scholarly journals Period Doubling Bifurcations in a Forced Cell-Free Genetic Oscillator

2021 ◽  
Author(s):  
Lukas Aufinger ◽  
Johann Brenner ◽  
Friedrich C Simmel

Complex non-linear dynamics such as period doubling and chaos have been previously found in computational models of the oscillatory gene networks of biological circadian clocks, but their experimental study is difficult. Here, we present experimental evidence of period doubling in a forced synthetic genetic oscillator operated in a cell-free gene expression system. To this end, an oscillatory negative feedback gene circuit is established in a microfluidic reactor, which allows continuous operation of the system over extended periods of time. We first thoroughly characterize the unperturbed oscillator and find good agreement with a four-species ODE model of the system. Guided by simulations, microfluidics is then used to periodically perturb the system by modulating the concentration of one of the oscillator components with a given amplitude and frequency. When the ratio of the external `zeitgeber' period and the intrinisic period is close to 1, we experimentally find period doubling and quadrupling in the oscillator dynamics, whereas for longer zeitgeber periods, we find stable entrainment. Our theoretical model suggests favorable conditions for which the oscillator can be utilized as an externally synchronized clock, but also demonstrates that related systems could, in principle, display chaotic dynamics.

Nano Letters ◽  
2018 ◽  
Vol 18 (4) ◽  
pp. 2650-2657 ◽  
Author(s):  
Matthaeus Schwarz-Schilling ◽  
Aurore Dupin ◽  
Fabio Chizzolini ◽  
Swati Krishnan ◽  
Sheref S. Mansy ◽  
...  

Nano Letters ◽  
2019 ◽  
Vol 19 (7) ◽  
pp. 4812-4812
Author(s):  
Matthaeus Schwarz-Schilling ◽  
Aurore Dupin ◽  
Fabio Chizzolini ◽  
Swati Krishnan ◽  
Sheref S. Mansy ◽  
...  

1992 ◽  
Vol 114 (4) ◽  
pp. 489-494 ◽  
Author(s):  
K. R. Asfar ◽  
K. K. Masoud

The phenomenon of period-doubling bifurcations in the Duffing’s oscillator with negative linear stiffness is investigated with the aid of approximate analytical methods and computer simulation. Making use of a Hill’s type variational equation together with the ideas drawn out from Floquet theory, it is found that a particular type of subharmonic instability is the one that is responsible for the occurrence of period-doublings in this system. This fact is confirmed by the good agreement between the true critical forcing frequency at which bifurcations are first observed, and the one obtained theoretically. Finally, a threshold criterion for the onset of period-doublings is also proposed and compared with computer simulation results.


2021 ◽  
Author(s):  
Adriaan-Alexander Ludl ◽  
Tom Michoel

Causal gene networks model the flow of information within a cell. Reconstructing causal networks from omics data is challenging because correlation does not imply causation. When genomics and transcriptomics data...


Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 266
Author(s):  
Shin-ichiro Takebayashi ◽  
Tyrone Ryba ◽  
Kelsey Wimbish ◽  
Takuya Hayakawa ◽  
Morito Sakaue ◽  
...  

Multiple epigenetic pathways underlie the temporal order of DNA replication (replication timing) in the contexts of development and disease. DNA methylation by DNA methyltransferases (Dnmts) and downstream chromatin reorganization and transcriptional changes are thought to impact DNA replication, yet this remains to be comprehensively tested. Using cell-based and genome-wide approaches to measure replication timing, we identified a number of genomic regions undergoing subtle but reproducible replication timing changes in various Dnmt-mutant mouse embryonic stem (ES) cell lines that included a cell line with a drug-inducible Dnmt3a2 expression system. Replication timing within pericentromeric heterochromatin (PH) was shown to be correlated with redistribution of H3K27me3 induced by DNA hypomethylation: Later replicating PH coincided with H3K27me3-enriched regions. In contrast, this relationship with H3K27me3 was not evident within chromosomal arm regions undergoing either early-to-late (EtoL) or late-to-early (LtoE) switching of replication timing upon loss of the Dnmts. Interestingly, Dnmt-sensitive transcriptional up- and downregulation frequently coincided with earlier and later shifts in replication timing of the chromosomal arm regions, respectively. Our study revealed the previously unrecognized complex and diverse effects of the Dnmts loss on the mammalian DNA replication landscape.


Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 229
Author(s):  
JunHyuk Woo ◽  
Hyesun Cho ◽  
YunHee Seol ◽  
Soon Ho Kim ◽  
Chanhyeok Park ◽  
...  

The brain needs more energy than other organs in the body. Mitochondria are the generator of vital power in the living organism. Not only do mitochondria sense signals from the outside of a cell, but they also orchestrate the cascade of subcellular events by supplying adenosine-5′-triphosphate (ATP), the biochemical energy. It is known that impaired mitochondrial function and oxidative stress contribute or lead to neuronal damage and degeneration of the brain. This mini-review focuses on addressing how mitochondrial dysfunction and oxidative stress are associated with the pathogenesis of neurodegenerative disorders including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease. In addition, we discuss state-of-the-art computational models of mitochondrial functions in relation to oxidative stress and neurodegeneration. Together, a better understanding of brain disease-specific mitochondrial dysfunction and oxidative stress can pave the way to developing antioxidant therapeutic strategies to ameliorate neuronal activity and prevent neurodegeneration.


VLSI Design ◽  
1998 ◽  
Vol 8 (1-4) ◽  
pp. 355-360 ◽  
Author(s):  
Stephen Bennett ◽  
Christopher M. Snowden ◽  
Stavros Iezekiel

A theoretical (using rate equations) and experimental study of the nonlinear dynamics of a distributed feedback multiple quantum well laser diode is presented. The analysis is performed under direct modulation. Period doubling and period tripling are identified in both the measurements and simulations. Period doubling is found over a wide range of modulation frequencies in the laser. Computational results using rate equations show good agreement with the experimental results.


2010 ◽  
Vol 6 (S271) ◽  
pp. 288-296
Author(s):  
Laurène Jouve ◽  
Michael R. E. Proctor ◽  
Geoffroy Lesur

AbstractWe present the effects of introducing results of 3D MHD simulations of buoyant magnetic fields in the solar convection zone in 2D mean-field Babcock-Leighton models. In particular, we take into account the time delay introduced by the rise time of the toroidal structures from the base of the convection zone to the solar surface. We find that the delays produce large temporal modulation of the cycle amplitude even when strong and thus rapidly rising flux tubes are considered. The study of a reduced model reveals that aperiodic modulations of the solar cycle appear after a sequence of period doubling bifurcations typical of non-linear systems. We also discuss the memory of such systems and the conclusions which may be drawn concerning the actual solar cycle variability.


Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 55
Author(s):  
Jassy Mary S. Lazarte ◽  
Young Rim Kim ◽  
Jung Seok Lee ◽  
Jin Hong Chun ◽  
Si Won Kim ◽  
...  

The causative agent of acute hepatopancreatic necrosis disease (AHPND) is the bacterium, Vibrio parahaemolyticus, which secretes toxins into the gastrointestinal tract of its host. Vibrio parahaemolyticus toxins A and B (PirAvp/PirBvp) have been implicated in the pathogenesis of this disease, and are, therefore, the focus of studies developing treatments for AHPND. We previously produced recombinant antibodies based on the hagfish variable lymphocyte receptor B (VLRB) capable of neutralizing some viruses, suggesting that this type of antibody may have a potential application for treatment of AHPND. Here, recombinant PirAvp/PirBvp, produced using a bacterial expression system, were used as antigens to screen a hagfish VLRB cDNA library to obtain PirAvp/PirBvp-specific antibodies. A cell line secreting these antibodies was established by screening and cloning the DNA extracted from hagfish B cells. Supernatants collected from cells secreting the PirAvp/PirBvp antibodies were collected and concentrated, and used to passively immunize shrimp to neutralize the toxins PirAvp or PirBvp associated with AHPND. Briefly, 10 μg of PirAvp and PirBvp antibodies, 7C12 and 9G10, respectively, were mixed with the shrimp feed, and fed to shrimp for three days consecutive days prior to experimentally infecting the shrimp with V. parahaemolyticus (containing toxins A and B), and resulting mortalities recorded for six days. Results showed significantly higher level of survival in shrimp fed with the PirBvp-9G10 antibody (60%) compared to the group fed the PirAvp-7C12 antibody (3%) and the control group (0%). This suggests that VLRB antibodies may be a suitable alternative to immunoglobulin-based antibodies, as passive immunization treatments for effective management of AHPND outbreaks within shrimp farms.


1990 ◽  
Vol 10 (12) ◽  
pp. 6607-6612
Author(s):  
J F Elliston ◽  
S E Fawell ◽  
L Klein-Hitpass ◽  
S Y Tsai ◽  
M J Tsai ◽  
...  

RNA synthesis was stimulated directly in a cell-free expression system by crude preparations of recombinant mouse estrogen receptor (ER). Receptor-stimulated transcription required the presence of estrogen response elements (EREs) in the test template and could be specifically inhibited by addition of competitor oligonucleotides containing EREs. Moreover, polyclonal antibodies directed against the DNA-binding region of ER inhibited ER-dependent transcription. In our cell-free expression system, hormone-free ER induced transcription in a hormone-independent manner. Evidence is presented suggesting that ER acts by facilitating the formation of a stable preinitiation complex at the target gene promoter and thus augments the initiation of transcription by RNA polymerase II. These observations lend support to our current understanding of the mechanism of steroid receptor-regulated gene expression and suggest strong conservation of function among members of the steroid receptor superfamily.


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