scholarly journals NF-κB oscillations translate into functionally related patterns of gene expression

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Samuel Zambrano ◽  
Ilario De Toma ◽  
Arianna Piffer ◽  
Marco E Bianchi ◽  
Alessandra Agresti
Keyword(s):  
Transcript Levels ◽  
Oscillatory Dynamics ◽  
The Past ◽  
External Perturbations ◽  
Sustained Oscillations ◽  
Mature Transcript ◽  
Small Periodic ◽  
Damped Oscillator ◽  
Biological Advantage ◽  
Receptor Mrnas

Several transcription factors (TFs) oscillate, periodically relocating between the cytoplasm and the nucleus. NF-κB, which plays key roles in inflammation and cancer, displays oscillations whose biological advantage remains unclear. Recent work indicated that NF-κB displays sustained oscillations that can be entrained, that is, reach a persistent synchronized state through small periodic perturbations. We show here that for our GFP-p65 knock-in cells NF-κB behaves as a damped oscillator able to synchronize to a variety of periodic external perturbations with no memory. We imposed synchronous dynamics to prove that transcription of NF-κB-controlled genes also oscillates, but mature transcript levels follow three distinct patterns. Two sets of transcripts accumulate fast or slowly, respectively. Another set, comprising chemokine and chemokine receptor mRNAs, oscillates and resets at each new stimulus, with no memory of the past. We propose that TF oscillatory dynamics is a means of segmenting time to provide renewing opportunity windows for decision.

Possible pathways to a Dansgaard-Oeschger (DO) PMIP protocol

2021 ◽  
Author(s):  
Irene Malmierca-Vallet ◽  
Louise C. Sime ◽  
Paul J. Valdes
Keyword(s):  
General Circulation ◽  
Climate Changes ◽  
General Circulation Models ◽  
Ice Age ◽  
Climate Change Projections ◽  
The Past ◽  
External Perturbations ◽  
Mis 3 ◽  
Last Ice Age ◽  
Earth System Models

<p>The DO events of the last ice age represent one of the best studied abrupt climate transitions, yet we still lack a comprehensive explanation for them. There is uncertainty whether current IPCC-relevant models can effectively represent the processes that cause DO events. Current Earth system models (ESMs) seem overly stable against external perturbations and incapable of reproducing most abrupt climate changes of the past (Valdes, 2011). If this holds true, this could noticeably influence their capability to predict future abrupt transitions, with significant consequences for the delivery of precise climate change projections.  In this task, the objectives of this study are (1) to cross compare existing simulations that show spontaneous DO-type oscillations using a common set of diagnostics so we can compare the mechanisms and the characteristics of the oscillations, and (2) to formulate possible pathways to a DO PMIP protocol that could help investigate cold-period instabilities through a range of insolation-, freshwater-, GHG-, and NH ice sheet-related forcings, as well as evaluating the possibility of spontaneous internal oscillations.</p><p>Although most abrupt DO events happened during MIS3, only few studies investigate DO events in coupled general circulation models under MIS 3 conditions (e.g., Kawamura et al., 2017; Zhang and Prange, 2020). Here, we thus propose that the MIS3 period could be the focus of such a DO-event modelling protocol. More specific sensitivity experiments performed under MIS 3 boundary conditions are needed in order to (1) better understand the mechanisms behind millennial-scale climate variability, (2) explore AMOC variability under intermediate glacial conditions, and (3) help answer the question: “are models too stable?”.</p>

scholarly journals Extended halo of NGC 2682 (M 67) from Gaia DR2

2019 ◽  
Vol 627 ◽  
pp. A119 ◽  
Author(s):  
R. Carrera ◽  
M. Pasquato ◽  
A. Vallenari ◽  
L. Balaguer-Núñez ◽  
T. Cantat-Gaudin ◽  
...  
Keyword(s):  
Spatial Distribution ◽  
Open Cluster ◽  
Star Clusters ◽  
Dynamical Evolution ◽  
Open Clusters ◽  
Galactic Disc ◽  
The Past ◽  
External Perturbations ◽  
Galactic Potential ◽  
Gaia Dr2

Context. NGC 2682 is a nearby open cluster that is approximately 3.5 Gyr old. Dynamically, most open clusters are expected to dissolve on shorter timescales of ≈1 Gyr. That it has survived until now means that NGC 2682 was likely much more massive in the past and is bound to have an interesting dynamical history. Aims. We investigate the spatial distribution of the stars in NGC 2682 to constrain dynamical evolution of the cluster. We particularly focus on the marginally bound stars in the cluster outskirts. Methods. We used Gaia DR2 data to identify NGC 2682 members up to a distance of ∼150 pc (10°). The two methods Clusterix and UPMASK were applied to this end. We estimated distances to obtain 3D stellar positions using a Bayesian approach to parallax inversion, with an appropriate prior for star clusters. We calculated the orbit of NGC 2682 using the GRAVPOT16 software. Results. The cluster extends up to 200′ (50 pc), which implies that its size is at least twice as large as previously believed. This exceeds the cluster Hill sphere based on the Galactic potential at the distance of NGC 2682. Conclusion. The extra-tidal stars in NGC 2682 may originate from external perturbations such as disc-shocking or dynamical evaporation from two-body relaxation. The former origin is plausible given the orbit of NGC 2682, which crossed the Galactic disc ≈40 Myr ago.

scholarly journals Genistein modulates gene activity in psoriatic patients

2019 ◽  
Author(s):  
Elwira Smolińska ◽  
Grzegorz Węgrzyn ◽  
Magdalena Gabig-Cimińska
Keyword(s):  
Inflammatory Mediators ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Severe Psoriasis ◽  
Peripheral Blood Cells ◽  
Transcript Levels ◽  
The Past ◽  
Naturally Occurring ◽  
Expression Of Genes ◽  
Mediators Of Inflammation

Despite the impressive advancements in the treatment of psoriasis over the past two decades, there is still a need for further improvement. As previously shown in the literature, genistein (5,7-dihydroxy-3-(4-hydroxyphenyl)chromen-4-one), naturally occurring plant compound displays multidirectional action, also in relation to alleviating psoriasis symptoms. In this work we focused our attention on genistein impact on expression of genes when treating moderate-to-severe psoriasis patients. Testing the effects of this isoflavone on transcript levels in both skin specimens and peripheral blood cells of four psoriatic subjects, we found that this compound modulated activities of genes coding for anti-psoriatic members and anti-inflammatory mediators of inflammation. It impairs the activity of certain genes which are overexpressed in psoriasis, while stimulating the expression of other transcripts that are repressed in dermatosis.

scholarly journals Role of intercellular coupling and delay on the synchronization of genetic oscillators

2020 ◽  
Author(s):  
Supravat Dey ◽  
Lee Tracey ◽  
Abhyudai Singh
Keyword(s):  
Coupling Strength ◽  
Order System ◽  
Biological Clocks ◽  
Intercellular Coupling ◽  
Interconnected System ◽  
Oscillatory Dynamics ◽  
Sustained Oscillations ◽  
Low Copy Number ◽  
Goodwin Oscillator ◽  
Open Question

AbstractLiving cells encode diverse biological clocks for circadian timekeeping and formation of rhythmic structures during embryonic development. A key open question is how these clocks synchronize across cells through intercellular coupling mechanisms. To address this question, we leverage the classical motif for genetic clocks the Goodwin oscillator where a gene product inhibits its own synthesis via time-delayed negative feedback. More specifically, we consider an interconnected system of two identical Goodwin oscillators (each operating in a single cell), where state information is conveyed between cells via a signaling pathway whose dynamics is modeled as a first-order system. In essence, the interaction between oscillators is characterized by an intercellular coupling strength and an intercellular time delay that represents the signaling response time. Systematic stability analysis characterizes the parameter regimes that lead to oscillatory dynamics, with high coupling strength found to destroy sustained oscillations. Within the oscillatory parameter regime we find both in-phase and anti-phase oscillations with the former more likely to occur for small intercellular time delays. Finally, we consider the stochastic formulation of the model with low-copy number fluctuations in biomolecular components. Interestingly, stochasticity leads to qualitatively different behaviors where in-phase oscillations are susceptible to the inherent fluctuations but not the anti-phase oscillations. In the context of the segmentation clock, such synchronized in-phase oscillations between cells are critical for the proper generation of repetitive segments during embryo development that eventually leads to the formation of the vertebral column.

scholarly journals A fundamental model exhibiting nonlinear oscillatory dynamics in solid oxide fuel cells

2014 ◽  
Vol 470 (2164) ◽  
pp. 20130551 ◽  
Author(s):  
J. D. Sands ◽  
D. J. Needham ◽  
J. Uddin
Keyword(s):  
Dynamical System ◽  
Fuel Cells ◽  
Solid Oxide Fuel Cells ◽  
Three Dimensional ◽  
Operating Conditions ◽  
Solid Oxide ◽  
Oxide Fuel ◽  
Planar Dynamical System ◽  
Oscillatory Dynamics ◽  
Sustained Oscillations

In this paper, we address the phenomenon of temporal, self-sustained oscillations which have been observed under quite general conditions in solid oxide fuel cells. Our objective is to uncover the fundamental mechanisms giving rise to the observed oscillations. To this end, we develop a model based on the fundamental chemical kinetics and transfer processes which take place within the fuel cell. This leads to a three-dimensional dynamical system, which, under typical operating conditions, is rationally reducible to a planar dynamical system. The structural dynamics of the planar dynamical system are studied in detail. Self-sustained oscillations are shown to arise through Hopf bifurcations in this planar dynamical system, and the key parameter ranges for the occurrence of such oscillations are identified.

scholarly journals Alternative splicing of mRNA in colorectal cancer: new strategies for tumor diagnosis and treatment

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Yanyan Chen ◽  
Mengxi Huang ◽  
Xiaolong Liu ◽  
Yadi Huang ◽  
Chao Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Alternative Splicing ◽  
Therapeutic Strategy ◽  
The Past ◽  
Mature Transcript ◽  
Posttranscriptional Gene Regulation ◽  
Therapeutic Value ◽  
Multistep Process ◽  
Effective Therapeutic Strategy ◽  
New Strategies

AbstractAlternative splicing (AS) is an important event that contributes to posttranscriptional gene regulation. This process leads to several mature transcript variants with diverse physiological functions. Indeed, disruption of various aspects of this multistep process, such as cis- or trans- factor alteration, promotes the progression of colorectal cancer. Therefore, targeting some specific processes of AS may be an effective therapeutic strategy for treating cancer. Here, we provide an overview of the AS events related to colorectal cancer based on research done in the past 5 years. We focus on the mechanisms and functions of variant products of AS that are relevant to malignant hallmarks, with an emphasis on variants with clinical significance. In addition, novel strategies for exploiting the therapeutic value of AS events are discussed.

scholarly journals Rethinking the importance of the structure of ecological networks under an environment-dependent framework

2017 ◽  
Author(s):  
Simone Cenci ◽  
Chuliang Song ◽  
Serguei Saavedra
Keyword(s):  
Network Structure ◽  
Community Dynamics ◽  
Environmental Changes ◽  
External Perturbation ◽  
Species Interaction ◽  
Ecological Networks ◽  
Relative Importance ◽  
The Past ◽  
External Perturbations ◽  
Structure Changes

AbstractA major quest in network and community ecology has been centered on understanding the importance of structural patterns in species interaction networks—the synthesis of who interacts with whom in a given location and time. In the past decades, much effort has been devoted to infer the importance of a particular structure by its capacity to tolerate an external perturbation on its structure or dynamics. Here we demonstrate that such a perspective leads to inconsistent conclusions. That is, the importance of a network structure changes as a function of the external perturbations acting on a community at any given point in time. Thus, we discuss a research agenda to investigate the relative importance of the structure of ecological networks under an environment-dependent framework. We hypothesize that only by studying systematically the link between network structure and community dynamics under an environment-dependent framework, we can uncover the limits at which communities can tolerate environmental changes.“Variation stands out as the only meaningful reality”Stephen J. Gould.

scholarly journals An upper limit for slow earthquakes zone: self-oscillatory behavior through the Hopf bifurcation mechanism from a model of spring-block under lubricated surfaces

2016 ◽  
Author(s):  
Valentina Castellanos-Rodríguez ◽  
Eric Campos-Cantón ◽  
Rafael Barboza-Gudiño ◽  
Ricardo Femat
Keyword(s):  
Hopf Bifurcation ◽  
Oscillatory Behavior ◽  
Complex Dynamic ◽  
Seismic Parameters ◽  
Bifurcation Mechanism ◽  
External Perturbations ◽  
Sustained Oscillations ◽  
Upper Limit ◽  
Slow Earthquakes ◽  
Frictional Coefficients

Abstract. The complex oscillatory behavior of a springblock model is analyzed via the Hopf bifurcation mechanism. The mathematical springblock model is generated by considering the Dieterich–Ruinas's friction law and the Stribeck's effect. The existence of self-sustained oscillations in the transition zone – where slow earthquakes are generated within the frictionally unstable region – is determined. An upper limit for this region is proposed as a function of seismic parameters and frictional coefficients which are concerned with presence of fluids in the system. The importance of the characteristic length scale L, the implications of fluids, and the effects of external perturbations in the complex dynamic oscillatory behavior as well as in the stationary solution, are take into consideration.

scholarly journals Glucocorticoid-Responsive Transcription Factor Krüppel-Like Factor 9 Regulates fkbp5 and Metabolism

2021 ◽  
Vol 9 ◽  
Author(s):  
Ian M. Gans ◽  
Janelle Grendler ◽  
Remy Babich ◽  
Nishad Jayasundara ◽  
James A. Coffman
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Oxygen Consumption ◽  
Consumption Rate ◽  
Promoter Regions ◽  
Binding Motifs ◽  
Transcript Levels ◽  
Oscillatory Dynamics ◽  
Feedforward Loop ◽  
Feedback Regulator

Krüppel-like factor 9 (Klf9) is a feedforward regulator of glucocorticoid receptor (GR) signaling. Here we show that in zebrafish klf9 is expressed with GR-dependent oscillatory dynamics in synchrony with fkbp5, a GR target that encodes a negative feedback regulator of GR signaling. We found that fkbp5 transcript levels are elevated in klf9–/– mutants and that Klf9 associates with chromatin at the fkbp5 promoter, which becomes hyperacetylated in klf9–/– mutants, suggesting that the GR regulates fkbp5 via an incoherent feedforward loop with klf9. As both the GR and Fkbp5 are known to regulate metabolism, we asked how loss of Klf9 affects metabolic rate and gene expression. We found that klf9–/– mutants have a decreased oxygen consumption rate (OCR) and upregulate glycolytic genes, the promoter regions of which are enriched for potential Klf9 binding motifs. Our results suggest that Klf9 functions downstream of the GR to regulate cellular glucocorticoid responsivity and metabolic homeostasis.

Observations of the continuum near the galactic centre

1967 ◽  
Vol 31 ◽  
pp. 405
Author(s):  
F. J. Kerr
Keyword(s):  
Galactic Centre ◽  
The Past ◽  
Centre Region ◽  
The Continuum

A continuum survey of the galactic-centre region has been carried out at Parkes at 20 cm wavelength over the areal11= 355° to 5°,b11= -3° to +3° (Kerr and Sinclair 1966, 1967). This is a larger region than has been covered in such surveys in the past. The observations were done as declination scans.

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