A checkpoint-oriented cell cycle simulation model.
Ontology highlight
ABSTRACT:
SUBMITTER: Bernard D
PROVIDER: S-EPMC6527278 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
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Project description:Cellular rhythms regulate various physiological functions in circadian oscillatory mechanisms. Weight cycling or 'yo-yo' dieting is an evitable process in human, because of subsequent loss and regain of body weight due to irregular diet. Human weight cycle (HWC) is the major factor for causing global epidemic diseases in human beings. Understanding the HWC process would provide potent additional knowledge to prevent obesity. However till date, there is no study dealing with examine the HWC model using virtual cell simulation based on system biological approach. Therefore, the present study was designed to develop a computational HWC model, which was simulated using E-cell system v3.0. The developed model has the cyclic feedback reactions of three significant variables (the consecutive cycles of weight loss in continuous food intake (Q) and regain of body weight (P) at highest threshold point of cognitive restraint (R)) which are obtained by mathematical modelling. The dynamic plot results supported that the PQR variables depicted sustained oscillation with reversible modification due to protein diet. By contrast, the virtual model simulation would provide extensive information on HWC, which might provide knowledge to develop HWC linked with obesity pathway. The presents study concludes that optimization of body weight is essential to prevent the obesity based diseases.
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Project description:BackgroundSocial science models find the ecological impacts of climate change (EICC) contribute to internal migration in developing countries and, less so, international migration. Projections expect massive climate-related migration in this century. Nascent research calls to study health, migration, population, and armed conflict potential together, accounting for EICC and other factors. System science offers a way: develop a dynamic simulation model (DSM). We aim to validate the feasibility and usefulness of a pilot DSM intended to serve as a proof-of-concept and a basis for identifying model extensions to make it less simplified and more realistic.MethodsStudies have separately examined essential parts. Our DSM integrates their results and computes composites of health problems (HP), health care (HC), non-EICC environmental health problems (EP), and environmental health services (ES) by origin site and by immigrants and natives in a destination site, and conflict risk and intensity per area. The exogenous variables include composites of EICC, sociopolitical, economic, and other factors. We simulate the model for synthetic input values and conduct sensitivity analyses.ResultsThe simulation results refer to generic origin and destination sites anywhere on Earth. The effects' sizes are likely inaccurate from a real-world view, as our input values are synthetic. Their signs and dynamics are plausible, internally consistent, and, like the sizes, respond logically in sensitivity analyses. Climate migration may harm public health in a host area even with perfect HC/ES qualities and full access; and no HP spillovers across groups, conflict, EICC, and EP. Deviations from these conditions may worsen everyone's health. We consider adaptation options.ConclusionsThis work shows we can start developing DSMs to understand climate migration and public health by examining each case with its own inputs. Validation of our pilot model suggests we can use it as intended. We lay a path to making it more realistic for policy analysis.
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Project description:G1/S and G2/M cell cycle checkpoints maintain genomic stability in eukaryotes in response to genotoxic stress. We report here both genetic and functional evidence of a Gadd45-mediated G2/M checkpoint in human and murine cells. Increased expression of Gadd45 via microinjection of an expression vector into primary human fibroblasts arrests the cells at the G2/M boundary with a phenotype of MPM2 immunopositivity, 4n DNA content and, in 15% of the cells, centrosome separation. The Gadd45-mediated G2/M arrest depends on wild-type p53, because no arrest was observed either in p53-null Li-Fraumeni fibroblasts or in normal fibroblasts coexpressed with p53 mutants. Increased expression of cyclin B1 and Cdc25C inhibited the Gadd45-mediated G2/M arrest in human fibroblasts, indicating that the mechanism of Gadd45-mediated G2/M checkpoint is at least in part through modulation of the activity of the G2-specific kinase, cyclin B1/p34(cdc2). Genetic and physiological evidence of a Gadd45-mediated G2/M checkpoint was obtained by using GADD45-deficient human or murine cells. Human cells with endogenous Gadd45 expression reduced by antisense GADD45 expression have an impaired G2/M checkpoint after exposure to either ultraviolet radiation or methyl methanesulfonate but are still able to undergo G2 arrest after ionizing radiation. Lymphocytes from gadd45-knockout mice (gadd45 -/-) also retained a G2/M checkpoint initiated by ionizing radiation and failed to arrest at G2/M after exposure to ultraviolet radiation. Therefore, the mammalian genome is protected by a multiplicity of G2/M checkpoints in response to specific types of DNA damage.
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