TY  - CONF
AU  - Maksimović, Jelena
AU  - Ivanović-Šašić, Ana
AU  - Maćešić, Stevan
AU  - Čupić, Željko
AU  - Kolar-Anić, Ljiljana
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7431
AB  - The impact of L-tyrosine amino acid on the kinetics of the BL oscillatory reaction was investigated
under closed reactor conditions. The study was focused on examining the sensitivity of the BL
reaction matrix to tyrosine perturbations. A high sensitivity of the BL matrix to very low tyrosine
concentrations was observed.
PB  - Serbian Society of Mechanics
C3  - 9th International Congress of the Serbian Society of Mechanics, Book of Proceedings, July 5-7, 2023, Vrnjačka Banja, Serbia
T1  - L-tyrosine influence on the reaction kinetics of iodatehydrogen peroxide oscillatory reaction
SP  - 457
EP  - 458
UR  - https://hdl.handle.net/21.15107/rcub_cer_7431
ER  - 

@conference{
author = "Maksimović, Jelena and Ivanović-Šašić, Ana and Maćešić, Stevan and Čupić, Željko and Kolar-Anić, Ljiljana",
year = "2023",
abstract = "The impact of L-tyrosine amino acid on the kinetics of the BL oscillatory reaction was investigated
under closed reactor conditions. The study was focused on examining the sensitivity of the BL
reaction matrix to tyrosine perturbations. A high sensitivity of the BL matrix to very low tyrosine
concentrations was observed.",
publisher = "Serbian Society of Mechanics",
journal = "9th International Congress of the Serbian Society of Mechanics, Book of Proceedings, July 5-7, 2023, Vrnjačka Banja, Serbia",
title = "L-tyrosine influence on the reaction kinetics of iodatehydrogen peroxide oscillatory reaction",
pages = "457-458",
url = "https://hdl.handle.net/21.15107/rcub_cer_7431"
}

Maksimović, J., Ivanović-Šašić, A., Maćešić, S., Čupić, Ž.,& Kolar-Anić, L.. (2023). L-tyrosine influence on the reaction kinetics of iodatehydrogen peroxide oscillatory reaction. in 9th International Congress of the Serbian Society of Mechanics, Book of Proceedings, July 5-7, 2023, Vrnjačka Banja, Serbia
Serbian Society of Mechanics., 457-458.
https://hdl.handle.net/21.15107/rcub_cer_7431

Maksimović J, Ivanović-Šašić A, Maćešić S, Čupić Ž, Kolar-Anić L. L-tyrosine influence on the reaction kinetics of iodatehydrogen peroxide oscillatory reaction. in 9th International Congress of the Serbian Society of Mechanics, Book of Proceedings, July 5-7, 2023, Vrnjačka Banja, Serbia. 2023;:457-458.
https://hdl.handle.net/21.15107/rcub_cer_7431 .

Maksimović, Jelena, Ivanović-Šašić, Ana, Maćešić, Stevan, Čupić, Željko, Kolar-Anić, Ljiljana, "L-tyrosine influence on the reaction kinetics of iodatehydrogen peroxide oscillatory reaction" in 9th International Congress of the Serbian Society of Mechanics, Book of Proceedings, July 5-7, 2023, Vrnjačka Banja, Serbia (2023):457-458,
https://hdl.handle.net/21.15107/rcub_cer_7431 .

TY  - CONF
AU  - Ivanović-Šašić, Ana
AU  - Maćešić, Stevan
AU  - Maksimović, Jelena
AU  - Čupić, Željko
AU  - Kolar-Anić, Ljiljana
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7430
AB  - It is well known that almost all living or biological systems are naturally in the oscillatory dynamic states and can be considered as biochemical reaction systems. These oscillatory dynamic states can be caused by internal self-organized phenomena, but also by external periodic variations of temperature, light, food, or seasonal changes. The hypothalamic-pituitary-thyroid (HPT) axis is one such nonlinear system with feedback that is always in an oscillatory dynamic state and L-tyrosine is its main representative.
The biological importance of L-tyrosine interactions with iodine species was the motivation for modelling of the oscillatory dynamics in the Bray-Liebhafsky (BL) reaction perturbed by L- tyrosine. Also, direct experimental investigation of metabolic processes in the human body is extremely complex to be done, and therefore any alternative approach is of great importance. Therefore, the BL reaction has the potential to be used as a model of the biological system due to certain characteristics shared with the considered processes; it is characterized by its oscillatory dynamics and based on the chemistry of hydrogen peroxide and iodine compounds commonly present in the thyroid gland, where L-tyrosine is iodinated.
The impact of L-tyrosine on the dynamics of the Bray-Lienbhafsky oscillatory reaction was investigated numerically using the proposed model. The study was focused on the examination of the sensitivity of the BL reaction to L-tyrosine perturbation. The obtained results indicated possible pathways of influence
PB  - Kragujevac, Serbia : Institute for Information Technologies, University of Kragujevac
C3  - 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, Book of proceedings, September 28-29, 2023, Kragujevac, Serbia
T1  - Numerical simulations of the oscillatory dynamics in the Bray-Liebhafsky reaction perturbed by L-tyrosine
VL  - 612
SP  - 609
DO  - 10.46793/ICCBI23.609IS
ER  - 

@conference{
author = "Ivanović-Šašić, Ana and Maćešić, Stevan and Maksimović, Jelena and Čupić, Željko and Kolar-Anić, Ljiljana",
year = "2023",
abstract = "It is well known that almost all living or biological systems are naturally in the oscillatory dynamic states and can be considered as biochemical reaction systems. These oscillatory dynamic states can be caused by internal self-organized phenomena, but also by external periodic variations of temperature, light, food, or seasonal changes. The hypothalamic-pituitary-thyroid (HPT) axis is one such nonlinear system with feedback that is always in an oscillatory dynamic state and L-tyrosine is its main representative.
The biological importance of L-tyrosine interactions with iodine species was the motivation for modelling of the oscillatory dynamics in the Bray-Liebhafsky (BL) reaction perturbed by L- tyrosine. Also, direct experimental investigation of metabolic processes in the human body is extremely complex to be done, and therefore any alternative approach is of great importance. Therefore, the BL reaction has the potential to be used as a model of the biological system due to certain characteristics shared with the considered processes; it is characterized by its oscillatory dynamics and based on the chemistry of hydrogen peroxide and iodine compounds commonly present in the thyroid gland, where L-tyrosine is iodinated.
The impact of L-tyrosine on the dynamics of the Bray-Lienbhafsky oscillatory reaction was investigated numerically using the proposed model. The study was focused on the examination of the sensitivity of the BL reaction to L-tyrosine perturbation. The obtained results indicated possible pathways of influence",
publisher = "Kragujevac, Serbia : Institute for Information Technologies, University of Kragujevac",
journal = "2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, Book of proceedings, September 28-29, 2023, Kragujevac, Serbia",
title = "Numerical simulations of the oscillatory dynamics in the Bray-Liebhafsky reaction perturbed by L-tyrosine",
volume = "612",
pages = "609",
doi = "10.46793/ICCBI23.609IS"
}

Ivanović-Šašić, A., Maćešić, S., Maksimović, J., Čupić, Ž.,& Kolar-Anić, L.. (2023). Numerical simulations of the oscillatory dynamics in the Bray-Liebhafsky reaction perturbed by L-tyrosine. in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, Book of proceedings, September 28-29, 2023, Kragujevac, Serbia
Kragujevac, Serbia : Institute for Information Technologies, University of Kragujevac., 612, 609.
https://doi.org/10.46793/ICCBI23.609IS

Ivanović-Šašić A, Maćešić S, Maksimović J, Čupić Ž, Kolar-Anić L. Numerical simulations of the oscillatory dynamics in the Bray-Liebhafsky reaction perturbed by L-tyrosine. in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, Book of proceedings, September 28-29, 2023, Kragujevac, Serbia. 2023;612:609.
doi:10.46793/ICCBI23.609IS .

Ivanović-Šašić, Ana, Maćešić, Stevan, Maksimović, Jelena, Čupić, Željko, Kolar-Anić, Ljiljana, "Numerical simulations of the oscillatory dynamics in the Bray-Liebhafsky reaction perturbed by L-tyrosine" in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, Book of proceedings, September 28-29, 2023, Kragujevac, Serbia, 612 (2023):609,
https://doi.org/10.46793/ICCBI23.609IS . .

TY  - JOUR
AU  - Kolar-Anić, Ljiljana
AU  - Čupić, Željko
AU  - Maćešić, Stevan
AU  - Ivanović-Šašić, Ana
AU  - Dietrich, Johannes
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/6416
AB  - The synthesis of thyroid hormones in the hypothalamic-pituitary-thyroid (HPT) axis was studied. For this purpose,
a reaction model for HPT axis with stoichiometric relations between the main reaction species was
postulated. Using the law of mass action, this model has been transformed into a set of nonlinear ordinary
differential equations. This new model has been examined by stoichiometric network analysis (SNA) with the aim
to see if it possesses the ability to reproduce oscillatory ultradian dynamics founded on the internal feedback
mechanism. In particular, a feedback regulation of TSH production based on the interplay between TRH, TSH,
somatostatin and thyroid hormones was proposed. Besides, the ten times larger amount of produced T4 with
respect to T3 in the thyroid gland was successfully simulated. The properties of SNA in combination with
experimental results, were used to determine the unknown parameters (19 rate constants of particular reaction
steps) necessary for numerical investigations. The steady-state concentrations of 15 reactive species were tuned
to be consistent with the experimental data. The predictive potential of the proposed model was illustrated on
numerical simulations of somatostatin influence on TSH dynamics investigated experimentally by Weeke et al. in
1975. In addition, all programs for SNA analysis were adapted for this kind of a large model. The procedure of
calculating rate constants from steady-state reaction rates and very limited available experimental data was
developed. For this purpose, a unique numerical method was developed to fine-tune model parameters while
preserving the fixed rate ratios and using the magnitude of the experimentally known oscillation period as the
only target value. The postulated model was numerically validated by perturbation simulations with somatostatin
infusion and the results were compared with experiments available in literature. Finally, as far as we know,
this reaction model with 15 variables is the most dimensional one that have been analysed mathematically to
obtain instability region and oscillatory dynamic states. Among the existing models of thyroid homeostasis this
theory represents a new class that may improve our understanding of basic physiological processes and helps to
develop new therapeutic approaches. Additionally, it may pave the way to improved diagnostic methods for
pituitary and thyroid disorders.
PB  - Elsevier
T2  - Computers in Biology and Medicine
T1  - Modelling of the thyroid hormone synthesis as a part of nonlinear reaction mechanism with feedback
VL  - 160
SP  - 106980
DO  - 10.1016/j.compbiomed.2023.106980
ER  - 

@article{
author = "Kolar-Anić, Ljiljana and Čupić, Željko and Maćešić, Stevan and Ivanović-Šašić, Ana and Dietrich, Johannes",
year = "2023",
abstract = "The synthesis of thyroid hormones in the hypothalamic-pituitary-thyroid (HPT) axis was studied. For this purpose,
a reaction model for HPT axis with stoichiometric relations between the main reaction species was
postulated. Using the law of mass action, this model has been transformed into a set of nonlinear ordinary
differential equations. This new model has been examined by stoichiometric network analysis (SNA) with the aim
to see if it possesses the ability to reproduce oscillatory ultradian dynamics founded on the internal feedback
mechanism. In particular, a feedback regulation of TSH production based on the interplay between TRH, TSH,
somatostatin and thyroid hormones was proposed. Besides, the ten times larger amount of produced T4 with
respect to T3 in the thyroid gland was successfully simulated. The properties of SNA in combination with
experimental results, were used to determine the unknown parameters (19 rate constants of particular reaction
steps) necessary for numerical investigations. The steady-state concentrations of 15 reactive species were tuned
to be consistent with the experimental data. The predictive potential of the proposed model was illustrated on
numerical simulations of somatostatin influence on TSH dynamics investigated experimentally by Weeke et al. in
1975. In addition, all programs for SNA analysis were adapted for this kind of a large model. The procedure of
calculating rate constants from steady-state reaction rates and very limited available experimental data was
developed. For this purpose, a unique numerical method was developed to fine-tune model parameters while
preserving the fixed rate ratios and using the magnitude of the experimentally known oscillation period as the
only target value. The postulated model was numerically validated by perturbation simulations with somatostatin
infusion and the results were compared with experiments available in literature. Finally, as far as we know,
this reaction model with 15 variables is the most dimensional one that have been analysed mathematically to
obtain instability region and oscillatory dynamic states. Among the existing models of thyroid homeostasis this
theory represents a new class that may improve our understanding of basic physiological processes and helps to
develop new therapeutic approaches. Additionally, it may pave the way to improved diagnostic methods for
pituitary and thyroid disorders.",
publisher = "Elsevier",
journal = "Computers in Biology and Medicine",
title = "Modelling of the thyroid hormone synthesis as a part of nonlinear reaction mechanism with feedback",
volume = "160",
pages = "106980",
doi = "10.1016/j.compbiomed.2023.106980"
}

Kolar-Anić, L., Čupić, Ž., Maćešić, S., Ivanović-Šašić, A.,& Dietrich, J.. (2023). Modelling of the thyroid hormone synthesis as a part of nonlinear reaction mechanism with feedback. in Computers in Biology and Medicine
Elsevier., 160, 106980.
https://doi.org/10.1016/j.compbiomed.2023.106980

Kolar-Anić L, Čupić Ž, Maćešić S, Ivanović-Šašić A, Dietrich J. Modelling of the thyroid hormone synthesis as a part of nonlinear reaction mechanism with feedback. in Computers in Biology and Medicine. 2023;160:106980.
doi:10.1016/j.compbiomed.2023.106980 .

Kolar-Anić, Ljiljana, Čupić, Željko, Maćešić, Stevan, Ivanović-Šašić, Ana, Dietrich, Johannes, "Modelling of the thyroid hormone synthesis as a part of nonlinear reaction mechanism with feedback" in Computers in Biology and Medicine, 160 (2023):106980,
https://doi.org/10.1016/j.compbiomed.2023.106980 . .

TY  - JOUR
AU  - Maćešić, Stevan
AU  - Čupić, Željko
AU  - Kolar-Anić, Ljiljana
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7185
AB  - The effect of diffusion on the steady-state stability of an oscillatory chemical reaction model was investigated using stoichiometric network analysis and numerical simulations. Under both spatially uniform and nonuniform conditions, steady-state stability was investigated. Under spatially uniform conditions, the model can simulate oscillatory dynamics by passing through the Andronov-Hopf bifurcation. When diffusion is introduced into the system, the results have shown that two scenarios through which instabilities can occur are possible. Either, oscillations may be caused by the same instability as it was in homogeneous case, or, diffusion may cause new type of instability. Using the exponent polytope method, we derived a system of inequalities that describes the conditions for the emergence of both, oscillations, and diffusion-driven instabilities.
PB  - Elsevier
T2  - Chaos, Solitons & Fractals
T1  - Effect of diffusion on steady state stability of an oscillatory reaction model
VL  - 174
SP  - 113783
DO  - 10.1016/j.chaos.2023.113783
ER  - 

@article{
author = "Maćešić, Stevan and Čupić, Željko and Kolar-Anić, Ljiljana",
year = "2023",
abstract = "The effect of diffusion on the steady-state stability of an oscillatory chemical reaction model was investigated using stoichiometric network analysis and numerical simulations. Under both spatially uniform and nonuniform conditions, steady-state stability was investigated. Under spatially uniform conditions, the model can simulate oscillatory dynamics by passing through the Andronov-Hopf bifurcation. When diffusion is introduced into the system, the results have shown that two scenarios through which instabilities can occur are possible. Either, oscillations may be caused by the same instability as it was in homogeneous case, or, diffusion may cause new type of instability. Using the exponent polytope method, we derived a system of inequalities that describes the conditions for the emergence of both, oscillations, and diffusion-driven instabilities.",
publisher = "Elsevier",
journal = "Chaos, Solitons & Fractals",
title = "Effect of diffusion on steady state stability of an oscillatory reaction model",
volume = "174",
pages = "113783",
doi = "10.1016/j.chaos.2023.113783"
}

Maćešić, S., Čupić, Ž.,& Kolar-Anić, L.. (2023). Effect of diffusion on steady state stability of an oscillatory reaction model. in Chaos, Solitons & Fractals
Elsevier., 174, 113783.
https://doi.org/10.1016/j.chaos.2023.113783

Maćešić S, Čupić Ž, Kolar-Anić L. Effect of diffusion on steady state stability of an oscillatory reaction model. in Chaos, Solitons & Fractals. 2023;174:113783.
doi:10.1016/j.chaos.2023.113783 .

Maćešić, Stevan, Čupić, Željko, Kolar-Anić, Ljiljana, "Effect of diffusion on steady state stability of an oscillatory reaction model" in Chaos, Solitons & Fractals, 174 (2023):113783,
https://doi.org/10.1016/j.chaos.2023.113783 . .

TY  - JOUR
AU  - Čupić, Željko
AU  - Maćešić, Stevan
AU  - Anić, Slobodan
AU  - Kolar-Anić, Ljiljana
AU  - Ivanović-Šašić, Ana
AU  - Novaković, Katarina
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5293
AB  - The study presents a mathematical model of Bruk Temkin-Gorodsky Novakovic (BT-GN) reaction system employing palladium-catalyzed oscillatory carbonylation reaction of mono alkyne-terminated poly(ethylene glycol) methyl ether. The proposed model advances simulation capabilities of this particular chemical oscillator but also BT-GN reactions in general. The model was verified using experimental data where good agreement is achieved and existence of complex pH oscillations like burst oscillations was matched. Furthermore, the model was used to predict reaction conditions capable of producing further complexities and initial conditions that would lead to desired period of pH oscillations. Having such a powerful tool, enhances our capabilities to study and further develop BT-GN oscillators with a reduced experimental effort.
PB  - Springer
T2  - Reaction Kinetics, Mechanisms and Catalysis
T1  - Oscillatory carbonylation of poly(ethylene glycol)methyl ether acetylene. Improved model of reaction mechanism
VL  - 135
IS  - 1
SP  - 3
EP  - 14
DO  - 10.1007/s11144-021-02148-9
ER  - 

@article{
author = "Čupić, Željko and Maćešić, Stevan and Anić, Slobodan and Kolar-Anić, Ljiljana and Ivanović-Šašić, Ana and Novaković, Katarina",
year = "2022",
abstract = "The study presents a mathematical model of Bruk Temkin-Gorodsky Novakovic (BT-GN) reaction system employing palladium-catalyzed oscillatory carbonylation reaction of mono alkyne-terminated poly(ethylene glycol) methyl ether. The proposed model advances simulation capabilities of this particular chemical oscillator but also BT-GN reactions in general. The model was verified using experimental data where good agreement is achieved and existence of complex pH oscillations like burst oscillations was matched. Furthermore, the model was used to predict reaction conditions capable of producing further complexities and initial conditions that would lead to desired period of pH oscillations. Having such a powerful tool, enhances our capabilities to study and further develop BT-GN oscillators with a reduced experimental effort.",
publisher = "Springer",
journal = "Reaction Kinetics, Mechanisms and Catalysis",
title = "Oscillatory carbonylation of poly(ethylene glycol)methyl ether acetylene. Improved model of reaction mechanism",
volume = "135",
number = "1",
pages = "3-14",
doi = "10.1007/s11144-021-02148-9"
}

Čupić, Ž., Maćešić, S., Anić, S., Kolar-Anić, L., Ivanović-Šašić, A.,& Novaković, K.. (2022). Oscillatory carbonylation of poly(ethylene glycol)methyl ether acetylene. Improved model of reaction mechanism. in Reaction Kinetics, Mechanisms and Catalysis
Springer., 135(1), 3-14.
https://doi.org/10.1007/s11144-021-02148-9

Čupić Ž, Maćešić S, Anić S, Kolar-Anić L, Ivanović-Šašić A, Novaković K. Oscillatory carbonylation of poly(ethylene glycol)methyl ether acetylene. Improved model of reaction mechanism. in Reaction Kinetics, Mechanisms and Catalysis. 2022;135(1):3-14.
doi:10.1007/s11144-021-02148-9 .

Čupić, Željko, Maćešić, Stevan, Anić, Slobodan, Kolar-Anić, Ljiljana, Ivanović-Šašić, Ana, Novaković, Katarina, "Oscillatory carbonylation of poly(ethylene glycol)methyl ether acetylene. Improved model of reaction mechanism" in Reaction Kinetics, Mechanisms and Catalysis, 135, no. 1 (2022):3-14,
https://doi.org/10.1007/s11144-021-02148-9 . .

TY  - CONF
AU  - Stojiljković, Aleksandra
AU  - Čupić, Željko
AU  - Maćešić, Stevan
AU  - Ivanović-Šašić, Ana
AU  - Kolar-Anić, Ljiljana
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/6413
AB  - The previously proposed stoichiometric model of the Hypothalamic-Pituitary-Adrenal (HPA)
axis activity that took into account arginine vasopressin (AVP), has been further developed to
emulate ultradian oscillations of corticotropin-releasing hormone (CRH) and AVP. With this
aim, additional coupling of HPA consisting hormones was introduced into this model by
reaction between CRH and cortisol (CORT). How additional coupling of hormones affects HPA
axis ultradian dynamics and reflects on ultradian oscillations of AVP and CRH concentrations
was examined by using numerical simulations and bifurcation analysis. Results show that the
rate constant of newly incorporated reaction alone is sufficient to be adjusted only for CRH to
exhibit oscillations with optimally prominent amplitudes. Also, oscillation frequencies of CRH
were found to be in accordance with findings in the literature under all investigated conditions
PB  - Society of Physical Chemists of Serbia
C3  - Proceedings - 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2022, September, 26-30, 2022, Belgrade, Serbia
T1  - Ultradian oscillations of corticotropin-releasing hormone (crh) and arginine vasopressin (avp) in modelling of hypothalamic-pituitary-adrenal axis: influence of feedback loop between crh and cortisol
VL  - I
SP  - 207
EP  - 210
UR  - https://hdl.handle.net/21.15107/rcub_cer_6413
ER  - 

@conference{
author = "Stojiljković, Aleksandra and Čupić, Željko and Maćešić, Stevan and Ivanović-Šašić, Ana and Kolar-Anić, Ljiljana",
year = "2022",
abstract = "The previously proposed stoichiometric model of the Hypothalamic-Pituitary-Adrenal (HPA)
axis activity that took into account arginine vasopressin (AVP), has been further developed to
emulate ultradian oscillations of corticotropin-releasing hormone (CRH) and AVP. With this
aim, additional coupling of HPA consisting hormones was introduced into this model by
reaction between CRH and cortisol (CORT). How additional coupling of hormones affects HPA
axis ultradian dynamics and reflects on ultradian oscillations of AVP and CRH concentrations
was examined by using numerical simulations and bifurcation analysis. Results show that the
rate constant of newly incorporated reaction alone is sufficient to be adjusted only for CRH to
exhibit oscillations with optimally prominent amplitudes. Also, oscillation frequencies of CRH
were found to be in accordance with findings in the literature under all investigated conditions",
publisher = "Society of Physical Chemists of Serbia",
journal = "Proceedings - 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2022, September, 26-30, 2022, Belgrade, Serbia",
title = "Ultradian oscillations of corticotropin-releasing hormone (crh) and arginine vasopressin (avp) in modelling of hypothalamic-pituitary-adrenal axis: influence of feedback loop between crh and cortisol",
volume = "I",
pages = "207-210",
url = "https://hdl.handle.net/21.15107/rcub_cer_6413"
}

Stojiljković, A., Čupić, Ž., Maćešić, S., Ivanović-Šašić, A.,& Kolar-Anić, L.. (2022). Ultradian oscillations of corticotropin-releasing hormone (crh) and arginine vasopressin (avp) in modelling of hypothalamic-pituitary-adrenal axis: influence of feedback loop between crh and cortisol. in Proceedings - 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2022, September, 26-30, 2022, Belgrade, Serbia
Society of Physical Chemists of Serbia., I, 207-210.
https://hdl.handle.net/21.15107/rcub_cer_6413

Stojiljković A, Čupić Ž, Maćešić S, Ivanović-Šašić A, Kolar-Anić L. Ultradian oscillations of corticotropin-releasing hormone (crh) and arginine vasopressin (avp) in modelling of hypothalamic-pituitary-adrenal axis: influence of feedback loop between crh and cortisol. in Proceedings - 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2022, September, 26-30, 2022, Belgrade, Serbia. 2022;I:207-210.
https://hdl.handle.net/21.15107/rcub_cer_6413 .

Stojiljković, Aleksandra, Čupić, Željko, Maćešić, Stevan, Ivanović-Šašić, Ana, Kolar-Anić, Ljiljana, "Ultradian oscillations of corticotropin-releasing hormone (crh) and arginine vasopressin (avp) in modelling of hypothalamic-pituitary-adrenal axis: influence of feedback loop between crh and cortisol" in Proceedings - 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2022, September, 26-30, 2022, Belgrade, Serbia, I (2022):207-210,
https://hdl.handle.net/21.15107/rcub_cer_6413 .

TY  - JOUR
AU  - Stojiljković, Aleksandra S.
AU  - Čupić, Željko
AU  - Maćešić, Stevan
AU  - Ivanović - Šašić, Ana
AU  - Kolar-Anić, Ljiljana
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5390
AB  - Numerous studies on humans and animals have indicated that the corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) stimulate both individually and synergistically secretion of adrenocorticotropic hormone (ACTH) by corticotropic cells in anterior pituitary. With aim to characterize and better comprehend the mechanisms underlying the effects of AVP on Hypothalamic-Pituitary-Adrenal (HPA) axis ultradian dynamics, AVP is here incorporated into our previously proposed stoichiometric model of HPA axis in humans. This extended nonlinear network reaction model took into account AVP by: reaction steps associated with two separate inflows of AVP into pituitary portal system, that is synthesized and released from hypothalamic parvocellular and magnocellular neuronal populations, as well as summarized reaction steps related to its individual and synergistic action with CRH on corticotropic cells. To explore the properties of extended model and its capacity to emulate the effects of AVP, nonlinear dynamical systems theory and bifurcation analyses based on numerical simulations were utilized to determine the dependence of ultradian oscillations on rate constants of the inflows of CRH and AVP from parvocellular neuronal populations, the conditions under which dynamical transitions occur due to their synergistic action and, moreover, the types of these transitions. The results show that under certain conditions, HPA system could enter into oscillatory dynamic states from stable steady state and vice versa under the influence of synergy reaction rate constant. Transitions between these dynamical states were always through supercritical Andronov-Hopf bifurcation point. Also, results revealed the conditions under which amplitudes of ultradian oscillations could increase several-fold due to CRH and AVP synergistic stimulation of ACTH secretion in accordance with results reported in the literature. Moreover, results showed experimentally observed superiority of CRH as a stimulator of ACTH secretion compared to AVP in humans. The proposed model can be very useful in studies related to the role of AVP and its synergistic action with CRH in life-threatening circumstances such as acute homeostasis dynamic crisis, autoimmune inflammations or severe hypovolemia requiring instant or several-days sustained corticosteroid excess levels. Moreover, the model can be helpful for investigations of indirect AVP-induced HPA activity by exogenously administered AVP used in therapeutic treatment.
PB  - Frontiers Media S.A.
T2  - Frontiers in Endokrinology
T1  - Influence of arginine vasopressin on the ultradian dynamics of Hypothalamic-Pituitary-Adrenal axis
VL  - 13
SP  - 976323
DO  - 10.3389/fendo.2022.976323
ER  - 

@article{
author = "Stojiljković, Aleksandra S. and Čupić, Željko and Maćešić, Stevan and Ivanović - Šašić, Ana and Kolar-Anić, Ljiljana",
year = "2022",
abstract = "Numerous studies on humans and animals have indicated that the corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) stimulate both individually and synergistically secretion of adrenocorticotropic hormone (ACTH) by corticotropic cells in anterior pituitary. With aim to characterize and better comprehend the mechanisms underlying the effects of AVP on Hypothalamic-Pituitary-Adrenal (HPA) axis ultradian dynamics, AVP is here incorporated into our previously proposed stoichiometric model of HPA axis in humans. This extended nonlinear network reaction model took into account AVP by: reaction steps associated with two separate inflows of AVP into pituitary portal system, that is synthesized and released from hypothalamic parvocellular and magnocellular neuronal populations, as well as summarized reaction steps related to its individual and synergistic action with CRH on corticotropic cells. To explore the properties of extended model and its capacity to emulate the effects of AVP, nonlinear dynamical systems theory and bifurcation analyses based on numerical simulations were utilized to determine the dependence of ultradian oscillations on rate constants of the inflows of CRH and AVP from parvocellular neuronal populations, the conditions under which dynamical transitions occur due to their synergistic action and, moreover, the types of these transitions. The results show that under certain conditions, HPA system could enter into oscillatory dynamic states from stable steady state and vice versa under the influence of synergy reaction rate constant. Transitions between these dynamical states were always through supercritical Andronov-Hopf bifurcation point. Also, results revealed the conditions under which amplitudes of ultradian oscillations could increase several-fold due to CRH and AVP synergistic stimulation of ACTH secretion in accordance with results reported in the literature. Moreover, results showed experimentally observed superiority of CRH as a stimulator of ACTH secretion compared to AVP in humans. The proposed model can be very useful in studies related to the role of AVP and its synergistic action with CRH in life-threatening circumstances such as acute homeostasis dynamic crisis, autoimmune inflammations or severe hypovolemia requiring instant or several-days sustained corticosteroid excess levels. Moreover, the model can be helpful for investigations of indirect AVP-induced HPA activity by exogenously administered AVP used in therapeutic treatment.",
publisher = "Frontiers Media S.A.",
journal = "Frontiers in Endokrinology",
title = "Influence of arginine vasopressin on the ultradian dynamics of Hypothalamic-Pituitary-Adrenal axis",
volume = "13",
pages = "976323",
doi = "10.3389/fendo.2022.976323"
}

Stojiljković, A. S., Čupić, Ž., Maćešić, S., Ivanović - Šašić, A.,& Kolar-Anić, L.. (2022). Influence of arginine vasopressin on the ultradian dynamics of Hypothalamic-Pituitary-Adrenal axis. in Frontiers in Endokrinology
Frontiers Media S.A.., 13, 976323.
https://doi.org/10.3389/fendo.2022.976323

Stojiljković AS, Čupić Ž, Maćešić S, Ivanović - Šašić A, Kolar-Anić L. Influence of arginine vasopressin on the ultradian dynamics of Hypothalamic-Pituitary-Adrenal axis. in Frontiers in Endokrinology. 2022;13:976323.
doi:10.3389/fendo.2022.976323 .

Stojiljković, Aleksandra S., Čupić, Željko, Maćešić, Stevan, Ivanović - Šašić, Ana, Kolar-Anić, Ljiljana, "Influence of arginine vasopressin on the ultradian dynamics of Hypothalamic-Pituitary-Adrenal axis" in Frontiers in Endokrinology, 13 (2022):976323,
https://doi.org/10.3389/fendo.2022.976323 . .

TY  - CONF
AU  - Ivanović-Šašić, Ana
AU  - Maćešić, Stevan
AU  - Čupić, Željko
AU  - Kolar-Anić, Ljiljana
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/6403
AB  - The Bray-Liebhafsky (BL) is one of the most analyzed oscillatory reaction both experimentally and 
numerically. Most of the experimentally obtained dynamical states of this reaction realized in a 
continuously fed well stirred tank reactor (CSTR) are successfully simulated. Beside others, 
numerous structured chaotic dynamical states were obtained between each two periodic states in the 
period doubling rout to chaos with respect to specific flow rate as the control parameter. It was an 
universal scenario throughout the whole mixed-mode region, as well as throughout other mixed-mode 
regions obtained under different initial conditions. However, the intermittent oscillations consistent 
of chaotic mixture of large-amplitude relaxation oscillations, grouped in bursts and small-amplitude 
sinusoidal ones or even quiescent parts between them known as gaps were also generated 
experimentally in the Bray–Liebhafsky reaction by varying different parameters such as temperature, 
flow rate or reactant concentrations under CSTR conditions. Nevertheless, it will be shown here that 
intermittent oscillations can be simulated by already published model of the BL reaction network.
PB  - Society of Physical Chemists of Serbia
C3  - Proceedings - 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2021, September 20-24 2021, Belgrade, Serbia
T1  - Various dinamical states in the Bray-Liebhafsky oscillatory reaction- from periodicity to intermittent chaos
VL  - I
SP  - 199
EP  - 199
UR  - https://hdl.handle.net/21.15107/rcub_cer_6403
ER  - 

@conference{
author = "Ivanović-Šašić, Ana and Maćešić, Stevan and Čupić, Željko and Kolar-Anić, Ljiljana",
year = "2021",
abstract = "The Bray-Liebhafsky (BL) is one of the most analyzed oscillatory reaction both experimentally and 
numerically. Most of the experimentally obtained dynamical states of this reaction realized in a 
continuously fed well stirred tank reactor (CSTR) are successfully simulated. Beside others, 
numerous structured chaotic dynamical states were obtained between each two periodic states in the 
period doubling rout to chaos with respect to specific flow rate as the control parameter. It was an 
universal scenario throughout the whole mixed-mode region, as well as throughout other mixed-mode 
regions obtained under different initial conditions. However, the intermittent oscillations consistent 
of chaotic mixture of large-amplitude relaxation oscillations, grouped in bursts and small-amplitude 
sinusoidal ones or even quiescent parts between them known as gaps were also generated 
experimentally in the Bray–Liebhafsky reaction by varying different parameters such as temperature, 
flow rate or reactant concentrations under CSTR conditions. Nevertheless, it will be shown here that 
intermittent oscillations can be simulated by already published model of the BL reaction network.",
publisher = "Society of Physical Chemists of Serbia",
journal = "Proceedings - 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2021, September 20-24 2021, Belgrade, Serbia",
title = "Various dinamical states in the Bray-Liebhafsky oscillatory reaction- from periodicity to intermittent chaos",
volume = "I",
pages = "199-199",
url = "https://hdl.handle.net/21.15107/rcub_cer_6403"
}

Ivanović-Šašić, A., Maćešić, S., Čupić, Ž.,& Kolar-Anić, L.. (2021). Various dinamical states in the Bray-Liebhafsky oscillatory reaction- from periodicity to intermittent chaos. in Proceedings - 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2021, September 20-24 2021, Belgrade, Serbia
Society of Physical Chemists of Serbia., I, 199-199.
https://hdl.handle.net/21.15107/rcub_cer_6403

Ivanović-Šašić A, Maćešić S, Čupić Ž, Kolar-Anić L. Various dinamical states in the Bray-Liebhafsky oscillatory reaction- from periodicity to intermittent chaos. in Proceedings - 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2021, September 20-24 2021, Belgrade, Serbia. 2021;I:199-199.
https://hdl.handle.net/21.15107/rcub_cer_6403 .

Ivanović-Šašić, Ana, Maćešić, Stevan, Čupić, Željko, Kolar-Anić, Ljiljana, "Various dinamical states in the Bray-Liebhafsky oscillatory reaction- from periodicity to intermittent chaos" in Proceedings - 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2021, September 20-24 2021, Belgrade, Serbia, I (2021):199-199,
https://hdl.handle.net/21.15107/rcub_cer_6403 .

TY  - CONF
AU  - Čupić, Željko
AU  - Ivanović-Šašić, Ana
AU  - Maćešić, Stevan
AU  - Anić, Slobodan
AU  - Kolar-Anić, Ljiljana
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/6404
AB  - The first discovered homogeneous oscillatory reaction was the Bray-Liebhafsky (BL) one, 
described in a paper published exactly 100 years ago. However, the applicability of oscillatory 
reactions in chemical computing was recently discovered. Here we intend to expose the native 
computing concept applied to intermittent states of the BL reaction, because we believe that 
this particular state may have some advantages. For this purpose, numerical simulations will be
used based on the known model. Sequences of perturbations will be introduced by adding iodate 
(IO3
-
) and hydrogen peroxide (H2O2), separately, as well as in various combinations with one 
another. It will be shown that dynamic states obtained after perturbations with same species 
depend very much on the sequence in which these species were used in perturbations. 
Additionally, it will be shown that obtained dynamic states shift the system from chaotic 
intermittent dynamic state to different complex periodic states. Hence, the applicability of the 
BL reaction system in chemical computing was demonstrated.
PB  - Kragujevac, Serbia : Institute for Information Technologies, University of Kragujevac
C3  - Book of proceedings - 1st International Conference on Chemo and BioInformatics  ICCBIKG 2021, October 26-27, 2021, Kragujevac, Serbia
T1  - Applicability of Bray-Liebhafsky reaction for chemical computing
SP  - 431
EP  - 434
DO  - 10.46793/ICCBI21.431C
ER  - 

@conference{
author = "Čupić, Željko and Ivanović-Šašić, Ana and Maćešić, Stevan and Anić, Slobodan and Kolar-Anić, Ljiljana",
year = "2021",
abstract = "The first discovered homogeneous oscillatory reaction was the Bray-Liebhafsky (BL) one, 
described in a paper published exactly 100 years ago. However, the applicability of oscillatory 
reactions in chemical computing was recently discovered. Here we intend to expose the native 
computing concept applied to intermittent states of the BL reaction, because we believe that 
this particular state may have some advantages. For this purpose, numerical simulations will be
used based on the known model. Sequences of perturbations will be introduced by adding iodate 
(IO3
-
) and hydrogen peroxide (H2O2), separately, as well as in various combinations with one 
another. It will be shown that dynamic states obtained after perturbations with same species 
depend very much on the sequence in which these species were used in perturbations. 
Additionally, it will be shown that obtained dynamic states shift the system from chaotic 
intermittent dynamic state to different complex periodic states. Hence, the applicability of the 
BL reaction system in chemical computing was demonstrated.",
publisher = "Kragujevac, Serbia : Institute for Information Technologies, University of Kragujevac",
journal = "Book of proceedings - 1st International Conference on Chemo and BioInformatics  ICCBIKG 2021, October 26-27, 2021, Kragujevac, Serbia",
title = "Applicability of Bray-Liebhafsky reaction for chemical computing",
pages = "431-434",
doi = "10.46793/ICCBI21.431C"
}

Čupić, Ž., Ivanović-Šašić, A., Maćešić, S., Anić, S.,& Kolar-Anić, L.. (2021). Applicability of Bray-Liebhafsky reaction for chemical computing. in Book of proceedings - 1st International Conference on Chemo and BioInformatics  ICCBIKG 2021, October 26-27, 2021, Kragujevac, Serbia
Kragujevac, Serbia : Institute for Information Technologies, University of Kragujevac., 431-434.
https://doi.org/10.46793/ICCBI21.431C

Čupić Ž, Ivanović-Šašić A, Maćešić S, Anić S, Kolar-Anić L. Applicability of Bray-Liebhafsky reaction for chemical computing. in Book of proceedings - 1st International Conference on Chemo and BioInformatics  ICCBIKG 2021, October 26-27, 2021, Kragujevac, Serbia. 2021;:431-434.
doi:10.46793/ICCBI21.431C .

Čupić, Željko, Ivanović-Šašić, Ana, Maćešić, Stevan, Anić, Slobodan, Kolar-Anić, Ljiljana, "Applicability of Bray-Liebhafsky reaction for chemical computing" in Book of proceedings - 1st International Conference on Chemo and BioInformatics  ICCBIKG 2021, October 26-27, 2021, Kragujevac, Serbia (2021):431-434,
https://doi.org/10.46793/ICCBI21.431C . .

TY  - CONF
AU  - Čupić, Željko
AU  - Maćešić, Stevan
AU  - Kolar-Anić, Ljiljana
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3746
UR  - http://imqf.ekof.bg.ac.rs/ConfNonlin/index.html
AB  - Stability analysis of reaction systems is described by the application of the Stoichiometric Network Analysis to the three-variable-autocatalator. Although simple, this model is complex enough to describe complex forms of nonlinear dynamics phenomena, like mixed-mode oscillations and chaos. Therefore, stability analysis of such model is not a trivial task. Using the Stoichiometric Network Analysis for this purpose makes the process clear and leads to the reliable result.
The method is described briefly in few general steps and all of them are further clarified through the application to the chosen example. First, the reaction rates in steady state are decomposed to contributions of independent pathways, called extreme currents. Then, linearized operator is constructed. Finally, through the analysis of the principal minors of the essential part of this operator, simple stability criterion is identified.
PB  - Serbian academy of nonlinear sciences
C3  - Proceedings - 1st Conference on nonlinearity
T1  - Instability region in models of nonlinear reaction systems. The Stoichiometric Network Analysis
SP  - 145
EP  - 159
UR  - https://hdl.handle.net/21.15107/rcub_cer_3746
ER  - 

@conference{
author = "Čupić, Željko and Maćešić, Stevan and Kolar-Anić, Ljiljana",
year = "2020",
abstract = "Stability analysis of reaction systems is described by the application of the Stoichiometric Network Analysis to the three-variable-autocatalator. Although simple, this model is complex enough to describe complex forms of nonlinear dynamics phenomena, like mixed-mode oscillations and chaos. Therefore, stability analysis of such model is not a trivial task. Using the Stoichiometric Network Analysis for this purpose makes the process clear and leads to the reliable result.
The method is described briefly in few general steps and all of them are further clarified through the application to the chosen example. First, the reaction rates in steady state are decomposed to contributions of independent pathways, called extreme currents. Then, linearized operator is constructed. Finally, through the analysis of the principal minors of the essential part of this operator, simple stability criterion is identified.",
publisher = "Serbian academy of nonlinear sciences",
journal = "Proceedings - 1st Conference on nonlinearity",
title = "Instability region in models of nonlinear reaction systems. The Stoichiometric Network Analysis",
pages = "145-159",
url = "https://hdl.handle.net/21.15107/rcub_cer_3746"
}

Čupić, Ž., Maćešić, S.,& Kolar-Anić, L.. (2020). Instability region in models of nonlinear reaction systems. The Stoichiometric Network Analysis. in Proceedings - 1st Conference on nonlinearity
Serbian academy of nonlinear sciences., 145-159.
https://hdl.handle.net/21.15107/rcub_cer_3746

Čupić Ž, Maćešić S, Kolar-Anić L. Instability region in models of nonlinear reaction systems. The Stoichiometric Network Analysis. in Proceedings - 1st Conference on nonlinearity. 2020;:145-159.
https://hdl.handle.net/21.15107/rcub_cer_3746 .

Čupić, Željko, Maćešić, Stevan, Kolar-Anić, Ljiljana, "Instability region in models of nonlinear reaction systems. The Stoichiometric Network Analysis" in Proceedings - 1st Conference on nonlinearity (2020):145-159,
https://hdl.handle.net/21.15107/rcub_cer_3746 .

TY  - JOUR
AU  - Maćešić, Stevan
AU  - Čupić, Željko
AU  - Novaković, Katarina
AU  - Parker, Julie
AU  - Anić, Slobodan
AU  - Kolar-Anić, Ljiljana
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2999
AB  - The reaction mechanism of palladium-catalysed oscillatory carbonylation of
poly(ethylene glycol)methyl ether acetylene (PEGA) was examined by stoichiometric
network analysis (SNA) of the stability of the dynamic states. The previously published
simplified reaction network proposed to account for the experimentally observed results was
modified in order to obtain a more realistic reaction network for the investigated process. In the modified reaction network, the direct autocatalytic steps were replaced with autocatalytic
loops. In this procedure some complex net reactions had to be resolved, while some new
reactions had to be taken into account, altering the reaction mechanism responsible for the
appearance of oscillation. Moreover, in the modified reaction network, the expressions for
reaction rates correspond formally to their stoichiometry in accordance to mass action
kinetics. The SNA identified the instability condition which was further tested and confirmed
by numerical simulation.
PB  - University of Kragujevac
T2  - Match: Communications in Mathematical and in Computer Chemistry
T1  - Oscillatory Carbonylation of Poly(Ethylene Glycol)Methyl Ether Acetylene. Modelling of Reaction Mechanism and Stoichiometric Network Stability Analysis
VL  - 81
SP  - 5
EP  - 34
UR  - https://hdl.handle.net/21.15107/rcub_cer_2999
ER  - 

@article{
author = "Maćešić, Stevan and Čupić, Željko and Novaković, Katarina and Parker, Julie and Anić, Slobodan and Kolar-Anić, Ljiljana",
year = "2019",
abstract = "The reaction mechanism of palladium-catalysed oscillatory carbonylation of
poly(ethylene glycol)methyl ether acetylene (PEGA) was examined by stoichiometric
network analysis (SNA) of the stability of the dynamic states. The previously published
simplified reaction network proposed to account for the experimentally observed results was
modified in order to obtain a more realistic reaction network for the investigated process. In the modified reaction network, the direct autocatalytic steps were replaced with autocatalytic
loops. In this procedure some complex net reactions had to be resolved, while some new
reactions had to be taken into account, altering the reaction mechanism responsible for the
appearance of oscillation. Moreover, in the modified reaction network, the expressions for
reaction rates correspond formally to their stoichiometry in accordance to mass action
kinetics. The SNA identified the instability condition which was further tested and confirmed
by numerical simulation.",
publisher = "University of Kragujevac",
journal = "Match: Communications in Mathematical and in Computer Chemistry",
title = "Oscillatory Carbonylation of Poly(Ethylene Glycol)Methyl Ether Acetylene. Modelling of Reaction Mechanism and Stoichiometric Network Stability Analysis",
volume = "81",
pages = "5-34",
url = "https://hdl.handle.net/21.15107/rcub_cer_2999"
}

Maćešić, S., Čupić, Ž., Novaković, K., Parker, J., Anić, S.,& Kolar-Anić, L.. (2019). Oscillatory Carbonylation of Poly(Ethylene Glycol)Methyl Ether Acetylene. Modelling of Reaction Mechanism and Stoichiometric Network Stability Analysis. in Match: Communications in Mathematical and in Computer Chemistry
University of Kragujevac., 81, 5-34.
https://hdl.handle.net/21.15107/rcub_cer_2999

Maćešić S, Čupić Ž, Novaković K, Parker J, Anić S, Kolar-Anić L. Oscillatory Carbonylation of Poly(Ethylene Glycol)Methyl Ether Acetylene. Modelling of Reaction Mechanism and Stoichiometric Network Stability Analysis. in Match: Communications in Mathematical and in Computer Chemistry. 2019;81:5-34.
https://hdl.handle.net/21.15107/rcub_cer_2999 .

Maćešić, Stevan, Čupić, Željko, Novaković, Katarina, Parker, Julie, Anić, Slobodan, Kolar-Anić, Ljiljana, "Oscillatory Carbonylation of Poly(Ethylene Glycol)Methyl Ether Acetylene. Modelling of Reaction Mechanism and Stoichiometric Network Stability Analysis" in Match: Communications in Mathematical and in Computer Chemistry, 81 (2019):5-34,
https://hdl.handle.net/21.15107/rcub_cer_2999 .

TY  - JOUR
AU  - Stanojević, A
AU  - Marković, V M
AU  - Maćešić, Stevan
AU  - Kolar-Anić, Ljiljana
AU  - Vukojević, V
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2920
AB  - The sex hormone testosterone (TTS) and the hypothalamic–pituitary–adrenal (HPA) axis mutually control one another’s activity, wherein TTS suppresses corticotrophin releasing hormone (CRH) stimulated HPA axis activity, whereas the activation of HPA axis has an inhibitory effect on TTS secretion. With an intention to explain these phenomena, a network reaction model is developed from the previously postulated stoichiometric models for HPA activity where main dynamic behaviors are controlled by two catalytic steps (one autocatalytic and one autoinhibitory) with respect to cortisol, both found experimentally. The capacity of the model to emulate TTS effects on HPA axis dynamics and its response to acute CRH-induced stress is examined using numerical simulations. Model predictions are compared with empirically obtained results reported in the literature. Thus, the reaction kinetic examinations of nonlinear biochemical transformations that constitute the HPA axis, including the negative feedback effect of TTS on HPA axis activity, recapitulates the well-established fact that TTS dampens HPA axis basal activity, decreasing both cortisol level and the amplitude of ultradian cortisol oscillations. The model also replicates TTS inhibitory action on the HPA axis response to acute environmental challenges, particularly CRH-induced stress. In addition, kinetic modelling revealed that TTS induced reduction in ultradian cortisol amplitude arises because the system moves towards a supercritical Hopf bifurcation as TTS is being increased. © 2017, The Author(s).
PB  - Springer Netherlands
T2  - Reaction Kinetics, Mechanisms and Catalysis
T1  - Kinetic modelling of testosterone-related differences in the hypothalamic–pituitary–adrenal axis response to stress
VL  - 123
IS  - 1
SP  - 17
EP  - 30
DO  - 10.1007/s11144-017-1315-7
ER  - 

@article{
author = "Stanojević, A and Marković, V M and Maćešić, Stevan and Kolar-Anić, Ljiljana and Vukojević, V",
year = "2018",
abstract = "The sex hormone testosterone (TTS) and the hypothalamic–pituitary–adrenal (HPA) axis mutually control one another’s activity, wherein TTS suppresses corticotrophin releasing hormone (CRH) stimulated HPA axis activity, whereas the activation of HPA axis has an inhibitory effect on TTS secretion. With an intention to explain these phenomena, a network reaction model is developed from the previously postulated stoichiometric models for HPA activity where main dynamic behaviors are controlled by two catalytic steps (one autocatalytic and one autoinhibitory) with respect to cortisol, both found experimentally. The capacity of the model to emulate TTS effects on HPA axis dynamics and its response to acute CRH-induced stress is examined using numerical simulations. Model predictions are compared with empirically obtained results reported in the literature. Thus, the reaction kinetic examinations of nonlinear biochemical transformations that constitute the HPA axis, including the negative feedback effect of TTS on HPA axis activity, recapitulates the well-established fact that TTS dampens HPA axis basal activity, decreasing both cortisol level and the amplitude of ultradian cortisol oscillations. The model also replicates TTS inhibitory action on the HPA axis response to acute environmental challenges, particularly CRH-induced stress. In addition, kinetic modelling revealed that TTS induced reduction in ultradian cortisol amplitude arises because the system moves towards a supercritical Hopf bifurcation as TTS is being increased. © 2017, The Author(s).",
publisher = "Springer Netherlands",
journal = "Reaction Kinetics, Mechanisms and Catalysis",
title = "Kinetic modelling of testosterone-related differences in the hypothalamic–pituitary–adrenal axis response to stress",
volume = "123",
number = "1",
pages = "17-30",
doi = "10.1007/s11144-017-1315-7"
}

Stanojević, A., Marković, V. M., Maćešić, S., Kolar-Anić, L.,& Vukojević, V.. (2018). Kinetic modelling of testosterone-related differences in the hypothalamic–pituitary–adrenal axis response to stress. in Reaction Kinetics, Mechanisms and Catalysis
Springer Netherlands., 123(1), 17-30.
https://doi.org/10.1007/s11144-017-1315-7

Stanojević A, Marković VM, Maćešić S, Kolar-Anić L, Vukojević V. Kinetic modelling of testosterone-related differences in the hypothalamic–pituitary–adrenal axis response to stress. in Reaction Kinetics, Mechanisms and Catalysis. 2018;123(1):17-30.
doi:10.1007/s11144-017-1315-7 .

Stanojević, A, Marković, V M, Maćešić, Stevan, Kolar-Anić, Ljiljana, Vukojević, V, "Kinetic modelling of testosterone-related differences in the hypothalamic–pituitary–adrenal axis response to stress" in Reaction Kinetics, Mechanisms and Catalysis, 123, no. 1 (2018):17-30,
https://doi.org/10.1007/s11144-017-1315-7 . .

TY  - CONF
AU  - Stanojević, Ana
AU  - Marković, Vladimir
AU  - Čupić, Željko
AU  - Maćešić, Stevan
AU  - Vukojević, Vladana
AU  - Kolar-Anić, Ljiljana
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4856
AB  - The hypothalamic-pituitary-adrenal (HPA) axis is a dynamic regulatory network
of biochemical reactions that integrates and synchronizes the nervous and the
endocrine systems functions at the organism level. In order to describe how this
vast network of biochemical interactions operates, we have developed a nonlinear
eleven-dimensional stoichiometric model that concisely describes key biochemical
transformations that comprise the HPA axis in rats. In a stoichiometric
model of a biochemical system, the outcomes of complex biochemical pathways
are succinctly described by stoichiometric relations. In this representation, substances
that initiate, i.e. enter a pathway are regarded to behave as reactants;
substances that are generated in a pathway are regarded to behave as products;
and the rates at which products of a pathway appear are jointly proportional
to the concentrations of the reactants. In order to derive rate constants for specific
biochemical reaction pathways, we have resorted to our recently developed
nonlinear reaction model that concisely describes biochemical transformations
in the HPA axis in humans. In this way, a mathematical framework is developed
to describe in the form of a system of ordinary differential equations (ODEs) the
integration of biochemical pathways that constitute the HPA axis on chemical kinetics
basis. This, in turn, allows us to use numerical simulations to investigate
how the underlying biochemical pathways are intertwined to give an integral
HPA axis response at the organism level to a variety of external or internal perturbators
of the HPA dynamics. Given that the HPA axis is a nonlinear dynamical
network, its response is complex and often cannot be intuitively predicted,
stoichiometric modeling can be harnessed for gaining additional insights into
dynamical functioning of this complex neuroendocrine system.
PB  - Belgrade : The Bioinformatics Research Group, University of Belgrade - Faculty of Mathematics
C3  - Book of Abstracts - Belgrade BioInformatics Conference 2016, BelBI 2016
T1  - Mathematical Modeling of the Hypothalamic-Pituitary-Adrenal Axis Dynamics in Rats
SP  - 98
EP  - 98
UR  - https://hdl.handle.net/21.15107/rcub_cer_4856
ER  - 

@conference{
author = "Stanojević, Ana and Marković, Vladimir and Čupić, Željko and Maćešić, Stevan and Vukojević, Vladana and Kolar-Anić, Ljiljana",
year = "2016",
abstract = "The hypothalamic-pituitary-adrenal (HPA) axis is a dynamic regulatory network
of biochemical reactions that integrates and synchronizes the nervous and the
endocrine systems functions at the organism level. In order to describe how this
vast network of biochemical interactions operates, we have developed a nonlinear
eleven-dimensional stoichiometric model that concisely describes key biochemical
transformations that comprise the HPA axis in rats. In a stoichiometric
model of a biochemical system, the outcomes of complex biochemical pathways
are succinctly described by stoichiometric relations. In this representation, substances
that initiate, i.e. enter a pathway are regarded to behave as reactants;
substances that are generated in a pathway are regarded to behave as products;
and the rates at which products of a pathway appear are jointly proportional
to the concentrations of the reactants. In order to derive rate constants for specific
biochemical reaction pathways, we have resorted to our recently developed
nonlinear reaction model that concisely describes biochemical transformations
in the HPA axis in humans. In this way, a mathematical framework is developed
to describe in the form of a system of ordinary differential equations (ODEs) the
integration of biochemical pathways that constitute the HPA axis on chemical kinetics
basis. This, in turn, allows us to use numerical simulations to investigate
how the underlying biochemical pathways are intertwined to give an integral
HPA axis response at the organism level to a variety of external or internal perturbators
of the HPA dynamics. Given that the HPA axis is a nonlinear dynamical
network, its response is complex and often cannot be intuitively predicted,
stoichiometric modeling can be harnessed for gaining additional insights into
dynamical functioning of this complex neuroendocrine system.",
publisher = "Belgrade : The Bioinformatics Research Group, University of Belgrade - Faculty of Mathematics",
journal = "Book of Abstracts - Belgrade BioInformatics Conference 2016, BelBI 2016",
title = "Mathematical Modeling of the Hypothalamic-Pituitary-Adrenal Axis Dynamics in Rats",
pages = "98-98",
url = "https://hdl.handle.net/21.15107/rcub_cer_4856"
}

Stanojević, A., Marković, V., Čupić, Ž., Maćešić, S., Vukojević, V.,& Kolar-Anić, L.. (2016). Mathematical Modeling of the Hypothalamic-Pituitary-Adrenal Axis Dynamics in Rats. in Book of Abstracts - Belgrade BioInformatics Conference 2016, BelBI 2016
Belgrade : The Bioinformatics Research Group, University of Belgrade - Faculty of Mathematics., 98-98.
https://hdl.handle.net/21.15107/rcub_cer_4856

Stanojević A, Marković V, Čupić Ž, Maćešić S, Vukojević V, Kolar-Anić L. Mathematical Modeling of the Hypothalamic-Pituitary-Adrenal Axis Dynamics in Rats. in Book of Abstracts - Belgrade BioInformatics Conference 2016, BelBI 2016. 2016;:98-98.
https://hdl.handle.net/21.15107/rcub_cer_4856 .

Stanojević, Ana, Marković, Vladimir, Čupić, Željko, Maćešić, Stevan, Vukojević, Vladana, Kolar-Anić, Ljiljana, "Mathematical Modeling of the Hypothalamic-Pituitary-Adrenal Axis Dynamics in Rats" in Book of Abstracts - Belgrade BioInformatics Conference 2016, BelBI 2016 (2016):98-98,
https://hdl.handle.net/21.15107/rcub_cer_4856 .

TY  - JOUR
AU  - Maćešić, Stevan
AU  - Čupić, Željko
AU  - Kolar-Anić, Ljiljana
PY  - 2012
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1079
AB  - Self-regulation, achieved through positive (autocatalytic) or negative (autoinhibitory) feedback is commonly encountered in natural, technological and economic systems. The dynamic behavior of such systems is often complex and cannot be easily predicted, necessitating mathematical modelling and theoretical analyses. The aim of this work is to analyze the dynamics of a minimal model system with autocatalytic and autoinhibitory steps coupled through the same species, in order to understand under which critical condition the system loses stability and passes through an Andronov-Hopf bifurcation. The analysis used was improved stoichiometric network analysis (SNA) in combination with bifurcation and sensitivity analysis.
AB  - Većina realnih sistema su nelinearni, zbog čega je ispitivanje nelinearnih sistema od velikog značaja za različite oblasti nauke. Među navedenim sistemima posebno su značajni nelinearni reakcioni sistemi sa povratnom spregom (autokataliza i autoinhibicija), za koje su karakteristične pojave kao što su oscilatorna evolucija ili haos, i koji se mogu sresti u prirodnim, tehnološkim i ekonomskim sistemima. Kako se autokataliza i autoinhibicija često istovremeno mogu naći u realnim sistemima, mi smo analizirali stabilnost jednog reakcionog modela u kome su ova dva procesa spregnuta i pokazali kako stabilnost ovog sistema zavisi od konstanti brzina i koncentracija hemijskih vrsta koje su uključene u model. Nelinearni procesi sa povratnom spregom i odgovarajući modeli uglavnom imaju veliki broj promenljivih, zbog čega analiza stabilnosti zahteva upotrebu posebnih matematičkih alata. Za izvođenje analize stabilnosti ispitivanog modela, koristili smo unapređeni metod stehiometrijske mrežne analize (SNA) u kombinaciji sa bifurkacionom analizom i analizom osetljivosti. Koristeći navedene metode analize, uspeli smo da izdvojimo reakcije koje predstavljaju jezgro nestabilnosti i koje su odgovorne za periodičnu evoluciju sistema, na osnovu čega smo uspeli da odredimo uslov koji je neophodan za postojanje Andronov-Hopf bifurkacije.
PB  - Association of Chemical Engineers of Serbia
T2  - Hemijska industrija
T1  - Model of a nonlinear reaction system with autocatalysis and autoinhibition: Stability of dynamic states
T1  - Nelinearni reakcioni sistem sa autokatalizom i autoinhibicijom - stabilnost dinamičkih stanja
VL  - 66
IS  - 5
SP  - 637
EP  - 646
DO  - 10.2298/HEMIND120210034M
ER  - 

@article{
author = "Maćešić, Stevan and Čupić, Željko and Kolar-Anić, Ljiljana",
year = "2012",
abstract = "Self-regulation, achieved through positive (autocatalytic) or negative (autoinhibitory) feedback is commonly encountered in natural, technological and economic systems. The dynamic behavior of such systems is often complex and cannot be easily predicted, necessitating mathematical modelling and theoretical analyses. The aim of this work is to analyze the dynamics of a minimal model system with autocatalytic and autoinhibitory steps coupled through the same species, in order to understand under which critical condition the system loses stability and passes through an Andronov-Hopf bifurcation. The analysis used was improved stoichiometric network analysis (SNA) in combination with bifurcation and sensitivity analysis., Većina realnih sistema su nelinearni, zbog čega je ispitivanje nelinearnih sistema od velikog značaja za različite oblasti nauke. Među navedenim sistemima posebno su značajni nelinearni reakcioni sistemi sa povratnom spregom (autokataliza i autoinhibicija), za koje su karakteristične pojave kao što su oscilatorna evolucija ili haos, i koji se mogu sresti u prirodnim, tehnološkim i ekonomskim sistemima. Kako se autokataliza i autoinhibicija često istovremeno mogu naći u realnim sistemima, mi smo analizirali stabilnost jednog reakcionog modela u kome su ova dva procesa spregnuta i pokazali kako stabilnost ovog sistema zavisi od konstanti brzina i koncentracija hemijskih vrsta koje su uključene u model. Nelinearni procesi sa povratnom spregom i odgovarajući modeli uglavnom imaju veliki broj promenljivih, zbog čega analiza stabilnosti zahteva upotrebu posebnih matematičkih alata. Za izvođenje analize stabilnosti ispitivanog modela, koristili smo unapređeni metod stehiometrijske mrežne analize (SNA) u kombinaciji sa bifurkacionom analizom i analizom osetljivosti. Koristeći navedene metode analize, uspeli smo da izdvojimo reakcije koje predstavljaju jezgro nestabilnosti i koje su odgovorne za periodičnu evoluciju sistema, na osnovu čega smo uspeli da odredimo uslov koji je neophodan za postojanje Andronov-Hopf bifurkacije.",
publisher = "Association of Chemical Engineers of Serbia",
journal = "Hemijska industrija",
title = "Model of a nonlinear reaction system with autocatalysis and autoinhibition: Stability of dynamic states, Nelinearni reakcioni sistem sa autokatalizom i autoinhibicijom - stabilnost dinamičkih stanja",
volume = "66",
number = "5",
pages = "637-646",
doi = "10.2298/HEMIND120210034M"
}

Maćešić, S., Čupić, Ž.,& Kolar-Anić, L.. (2012). Model of a nonlinear reaction system with autocatalysis and autoinhibition: Stability of dynamic states. in Hemijska industrija
Association of Chemical Engineers of Serbia., 66(5), 637-646.
https://doi.org/10.2298/HEMIND120210034M

Maćešić S, Čupić Ž, Kolar-Anić L. Model of a nonlinear reaction system with autocatalysis and autoinhibition: Stability of dynamic states. in Hemijska industrija. 2012;66(5):637-646.
doi:10.2298/HEMIND120210034M .

Maćešić, Stevan, Čupić, Željko, Kolar-Anić, Ljiljana, "Model of a nonlinear reaction system with autocatalysis and autoinhibition: Stability of dynamic states" in Hemijska industrija, 66, no. 5 (2012):637-646,
https://doi.org/10.2298/HEMIND120210034M . .