TY  - CONF
AU  - Stojiljković, Aleksandra
AU  - Stanojević, Ana
AU  - Ivanović-Šašić, Ana
AU  - Čupić, Željko
AU  - Kolar-Anić, Ljiljana
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/6410
AB  - An upgraded model of the Hypothalamic-Pituitary-Adrenal (HPA) axis has been developed that 
advances our previously proposed low-dimensional HPA model by including the effects of arginine 
vasopressin (AVP) that is a key modulator of HPA axis function. The upgraded model allows us to 
emulate AVP effects on HPA axis dynamics individually and in synergy with the corticotropin-releasing hormone (CRH). In this work, we examine how coupling of the circadian function through 
summarised reaction steps describing CRH and AVP biosynthesis in the same neuronal cell group of the hypothalamic paraventricular nucleus (PVN) affects HPA axis dynamics. Results of numerical simulations show that coupling of the circadian function through both, CRH and AVP summarised biosynthesis reaction steps simultaneously, emulates best the HPA axis dynamics, in line with literature findings.
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  - Circadian rhythm function coupling to the upgraded hypothalamic-pituitary-adrenal (hpa) axis with incorporated arginine vasopressin
VL  - I
SP  - 246
EP  - 249
UR  - https://hdl.handle.net/21.15107/rcub_cer_6410
ER  - 

@conference{
author = "Stojiljković, Aleksandra and Stanojević, Ana and Ivanović-Šašić, Ana and Čupić, Željko and Kolar-Anić, Ljiljana",
year = "2021",
abstract = "An upgraded model of the Hypothalamic-Pituitary-Adrenal (HPA) axis has been developed that 
advances our previously proposed low-dimensional HPA model by including the effects of arginine 
vasopressin (AVP) that is a key modulator of HPA axis function. The upgraded model allows us to 
emulate AVP effects on HPA axis dynamics individually and in synergy with the corticotropin-releasing hormone (CRH). In this work, we examine how coupling of the circadian function through 
summarised reaction steps describing CRH and AVP biosynthesis in the same neuronal cell group of the hypothalamic paraventricular nucleus (PVN) affects HPA axis dynamics. Results of numerical simulations show that coupling of the circadian function through both, CRH and AVP summarised biosynthesis reaction steps simultaneously, emulates best the HPA axis dynamics, in line with literature findings.",
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 = "Circadian rhythm function coupling to the upgraded hypothalamic-pituitary-adrenal (hpa) axis with incorporated arginine vasopressin",
volume = "I",
pages = "246-249",
url = "https://hdl.handle.net/21.15107/rcub_cer_6410"
}

Stojiljković, A., Stanojević, A., Ivanović-Šašić, A., Čupić, Ž.,& Kolar-Anić, L.. (2021). Circadian rhythm function coupling to the upgraded hypothalamic-pituitary-adrenal (hpa) axis with incorporated arginine vasopressin. 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, 246-249.
https://hdl.handle.net/21.15107/rcub_cer_6410

Stojiljković A, Stanojević A, Ivanović-Šašić A, Čupić Ž, Kolar-Anić L. Circadian rhythm function coupling to the upgraded hypothalamic-pituitary-adrenal (hpa) axis with incorporated arginine vasopressin. in Proceedings - 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2021, September 20-24 2021, Belgrade, Serbia. 2021;I:246-249.
https://hdl.handle.net/21.15107/rcub_cer_6410 .

Stojiljković, Aleksandra, Stanojević, Ana, Ivanović-Šašić, Ana, Čupić, Željko, Kolar-Anić, Ljiljana, "Circadian rhythm function coupling to the upgraded hypothalamic-pituitary-adrenal (hpa) axis with incorporated arginine vasopressin" in Proceedings - 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Physical Chemistry 2021, September 20-24 2021, Belgrade, Serbia, I (2021):246-249,
https://hdl.handle.net/21.15107/rcub_cer_6410 .

TY  - JOUR
AU  - Stanojević, Ana
AU  - Milovanović, Branislav
AU  - Stanković, Ivana
AU  - Etinski, Mihajlo
AU  - Petković, Milena
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4838
AB  - The planarity and the appropriate size of the porphyrin ring make porphyrin derivatives ideal ligands for stacking to guanine quartets and they could thus be used as anti-cancer drugs. In this contribution we analyzed complexes of a guanine quartet with a porphyrin molecule, magnesium porphyrin and calcium porphyrin. As magnesium and calcium ions are located in the center and above the porphyrin ring, respectively, the two metalloporphyrins are expected to have different impacts on the target. The optimized structures of the three systems revealed geometrical changes in the guanine quartet upon complexation: while stacking of porphyrin and magnesium porphyrin does not induce significant changes, calcium porphyrin considerably distorts the quartet's structure, which has significant implications for the binding properties among guanine molecules. Ab initio molecular dynamics simulations revealed that the systems perform small fluctuations around the equilibrium structures. The largest atom displacements are performed by the calcium ion. The interacting quantum atoms methodology enabled analysis of the binding properties in the studied complexes. Interestingly, although the proximity of the calcium ion is responsible for the quartet's pronounced deformation and weakening of guanine-guanine binding, it also enables stronger binding of the metal ion to the quartet, resulting in a more stable complex. These results imply that metalloporphyrin-like ligands with out-of-plane central ions might represent promising drug candidates in anti-tumor treatment.
PB  - Royal Society of Chemistry
T2  - Physical Chemistry Chemical Physics
T1  - The significance of the metal cation in guanine-quartet - metalloporphyrin complexes
VL  - 23
IS  - 1
IS  - 574
EP  - 584
DO  - 10.1039/d0cp05798c
ER  - 

@article{
author = "Stanojević, Ana and Milovanović, Branislav and Stanković, Ivana and Etinski, Mihajlo and Petković, Milena",
year = "2021",
abstract = "The planarity and the appropriate size of the porphyrin ring make porphyrin derivatives ideal ligands for stacking to guanine quartets and they could thus be used as anti-cancer drugs. In this contribution we analyzed complexes of a guanine quartet with a porphyrin molecule, magnesium porphyrin and calcium porphyrin. As magnesium and calcium ions are located in the center and above the porphyrin ring, respectively, the two metalloporphyrins are expected to have different impacts on the target. The optimized structures of the three systems revealed geometrical changes in the guanine quartet upon complexation: while stacking of porphyrin and magnesium porphyrin does not induce significant changes, calcium porphyrin considerably distorts the quartet's structure, which has significant implications for the binding properties among guanine molecules. Ab initio molecular dynamics simulations revealed that the systems perform small fluctuations around the equilibrium structures. The largest atom displacements are performed by the calcium ion. The interacting quantum atoms methodology enabled analysis of the binding properties in the studied complexes. Interestingly, although the proximity of the calcium ion is responsible for the quartet's pronounced deformation and weakening of guanine-guanine binding, it also enables stronger binding of the metal ion to the quartet, resulting in a more stable complex. These results imply that metalloporphyrin-like ligands with out-of-plane central ions might represent promising drug candidates in anti-tumor treatment.",
publisher = "Royal Society of Chemistry",
journal = "Physical Chemistry Chemical Physics",
title = "The significance of the metal cation in guanine-quartet - metalloporphyrin complexes",
volume = "23",
number = "1, 574",
pages = "584",
doi = "10.1039/d0cp05798c"
}

Stanojević, A., Milovanović, B., Stanković, I., Etinski, M.,& Petković, M.. (2021). The significance of the metal cation in guanine-quartet - metalloporphyrin complexes. in Physical Chemistry Chemical Physics
Royal Society of Chemistry., 23(1).
https://doi.org/10.1039/d0cp05798c

Stanojević A, Milovanović B, Stanković I, Etinski M, Petković M. The significance of the metal cation in guanine-quartet - metalloporphyrin complexes. in Physical Chemistry Chemical Physics. 2021;23(1):null-584.
doi:10.1039/d0cp05798c .

Stanojević, Ana, Milovanović, Branislav, Stanković, Ivana, Etinski, Mihajlo, Petković, Milena, "The significance of the metal cation in guanine-quartet - metalloporphyrin complexes" in Physical Chemistry Chemical Physics, 23, no. 1 (2021),
https://doi.org/10.1039/d0cp05798c . .

TY  - JOUR
AU  - Čupić, Željko
AU  - Stanojevic, Ana
AU  - Marković, Vladimir M.
AU  - Kolar-Anić, Ljiljana
AU  - Terenius, Lars
AU  - Vukojevic, Vladana
PY  - 2017
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2087
AB  - Stress and alcohol use are interrelatedstress contributes to the initiation and upholding of alcohol use and alcohol use alters the way we perceive and respond to stress. Intricate mechanisms through which ethanol alters the organism's response to stress remain elusive. We have developed a stoichiometric network model to succinctly describe neurochemical transformations underlying the stress response axis and use numerical simulations to model ethanol effects on complex daily changes of blood levels of cholesterol, 6 peptide and 8 steroid hormones. Modelling suggests that ethanol alters the dynamical regulation of hypothalamic-pituitary-adrenal (HPA) axis activity by affecting the amplitude of ultradian oscillations of HPA axis hormones, which defines the threshold with respect to which the response to stress is being set. These effects are complexlow/moderate acute ethanol challenge ( LT  8mM) may reduce, leave unaltered or increase the amplitude of ultradian cortisol (CORT) oscillations, giving rise to an intricate response at the organism level, offering also a potential explanation as to why apparently discordant results were observed in experimental studies. In contrast, high-dose acute ethanol challenge (> 8mM) increases instantaneous CORT levels and the amplitude of ultradian CORT oscillations in a dose-dependent manner, affecting the HPA axis activity also during the following day(s). Chronic exposure to ethanol qualitatively changes the HPA axis dynamics, whereas ethanol at intoxicating levels shuts down this dynamic regulation mechanism. Mathematical modelling gives a quantitative biology-based framework that can be used for predicting how the integral HPA axis response is perturbed by alcohol.
PB  - Wiley, Hoboken
T2  - Addiction Biology
T1  - The HPA axis and ethanol: a synthesis of mathematical modelling and experimental observations
VL  - 22
IS  - 6
SP  - 1486
EP  - 1500
DO  - 10.1111/adb.12409
ER  - 

@article{
author = "Čupić, Željko and Stanojevic, Ana and Marković, Vladimir M. and Kolar-Anić, Ljiljana and Terenius, Lars and Vukojevic, Vladana",
year = "2017",
abstract = "Stress and alcohol use are interrelatedstress contributes to the initiation and upholding of alcohol use and alcohol use alters the way we perceive and respond to stress. Intricate mechanisms through which ethanol alters the organism's response to stress remain elusive. We have developed a stoichiometric network model to succinctly describe neurochemical transformations underlying the stress response axis and use numerical simulations to model ethanol effects on complex daily changes of blood levels of cholesterol, 6 peptide and 8 steroid hormones. Modelling suggests that ethanol alters the dynamical regulation of hypothalamic-pituitary-adrenal (HPA) axis activity by affecting the amplitude of ultradian oscillations of HPA axis hormones, which defines the threshold with respect to which the response to stress is being set. These effects are complexlow/moderate acute ethanol challenge ( LT  8mM) may reduce, leave unaltered or increase the amplitude of ultradian cortisol (CORT) oscillations, giving rise to an intricate response at the organism level, offering also a potential explanation as to why apparently discordant results were observed in experimental studies. In contrast, high-dose acute ethanol challenge (> 8mM) increases instantaneous CORT levels and the amplitude of ultradian CORT oscillations in a dose-dependent manner, affecting the HPA axis activity also during the following day(s). Chronic exposure to ethanol qualitatively changes the HPA axis dynamics, whereas ethanol at intoxicating levels shuts down this dynamic regulation mechanism. Mathematical modelling gives a quantitative biology-based framework that can be used for predicting how the integral HPA axis response is perturbed by alcohol.",
publisher = "Wiley, Hoboken",
journal = "Addiction Biology",
title = "The HPA axis and ethanol: a synthesis of mathematical modelling and experimental observations",
volume = "22",
number = "6",
pages = "1486-1500",
doi = "10.1111/adb.12409"
}

Čupić, Ž., Stanojevic, A., Marković, V. M., Kolar-Anić, L., Terenius, L.,& Vukojevic, V.. (2017). The HPA axis and ethanol: a synthesis of mathematical modelling and experimental observations. in Addiction Biology
Wiley, Hoboken., 22(6), 1486-1500.
https://doi.org/10.1111/adb.12409

Čupić Ž, Stanojevic A, Marković VM, Kolar-Anić L, Terenius L, Vukojevic V. The HPA axis and ethanol: a synthesis of mathematical modelling and experimental observations. in Addiction Biology. 2017;22(6):1486-1500.
doi:10.1111/adb.12409 .

Čupić, Željko, Stanojevic, Ana, Marković, Vladimir M., Kolar-Anić, Ljiljana, Terenius, Lars, Vukojevic, Vladana, "The HPA axis and ethanol: a synthesis of mathematical modelling and experimental observations" in Addiction Biology, 22, no. 6 (2017):1486-1500,
https://doi.org/10.1111/adb.12409 . .

TY  - JOUR
AU  - Abulseoud, Osama A.
AU  - Ho, Man Choi
AU  - Choi, Doo-Sup
AU  - Stanojevic, Ana
AU  - Čupić, Željko
AU  - Kolar-Anić, Ljiljana
AU  - Vukojevic, Vladana
PY  - 2017
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2269
AB  - Changes in the hypothalamic-pituitary-adrenal (HPA) axis activity constitute a key component of bipolar mania, but the extent and nature of these alterations are not fully understood. We use here the lateral hypothalamic-kindled (LHK) rat model to deliberately induce an acute manic-like episode and measure serum corticosterone concentrations to assess changes in HPA axis activity. A mathematical model is developed to succinctly describe the entwined biochemical transformations that underlay the HPA axis and emulate by numerical simulations the considerable increase in serum corticosterone concentration induced by LHK. Synergistic combination of the LHK rat model and dynamical systems theory allows us to quantitatively characterize changes in HPA axis activity under controlled induction of acute manic-like states and provides a framework to study in silico how the dynamic integration of neurochemical transformations underlying the HPA axis is disrupted in these states.
PB  - Public Library of Science (PLoS)
T2  - Plos One
T1  - Corticosterone oscillations during mania induction in the lateral hypothalamic kindled rat-Experimental observations and mathematical modeling
VL  - 12
IS  - 5
DO  - 10.1371/journal.pone.0177551
ER  - 

@article{
author = "Abulseoud, Osama A. and Ho, Man Choi and Choi, Doo-Sup and Stanojevic, Ana and Čupić, Željko and Kolar-Anić, Ljiljana and Vukojevic, Vladana",
year = "2017",
abstract = "Changes in the hypothalamic-pituitary-adrenal (HPA) axis activity constitute a key component of bipolar mania, but the extent and nature of these alterations are not fully understood. We use here the lateral hypothalamic-kindled (LHK) rat model to deliberately induce an acute manic-like episode and measure serum corticosterone concentrations to assess changes in HPA axis activity. A mathematical model is developed to succinctly describe the entwined biochemical transformations that underlay the HPA axis and emulate by numerical simulations the considerable increase in serum corticosterone concentration induced by LHK. Synergistic combination of the LHK rat model and dynamical systems theory allows us to quantitatively characterize changes in HPA axis activity under controlled induction of acute manic-like states and provides a framework to study in silico how the dynamic integration of neurochemical transformations underlying the HPA axis is disrupted in these states.",
publisher = "Public Library of Science (PLoS)",
journal = "Plos One",
title = "Corticosterone oscillations during mania induction in the lateral hypothalamic kindled rat-Experimental observations and mathematical modeling",
volume = "12",
number = "5",
doi = "10.1371/journal.pone.0177551"
}

Abulseoud, O. A., Ho, M. C., Choi, D., Stanojevic, A., Čupić, Ž., Kolar-Anić, L.,& Vukojevic, V.. (2017). Corticosterone oscillations during mania induction in the lateral hypothalamic kindled rat-Experimental observations and mathematical modeling. in Plos One
Public Library of Science (PLoS)., 12(5).
https://doi.org/10.1371/journal.pone.0177551

Abulseoud OA, Ho MC, Choi D, Stanojevic A, Čupić Ž, Kolar-Anić L, Vukojevic V. Corticosterone oscillations during mania induction in the lateral hypothalamic kindled rat-Experimental observations and mathematical modeling. in Plos One. 2017;12(5).
doi:10.1371/journal.pone.0177551 .

Abulseoud, Osama A., Ho, Man Choi, Choi, Doo-Sup, Stanojevic, Ana, Čupić, Željko, Kolar-Anić, Ljiljana, Vukojevic, Vladana, "Corticosterone oscillations during mania induction in the lateral hypothalamic kindled rat-Experimental observations and mathematical modeling" in Plos One, 12, no. 5 (2017),
https://doi.org/10.1371/journal.pone.0177551 . .

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 .