scholarly journals Development of a Coupled Simulation Toolkit for Computational Radiation Biology Based on Geant4 and CompuCell3D

2020 ◽  
Author(s):  
Ruirui Liu ◽  
Kathryn A. Higley ◽  
Maciej H. Swat ◽  
Mark A. J Chaplain ◽  
Gibin G. Powathil ◽  
...  
Keyword(s):  
Dna Damage ◽  
Radiation Therapy ◽  
Cell Biology ◽  
Tumor Response ◽  
Transport Model ◽  
Radiation Transport ◽  
Simulation Platform ◽  
Coupled Simulation ◽  
Transport Simulation ◽  
A Cell

AbstractUnderstanding and designing clinical radiation therapy is one of the most important areas of state-of-the-art oncological treatment regimens. Decades of research have gone into developing sophisticated treatment devices and optimization protocols for schedules and dosages. In this paper, we presented a comprehensive computational platform that facilitates building of the sophisticated multi-cell-based model of how radiation affects the biology of living tissue. We designed and implemented a coupled simulation method, including a radiation transport model, and a cell biology model, to simulate the tumor response after irradiation. The radiation transport simulation was implemented through Geant4 which is an open-source Monte Carlo simulation platform that provides many flexibilities for users, as well as low energy DNA damage simulation physics, Geant4-DNA. The cell biology simulation was implemented using CompuCell3D (CC3D) which is a cell biology simulation platform. In order to couple Geant4 solver with CC3D, we developed a “bridging” module that extracts tumor cellular geometry of the CC3D simulation (including specification of the individual cells) and ported it to the Geant4 for radiation transport simulation. The cell dose and cell DNA damage distribution in multicellular system were obtained using Geant4. The tumor response was simulated using cell-based tissue models based on CC3D. By merging two powerful and widely used modeling platforms, CC3D and Geant4, we delivered a novel tool that can give us the ability to simulate the dynamics of biological tissue in the presence of ionizing radiation, which provides a powerful framework for quantifying the biological consequences of radiation therapy. The developed tool has an advantage on that it has strong extensibility due to the exploitability of two modeling platforms. In this introductory methods paper, we described our modeling platform in detail and showed how it can be applied to study the application of radiotherapy to a vascularized tumor.

scholarly journals Crosstalk between the mTOR and DNA Damage Response Pathways in Fission Yeast

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 305
Author(s):  
John-Patrick Alao ◽  
Luc Legon ◽  
Charalampos Rallis
Keyword(s):  
Dna Damage ◽  
Fission Yeast ◽  
Dna Damage Response ◽  
Cell Biology ◽  
Environmental Changes ◽  
Energy Levels ◽  
Protein Translation ◽  
Mtor Pathway ◽  
Age Related ◽  
Damage Response

Cells have developed response systems to constantly monitor environmental changes and accordingly adjust growth, differentiation, and cellular stress programs. The evolutionarily conserved, nutrient-responsive, mechanistic target of rapamycin signaling (mTOR) pathway coordinates basic anabolic and catabolic cellular processes such as gene transcription, protein translation, autophagy, and metabolism, and is directly implicated in cellular and organismal aging as well as age-related diseases. mTOR mediates these processes in response to a broad range of inputs such as oxygen, amino acids, hormones, and energy levels, as well as stresses, including DNA damage. Here, we briefly summarize data relating to the interplays of the mTOR pathway with DNA damage response pathways in fission yeast, a favorite model in cell biology, and how these interactions shape cell decisions, growth, and cell-cycle progression. We, especially, comment on the roles of caffeine-mediated DNA-damage override. Understanding the biology of nutrient response, DNA damage and related pharmacological treatments can lead to the design of interventions towards improved cellular and organismal fitness, health, and survival.

scholarly journals e-Book on plant virus infection—a cell biology perspective

2013 ◽  
Vol 4 ◽  
Author(s):  
Jean-François Laliberté ◽  
Peter Moffett ◽  
Hélène Sanfaçon ◽  
Aiming Wang ◽  
Richard S. Nelson ◽  
...  
Keyword(s):  
Virus Infection ◽  
Cell Biology ◽  
Plant Virus ◽  
A Cell

(A) Cell biology of epithelia

1991 ◽  
Vol 7 (3) ◽  
pp. 313-338 ◽  
Author(s):  
Martin Mackay ◽  
Ian Williamson ◽  
John Hastewell
Keyword(s):  
Cell Biology ◽  
A Cell

Radiation therapy for intracranial germ cell tumors: Predictive value of tumor response as evaluated by computed tomography

1997 ◽  
Vol 2 (2) ◽  
pp. 67-72 ◽  
Author(s):  
Kazuhiko Ogawa ◽  
Takafumi Toita ◽  
Yasumasa Kakinohana ◽  
Keiichiro Yamaguchi ◽  
Koichi Miyagi ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Radiation Therapy ◽  
Germ Cell ◽  
Predictive Value ◽  
Tumor Response ◽  
Germ Cell Tumors ◽  
Intracranial Germ Cell Tumors

scholarly journals KCTD19 and its associated protein ZFP541 are independently essential for meiosis in male mice

PLoS Genetics ◽  
2021 ◽  
Vol 17 (5) ◽  
pp. e1009412
Author(s):  
Seiya Oura ◽  
Takayuki Koyano ◽  
Chisato Kodera ◽  
Yuki Horisawa-Takada ◽  
Makoto Matsuyama ◽  
...  
Keyword(s):  
Dna Damage ◽  
Reproductive Tract ◽  
Zinc Finger Protein ◽  
Male Mice ◽  
Late Pachytene ◽  
Histone Deacetylase 1 ◽  
Tetramerization Domain ◽  
Evolutionarily Conserved ◽  
Division Process ◽  
A Cell

Meiosis is a cell division process with complex chromosome events where various molecules must work in tandem. To find meiosis-related genes, we screened evolutionarily conserved and reproductive tract-enriched genes using the CRISPR/Cas9 system and identified potassium channel tetramerization domain containing 19 (Kctd19) as an essential factor for meiosis. In prophase I, Kctd19 deficiency did not affect synapsis or the DNA damage response, and chiasma structures were also observed in metaphase I spermatocytes of Kctd19 KO mice. However, spermatocytes underwent apoptotic elimination during the metaphase-anaphase transition. We were able to rescue the Kctd19 KO phenotype with an epitope-tagged Kctd19 transgene. By immunoprecipitation-mass spectrometry, we confirmed the association of KCTD19 with zinc finger protein 541 (ZFP541) and histone deacetylase 1 (HDAC1). Phenotyping of Zfp541 KO spermatocytes demonstrated XY chromosome asynapsis and recurrent DNA damage in the late pachytene stage, leading to apoptosis. In summary, our study reveals that KCTD19 associates with ZFP541 and HDAC1, and that both KCTD19 and ZFP541 are essential for meiosis in male mice.

scholarly journals Circulating tumor cells: A promising marker of predicting tumor response in rectal cancer patients receiving neoadjuvant chemo-radiation therapy

Oncotarget ◽  
2016 ◽  
Vol 7 (43) ◽  
pp. 69507-69517 ◽  
Author(s):  
Wenjie Sun ◽  
Guichao Li ◽  
Juefeng Wan ◽  
Ji Zhu ◽  
Weiqi Shen ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Radiation Therapy ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Tumor Response

scholarly journals Viral regulation of host cell biology by hijacking of the nucleolar DNA-damage response

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Stephen M. Rawlinson ◽  
Tianyue Zhao ◽  
Ashley M. Rozario ◽  
Christina L. Rootes ◽  
Paul J. McMillan ◽  
...  
Keyword(s):  
Dna Damage ◽  
Host Cell ◽  
Dna Damage Response ◽  
Cell Biology ◽  
Damage Response

Evaluation of the Effect of Horizontal Diffusion on the Long-Range Atmospheric Transport Simulation with Chernobyl Data

1995 ◽  
Vol 34 (7) ◽  
pp. 1653-1665 ◽  
Author(s):  
Hirohiko Ishikawa
Keyword(s):  
Long Range ◽  
Transport Model ◽  
Atmospheric Transport ◽  
Mean Square Displacement ◽  
Empirical Formulas ◽  
Measured Concentration ◽  
Transport Simulation ◽  
Horizontal Diffusion ◽  
Low Concentrations ◽  
Lagrangian Particle Transport

Abstract The effect of horizontal diffusion on the long-range transport simulation is examined with a Lagrangian particle transport model. The transport of radioactivity released from Chernobyl is simulated by the model with different values of horizontal diffusivity. The computed concentrations are statistically compared with measured concentration. The best simulation is found when the magnitude of the horizontal diffusivity is between 3.3 × 104 and 1.0 × 105 m2 s−1. The performance of empirical formulas of horizontal diffusion, in which mean-square displacement σy is specified as a function of time, is also examined. A part of measured concentrations, which are relatively low concentrations, cannot be explained by transport and diffusion only. It is shown that these measured concentrations can be explained by resuspension of deposited radioactivity.

scholarly journals DNA double-strand break repair: a theoretical framework and its application

2016 ◽  
Vol 13 (114) ◽  
pp. 20150679 ◽  
Author(s):  
Philip J. Murray ◽  
Bart Cornelissen ◽  
Katherine A. Vallis ◽  
S. Jon Chapman
Keyword(s):  
Dna Damage ◽  
Auger Electron ◽  
Strand Break ◽  
Dna Double Strand Breaks ◽  
Dsb Repair ◽  
Histone H2ax ◽  
Dna Double Strand Break ◽  
A Cell

DNA double-strand breaks (DSBs) are formed as a result of genotoxic insults, such as exogenous ionizing radiation, and are among the most serious types of DNA damage. One of the earliest molecular responses following DSB formation is the phosphorylation of the histone H2AX, giving rise to γ H2AX. Many copies of γ H2AX are generated at DSBs and can be detected in vitro as foci using well-established immuno-histochemical methods. It has previously been shown that anti- γ H2AX antibodies, modified by the addition of the cell-penetrating peptide TAT and a fluorescent or radionuclide label, can be used to visualize and quantify DSBs in vivo . Moreover, when labelled with a high amount of the short-range, Auger electron-emitting radioisotope, 111 In, the amount of DNA damage within a cell can be increased, leading to cell death. In this report, we develop a mathematical model that describes how molecular processes at individual sites of DNA damage give rise to quantifiable foci. Equations that describe stochastic mean behaviours at individual DSB sites are derived and parametrized using population-scale, time-series measurements from two different cancer cell lines. The model is used to examine two case studies in which the introduction of an antibody (anti- γ H2AX-TAT) that targets a key component in the DSB repair pathway influences system behaviour. We investigate: (i) how the interaction between anti- γ H2AX-TAT and γ H2AX effects the kinetics of H2AX phosphorylation and DSB repair and (ii) model behaviour when the anti- γ H2AX antibody is labelled with Auger electron-emitting 111 In and can thus instigate additional DNA damage. This work supports the conclusion that DSB kinetics are largely unaffected by the introduction of the anti- γ H2AX antibody, a result that has been validated experimentally, and hence the hypothesis that the use of anti- γ H2AX antibody to quantify DSBs does not violate the image tracer principle. Moreover, it provides a novel model of DNA damage accumulation in the presence of Auger electron-emitting 111 In that is supported qualitatively by the available experimental data.

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