@article{PloentzkeBergEhrigetal.2022, author = {Pl{\"o}ntzke, Julia and Berg, Mascha and Ehrig, Rainald and Leonhard-Marek, Sabine and M{\"u}ller, Kerstin-Elisabeth and R{\"o}blitz, Susanna}, title = {Model Based Exploration of Hypokalemia in Dairy Cows}, volume = {12, 19781}, journal = {Scientific Reports}, doi = {10.1038/s41598-022-22596-0}, year = {2022}, abstract = {Hypokalemia, characterized by too low serum potassium levels, is a severe mineral disorder which can be life threatening. It is increasingly diagnosed in veterinarian healthcare and a topic of ongoing research. In this paper, we explore the different originating conditions of hypokalemia: reduced potassium intake, increased excretion, acid-base disturbances, or increased insulin, by using a dynamic mathematical model for potassium balance in non-lactating and lactating cows. Simulations are compared with literature. The results give insights into the network dynamics and point to scenarios on which experimental effort should be focused. Application of mathematical models can assist in experimental planning as well as the reduction, refinement and replacement of animal experiments.}, language = {en} } @misc{PloentzkeBergRoeblitz2018, author = {Pl{\"o}ntzke, Julia and Berg, Mascha and R{\"o}blitz, Susanna}, title = {A mathematical modelling approach to the insight of dynamic networks: Potassium homeostasis and glucose-insulin in dairy cows}, volume = {101 Suppl. 2}, journal = {ADSA 2018 Annual Meeting}, edition = {Journal of Dairy Science}, publisher = {American Dairy Science Association}, pages = {226 -- 227}, year = {2018}, abstract = {Lactating dairy cows require a particular composition of nutritional ingredients depending on their production status. The optimal supply of energy and minerals in diet, one of them potassium, is indispensable for the prevention of disbalances like hypokalemia or hypoglycaemia. Potassium balance in cows is the result of potassium intake, distribution in the organism, and excretion, and closely interacts with glucose and electrolyte metabolism, in which postpartum veterinary treatments frequently intervene. We present a mechanistic, dynamic model for potassium balance together with a glucose insulin model in non-lactating and lactating dairy cows based on ordinary differential equations. Parameter values were obtained from data of a clinical trial as well as from literature. To verify the mechanistic functioning of the model, we validate the model by comparing simulation outcomes with clinical study findings. Furthermore we perform numerical experiments and compare them with expected behaviour according to mechanistic knowledge. The results give insight into the dynamic behaviour of the network and open the way for further open questions and hypothesis to be tested.}, language = {en} } @article{SchwiegerSiebertRoeblitz2018, author = {Schwieger, Robert and Siebert, Heike and R{\"o}blitz, Susanna}, title = {Correspondence of Trap Spaces in Different Models of Bioregulatory Networks}, volume = {17}, journal = {SIAM Journal on Applied Dynamical Systems}, number = {2}, doi = {https://doi.org/10.1137/17M1155302}, pages = {1742 -- 1765}, year = {2018}, abstract = {Mathematical models for bioregulatory networks can be based on different formalisms, depending on the quality of available data and the research question to be answered. Discrete boolean models can be constructed based on qualitative data, which are frequently available. On the other hand, continuous models in terms of ordinary differential equations (ODEs) can incorporate time-series data and give more detailed insight into the dynamics of the underlying system. A few years ago, a method based on multivariate polynomial interpolation and Hill functions has been developed for an automatic conversion of boolean models to systems of ordinary differential equations. This method is frequently used by modellers in systems biology today, but there are only a few results available about the conservation of mathematical structures and properties across the formalisms. Here, we consider subsets of the phase space where some components stay fixed, called trap spaces, and demonstrate how boolean trap spaces can be linked to invariant sets in the continuous state space. This knowledge is of practical relevance since finding trap spaces in the boolean setting, which is relatively easy, allows for the construction of reduced ODE models.}, language = {en} } @article{LangeSchwiegerPloentzkeetal.2018, author = {Lange, Alexander and Schwieger, Robert and Pl{\"o}ntzke, Julia and Sch{\"a}fer, Stefan and R{\"o}blitz, Susanna}, title = {Follicular competition in cows: the selection of dominant follicles as a synergistic effect}, journal = {Journal of Mathematical Biology}, doi = {https://doi.org/10.1007/s00285-018-1284-0}, year = {2018}, abstract = {The reproductive cycle of mono-ovulatory species such as cows or humans is known to show two or more waves of follicular growth and decline between two successive ovulations. Within each wave, there is one dominant follicle escorted by subordinate follicles of varying number. Under the surge of the luteinizing hormone a growing dominant follicle ovulates. Rarely the number of ovulating follicles exceeds one. In the biological literature, the change of hormonal concentrations and individually varying numbers of follicular receptors are made responsible for the selection of exactly one dominant follicle, yet a clear cause has not been identified. In this paper, we suggest a synergistic explanation based on competition, formulated by a parsimoniously defined system of ordinary differential equations (ODEs) that quantifies the time evolution of multiple follicles and their competitive interaction during one wave. Not discriminating between follicles, growth and decline are given by fixed rates. Competition is introduced via a growth-suppressing term, equally supported by all follicles. We prove that the number of dominant follicles is determined exclusively by the ratio of follicular growth and competition. This number turns out to be independent of the number of subordinate follicles. The asymptotic behavior of the corresponding dynamical system is investigated rigorously, where we demonstrate that the ω-limit set only contains fixed points. When also including follicular decline, our ODEs perfectly resemble ultrasound data of bovine follicles. Implications for the involved but not explicitly modeled hormones are discussed.}, language = {en} } @inproceedings{LangePloentzkeSchaeferetal.2016, author = {Lange, Alexander and Pl{\"o}ntzke, Julia and Sch{\"a}fer, Stefan and R{\"o}blitz, Susanna}, title = {Follicular maturation in cows: mathematical models and data}, booktitle = {10. European Conference on Mathematical and Theoretical Biology}, year = {2016}, language = {en} } @misc{OmariPloentzkeBergetal.2016, author = {Omari, Mohamed and Pl{\"o}ntzke, Julia and Berg, Mascha and R{\"o}blitz, Susanna}, title = {Modelling of glucose-insulin metabolism and its effect on the estrous cycle in bovine}, journal = {Annual Meeting of the Population Approach Group in Europe}, year = {2016}, language = {en} } @article{StoetzelPloentzkeHeuwieseretal.2012, author = {St{\"o}tzel, Claudia and Pl{\"o}ntzke, Julia and Heuwieser, Wolfgang and R{\"o}blitz, Susanna}, title = {Advances in modelling of the bovine estrous cycle: Synchronization with PGF2alpha}, volume = {78}, journal = {Theriogenology}, doi = {10.1016/j.theriogenology.2012.04.017}, pages = {1415 -- 1428}, year = {2012}, language = {en} } @inproceedings{SchaeferPloentzkeRoeblitz2016, author = {Sch{\"a}fer, Stefan and Pl{\"o}ntzke, Julia and R{\"o}blitz, Susanna}, title = {Mathematical Modelling of Follicular Maturation in Cows and Women}, booktitle = {49. Jahrestagung der Physiologie und Pathologie der Fortpflanzung und gleichzeitig 41. Veterin{\"a}r-Humanmedizinische Gemeinschaftstagung 2016, Leipzig.}, year = {2016}, language = {en} } @article{OmariLangePloentzkeetal.2020, author = {Omari, Mohamed and Lange, Alexander and Pl{\"o}ntzke, Julia and R{\"o}blitz, Susanna}, title = {Model-based exploration of the impact of glucose metabolism on the estrous cycle dynamics in dairy cows}, volume = {15}, journal = {Biology Direct}, doi = {10.1186/s13062-019-0256-7}, year = {2020}, language = {en} } @article{BoerStoetzelRoeblitzetal.2011, author = {Boer, H. Marike T. and St{\"o}tzel, Claudia and R{\"o}blitz, Susanna and Deuflhard, Peter and Veerkamp, Roel F. and Woelders, Henri}, title = {A simple mathematical model of the bovine estrous cycle}, volume = {278}, journal = {Journal of Theoretical Biology}, number = {1}, doi = {10.1016/j.jtbi.2011.02.021}, pages = {20 -- 31}, year = {2011}, language = {en} } @article{BoerRoeblitzStoetzeletal.2011, author = {Boer, H. Marike T. and R{\"o}blitz, Susanna and St{\"o}tzel, Claudia and Veerkamp, Roel F. and Kemp, Bas and Woelders, Henri}, title = {Mechanisms regulating follicle wave patterns in the bovine estrous cycle investigated with a mathematical model}, volume = {94}, journal = {Journal of Dairy Science}, number = {12}, doi = {10.3168/jds.2011-4400}, pages = {5987 -- 6000}, year = {2011}, language = {en} } @incollection{BoerStoetzelRoeblitzetal.2012, author = {Boer, H. Marike T. and St{\"o}tzel, Claudia and R{\"o}blitz, Susanna and Woelders, Henri}, title = {A differential equation model to investigate the dynamics of the bovine estrous cycle}, volume = {736}, booktitle = {Advances in Systems Biology}, doi = {10.1007/978-1-4419-7210-1_35}, pages = {597 -- 606}, year = {2012}, language = {en} } @article{BoerApriMolenaaretal.2012, author = {Boer, H. Marike T. and Apri, Mochamad and Molenaar, Jaap and St{\"o}tzel, Claudia and Veerkamp, Roel F. and Woelders, Henri}, title = {Candidate mechanisms underlying atypical progesterone profiles as deduced from parameter perturbations in a mathematical model of the bovine estrous cycle}, volume = {95}, journal = {Journal of Dairy Science}, number = {7}, doi = {10.3168/jds.2011-5241}, pages = {3837 -- 3851}, year = {2012}, language = {en} } @book{DeuflhardRoeblitz2015, author = {Deuflhard, Peter and R{\"o}blitz, Susanna}, title = {A guide to numerical modelling in systems biology}, volume = {12}, publisher = {Springer}, isbn = {978-3-319-20058-3}, doi = {10.1007/978-3-319-20059-0}, year = {2015}, language = {en} } @inproceedings{PloentzkeBergStoetzeletal.2015, author = {Pl{\"o}ntzke, Julia and Berg, Mascha and St{\"o}tzel, Claudia and R{\"o}blitz, Susanna}, title = {A systems biology approach to bovine fertility and metabolism: Introduction of a glucose insulin model}, booktitle = {15th International Symposium on Mathematical and Computational Biology, Rorkee, India}, year = {2015}, language = {en} } @article{StoetzelEhrigBoeretal.2014, author = {St{\"o}tzel, Claudia and Ehrig, Rainald and Boer, H. Marike T. and Pl{\"o}ntzke, Julia and R{\"o}blitz, Susanna}, title = {Exploration of different wave patterns in a model of the bovine estrous cycle by Fourier analysis}, journal = {BIOMAT - Proceedings of the 14th International Symposium on Mathematical and Computational Biology, Bedlewo, Poland}, year = {2014}, abstract = {Cows typically have different numbers of follicular waves during their hormonal cycle. Understanding the underlying regulations leads to insights into the reasons for declined fertility, a phenomenon that has been observed during the last decades. We present a systematic approach based on Fourier analysis to examine how parameter changes in a model of the bovine estrous cycle lead to different wave patterns. Even without any biological considerations, this allows to detect the responsible model parameters that control the type of periodicity of the solution, thus supporting experimental planning of animal scientists.}, language = {en} } @phdthesis{Stoetzel2014, author = {St{\"o}tzel, Claudia}, title = {Numerical and Discrete Modeling of Reproductive Endocrinological Networks}, year = {2014}, abstract = {This thesis deals with the mathematical modeling of endocrinological networks that are underlying the female hormone cycle. These networks consist of a variety of biological mechanisms in different parts of the organism. Their interaction leads to periodic changes of various substances that are necessary for reproduction. In every cycle, hormones are secreted from the hypothalamic-pituitary-gonadal axis into the bloodstream, where they distribute and influence several functions in the body. Their most important task in reproduction is to regulate processes in the ovaries, where follicles and corpus luteum develop. These produce steroids that are released into the blood and from therein regulate the processes in the hypothalamic-pituitary-gonadal axis. The hormonal cycle is thus a result of a large feedback loop, whose self-regulation is a complex interplay of multiple components. For the modeling of these processes, a high abstraction level is required, which can be realized by various modeling approaches. In this work, some of these approaches are implemented. The first step in all approaches is the representation of the most important mechanisms in a flowchart. In the next step, this can be implemented as a system of ordinary differential equations using Hill functions, as a piecewise defined affine differential equation model, or directly as a purely regulatory model. Using this approach, a differential equation model for the hormonal cycle of cows is developed. This is compared with a more advanced model of the menstrual cycle in humans. Both models are validated by comparing simulations with measured values, and by studying external influences such as drug administration. For the example of the bovine estrous cycle, continuous analysis methods are used to investigate stability, follicular wave patterns, and robustness with respect to parameter perturbations. Furthermore, the model is substantially reduced while preserving the main simulation results. To take a look at alternative modeling approaches, corresponding discrete models are derived, exemplified for the bovine model. For a piecewise affine version of the model, parameter constraints for the continuous model are calculated. Stability is analyzed globally for a purely discrete model. In addition, core discrete models are derived, which retain the dynamic properties of the original model.}, language = {en} } @article{StoetzelRoeblitzSiebert2015, author = {St{\"o}tzel, Claudia and R{\"o}blitz, Susanna and Siebert, Heike}, title = {Complementing ODE-based System Analysis Using Boolean Networks Derived from an Euler-like Transformation}, journal = {PLOS ONE}, doi = {10.1371/journal.pone.0140954}, year = {2015}, language = {en} } @article{BergPloentzkeLeonhardMareketal.2017, author = {Berg, Mascha and Pl{\"o}ntzke, Julia and Leonhard-Marek, Sabine and M{\"u}ller, Kerstin-Elisabeth and R{\"o}blitz, Susanna}, title = {A dynamic model to simulate potassium balance in dairy cows}, volume = {100}, journal = {Journal of Dairy Science}, number = {12}, doi = {10.3168/jds.2016-12443}, pages = {9799 -- 9814}, year = {2017}, abstract = {High-performing dairy cows require a particular composition of nutritional ingredients, adapted to their individual requirements and depending on their production status. The optimal dimensioning of minerals in the diet, one being potassium, is indispensable for the prevention of imbalances. Potassium balance in cows is the result of potassium intake, distribution in the organism, and excretion, and it is closely related to glucose and electrolyte metabolism. In this paper, we present a dynamical model for potassium balance in lactating and nonlactating dairy cows based on ordinary differential equations. Parameter values were obtained from clinical trial data and from the literature. To verify the consistency of the model, we present simulation outcomes for 3 different scenarios: potassium balance in (1) nonlactating cows with varying feed intake, (2) nonlactating cows with varying potassium fraction in the diet, and (3) lactating cows with varying milk production levels. The results give insights into the short- and long-term potassium metabolism, providing an important step toward the understanding of the potassium network, the design of prophylactic feed additives, and possible treatment strategies.}, language = {en} } @article{BergPloentzkeSiebertetal.2021, author = {Berg, Mascha and Pl{\"o}ntzke, Julia and Siebert, Heike and R{\"o}blitz, Susanna}, title = {Modelling Oscillatory Patterns in the Bovine Estrous Cycle with Boolean Delay Equations}, volume = {83}, journal = {Bulletin of Mathematical Biology}, number = {121}, doi = {10.1007/s11538-021-00942-z}, pages = {1 -- 25}, year = {2021}, abstract = {Boolean delay equations (BDEs), with their relatively simple and intuitive mode of modelling, have been used in many research areas including, for example, climate dynamics and earthquake propagation. Their application to biological systems has been scarce and limited to the molecular level. Here, we derive and present two BDE models. One is directly derived from a previously published ordinary differential equation (ODE) model for the bovine estrous cycle, whereas the second model includes a modification of a particular biological mechanism. We not only compare the simulation results from the BDE models with the trajectories of the ODE model, but also validate the BDE models with two additional numerical experiments. One experiment induces a switch in the oscillatory pattern upon changes in the model parameters, and the other simulates the administration of a hormone that is known to shift the estrous cycle in time. The models presented here are the first BDE models for hormonal oscillators, and the first BDE models for drug administration. Even though automatic parameter estimation still remains challenging, our results support the role of BDEs as a framework for the systematic modelling of complex biological oscillators.}, language = {en} }