scholarly journals An automaton model for the cell cycle

2010 ◽  
Vol 1 (1) ◽  
pp. 36-47 ◽  
Author(s):  
Atilla Altinok ◽  
Didier Gonze ◽  
Francis Lévi ◽  
Albert Goldbeter
Keyword(s):  
Cell Cycle ◽  
Steady State ◽  
Deterministic Model ◽  
Initial Conditions ◽  
Cell Number ◽  
Time Step ◽  
M Phase ◽  
Random Manner ◽  
The Mean ◽  
Cell Cycle Phases

We consider an automaton model that progresses spontaneously through the four successive phases of the cell cycle: G1, S (DNA replication), G2 and M (mitosis). Each phase is characterized by a mean duration τ and a variability V . As soon as the prescribed duration of a given phase has passed, the transition to the next phase of the cell cycle occurs. The time at which the transition takes place varies in a random manner according to a distribution of durations of the cell cycle phases. Upon completion of the M phase, the cell divides into two cells, which immediately enter a new cycle in G1. The duration of each phase is reinitialized for the two newborn cells. At each time step in any phase of the cycle, the cell has a certain probability to be marked for exiting the cycle and dying at the nearest G1/S or G2/M transition. To allow for homeostasis, which corresponds to maintenance of the total cell number, we assume that cell death counterbalances cell replication at mitosis. In studying the dynamics of this automaton model, we examine the effect of factors such as the mean durations of the cell cycle phases and their variability, the type of distribution of the durations, the number of cells, the regulation of the cell population size and the independence of steady-state proportions of cells in each phase with respect to initial conditions. We apply the stochastic automaton model for the cell cycle to the progressive desynchronization of cell populations and to their entrainment by the circadian clock. A simple deterministic model leads to the same steady-state proportions of cells in the four phases of the cell cycle.

scholarly journals Deterministic Model of the Eddy Dynamics for a Midlatitude Ocean Model

2021 ◽  
Author(s):  
Takaya Uchida ◽  
Bruno Deremble ◽  
Stephane Popinet
Keyword(s):  
Deterministic Model ◽  
North Atlantic Ocean ◽  
Ocean Model ◽  
Global Ocean ◽  
Mean Flow ◽  
Flux Divergence ◽  
Time Step ◽  
Weather System ◽  
Basin Scale ◽  
The Mean

Mesoscale eddies, the weather system of the oceans, although being on the scales of O(20-100km), have a disproportionate role in shaping the mean jets such as the separated Gulf Stream in the North Atlantic Ocean, which is on the scale of O(1000km) in the along-jet direction. With the increase in computational power, we are now able to partially resolve the eddies in basin-scale and global ocean simulations, a model resolution often referred to as mesoscale permitting. It is well known, however, that due to grid-scale numerical viscosity, mesoscale permitting simulations have less energetic eddies and consequently weaker eddy feedback onto the mean flow. In this study, we run a quasi-geostrophic model at mesoscale resolving resolution in a double gyre configuration and formulate a deterministic parametrization for the eddy rectification term of potential vorticity (PV), namely, the eddy PV flux divergence. We have moderate success in reproducing the spatial patterns and magnitude of eddy kinetic and potential energy diagnosed from the model. One novel point about our approach is that we account for non-local eddy feedbacks onto the mean flow by solving the eddy PV equation prognostically in addition to the mean flow. In return, we are able to parametrize the variability in total (mean+eddy) PV at each time step instead of solely the mean PV. A closure for the total PV is beneficial as we are able to account for both the mean state and extreme events.

Phosphatidylcholine catabolism in the MCF-7 cell cycle

2006 ◽  
Vol 84 (5) ◽  
pp. 737-744 ◽  
Author(s):  
Weiyang Lin ◽  
Gilbert Arthur
Keyword(s):  
Cell Cycle ◽  
S Phase ◽  
Specific Cell ◽  
Synchronized Cells ◽  
M Phase ◽  
G2 Phase ◽  
Cell Cycle Phases ◽  
Kinetics Of ◽  
Mcf 7

The catabolism of phosphatidylcholine (PtdCho) appears to play a key role in regulating the net accumulation of the lipid in the cell cycle. Current protocols for measuring the degradation of PtdCho at specific cell-cycle phases require prolonged periods of incubation with radiolabelled choline. To measure the degradation of PtdCho at the S and G2 phases in the MCF-7 cell cycle, protocols were developed with radiolabelled lysophosphatidylcholine (lysoPtdCho), which reduces the labelling period and minimizes the recycling of labelled components. Although most of the incubated lysoPtdCho was hydrolyzed to glycerophosphocholine (GroPCho) in the medium, the kinetics of the incorporation of label into PtdCho suggests that the labelled GroPCho did not contribute significantly to cellular PtdCho formation. A protocol which involved exposing the cells twice to hydroxyurea, was also developed to produce highly synchronized MCF-7 cells with a profile of G1:S:G2/M of 90:5:5. An analysis of PtdCho catabolism in the synchronized cells following labelling with lysoPtdCho revealed that there was increased degradation of PtdCho in early to mid-S phase, which was attenuated in the G2/M phase. The results suggest that the net accumulation of PtdCho in MCF-7 cells may occur in the G2 phase of the cell cycle.

scholarly journals Transcriptional landscape of the human cell cycle

2017 ◽  
Vol 114 (13) ◽  
pp. 3473-3478 ◽  
Author(s):  
Yin Liu ◽  
Sujun Chen ◽  
Su Wang ◽  
Fraser Soares ◽  
Martin Fischer ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Steady State ◽  
Histone Modification ◽  
Human Cell ◽  
Rna Seq ◽  
Motif Analysis ◽  
Chip Sequencing ◽  
Histone 3 ◽  
M Phase ◽  
Transcriptional Landscape

Steady-state gene expression across the cell cycle has been studied extensively. However, transcriptional gene regulation and the dynamics of histone modification at different cell-cycle stages are largely unknown. By applying a combination of global nuclear run-on sequencing (GRO-seq), RNA sequencing (RNA-seq), and histone-modification Chip sequencing (ChIP-seq), we depicted a comprehensive transcriptional landscape at the G0/G1, G1/S, and M phases of breast cancer MCF-7 cells. Importantly, GRO-seq and RNA-seq analysis identified different cell-cycle–regulated genes, suggesting a lag between transcription and steady-state expression during the cell cycle. Interestingly, we identified genes actively transcribed at early M phase that are longer in length and have low expression and are accompanied by a global increase in active histone 3 lysine 4 methylation (H3K4me2) and histone 3 lysine 27 acetylation (H3K27ac) modifications. In addition, we identified 2,440 cell-cycle–regulated enhancer RNAs (eRNAs) that are strongly associated with differential active transcription but not with stable expression levels across the cell cycle. Motif analysis of dynamic eRNAs predicted Kruppel-like factor 4 (KLF4) as a key regulator of G1/S transition, and this identification was validated experimentally. Taken together, our combined analysis characterized the transcriptional and histone-modification profile of the human cell cycle and identified dynamic transcriptional signatures across the cell cycle.

scholarly journals Impaired Mitotic Progression and Preimplantation Lethality in Mice Lacking OMCG1, a New Evolutionarily Conserved Nuclear Protein

2005 ◽  
Vol 25 (14) ◽  
pp. 6289-6302 ◽  
Author(s):  
Jérôme Artus ◽  
Sandrine Vandormael-Pournin ◽  
Morten Frödin ◽  
Karim Nacerddine ◽  
Charles Babinet ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Zinc Finger Protein ◽  
Cell Number ◽  
Cell Cycle Regulators ◽  
Mammalian Embryo ◽  
Mouse Mutants ◽  
M Phase ◽  
Development In Vitro ◽  
Mitotic Figures

ABSTRACT While highly conserved through evolution, the cell cycle has been extensively modified to adapt to new developmental programs. Recently, analyses of mouse mutants revealed that several important cell cycle regulators are either dispensable for development or have a tissue- or cell-type-specific function, indicating that many aspects of cell cycle regulation during mammalian embryo development remain to be elucidated. Here, we report on the characterization of a new gene, Omcg1, which codes for a nuclear zinc finger protein. Embryos lacking Omcg1 die by the end of preimplantation development. In vitro cultured Omcg1-null blastocysts exhibit a dramatic reduction in the total cell number, a high mitotic index, and the presence of abnormal mitotic figures. Importantly, we found that Omcg1 disruption results in the lengthening of M phase rather than in a mitotic block. We show that the mitotic delay in Omcg1 −/− embryos is associated with neither a dysfunction of the spindle checkpoint nor abnormal global histone modifications. Taken together, these results suggest that Omcg1 is an important regulator of the cell cycle in the preimplantation embryo.

THE EFFECTS OF OESTROGEN ON THE CELL CYCLE IN EPITHELIAL AND CONNECTIVE TISSUES OF THE MOUSE UTERUS

1972 ◽  
Vol 55 (1) ◽  
pp. 21-30 ◽  
Author(s):  
R. M. DAS
Keyword(s):  
Cell Cycle ◽  
Steady State ◽  
S Phase ◽  
Luminal Epithelium ◽  
Connective Tissues ◽  
Mouse Uterus ◽  
Oestrogen Treatment ◽  
Ovariectomized Mice ◽  
Generation Times ◽  
The Mean

SUMMARY The duration of stages of the cell cycle in the uterine epithelial and stromal tissues of ovariectomized mice was estimated by the labelled mitosis method. In untreated animals the mean duration of the S phase (DNA synthesis) was 10·5 h in the glandular and luminal epithelium. Oestrogen treatment shortened it to 6 h in both tissues. In the endometrial stroma of progesterone-treated mice the duration of S was 8 h; when oestrogen was given it increased slightly. The generation times estimated under steady-state conditions were 270,156 and 383 h respectively in the lumen, glands and stroma of untreated mice. After oestrogen stimulation the responses became highly synchronized.

Flow Cytometric Quantification of All Cell Cycle Phases and Apoptosis in a Two-Color Fluorescence Plot

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4720-4720
Author(s):  
Olivier Herault ◽  
Christine Vignon
Keyword(s):  
Cell Cycle ◽  
Cell Line ◽  
Histone H3 ◽  
Leukemic Cells ◽  
Becton Dickinson ◽  
Alexa Fluor ◽  
Flow Cytometric ◽  
M Phase ◽  
Cell Cycle Phases ◽  
The Impact

Abstract Abstract 4720 An optimal technology for cell cycle analysis would allow measuring concomitantly apoptosis, G0, G1, S, G2 and M phases in combination with cell surface phenotyping. We propose an easy method in flow cytometry allowing this discrimination in an only two-color fluorescent plot. It is based on the concomitant use of 7-amino-actinomycin D and antibodies anti-Ki67 and anti-phospho(Ser10)-histone H3 conjugated to Alexa Fluor.. 488 to discriminate G0 et M phases, respectively. The proposed method is particularly valuable in a clinical setting as verified by analyzing human leukemic cells from marrow samples or exposed to cell cycle modifiers. The method was established using the human KG1a cell line and was applied to charcterize the cell cycle and apoptosis of fresh human marrow leukemic cells. The cells were permeabilized with 1 mL of ice cold ethanol (1 h, 4°C). Following two washes with PBS, 1% FBS and 0.25% Triton X-100 (PFT), the cells were stained in 200 μL of PFT for 30 min at room temperature in the dark with 1 μg 7-AAD (Sigma-Aldrich), 5 μL Alexa Fluor.. 488-conjugated anti-human Ki67 mAb (B56, Becton-Dickinson) and 3 μL Alexa Fluor.. 488-conjugated anti-phospho(ser10)-histone H3 polyclonal antibody (Cell Signaling Technology). A control tube was prepared with 1 μg 7-AAD and 5 μL of mouse IgG1 Alexa Fluor.. 488 (Becton-Dickinson). After 2 washes with PFT, the cells were stained with 10 μL of APC-Cy7-conjugated anti-CD45 (A20, Becton-Dickinson) followed by incubation for 20 min at 4°C. Cells were then washed twice with PBS, centrifuged for 5 min at 500 g and resuspended in 300 μL of PBS. This flow cytometric method allows for a precise analysis of the impact on the cell cycle of various functional modulators. As an example, it was applied to analyze the pro-quiescent effects of contact with bone marrow MSCs as well as and the apoptosis induction and mitosis inhibition of the human KG1a leukemic cell line by camptothecin. The cell cycle characteristics of untreated KG1a cells were clearly quantified as follows: 0.4% sub-G1, 0.8% G0, 67.9% G1, 14.9% S, 14.2% G2 and 1.8% M phase. The contact with marrow MSCs during 72 h induced an increase in G0 phase and a decrease in M phase (5.3% and 0.4%, respectively). We verified the anti-proliferative and pro-apoptotic effects of 24 h exposure to camptothecin, which induced a decrease in S, G2 and M phases (6.1%, 6.2% and 0.4%, respectively) and an increase in sub-G1 phase (1.7%). Moreover, it is interesting to note that the staining protocol preserved the integrity of the plasma membrane and allows for the analysis of heterogeneous cell populations. We document here the successful utilization of this method to discriminate concomitantly apoptosis and the cell cycle phases in a model of leukemic cells exposed to inducers of cell cycle perturbations. The value of this method to analyze heterogeneous populations was shown by discriminating the marrow cells from acute myeloid leukemia. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Exploring the Role of a Cytokinin-Activating Enzyme LONELY GUY in Unicellular Microalga Chlorella variabilis

2021 ◽  
Vol 11 ◽  
Author(s):  
Saraswati Nayar
Keyword(s):  
Cell Cycle ◽  
Cell Number ◽  
Total Carbohydrate ◽  
Stay Green ◽  
Delayed Senescence ◽  
Direct Activation ◽  
Chlorella Variabilis ◽  
Green Microalga ◽  
M Phase

LONELY GUY has been previously characterized in flowering plants to be involved in the direct activation of cytokinins. In this study, the function of the only LONELY GUY gene (CvarLOG1) from unicellular green microalga Chlorella variabilis NC64A has been investigated. CvarLOG1 expressed mainly in the lag and log phases of growth and was confirmed to be a cytokinin-activating enzyme. Overexpression of CvarLOG1 in Chlorella led to extended life in culture by almost 10–20 days, creating a “stay-green” phenotype. In the transformed alga, the cell cycle was lengthened due to delayed entry into the G2/M phase contrary to the known role of cytokinins in stimulating G2/M transition possibly due to excessive levels of this hormone. However, due to the sustained growth and delayed senescence, there was an increase in cell number by 11% and in biomass by 46% at the stationary phase, indicating a potential application for the biofuel industry. The total carbohydrate and lipid yield increased by approximately 30 and 20%, respectively. RNA-Seq-based transcriptomic analysis revealed that the genes associated with light and dark reactions of photosynthesis were upregulated, which may be the reason for the increased biomass. These data show that LOG plays an essential role during the cell cycle and in the functioning of the chloroplast and that the pathway leading to direct activation of cytokinins via LOG is functional in algae.

scholarly journals An advanced cell cycle tag toolbox reveals principles underlying temporal control of structure-selective nucleases

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Julia Bittmann ◽  
Rokas Grigaitis ◽  
Lorenzo Galanti ◽  
Silas Amarell ◽  
Florian Wilfling ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Regulation ◽  
Cell Cycle Control ◽  
S Phase ◽  
Specific Cell ◽  
Protein Functionality ◽  
M Phase ◽  
Cell Cycle Phases ◽  
Cycle Regulation

Cell cycle tags allow to restrict target protein expression to specific cell cycle phases. Here, we present an advanced toolbox of cell cycle tag constructs in budding yeast with defined and compatible peak expression that allow comparison of protein functionality at different cell cycle phases. We apply this technology to the question of how and when Mus81-Mms4 and Yen1 nucleases act on DNA replication or recombination structures. Restriction of Mus81-Mms4 to M phase but not S phase allows a wildtype response to various forms of replication perturbation and DNA damage in S phase, suggesting it acts as a post-replicative resolvase. Moreover, we use cell cycle tags to reinstall cell cycle control to a deregulated version of Yen1, showing that its premature activation interferes with the response to perturbed replication. Curbing resolvase activity and establishing a hierarchy of resolution mechanisms are therefore the principal reasons underlying resolvase cell cycle regulation.

scholarly journals Deterministic model of the eddy dynamics for a midlatitude ocean model

2021 ◽  
Author(s):  
Takaya Uchida ◽  
Bruno Deremble ◽  
Stephane Popinet
Keyword(s):  
Deterministic Model ◽  
North Atlantic Ocean ◽  
Ocean Model ◽  
Global Ocean ◽  
Mean Flow ◽  
Flux Divergence ◽  
Time Step ◽  
Weather System ◽  
Basin Scale ◽  
The Mean

Mesoscale eddies, the weather system of the oceans, although being on the scales of O(20-100 km), have a disproportionate role in shaping the mean jets such as the separated Gulf Stream in the North Atlantic Ocean, which is on the scale of O(1000 km) in the along-jet direction. With the increase in computational power, we are now able to partially resolve the eddies in basin-scale and global ocean simulations, a model resolution often referred to as mesoscale permitting. It is well known, however, that due to grid-scale numerical viscosity, mesoscale-permitting simulations have less energetic eddies and consequently weaker eddy feedback onto the mean flow. In this study, we run a quasi-geostrophic model at mesoscale-resolving resolution in a double gyre configuration and formulate a deterministic closure for the eddy rectification term of potential vorticity (PV), namely, the eddy PV flux divergence. We successfully reproduce the spatial patterns and magnitude of eddy kinetic and potential energy diagnosed from the model. One novel point about our approach is that we account for non-local eddy feedbacks onto the mean flow by solving the `sub-grid' eddy PV equation prognostically in addition to the mean PV. In return, we are able to parametrize the variability in total (mean+eddy) PV at each time step instead of solely the mean PV. A closure for the total PV is beneficial as we are able to account for both the mean state and extreme events.

71 WHAT IS THE UTERINE RESPONSE IN A CLONED BOVINE PREGNANCY?

2006 ◽  
Vol 18 (2) ◽  
pp. 144 ◽  
Author(s):  
T. C. Santos ◽  
F. T. V. Pereira ◽  
A. C. Assis Neto ◽  
C. E. Ambrósio ◽  
F. V. Meirelles ◽  
...  
Keyword(s):  
Cell Cycle ◽  
First Trimester ◽  
Giant Cells ◽  
Differential Analysis ◽  
Placental Development ◽  
Trophoblastic Cells ◽  
M Phase ◽  
Cell Cycle Phases ◽  
Cloned Bovine ◽  
Trophoblast Giant Cells

Bovine has a synepitheliochorial placenta and characteristically there is no invasion of the trophoblast, but there is migration of the binucleate trophoblast giant cells into the maternal endometrium. The feto-maternal interface occurs in placentome where a tridimensional organization permits interactions between maternal epithelium and trophoblast, and in the intercaruncular area it is possible to observe a few mini-placentomes and the uterine glands opening. The objective of the present investigation was to study the morphological aspects of the uterus in bovine that had a cloned cattle gestations to understand the differences with natural gestation. The uterus and fetal membranes from natural and cloned cattle gestations were collected, fixed in 10% formaldehyde, processed, and stained for light microscopy and immunohistochemistry. The morphological differences observed in the surrogate uterus were: extensive areas without placentome, hemorrhagic uterine areas, caruncular fusion giving a reduced number of caruncules, increase in size and weight (megacaruncules), and a significant number of mini-caruncules giving miniplacentomes (diameter < 1 cm). In particular the mini-placentome showed functional trophoblastic cells with PAS+ granules in the binucleate trophoblast giant cells and an intense subepithelial capillary organization in maternal and fetal sides. The normal and clone placentomal cell populations were analyzed throughout pregnancy. The population of tetraploid and diploid trophoblastic cells was stained; detached cell cycle and DNA content was measured in FL2 using a FACscalibur flow cytometric system. We determined the percentage of cells in apoptosis (sub-G1), quiescent cells (G0/G1), synthesis (S), and proliferative cells (G2/M) with the aid of ModFit software. In addition, a cell cycle differential analysis was performed, and the tetraploid population presented statistical differences in cell cycle phases and populations relative to the apoptosis rate for the first (7.5 � 3.1%), second (15.2 � 5.0%) and third (17.3 � 4.3%) trimesters. The number of apoptotic cells increased significantly during pregnancy stages. The results showed that first trimester presented the majority of its cells in the G0-G1 phase, starting the cell cycle. On the other hand, the second and third trimesters presented the majority of their cells in the G2-M phase, ending the cell cycle. The relationship between cell cycle phases/rate of apoptosis in mononucleate cells, days of normal and cloned pregnancy, the number of binucleate cells, and their metabolic activity as well as their developmental kinetics could be important data in several studies that involve placental development in natural pregnancy or that derived from laboratory-manipulated embryos. This work was supported by FAPESP and CNPq.

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