Different signal transduction pathways contribute to the differentiation and metabolic activities of osteoblasts, with special regard to the calcium-related pathway of phosphoinositide specific phospholipase C (PLC) enzyme family. PLC enzymes were demonstrated to be involved in the differentiation of osteoblasts and differently localize in the nucleus, cytoplasm or both depending on the isoform. The amino-steroid molecule U-73122 inhibits the enzymes belonging to the PLC family. In addition to the temporary block of the enzymatic activity, U-73122 promotes off-target effects, including modulation of the expression of selected PLC genes and different localization of PLC enzymes, depending on the cell line, in different cell lines.
In order to evaluate possible off-target effects of the molecule in human osteoblasts, we investigated the expression of PLC genes and the localization of PLC enzymes in cultured human osteoblasts (hOBs) in the presence of low dose U-73122.
Our results confirm that all PLC genes are transcribed in hOBs, that probably splicing variants of selected PLC genes are expressed and that all PLC enzymes are present in hOBs, except for PLC δ3 in quiescent hOBs at seeding. Our results confirm literature data excluding toxicity of U-73122 on cell survival. Our results indicate that U-73122 did not significantly affect the transcription of PLC genes. It acts upon the localization of PLC enzymes, as PLC enzymes are detected in cell protrusions or pseudopodia-like structures, at the nuclear or the plasma membrane, in membrane ruffles and/or in the endoplasmic reticulum.
Citation: Matteo Corradini, Marta Checchi, Marzia Ferretti, Francesco Cavani, Carla Palumbo, Vincenza Rita Lo Vasco. Endoplasmic reticulum localization of phosphoinositide specific phospholipase C enzymes in U73122 cultured human osteoblasts[J]. AIMS Biophysics, 2023, 10(1): 25-49. doi: 10.3934/biophy.2023004
Related Papers:
[1]
San-Xing Wu, Xin-You Meng .
Dynamics of a delayed predator-prey system with fear effect, herd behavior and disease in the susceptible prey. AIMS Mathematics, 2021, 6(4): 3654-3685.
doi: 10.3934/math.2021218
[2]
Binfeng Xie, Na Zhang .
Influence of fear effect on a Holling type III prey-predator system with the prey refuge. AIMS Mathematics, 2022, 7(2): 1811-1830.
doi: 10.3934/math.2022104
[3]
Fatao Wang, Ruizhi Yang, Yining Xie, Jing Zhao .
Hopf bifurcation in a delayed reaction diffusion predator-prey model with weak Allee effect on prey and fear effect on predator. AIMS Mathematics, 2023, 8(8): 17719-17743.
doi: 10.3934/math.2023905
[4]
Jie Liu, Qinglong Wang, Xuyang Cao, Ting Yu .
Bifurcation and optimal harvesting analysis of a discrete-time predator–prey model with fear and prey refuge effects. AIMS Mathematics, 2024, 9(10): 26283-26306.
doi: 10.3934/math.20241281
[5]
A. Q. Khan, Ibraheem M. Alsulami .
Complicate dynamical analysis of a discrete predator-prey model with a prey refuge. AIMS Mathematics, 2023, 8(7): 15035-15057.
doi: 10.3934/math.2023768
[6]
Xiaoming Su, Jiahui Wang, Adiya Bao .
Stability analysis and chaos control in a discrete predator-prey system with Allee effect, fear effect, and refuge. AIMS Mathematics, 2024, 9(5): 13462-13491.
doi: 10.3934/math.2024656
[7]
Kottakkaran Sooppy Nisar, G Ranjith Kumar, K Ramesh .
The study on the complex nature of a predator-prey model with fractional-order derivatives incorporating refuge and nonlinear prey harvesting. AIMS Mathematics, 2024, 9(5): 13492-13507.
doi: 10.3934/math.2024657
[8]
Weili Kong, Yuanfu Shao .
Bifurcations of a Leslie-Gower predator-prey model with fear, strong Allee effect and hunting cooperation. AIMS Mathematics, 2024, 9(11): 31607-31635.
doi: 10.3934/math.20241520
[9]
Yaping Wang, Yuanfu Shao, Chuanfu Chai .
Dynamics of a predator-prey model with fear effects and gestation delays. AIMS Mathematics, 2023, 8(3): 7535-7559.
doi: 10.3934/math.2023378
[10]
Jing Zhang, Shengmao Fu .
Hopf bifurcation and Turing pattern of a diffusive Rosenzweig-MacArthur model with fear factor. AIMS Mathematics, 2024, 9(11): 32514-32551.
doi: 10.3934/math.20241558
Abstract
Different signal transduction pathways contribute to the differentiation and metabolic activities of osteoblasts, with special regard to the calcium-related pathway of phosphoinositide specific phospholipase C (PLC) enzyme family. PLC enzymes were demonstrated to be involved in the differentiation of osteoblasts and differently localize in the nucleus, cytoplasm or both depending on the isoform. The amino-steroid molecule U-73122 inhibits the enzymes belonging to the PLC family. In addition to the temporary block of the enzymatic activity, U-73122 promotes off-target effects, including modulation of the expression of selected PLC genes and different localization of PLC enzymes, depending on the cell line, in different cell lines.
In order to evaluate possible off-target effects of the molecule in human osteoblasts, we investigated the expression of PLC genes and the localization of PLC enzymes in cultured human osteoblasts (hOBs) in the presence of low dose U-73122.
Our results confirm that all PLC genes are transcribed in hOBs, that probably splicing variants of selected PLC genes are expressed and that all PLC enzymes are present in hOBs, except for PLC δ3 in quiescent hOBs at seeding. Our results confirm literature data excluding toxicity of U-73122 on cell survival. Our results indicate that U-73122 did not significantly affect the transcription of PLC genes. It acts upon the localization of PLC enzymes, as PLC enzymes are detected in cell protrusions or pseudopodia-like structures, at the nuclear or the plasma membrane, in membrane ruffles and/or in the endoplasmic reticulum.
1.
Introduction
In population ecology, understanding how predators and primary producers influence nutrient flow relative to each other is important. Ecosystem interactions and predator-prey relationships are governed by predation and the delivery of resource processes. The identification of ecological factors that can alter or control dynamic behavior requires theoretical and experimental research. One way to study these questions is by means of experimental control, and another useful way is via mathematical modeling as well as computer simulations. Over decades of theoretical ecology and biomathematics development, mathematical modeling has become an indispensable tool for scientists in related fields to study ecosystems. Since Lotka [1] and Volterra [2], as cornerstones of theoretical ecology, published the first study of predator-prey dynamics, any species in nature can be a predator or prey, and due to its prevalence, it has become one of the most popular topics for researchers to study [3,4,5]. Besides, because biological resources are renewable and have the most unique development mechanisms, the over-utilization of biological resources and the destruction of the environment by humans will directly affect the balance of the ecosystem. Maintaining ecological balance and meeting humans material needs have attracted the most attention from researchers focused on the scientific management of renewable resource development [6,7,8].
Shelter serves as a defense strategy. It refers broadly to a series of behaviors by prey to avoid predators in order to increase their survival rate. The concept of sanctuary was first developed by Maynard-Smith [9] and Gause et al. [10], and its popularity has been very high, garnering widespread attention from many scholars [11,12,13,14,15]. Sih et al.[16] investigated the effects of prey refuge in a three-species model and concluded that the system's stability is strongly related to the refuge. Also, similar findings can be displayed in [17,18,19,20,21,22]. The two modes of refuge analyzed by Gonzalez-Olivares et al. [17] have diverse stability domains in terms of the parameter space. Qi et al.[21] ensure the stability of the system by varying the strength of the refuge.
Through reviewing a large amount of literature, we begin to consider [23,24] as a basis for the two prey and one predator species that will be modeled in this article. We assume that at a certain time t, the populations of the two prey and one predator are x1(t), x2(t), and y(t), respectively. Based on the above, we construct the following model:
Most species in nature, including humans, are influenced by fear. Fear may cause an abnormal state and behavior to arise. As usual, prey have an innate fear of predators. The ecology of fear is related to combining the optimal behavior of prey and predators with their population densities [25,26]. In view of reality, it is a fact that prey fear predators, which is seen as a psychological effect that can have a lasting impact on prey populations. This psychological influence is often easy to overlook, but it is necessary to consider it in the context of practical ecology [27]. Wang et al. [28] first considered the effect of the fear factor on the model and first proposed the fear of prey F(k,y). Afterwards, some researchers have investigated the effects of the fear effect and predator interferences in some three-dimensional systems as well as explored the generation of Hopf bifurcation conditions in the presence of a fear parameter as a bifurcation parameter [29,30,31,32]. Zanette et al. [33] observed that prey will reduce reproducing because of fear of being killed by predators, thus decreasing the risk of being killed after giving birth, which also leads directly to a decline in prey birth rates. According to the above discussion, our paper considers the different fears ki caused by predators for the two prey species.
In reality, when prey feel the crisis of being hunted, they will reproduce less and increase their survival rate. These conditions about the fear factor F(ki,y)(i=1,2) are listed as follows:
1)F(0,y)=1: prey production does not decrease when the prey does not fear the predator;
2)F(ki,0)=1: even though the prey will develop a fear of predators and there will be no predators, prey production will still not decline;
3)limki→∞F(ki,y)=0: when the prey's fear of the predator is very high, this will result in the prey production tending to zero;
4)limy→∞F(ki,y)=0: prey have a fear of predators, and when predator numbers are too large, this can also lead to prey production tending to zero;
5)∂F(ki,y)∂ki<0: the greater the prey's fear of predators, the less productive it will be;
6)∂F(ki,y)∂y<0: predators are inversely proportional to their prey.
For ease of analysis, we draw on Wang et al. [28] to consider the fear effect:
F(ki,y)=11+kiy(i=1,2),
(1.2)
obviously, F(ki,y)(i=1,2) in (1.2) satisfies conditions 1)–6). Based on the above conditions, this study will consider the effect of fear on system (1.1) to obtain system (1.3).
Notably, most biological parameters in much of the literature are fixed constants. However, in reality, the survival of species is full of unknowns, and all data are not always constant, which can lead to deviations from the ideal model with fixed parameters. In order to make the model more relevant and the results more accurate, we cannot just consider fixed parameters. Therefore, to make the study more convincing, it is necessary to target imprecise parameters. Professor Zadeh [34], who first proposed the fuzzy set theory, also argued that the application of fuzzy differential equations is a more accurate method for modeling biological dynamics in the absence of accurate data conditions [35]. Moreover, the first introduction of the idea of fuzzy derivatives came from Chang and Zadeh [36]. Further, Kaleva [37] studied the generalized fuzzy derivatives based on Hukuhara differentiability, the Zadeh extension principle, and the strong generalized differentiability concept. Bede et al. [38] employed the notion of strongly generalized differentiability to investigate fuzzy differential equations. Khastan and Nieto [39] solved the margin problem for fuzzy differential equations in their article. Motivated by the method of Pal [13] and Wang [23], we assume that the imprecise parameters ~r1, ~r2, ~a1, ~a2, ~c1, ~c2, ~e1, ~e1 and ˜d represent all triangular fuzzy numbers (the relevant theories of fuzzy sets are detailed in Appendix A), then the system (1.3) can be written as
The rest of the paper is shown below: In Section 2, we first prove the nonnegativity and boundedness of the system (1.7). Sections 3 and 4 discuss all possible equilibria and give conditions for the local asymptotic stability and global asymptotic stability of the equilibria. Immediately after that, in Section 5, we analyze the Hopf bifurcation by using the normal form theory. In Section 6, we numerically simulate the theoretical results of Sections 4 and 5. Finally, the article ends with detailed conclusions.
2.
Nonnegativity and boundedness
In this section, we give the following theorem to ensure the boundedness and nonnegativity of the solutions of the system (1.7).
Theorem 2.1.Provided that the initial values x1(0)>0, x2(0)>0, and y(0)>0, all solutions of system (1.7) are nonnegative.
Proof. It is not difficult to find that the right half of the system (1.7) fulfills the local Lipschitzian condition. Integrating both sides of the system (1.7) at the same time yields
If the solution curve starts at any internal point of R3+={(x1(t),x2(t),y(t))∈R3:x1(t)≥0, x2(t)≥0, y(t)≥0}, then x1(t), x2(t), and y(t) will always be nonnegative. □
Theorem 2.2.Assume that the initial values x1(0), x2(0), and y(0) are all greater than zero. The feasible region Ω is a positive invariant set of the system (1.7) defined by
It follows from the Descartes law of signs that Eq (3.4) has one and only one solution y∗ greater than zero if and only if g3>0, i.e., B1>x2K2B2+B3x1+q2E2. Substituting y∗ into the algebra expression on the right side of the first equation of the system (1.7) equals zero; furthermore, we obtain
Reusing the Descartes law of signs, we can assert that there exists at least one positive solution x∗1 of Eq (3.6) if and only if g4g5<0. And then we can deduce that
then the interior equilibrium P7(x∗1,x∗2,y∗) exists.□
4.
Stability analysis
In this section, the Jocabian matrix will be used to prove the local stability of all equilibria. Moreover, we prove the global stability of the internal equilibrium P7 by constructing a Lyapunov function.
4.1. Local stability
The Jocabian matrix for system (1.7) is given below:
The Routh-Hurwitz criterion shows that the internal equilibrium P7 is locally asymptotically stable; the following conditions need to be met: ψ1>0, ψ1ψ2>0, and ψ3>0.□
4.2. Global stability
This subsection studies the global asymptotic stability of interior equilibrium P7.
Theorem 4.2.If condition 4Γ1Γ2l1l2A2B2(1+k1y)(1+k2y) > (l1A3+l2B3)2 (i.e. 4Γ1Γ2l1l2(w1rα1R+w2rα1L)(w1rα2R+w2rα2L)(1+k1y)(1+k2y) > (l1(w1aα1R+w2aα1L)+l2(w1aα2R+w2aα2L))2) holds, then P7 is globally asymptotically stable.
Therefore, dVdt<0 if and only if 4Γ1Γ2l1l2A2B2(1+k1y)(1+k2y)>(l1A3+l2B3)2. □
5.
Hopf bifurcation
In this section, we will use the normal form theory introduced by Hassard et al.[40] and the central manifold theory [41] to study the Hopf bifurcation of the system (1.7). When the system (1.7) undergoes Hopf bifurcation, the corresponding characteristic equation must have a pair of conjugate pure imaginary roots, that is,
η1,2=±iω,i=√−1.
(5.1)
Consider the parameter k1 as a bifurcation parameter. When the value of parameter k1 changes near the critical point kΞ1 of Hopf bifurcation, the pure imaginary roots ±iω will become a complex eigenvalue η=ρ+i˜ω. Substituting η=ρ+i˜ω into Eq (4.12), we need to separate the imaginary and real parts to get
ρ3+ψ3+ρψ2+ρ2ψ1−3ρ˜ω2−ψ1˜ω2=0,
(5.2)
3ρ2˜ω+ψ2˜ω+2ρψ1˜ω−˜ω3=0.
(5.3)
By simplifying Eqs (5.2) and (5.3), we obtain
ψ3−8ρ3−2ρψ2−8ρ2ψ1−ψ1ψ2−2ρψ21=0,
(5.4)
at k1=kΞ1, taking the derivative of Eq (5.4) over k1 yields
If it satisfies dρdk1|k1=kΞ1≠0, the system (1.7) will generate Hopf bifurcation, which indicates that when parameter k1 crosses the bifurcation critical point kΞ1, the population state evolves from stable equilibrium to periodic oscillation over time.
When the system (1.7) undergoes Hopf bifurcation at k1=kΞ1, the final decision condition is also met. Considering that the characteristic roots of Eq (4.12) are η1,2=±iω and η3=−ψ1, in order to obtain this condition, we introduce
z1=x1−x∗1,z2=x2−x∗2,z3=y−y∗.
(5.6)
Substituting (5.6) into the system (1.7) and separating the linear and nonlinear parts, it can be obtained that
where O((|z1|+|z2|+|z3|)4) is a fourth-order polynomial function about variables (|z1|,|z2|,|z3|), while tj1j2j3, nj1j2j3, and lj1j2j3 can be obtained through calculation:
Correspondingly, the dynamic properties of the system are limited to the central flow Wc(0,0,0), and in conjunction with Eq (5.14), system (5.12) can be simplified as
where subscripts y1 and y2 indicate partial derivatives for the first and second variable, respectively. Based on Eq (5.18), it can be obtained that Uy1=0, Uy2≠0, Ny1≠0, Ny2=0, and Uy2Ny1≠0. In addition, it ensures that the system (5.18) has pure virtual feature roots ±i√|Uy2Ny1|. Thus, it can be determined that system (1.7) produces Hopf bifurcation; the direction of the bifurcation is determined by the following equation:
QkΞ1=116ω(ℓ3+ℓ5+ȷ5+ȷ7)+116ω(ℓ1ℓ3−ȷ2ȷ3−ȷ1ȷ2−ȷ1ℓ1).
(5.21)
Theorem 5.1.If dρdk1|k1=kΞ1≠0, then system (1.7) will generate Hopf bifurcation at interior equilibrium P7. In addition, when dρdk1|k1=kΞ1<0, if QkΞ1<0 and 0<k1−kΞ1≪1, then system (1.7) will generate supercritical Hopf bifurcation and form a stable periodic orbit, or if QkΞ1>0 and 0<k1−kΞ1≪1, then system (1.7) will generate subcritical Hopf bifurcation and form a stable periodic orbit.
6.
Numerical simulations
In this section, we first discussed equilibria P1 to P7 of system (1.7) with distinct values of α, w1, and w2. Consider the parameter values as follows: ~r1=(2.8,3,3.2), ~r2=(2.8,3,3.2), ~c1=(0.1,0.2,0.3), ~c2=(0.5,0.6,0.7), ~a1=(0.1,0.2,0.3), ~a2=(0.2,0.3,0.4), ~e1=(0.2,0.3,0.4), ~e2=(0.3,0.4,0.5), and ˜d=(0.1,0.2,0.3). Tables 2–8 showed that the trivial equilibrium P1 retained constant at (0, 0, 0), the values of prey x1, prey x2, and predator y always maintained at 0; the values of prey x1 in P2 and prey x2 in P3 severally decreased with increasing w1 under the same α; the values of prey x1 and predator y in P4 increased with increasing w1, and for P5 the value of prey x2 and predator y rose with growing w1; the values of prey x1 and x2 in P6 decreased with growing w1; and for the same α, considering interior equilibrium P7, the values of prey x1, prey x2, and predator y decreased with growing w1.
Table 2.
The trivial equilibrium P1 for k1=0.1, k2=0.7, q1=0.7, q2=0.5, q3=0.7, E1=0.3, E2=0.2, E3=0.2, K1=5, K2=5, m1=0.9, m2=0.3.
Considering four sets of different initial values, it could be seen from Figure 1 that different orbits eventually converged to the same value, which concluded that the interior equilibrium of the system (1.7) fulfills the character of globally asymptotical stability. Figure 2 plotted the bifurcation graph of system (1.7) with the horizontal coordinates k1, and the Hopf bifurcation of the system occurred with k1 taking values in the range of 0.01≤k1≤0.7. When 0.01≤k1<0.384, the system oscillates periodically, while it maintains a stable steady-state when 0.384<k1≤0.7. Therefore, based on Figure 2, it could be concluded that the fear of prey x1 for predator y affected the stability of the system. We further observed that as k1 increased, the prey x1 density continued to decrease while the predator y density kept increasing. Thus, the result also suggested that greater fear of predators had a negative impact on prey populations while having a positive impact on predator populations. Correspondingly, Figures 3 and 4 showed the waveform plots and phase diagram at k1=0.1 and k1=0.7, respectively.
Figure 1.
Global stability of the internal equilibrium P7 = (5.665, 1.668, 2.047) of system (1.7) is given by the following parameter values: α=1, w1+w2=1, A1=2.0, A2=2.0, B1=2.0, B2=2.0, k1=0.2, k2=0.1, q1=0.4, q2=0.4, q3=0.2, E1=0.2, E2=0.2, E3=0.2, A3=0.1, B3=0.1, A4=0.3, B4=0.6, K1=10, K2=10, m1=0.4, m2=0.4, C1=0.1, C2=0.2, C3=0.5.
In addition, Figure 5 also plots the bifurcation graph with changing m1. As can be seen in Figure 5, m1 took values from 0.3 to 1, in which the system also underwent a Hopf bifurcation. When the value m1 ranged from 0.3 to 0.657, the system (1.7) was stable; nevertheless, it would become unstable at 0.657<m1≤1. Correspondingly, Figures 6 and 7 showed the waveform plots and phase diagram at m1=0.6 and m1=0.9, respectively.
Figure 5.
Hopf bifurcation occurs as a bifurcation parameter of system (1.7) parameter m1, and the remaining parameters take the following values: α=1, w1+w2=1, A1=2.0, A2=2.0, B1=2.0, B2=2.0, k1=0.1, k2=0.4, q1=0.7, q2=0.4, q3=0.2, E1=0.2, E2=0.2, E3=0.3, A3=0.1, B3=0.1, A4=0.3, B4=0.6, K1=10, K2=70, m2=0.4, C1=0.1, C2=0.2, C3=0.5.
Further, we find an interesting dynamic phenomenon through some numerical simulations. System (1.7) appears as a chaotic phenomenon, as shown in Figure 8.
Figure 8.
Waveform plots and phase diagram of chaotic phenomena with the following parameter values: α=1, w1+w2=1, A1=2.0, A2=2.0, B1=3.0, B2=3.0, k1=0.2, k2=0.5, q1=0.6, q2=0.4, q3=0.2, E1=0.2, E2=0.3, E3=0.2, A3=0.2, B3=0.3, A4=0.3, B4=0.6, K1=10, K2=70, m1=0.9, m2=0.3, C1=0.1, C2=0.2, C3=0.5.
In this work, we develop a model of one-predator and two-prey interactions in a fuzzy environment, examine the effects of fear and prey refuge on the system, and provide insight into the dynamic complexity. The proofs of the theoretical parts of this paper are based on system (1.7). It has been proven that all equilibria in system (1.7) are locally asymptotically stable, and interior equilibrium P7 is also globally asymptotically stable. We have been further concerned about the appearance and direction of Hopf bifurcation. With the support of theoretical research, our numerical simulations have been able to display a wealth of charts and graphs.
First of all, different equilibria are displayed from Tables 2–8 with different α,w1,w2, respectively. Throughout Figure 1, we have verified the global asymptotical stability of interior equilibrium P7, and find that the system is from unstable to stable with the increase of fear k1, which demonstrates that the fear effect may be an important factor influencing the stability of the system (see Figures 2–4). Furthermore, it has also been observed that an increase in prey refuge m1 leads to oscillatory phenomena (see Figures 5–7). Finally, through studying the Hopf bifurcation, we have discovered some interesting biological phenomena, namely that system (1.7) appears to be in a chaotic state (see Figure 8).
Author contributions
Xuyang Cao: Conceptualization, Investigation, Methodology, Validation, Writing-original draft, Formal analysis, Software; Qinglong Wang: Conceptualization, Methodology, Formal analysis, Writing-review and editing, Supervision; Jie Liu: Validation, Visualization, Data curation.
Use of AI tools declaration
The authors declare they have not used Artificial Intelligence (AI) tools in the creation of this article.
Acknowledgments
The authors thank the editor and referees for their careful reading and valuable comments.
The work is supported by the Natural Science Foundation of Hubei Province (No. 2023AFB1095) and the National Natural Science Foundation of China (No. 12101211) and the Program for Innovative Research Team of the Higher Education Institution of Hubei Province (No. T201812) and the Teaching Research Project of Education Department of Hubei Province (No. 2022367) and the Graduate Education Innovation Project of Hubei Minzu University (Nos. MYK2024071, MYK2023042).
Conflict of interest
The authors declare that there are no conflicts of interest regarding the publication of this paper.
Appendix A
Definition 1.[34] Fuzzy set: A fuzzy set ˜ℏ in a universe of discourse S is denoted by the set of pairs
˜ℏ={(s,μ˜ℏ(s)):s∈S},
where the mapping μ˜ℏ:S→[0,1] is the membership function of the fuzzy set ˜ℏ and μ˜ℏ is the membership value or degree of membership of s∈S in the fuzzy set ˜ℏ.
Definition 2.[42] α-cut of fuzzy set: For any α∈(0,1], the α-cut of fuzzy set ˜ℏ defined by ℏα={s:μ˜ℏ(s))≥α} is a crisp set. For α=0 the support of ˜ℏ is defined as ℏ0=Supp(˜ℏ)=¯{s∈R,μ˜ℏ(s)>0}.
Definition 3.[43] Fuzzy number: A fuzzy number satisfying the property S=R is called a convex fuzzy set.
Definition 4.[44] Triangular fuzzy number: A triangular fuzzy number (TFN) ˜ℏ≡(b1,b2,b3) represent fuzzy set of the real line R satisfying the property that the membership function μ˜ℏ:R→[0,1] can be espressed by
Hence, the α-cut of triangular fuzzy number meets boundedness and encapsulation on [ℏL(α),ℏR(α)], in which ℏL(α)=infs:μ˜ℏ(s)≥α=b1+α(b2−b1) and ℏR(α)=sup{s:μ˜ℏ(s)≥α}=b3+α(b3−b2).
Lemma 1.[45] In weighted sum method, wj stands for the weight of jth objective. wjgj represent a utility function for jth objective, and the total utility function π is represented by
π=l∑jwjgj,j=1,2,⋯,l,
where wj>0 and ∑ljwj=1 are satisfied.
Acknowledgments
The present research work was funded by the University of Modena and Reggio Emilia, Grant COFIFAR2021DIPARTIMENTO to VR Lo Vasco.
Conflict of interest
All authors declare no conflicts of interest in this paper.
Author contribution
Matteo Corradini: formal analysis, methodology. Marta Checchi: methodology. Carla Palumbo: conceptualization, funding acquisition. Vincenza R. Lo Vasco: conceptualization, project administration, supervision, funding acquisition, writing.
References
[1]
Sharma A, Sharma L, Goyal R (2021) Molecular signaling pathways and essential metabolic elements in bone remodeling: An implication of therapeutic targets for bone diseases. Curr Drug Targets 22: 77-104. https://doi.org/10.2174/1389450121666200910160404
Khosla S, Riggs BL (2005) Pathophysiology of age-related bone loss and osteoporosis. Endocrin Metab Clin North Am 34: 1015-1030. https://doi.org/10.1016/j.ecl.2005.07.009
[4]
Marie PJ (2015) Osteoblast dysfunctions in bone diseases: from cellular and molecular mechanisms to therapeutic strategies. Cell Mol Life Sci 72: 1347-1361. https://doi.org/10.1007/s00018-014-1801-2
[5]
Kawai M, Modder UI, Khosla S, et al. (2011) Emerging therapeutic opportunities for skeletal restoration. Nat Rev Drug Discov 10: 141-156. https://doi.org/10.1038/nrd3299
[6]
Gether U (2000) Uncovering molecular mechanisms involved in activation of G protein-coupled receptors. Endocr Rev 21: 90-113. https://doi.org/10.1210/edrv.21.1.0390
[7]
Wu M, Deng L, Zhu G, et al. (2010) G Protein and its signaling pathway in bone development and disease. Front Biosci (Landmark Ed) 15: 957-985. https://doi.org/10.2741/3656
[8]
Bowler WB, Gallagher JA, Bilbe G (1998) G-protein coupled receptors in bone. Front Biosci 3: 769-780. https://doi.org/10.2741/a320
[9]
Conklin BR, Hsiao EC, Claeysen S, et al. (2008) Engineering GPCR signaling pathways with RASSLs. Nat Methods 5: 673-678. https://doi.org/10.1038/nmeth.1232
[10]
Saggio I, Remoli C, Spica E, et al. (2014) Constitutive expression of Gsα(R201C) in mice produces a heriTable, direct replica of human fibrous dysplasia bone pathology and demonstrates its natural history. J Bone Miner Res 29: 2357-2368. https://doi.org/10.1002/jbmr.2267
[11]
Remoli C, Michienzi S, Sacchetti B, et al. (2015) Osteoblast-specific expression of the fibrous dysplasia (FD)-causing mutation Gsα(R201C) produces a high bone mass phenotype but does not reproduce FD in the mouse. J Bone Miner Res 30: 1030-1043. https://doi.org/10.1002/jbmr.2425
[12]
Daisy CS, Romanelli A, Checchi M, et al. (2022) Expression and localization of Phosphoinositide-specific Phospholipases C in cultured, differentiating and stimulated human osteoblasts. J Cell Signal 3: 44-61. https://doi.org/10.33696/Signaling.3.067
[13]
Berridge MJ, Irvine RF (1984) Inositol triphosphate, a novel second messenger in cellular signal transduction. Nature 312: 315-321. https://doi.org/10.1038/312315a0
Tang X, Edwards EM, Holmes BB, et al. (2006) Role of phospholipase C and diacylglyceride lipase pathway in arachidonic acid release and acetylcholine-induced vascular relaxation in rabbit aorta. Am J Physiol Heart Circ Physiol 290: H37-H45. https://doi.org/10.1152/ajpheart.00491.2005
[17]
Suh PG, Park J, Manzoli L, et al. (2008) Multiple roles of phosphoinositide-specific phospholipase C isozymes. BMB Rep 41: 415-434. https://doi.org/10.5483/bmbrep.2008.41.6.415
[18]
Mebarek S, Abousalham A, Magne D, et al. (2013) Phospholipases of mineralization competent cells and matrix vesicles: roles in physiological and pathological mineralizations. Int J Mol Sci 14: 5036-5129. https://doi.org/10.3390/ijms14035036
[19]
Bahk YY, Song H, Baek SH, et al. (1998) Localization of two forms of phospholipase C-beta1, a and b, in C6Bu-1 cells. Biochim Biophys Acta 1389: 76-80. https://doi.org/10.1016/S0005-2760(97)00128-8
[20]
Mao GF, Kunapuli SP, Koneti Rao A (2000) Evidence for two alternatively spliced forms of phospholipase C-beta2 in haematopoietic cells. Brit J Haematol 110: 402-408. https://doi.org/10.1046/j.1365-2141.2000.02201.x
[21]
Kim MJ, Min DS, Ryu SH, et al. (1998) A cytosolic, galphaq- and betagamma-insensitive splice variant of phospholipase C-beta4. J Biol Chem 273: 3618-3624. https://doi.org/10.1074/jbc.273.6.3618
[22]
Lee SB, Rhee SG (1996) Molecular cloning, splice variants, expression, and purification of phospholipase C-delta 4. J Biol Chem 271: 25-31. https://doi.org/10.1074/jbc.271.1.25
[23]
Sorli SC, Bunney TD, Sugden PH, et al. (2005) Signaling properties and expression in normal and tumor tissues of two phospholipase C epsilon splice variants. Oncogene 24: 90-100. https://doi.org/10.1038/sj.onc.1208168
[24]
Lo Vasco VR, Fabrizi C, Artico M, et al. (2007) Expression of phosphoinositide-specific phospholipase C isoenzymes in cultured astrocytes. J Cell Biochem 100: 952-959. https://doi.org/10.1002/jcb.21048
[25]
Lo Vasco VR, Pacini L, Di Raimo T (2011) Expression of phosphoinositide-specific phospholipase C isoforms in human umbilical vein endothelial cells. J Clin Pathol 64: 911-915. http://dx.doi.org/10.1136/jclinpath-2011-200096
[26]
Lo Vasco VR, Leopizzi M, Chiappetta C, et al. (2012) Expression of Phosphoinositide-specific Phospholipase C enzymes in normal endometrium and in endometriosis. Fertil Steril 98: 410-414. https://doi.org/10.1016/j.fertnstert.2012.04.020
[27]
Lo Vasco VR, Leopizzi M, Chiappetta C, et al. (2013) Expression of Phosphoinositide-specific phospholipase C enzymes in human osteosarcoma cell lines. J Cell Commun Signal 7: 141-150. https://doi.org/10.1007/s12079-013-0194-6
[28]
Fais P, Leopizzi M, Di Maio V, et al. (2019) Phosphoinositide-specific Phospholipase C in normal human liver and in alcohol abuse. J Cell Biochem 120: 7907-7917. https://doi.org/10.1002/jcb.28067
[29]
Leopizzi M, Di Maio V, Della Rocca C, et al. (2020) Supernatants from human osteosarcoma cultured cell lines induce modifications in growth and differentiation of THP-1 cells and phosphoinositide-specific phospholipase C enzymes. Multidiscip Cancer Invest 4: 1-12. https://doi.org/10.30699/mci.4.4.430
[30]
Hwang JI, Kim HS, Lee JR, et al. (2005) The interaction of phospholipase C-beta3 with Shank2 regulates mGluR-mediated calcium signal. J Biol Chem 280: 12467-12473. https://doi.org/10.1074/jbc.M410740200
[31]
Bertagnolo V, Mazzoni M, Ricci D, et al. (1995) Identification of PI-PLC beta 1, gamma 1, and delta 1 in rat liver: subcellular distribution and relationship to inositol lipid nuclear signalling. Cell Signal 7: 669-678. https://doi.org/10.1016/0898-6568(95)00036-O
[32]
Nishida T, Huang TP, Seiyama A, et al. (1998) Endothelin A-receptor blockade worsens endotoxin-induced hepatic microcirculatory changes and necrosis. Gastroenterology 115: 412-420. https://doi.org/10.1016/s0016-5085(98)70208-2
[33]
Lo Vasco VR, Fabrizi C, Fumagalli L, et al. (2010) Expression of phosphoinositide specific phospholipase C isoenzymes in cultured astrocytes activated after stimulation with Lipopolysaccharide. J Cell Biochem 109: 1006-1012. https://doi.org/10.1002/jcb.22480
[34]
Lo Vasco VR, Leopizzi M, Chiappetta C, et al. (2013) Lypopolysaccharide down-regulates the expression of selected phospholipase C genes in cultured endothelial cells. Inflammation 36: 862-868. https://doi.org/10.1007/s10753-013-9613-3
[35]
Lo Vasco VR, Leopizzi M, Puggioni C, et al. (2014) Neuropeptide Y significantly reduces the expression of PLCB2, PLCD1 and moderately decreases selected PLC genes in endothelial cells. Mol Cell Biochem 394: 43-52. https://doi.org/10.1007/s11010-014-2079-2
[36]
Lo Vasco VR, Leopizzi M, Puggioni C, et al. (2014) Fibroblast growth factor acts upon the transcription of phospholipase C genes in human umbilical vein endothelial cells. Mol Cell Biochem 388: 51-59. https://doi.org/10.1007/s11010-013-1898-x
[37]
Di Raimo T, Leopizzi M, Mangino G, et al. (2016) Different expression and subcellular localization of Phosphoinositide-specific Phospholipase C enzymes in differently polarized macrophages. J Cell Commun Signal 10: 283-293. https://doi.org/0.1007/s12079-016-0335-9
[38]
Lo Vasco VR, Fabrizi C, Panetta B, et al. (2010) Expression pattern and sub cellular distribution of Phosphoinositide specific Phospholipase C enzymes after treatment with U-73122 in rat astrocytoma cells. J Cell Biochem 110: 1005-1012. https://doi.org/10.1002/jcb.22614
[39]
Lo Vasco VR, Leopizzi M, Di Maio V, et al. (2016) U-73122 reduces the cell growth in cultured MG-63 ostesarcoma cell line involving Phosphoinositide-specific Phospholipases C. Springerplus 5: 156. https://doi.org/10.1186/s40064-016-1768-6
Urciuoli E, Leopizzi M, Di Maio V, et al. (2020) Phosphoinositide-specific phospholipase C isoforms are conveyed by osteosarcoma-derived extracellular vesicles. J Cell Commun Signal 14: 417-426. https://doi.org/10.1007/s12079-020-00571-6
[42]
Bleasdale JE, Thakur NR, Gremban RS, et al. (1990) Selective inhibition of receptor-coupled phospholipase C dependent processes in human platelets and polymorphonuclear neutrophils. J Pharmacol Exp Ther 255: 756-768.
[43]
Hellberg C, Molony L, Zheng L, et al. (1996) Ca2+ signalling mechanisms of the β2 integrin on neutrophils: involvement of phospholipase Cγ2 and Ins (1, 4, 5) P3. Biochem J 317: 403-409. https://doi.org/10.1042/bj3170403
[44]
Smallridge RC, Kiang JG, Gist ID, et al. (1992) U-73122, an aminosteroid phospholipase C antagonist, non-competitively inhibits thyrotropin-releasing hormone effects in GH3 rat pituitary cells. Endocrinology 131: 1883-1888. https://doi.org/10.1210/endo.131.4.1396332
Ramazzotti G, Bavelloni A, Blalock W, et al. (2016) BMP-2 Induced Expression of PLCβ1 That is a Positive Regulator of Osteoblast Differentiation. J Cell Physiol 231: 623-629. https://doi.org/10.1002/jcp.25107
Li X, Majdi S, Dunevall J, et al. (2015) Quantitative measurement of transmitters in individual vesicles in the cytoplasm of single cells with nanotip electrodes. Angew Chem Int Ed Engl 54: 11978-11982. https://doi.org/10.1002/anie.201504839
Norwood TH, Zeigler CJ (1982) The use of dimethyl sulfoxide in mammalian cell fusion. Techniques in Somatic Cell Genetics. Boston: Springer. https://doi.org/10.1007/978-1-4684-4271-7_4
[52]
Santos NC, Figueira-Coelho J, Martins-Silva J, et al. (2003) Multidisciplinary utilization of dimethyl sulfoxide: pharmacological, cellular, and molecular aspects. Biochem Pharmacol 65: 1035-1041. https://doi.org/10.1016/s0006-2952(03)00002-9
[53]
Spray DC, Campos de Carvalho AC, Mendez-Otero R (2010) Chemical induction of cardiac differentiation in p19 embryonal carcinoma stem cells. Stem Cells Dev 19: 403-412. https://doi.org/10.1089/scd.2009.0234
[54]
Galvao J, Davis B, Tilley M (2013) Unexpected low-dose toxicity of the universal solvent DMSO. FASEB J 28: 1317-1330. https://doi.org/10.1096/fj.13-235440
Majdi S, Najafinobar N, Dunevall J, et al. (2017) DMSO chemically alters cell membranes to slow exocytosis and increase the fraction of partial transmitter released. Chembiochem 18: 1898-1902. https://doi.org/10.1002/cbic.201700410
[57]
de Ménorval MA, Mir LM, Fernández ML, et al. (2012) Effects of dimethyl sulfoxide in cholesterol-containing lipid membranes: a comparative study of experiments in silico and with cells. PLoS One 7: e41733. https://doi.org/10.1371/journal.pone.0041733
[58]
Notman R, Noro M, O'Malley B, et al. (2006) Molecular basis for dimethylsulfoxide (DMSO) action on lipid membranes. J Am Chem Soc 128: 13982-13983. https://doi.org/10.1021/ja063363t
[59]
Gurtovenko AA, Anwar J (2007) Modulating the structure and properties of cell membranes: the molecular mechanism of action of dimethyl sulfoxide. J Phys Chem B 111: 10453-10460. https://doi.org/10.1021/jp073113e
[60]
Hughes ZE, Mark AE, Mancera RL (2012) Molecular dynamics simulations of the interactions of DMSO with DPPC and DOPC phospholipid membranes. J Phys Chem B 116: 11911-11923. https://doi.org/10.1021/jp3035538
[61]
Gironi B, Kahveci Z, McGill B, et al. (2020) Effect of DMSO on the mechanical and structural properties of mmodel and biological mmembranes. Biophys J 119: 274-286. https://doi.org/10.1016/j.bpj.2020.05.037
Thomas MJ, Smith A, Head DH, et al. (2005) Airway inflammation: chemokine-induced neutrophilia and the class I phosphoinositide 3-kinases. Eur J Immunol 35: 1283-1291. https://doi.org/10.1002/eji.200425634
[64]
Cenni B, Picard D (1999) Two compounds commonly used for phospholipase C inhibition activate the nuclear estrogen receptors. Biochem Biophys Res Commun 261: 340-344. https://doi.org/10.1006/bbrc.1999.1017
[65]
Feisst C, Albert D, Steinhilber D, et al. (2005) The aminosteroid phospholipase C antagonist U-73122 (1-[6-[[17-beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1Hpyrrole-2,5-dione) potently inhibits human 5-lipoxygenase in vivo and in vitro. Mol Pharmacol 67: 1751-1757. https://doi.org/10.1124/mol.105.011007
[66]
Hughes S, Gibson WJ, Young JM (2000) The interaction of U-73122 with the histamine H-1 receptor: implications for the use of U-73122 in defining H-1 receptor-coupled signalling pathways. Naunyn Schmiedeberg's Arch Pharmacol 362: 555-558. https://doi.org/10.1007/s002100000326
[67]
Walker EM, Bispham JR, Hill SJ (1998) Nonselective effects of the putative phospholipase C inhibitor, U73122, on adenosine A(1) receptor-mediated signal transduction events in Chinese hamster ovary cells. Biochem Pharmacol 56: 1455-1462. https://doi.org/10.1016/s0006-2952(98)00256-1
[68]
Berven LA, Barritt GJ (1995) Evidence obtained using single hepatocytes for inhibition by the phospholipase-C inhibitor U73122 of store-operated Ca2+ inflow. Biochem Pharmacol 49: 1373-1379. https://doi.org/10.1016/0006-2952(95)00050-a
[69]
Pulcinelli FM, Gresele P, Bonuglia M, et al. (1998) Evidence for separate effects of U73122 on phospholipase C and calcium channels in human platelets. Biochem Pharmacol 56: 1481-1484. https://doi.org/10.1016/s0006-2952(98)00146-4
[70]
Boujard D, Anselme B, Cullin C, et al. (2014) Vesikulärer Transport. Zell- und Molekularbiologie im Überblick. Berlin: Springer Spektrum. https://doi.org/10.1007/978-3-642-41761-0
Chan AY, Raft S, Bailly M, et al. (1998) EGF stimulates an increase in actin nucleation and filament number at the leading edge of the lamellipod in mammary adenocarcinoma cells. J Cell Sci 111: 199-211. https://doi.org/10.1242/jcs.111.2.199
Beningo KA, Dembo M, Kaverina I, et al. (2001) Nascent focal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts. J Cell Biol 153: 881-888. https://doi.org/10.1083/jcb.153.4.881
[85]
Balaban NQ, Schwarz US, Riveline D, et al. (2001) Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. Nat Cell Biol 3: 466-472. https://doi.org/10.1038/35074532
[86]
Abercrombie M (1980) The Croonian Lecture, 1978-The crawling movement of metazoan cells. Proc R Soc Lond, Ser B 207: 129-147. https://doi.org/10.1098/rspb.1980.0017
[87]
Hinz B, Alt W, Johnen C, et al. (1999) Quantifying lamella dynamics of cultured cells by SACED, a new computer-assisted motion analysis. Exp Cell Res 251: 234-243. https://doi.org/10.1006/excr.1999.4541
[88]
Araki N, Egami Y, Watanabe Y, et al. (2007) Phosphoinositide metabolism during membrane ruffling and macropinosome formation in EGF-stimulated A431 cells. Exp Cell Res 313: 1496-1507. https://doi.org/10.1016/j.yexcr.2007.02.012
[89]
Rilla K, Koistinen A (2015) Correlative light and electron microscopy reveals the HAS3-induced dorsal plasma membrane ruffles. Int J Cell Biol 2015: 769163. https://doi.org/10.1155/2015/769163
[90]
Hoon JL, Wong WK, Koh CG (2012) Functions and regulation of circular dorsal ruffles. Mol Cell Biol 32: 4246-4257. https://doi.org/10.1128/MCB.00551-12
[91]
Bernitt E, Döbereiner HG, Gov NS, et al. (2017) Fronts and waves of actin polymerization in a bistability-based mechanism of circular dorsal ruffles. Nat Commun 8: 15863. https://doi.org/10.1038/ncomms15863
[92]
Li G, D'Souza-Schorey C, Barbieri MA, et al. (1997) Uncoupling of membrane ruffling and pinocytosis during Ras signal transduction. J Biol Chem 272: 10337-10340. https://doi.org/10.1074/jbc.272.16.10337
[93]
Jones SJ, Boyde A (1976) Morphological changes of osteoblasts in vitro. Cell Tissue Res 166: 101-107. https://doi.org/10.1007/BF00215129
[94]
Lohmann CH, Schwartz Z, Köster G, et al. (2000) Phagocytosis of wear debris by osteoblasts affects differentiation and local factor production in a manner dependent on particle composition. Biomaterials 21: 551-561. https://doi.org/10.1016/s0142-9612(99)00211-2
[95]
Sala G, Dituri F, Raimondi C, et al. (2008) PPhospholipase Cγ1 is required for metastasis development and progression. Cancer Res 68: 10187-10196. https://doi.org/10.1158/0008-5472.CAN-08-1181
[96]
Barber MA, Welch HCE (2006) PI3K and RAC signaling in leukocyte and cancer cell migration. Bull Cancer 93: 10044-10052.
[97]
Marée AF, Grieneisen VA, Edelstein-Keshet L (2012) How cells integrate complex stimuli: the effect of feedback from phosphoinositides and cell shape on cell polarization and motility. PLoS computational biology 8: e1002402. https://doi.org/10.1371/journal.pcbi.1002402
[98]
Razzini G, Berrie CP, Vignati S, et al. (2000) Novel functional PI 3-kinase antagonists inhibit cell growth and tumorigenicity in human cancer cell lines. FASEB J 14: 1179-1187. https://doi.org/10.1096/fasebj.14.9.1179
[99]
Baugher PJ, Krishnamoorthy L, Price JE (2005) Rac1 and Rac3 isoform activation is involved in the invasive and metastatic phenotype of human breast cancer cells. Breast Cancer Res 7: R965-R974. https://doi.org/10.1186/bcr1329
[100]
Takenawa T, Miki H (2001) WASP and WAVE family proteins: key molecules for rapid rearrangement of cortical actin filaments and cell movement. J Cell Sci 114: 1801-1809. https://doi.org/10.1242/jcs.114.10.1801
[101]
Zhao B, Wang HB, Lu YJ, et al. (2011) Transport of receptors, receptor signaling complexes and ion channels via neuropeptide-secretory vesicles. Cell Res 21: 741-753. https://doi.org/10.1038/cr.2011.29
[102]
Illenberger D, Schwald F, Gierschik P (1997) Characterization and purification from bovine neutrophils of a soluble guanine-nucleotide-binding protein that mediates isozyme-specific stimulation of phospholipase C beta2. Eur J Biochem 246: 71-77. https://doi.org/10.1111/j.1432-1033.1997.t01-1-00071.x
[103]
Illenberger D, Schwald F, Pimmer D, et al. (1998) Stimulation of phospholipase C-β2 by the Rho GTPases Cdc42Hs and Rac1. EMBO J 17: 6241-6249. https://doi.org/10.1093/emboj/17.21.6241
[104]
Illenberger D, Walliser C, Strobel J, et al. (2003) Rac2 regulation of phospholipase C-β 2 activity and mode of membrane interactions in intact cells. J Biol Chem 278: 8645-8652. https://doi.org/10.1074/jbc.m211971200
[105]
Reid DW, Nicchitta CV (2015) Diversity and selectivity in mRNA translation on the endoplasmic reticulum. Nat Rev Mol Cell Biol 16: 221-231. https://doi.org/10.1038/nrm3958
[106]
Rapoport TA (2007) Protein translocation across the eukaryotic endoplasmic reticulum and bacterial plasma membranes. Nature 450: 663-669. https://doi.org/10.1038/nature06384
Hebert DN, Garman SC, Molinari M (2005) The glycan code of the endoplasmic reticulum: asparagine-linked carbohydrates as protein maturation and quality-control tags. Trends Cell Biol 15: 364-370. https://doi.org/10.1016/j.tcb.2005.05.007
Jan CH, Williams CC, Weissman JS (2014) Principles of ER cotranslational translocation revealed by proximity-specific ribosome profiling. Science 346: 1257521. https://doi.org/10.1126/science.1257521
Appenzeller-Herzog C, Hauri HP (2006) The ER-Golgi intermediate compartment (ERGIC): in search of its identity and function. J Cell Sci 119: 2173-2183. https://doi.org/10.1242/jcs.03019
Eisen A, Reynolds GT (1985) Source and sinks for the calcium released during fertilization of single sea urchin eggs. J Cell Biol 100: 1522-1527. https://doi.org/10.1083/jcb.100.5.1522
[117]
Samtleben S, Jaepel J, Fecher C, et al. (2013) Direct imaging of ER calcium with targeted-esterase induced dye loading (TED). J Vis Exp 75: e50317. https://doi.org/10.3791/50317
[118]
Oude Weernink PA, Han L, Jakobs KH, et al. (2007) Dynamic phospholipid signaling by G protein-coupled receptors. Biochim Biophys Acta 1768: 888-900. https://doi.org/10.1016/j.bbamem.2006.09.012
[119]
Kanehara K, Yu CY, Cho Y, et al. (2015) Arabidopsis AtPLC2 is a primary phosphoinositide-specific phospholipase C in phosphoinositide metabolism and the endoplasmic reticulum stress response. PLoS Genet 11: e1005511. https://doi.org/10.1371/journal.pgen.1005511
This article has been cited by:
1.
Yuan Tian, Hua Guo, Wenyu Shen, Xinrui Yan, Jie Zheng, Kaibiao Sun,
Dynamic analysis and validation of a prey-predator model based on fish harvesting and discontinuous prey refuge effect in uncertain environments,
2025,
33,
2688-1594,
973,
10.3934/era.2025044
Matteo Corradini, Marta Checchi, Marzia Ferretti, Francesco Cavani, Carla Palumbo, Vincenza Rita Lo Vasco. Endoplasmic reticulum localization of phosphoinositide specific phospholipase C enzymes in U73122 cultured human osteoblasts[J]. AIMS Biophysics, 2023, 10(1): 25-49. doi: 10.3934/biophy.2023004
Matteo Corradini, Marta Checchi, Marzia Ferretti, Francesco Cavani, Carla Palumbo, Vincenza Rita Lo Vasco. Endoplasmic reticulum localization of phosphoinositide specific phospholipase C enzymes in U73122 cultured human osteoblasts[J]. AIMS Biophysics, 2023, 10(1): 25-49. doi: 10.3934/biophy.2023004
Interspecific competition between prey x1 and prey x2
c1,c2
Predation coefficients for prey x1 and prey x2
m1,m2
Refuge rates of prey x1 and prey x2
e1,e2
Conversion factors for prey x1 and prey x2
q1,q2,q3
Captureability factors for prey x1, prey x2 and predator y
E1,E2,E3
Harvesting efforts for prey x1, prey x2 and predator y
d
Predator y mortality rate
w1
w2
P1 at α=0
P1 at α=0.3
P1 at α=0.6
P1 at α=0.9
0
1
(0,0,0)
(0,0,0)
(0,0,0)
(0,0,0)
0.2
0.8
(0,0,0)
(0,0,0)
(0,0,0)
(0,0,0)
0.4
0.6
(0,0,0)
(0,0,0)
(0,0,0)
(0,0,0)
0.6
0.4
(0,0,0)
(0,0,0)
(0,0,0)
(0,0,0)
0.8
0.2
(0,0,0)
(0,0,0)
(0,0,0)
(0,0,0)
1
0
(0,0,0)
(0,0,0)
(0,0,0)
(0,0,0)
w1
w2
P2 at α=0
P2 at α=0.3
P2 at α=0.6
P2 at α=0.9
0
1
(5.3393,0,0)
(5.1224,0,0)
(4.9144,0,0)
(4.7148,0,0)
0.2
0.8
(5.0521,0,0)
(4.9280,0,0)
(4.8069,0,0)
(4.6888,0,0)
0.4
0.6
(4.7804,0,0)
(4.7409,0,0)
(4.7017,0,0)
(4.6629,0,0)
0.6
0.4
(4.5230,0,0)
(4.5608,0,0)
(4.5988,0,0)
(4.6372,0,0)
0.8
0.2
(4.2788,0,0)
(4.3872,0,0)
(4.4980,0,0)
(4.6116,0,0)
1
0
(4.0469,0,0)
(4.2197,0,0)
(4.3994,0,0)
(4.5861,0,0)
w1
w2
P3 at α=0
P3 at α=0.3
P3 at α=0.6
P3 at α=0.9
0
1
(0,5.5357,0)
(0,5.3147,0)
(0,5.1027,0)
(0,4.8993,0)
0.2
0.8
(0,5.2431,0)
(0,5.1166,0)
(0,4.9932,0)
(0,4.8728,0)
0.4
0.6
(0,4.9662,0)
(0,4.9260,0)
(0,4.8861,0)
(0,4.8465,0)
0.6
0.4
(0,4.7039,0)
(0,4.7424,0)
(0,4.7812,0)
(0,4.8202,0)
0.8
0.2
(0,4.4551,0)
(0,4.5655,0)
(0,4.6785,0)
(0,4.7942,0)
1
0
(0,4.2187,0)
(0,4.3949,0)
(0,4.5779,0)
(0,4.7682,0)
w1
w2
P4 at α=0
P4 at α=0.3
P4 at α=0.6
P4 at α=0.9
0
1
(0.4800,0,0.1496)
(0.5838,0,0.1767)
(0.7059,0,0.2040)
(0.8516,0,0.2317)
0.2
0.8
(0.6222,0,0.1858)
(0.6971,0,0.2022)
(0.7802,0,0.2188)
(0.8732,0,0.2354)
0.4
0.6
(0.8000,0,0.2224)
(0.8306,0,0.2280)
(0.8623,0,0.2335)
(0.8954,0,0.2391)
0.6
0.4
(1.0286,0,0.2595)
(0.9902,0,0.2539)
(0.9534,0,0.2484)
(0.9181,0,0.2428)
0.8
0.2
(1.3333,0,0.2969)
(1.1845,0,0.2801)
(1.0551,0,0.2633)
(0.9415,0,0.2465)
1
0
(1.7600,0,0.3343)
(1.4261,0,0.3062)
(1.1692,0,0.2782)
(0.9655,0,0.2502)
w1
w2
P5 at α=0
P5 at α=0.3
P5 at α=0.6
P5 at α=0.9
0
1
(0,0.1920,0.3638)
(0,0.2298,0.3833)
(0,0.2727,0.4029)
(0,0.3220,0.4226)
0.2
0.8
(0,0.2435,0.3899)
(0,0.2697,0.4016)
(0,0.2981,0.4134)
(0,0.3291,0.4252)
0.4
0.6
(0,0.3048,0.4160)
(0,0.3150,0.4199)
(0,0.3255,0.4239)
(0,0.3363,0.4278)
0.6
0.4
(0,0.3789,0.4422)
(0,0.3668,0.4383)
(0,0.3551,0.4343)
(0,0.3437,0.4304)
0.8
0.2
(0,0.4706,0.4683)
(0,0.4268,0.4566)
(0,0.3872,0.4448)
(0,0.3513,0.4330)
1
0
(0,0.5867,0.4942)
(0,0.4970,0.4748)
(0,0.4222,0.4553)
(0,0.3590,0.4357)
w1
w2
P6 at α=0
P6 at α=0.3
P6 at α=0.6
P6 at α=0.9
0
1
(4.9826,3.8455,0)
(4.6419,3.5356,0)
(4.3385,3.2568,0)
(4.0671,3.0043,0)
0.2
0.8
(4.5369,3.4395,0)
(4.3577,3.2745,0)
(4.1901,3.1191,0)
(4.0331,2.9724,0)
0.4
0.6
(4.1543,3.0858,0)
(4.1016,3.0366,0)
(4.0500,2.9883,0)
(3.9995,2.9408,0)
0.6
0.4
(3.8232,2.7740,0)
(3.8700,2.8184,0)
(3.9177,2.8636,0)
(3.9665,2.9097,0)
0.8
0.2
(3.5351,2.4958,0)
(3.6599,2.6172,0)
(3.7926,2.7447,0)
(3.9338,2.8789,0)
1
0
(3.2834,2.2448,0)
(3.4690,2.4307,0)
(3.6742,2.6311,0)
(3.9017,2.8485,0)
w1
w2
P7 at α=0
P7 at α=0.3
0
1
(1.7240,3.6276,1.1986)
(1.5910,3.4597,1.0271)
0.2
0.8
(1.6168,3.5123,1.0583)
(1.5042,3.3223,0.9139)
0.4
0.6
(1.5417,3.4296,0.9337)
(1.4211,3.1793,0.8023)
0.6
0.4
(1.4309,3.2886,0.7930)
(1.3913,3.1413,0.7269)
0.8
0.2
(1.4291,3.2451,0.6884)
(1.3195,3.0467,0.6350)
1
0
(1.3764,2.9890,0.5245)
(1.2797,2.9766,0.5529)
w1
w2
P7 at α=0.6
P7 at α=0.9
0
1
(1.7066,3.7444,1.0113)
(1.5325,3.4231,0.7999)
0.2
0.8
(1.5291,3.4203,0.8678)
(1.4899,3.3773,0.7762)
0.4
0.6
(1.5273,3.4215,0.8306)
(1.4789,3.3677,0.7638)
0.6
0.4
(1.4894,3.3737,0.7779)
(1.4685,3.3587,0.7516)
0.8
0.2
(1.4594,3.3320,0.7279)
(1.4590,3.3504,0.7397)
1
0
(1.4328,3.2552,0.6687)
(1.4124,3.2841,0.7105)
Figure 1. Histogram of the cell growth data. Histogram of the cell growth data in Table 1 with error bars [Ctrl: control cells; DMSO: cells grown in the presence of DMSO; U-73122: cells grown in the presence of U-73122 dissolved in DMSO before adding molecules to the cultures (G0) and after 1 (G1), 3 (G3), 7 (G7) and 14 (G14) days]
Figure 2. Gel electrophoresis of PCR results. PCR results. Agarose gel electrophoresis of PCR amplified reverse transcripts of PLC genes and of GAPDH gene as a positive control. See the left column for reference transcript length
Figure 3. Fluorescence immunocytochemistry location of PLC β2 and PLC β3 (40X). Fluorescence immunocytochemistry. Intracellular localization of PLC β2 and PLC β3 (red). Nuclei counterstain with DAPI (blue). White arrows: PLCs in cell protrusions. [Caption 40X]
Figure 4. Fluorescence immunocytochemistry location of PLC ϵ at the ER (40X). Double fluorescence immunocytochemistry. Localization of PLC ϵ (red) at the ER (Calnexin, green). Nuclei counterstain with DAPI (blue). White arrows: co-localization site. [Caption 40X]