of delay and inertial properties of the mean field on the collective behavior of globally coupled oscillators is investigated. A variety of oscillation regimes in the network results from the presence of bistable states with substantially different frequencies in coupled oscillators. In the physical experiment and numerical simulation we demonstrate the existence of chimeralike states, in which some of the oscillators in the network exhibit synchronous oscillations, while all other oscillators remain asynchronous...
August 2017: Physical Review. E
Anton S Zadorin, Yannick Rondelez, Guillaume Gines, Vadim Dilhas, Georg Urtel, Adrian Zambrano, Jean-Christophe Galas, André Estevez-Torres
During embryo development, patterns of protein concentration appear in response to morphogen gradients. These patterns provide spatial and chemical information that directs the fate of the underlying cells. Here, we emulate this process within non-living matter and demonstrate the autonomous structuration of a synthetic material. First, we use DNA-based reaction networks to synthesize a French flag, an archetypal pattern composed of three chemically distinct zones with sharp borders whose synthetic analogue has remained elusive...
October 2017: Nature Chemistry
Elisa M Tartaglia, Nicolas Brunel
Electrophysiological recordings in cortex in vivo have revealed a rich variety of dynamical regimes ranging from irregular asynchronous states to a diversity of synchronized states, depending on species, anesthesia, and external stimulation. The average population firing rate in these states is typically low. We study analytically and numerically a network of sparsely connected excitatory and inhibitory integrate-and-fire neurons in the inhibition-dominated, low firing rate regime. For sufficiently high values of the external input, the network exhibits an asynchronous low firing frequency state (L)...
September 20, 2017: Scientific Reports
Michael Hopkins, John J Tyson, Béla Novák
The cell division cycle is the process by which eukaryotic cells replicate their chromosomes and partition them to two daughter cells. To maintain the integrity of the genome, proliferating cells must be able to block progression through the division cycle at key transition points (called "checkpoints") if there have been problems in the replication of the chromosomes or their biorientation on the mitotic spindle. These checkpoints are governed by protein-interaction networks, composed of phase-specific cell-cycle activators and inhibitors...
November 7, 2017: Molecular Biology of the Cell
Dipali Kosey, Shailza Singh
Cutaneous leishmaniasis is the most common form of lesihmaniasis, caused by Leishmania major and is spread by the bite of a sandfly .This species infects the macrophages and dendritic cells Due to multi-drug resistance, there is a need for a new therapeutic technique. Recently, a novel molecular motor of Leishmania, Myosin XXI, was classified and characterized. In addition, the drug resistance in this organism has been linked with the overexpression of ABC transporters. Systems biology aims to study the simulation and modeling of natural biological systems whereas synthetic biology deals with building novel and artificial biological parts and devices  Together they have contributed enormously to drug discovery, vaccine design and development, infectious disease detection and diagnostics...
2017: F1000Research
Lukas H Hutter, Scott Rata, Helfrid Hochegger, Béla Novák
The transitions between phases of the cell cycle have evolved to be robust and switch-like, which ensures temporal separation of DNA replication, sister chromatid separation, and cell division. Mathematical models describing the biochemical interaction networks of cell cycle regulators attribute these properties to underlying bistable switches, which inherently generate robust, switch-like, and irreversible transitions between states. We have recently presented new mathematical models for two control systems that regulate crucial transitions in the cell cycle: mitotic entry and exit, (1) and the mitotic checkpoint...
October 18, 2017: Cell Cycle
Albert S Y Wong, Wilhelm T S Huck
A new discipline of "systems chemistry" is emerging, which aims to capture the complexity observed in natural systems within a synthetic chemical framework. Living systems rely on complex networks of chemical reactions to control the concentration of molecules in space and time. Despite the enormous complexity in biological networks, it is possible to identify network motifs that lead to functional outputs such as bistability or oscillations. To truly understand how living systems function, we need a complete understanding of how chemical reaction networks (CRNs) create function...
2017: Beilstein Journal of Organic Chemistry
Yu-Yu Cheng, Andrew J Hirning, Krešimir Josić, Matthew R Bennett
Transcription factors and their target promoters are central to synthetic biology. By arranging these components into novel gene regulatory circuits, synthetic biologists have been able to create a wide variety of phenotypes, including bistable switches, oscillators, and logic gates. However, transcription factors (TFs) do not instantaneously regulate downstream targets. After the gene encoding a TF is turned on, the gene must first be transcribed, the transcripts must be translated, and sufficient TF must accumulate in order to bind operator sites of the target promoter...
September 5, 2017: ACS Synthetic Biology
Daniel Jercog, Alex Roxin, Peter Barthó, Artur Luczak, Albert Compte, Jaime de la Rocha
In the idling brain, neuronal circuits transition between periods of sustained firing (UP state) and quiescence (DOWN state), a pattern the mechanisms of which remain unclear. Here we analyzed spontaneous cortical population activity from anesthetized rats and found that UP and DOWN durations were highly variable and that population rates showed no significant decay during UP periods. We built a network rate model with excitatory (E) and inhibitory (I) populations exhibiting a novel bistable regime between a quiescent and an inhibition-stabilized state of arbitrarily low rate...
August 4, 2017: ELife
Blanche Capel
The discovery of the Sry gene in 1990 triggered a revolution in our understanding of sex determination. More recently, advances in non-model organisms have been fuelled by the rapid evolution of affordable genome and transcriptome technologies. This Review considers the unusual plasticity in the bipotential system of sex determination and some of the diverse mechanisms that have evolved to control this critical developmental decision, including strong genetic pathways, environmental influences and epigenetic regulation...
November 2017: Nature Reviews. Genetics
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