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Stability Analysis for the Cellular Signaling Systems Composed of Two Phosphorylation-Dephosphorylation Cyclic Reactions  [PDF]
Chinasa Sueyoshi, Takashi Naka
Computational Molecular Bioscience (CMB) , 2017, DOI: 10.4236/cmb.2017.73003
Abstract: The regulatory mechanisms in cellular signaling systems have been studied intensively from the viewpoint that the malfunction of the regulation is thought to be one of the substantial causes of cancer formation. On the other hand, it is rather difficult to develop the theoretical framework for investigation of the regulatory mechanisms due to their complexity and nonlinearity. In this study, more general approach is proposed for elucidation of characteristics of the stability in cellular signaling systems by construction of mathematical models for a class of cellular signaling systems and stability analysis of the models over variation of the network architectures and the parameter values. The model system is formulated as regulatory network in which every node represents a phosphorylation-dephosphorylation cyclic reaction for respective constituent enzyme. The analysis is performed for all variations of the regulatory networks comprised of two nodes with multiple feedback regulation loops. It is revealed from the analysis that the regulatory networks become mono-stable, bi-stable, tri-stable, or oscillatory and that the negative mutual feedback or positive mutual feedback is favorable for multi-stability, which is augmented by a negatively regulated node with a positive auto-regulation. Furthermore, the multi-stability or the oscillation is more likely to emerge in the case of low value of the Michaelis constant than in the case of high value, implying that the condition of higher saturation levels induces stronger nonlinearity in the networks. The analysis for the parameter regions yielding the multi-stability and the oscillation clarified that the stronger regulation shifts the systems toward multi-stability.
Book Review:First Contact: Teaching and Learning in Introductory Sociology
Tomomi Naka
The Journal of Scholarship of Teaching and Learning , 2013,
Various Wrapped Branes from Gauged Supergravities
Michihiro Naka
Physics , 2002,
Abstract: We study wrapped brane configurations via possible maximally supersymmetric gauged supergravities. First, we construct various supersymmetric wrapped D3 brane configurations from D=5 N=8 SO(6) gauged supergravity. This procedure provides certain new examples of wrapped D3 branes around supersymmetric cycles inside non-compact special holonomy manifolds. We analyze their behaviors numerically in order to discuss a correspondence to Higgs and Coulomb branches of sigma models on wrapped D3 branes. We also realize supersymmetric wrapped M2 branes from D=4 N=8 SO(8) gauged supergravity. Then, we study supersymmetric wrapped type IIB NS5 branes by D=7 N=4 SO(4) gauged supergravity. We show a method to derive them by using supersymmetric wrapped M5 branes in D=7 N=4 SO(5) gauged supergravity. This method is based on a domain wall like reduction. Solutions include NS5 branes wrapped around holomorphic $CP^2$ inside non-compact Calabi-Yau threefold. Their behavior shows a similar feature to that for NS5 branes wrapped around holomorphic $CP^1$ inside non-compact $K3$ surface. This construction also provides a check of preserved supersymmetry for a solution interpreted within a string world-sheet theory introduced by Hori and Kapustin. Finally, we find new non-supersymmetric solutions including AdS space-times in D=6 N=2 $SU(2)\times U(1)$ massive gauged supergravity. These solutions can be interpreted as non-supersymmetric wrapped D4-D8 configurations which are dual to non-supersymmetric conformal field theories realized on wrapped D4 branes.
A Realization of N=1 ${\cal SW}(3/2,2)$ Algebras with Wolf Spaces
Michihiro Naka
Physics , 2002, DOI: 10.1088/1126-6708/2002/12/059
Abstract: We find out that some unitary minimal models of the N=1 ${\cal SW}(3/2,2)$ superconformal algebra can be realized as the level one coset models based on the Wolf spaces $SU(n)/(SU(n-2)\times SU(2))$. We obtain the expression of the fermionic current with the conformal weight 5/2 in the algebra. Then, these models are twisted to give the topological conformal field theories.
On Pure Hyperradical in Semihypergroups
Kostaq Hila,Krisanthi Naka
International Journal of Mathematics and Mathematical Sciences , 2012, DOI: 10.1155/2012/876919
Abstract: This paper deals with a class of algebraic hyperstructures called semihypergroups, which are a generalization of semigroups. In this paper, we introduce pure hyperradical of a hyperideal in a semihypergroup with zero element. For this purpose, we define pure, semipure, and other related types of hyperideals and establish some of their basic properties in semihypergroups. 1. Introduction and Preliminaries The applications of mathematics in other disciplines, for example, in informatics, play a key role and they represent, in the last decades, one of the purpose, of the study of the experts of hyperstructures theory all over the world. Hyperstructure theory was introduced in 1934 by the French mathematician Marty [1], at the 8th Congress of Scandinavian Mathematicians, where he defined hypergroups based on the notion of hyperoperation, began to analyze their properties, and applied them to groups. In the following decades and nowadays, a number of different hyperstructures are widely studied from the theoretical point of view and for their applications to many subjects of pure and applied mathematics by many mathematicians. In a classical algebraic structure, the composition of two elements is an element, while in an algebraic hyperstructure, the composition of two elements is a set. Several books have been written on hyperstructure theory, see [2–5]. A recent book on hyperstructures [3] points out on their applications in rough set theory, cryptography, codes, automata, probability, geometry, lattices, binary relations, graphs and hypergraphs. Another book [4] is devoted especially to the study of hyperring theory. Several kinds of hyperrings are introduced and analyzed. The volume ends with an outline of applications in chemistry and physics, analyzing several special kinds of hyperstructures: -hyperstructures and transposition hypergroups. Some principal notions about semihypergroups theory can be found in [6–18]. Recently, Davvaz et al. [19–23] introduced the notion of -semihypergroup as a generalization of a semigroup, a generalization of a semihypergroup, and a generalization of a -semigroup. They presented many interesting examples and obtained a several characterizations of -semihypergroups. In this paper, we introduce pure hyperradical of a hyperideal in a semihypergroup with zero element. For this purpose, we define pure, semipure, and other related types of hyperideals, and we establish some of their basic properties in semihypergroups. Recall first the basic terms and definitions from the hyperstructure theory. A map is called hyperoperation
SOCS1, a Negative Regulator of Cytokine Signals and TLR Responses, in Human Liver Diseases
Minoru Fujimoto,Tetsuji Naka
Gastroenterology Research and Practice , 2010, DOI: 10.1155/2010/470468
Abstract: Toll-like receptor (TLR) signaling pathways are strictly coordinated by several mechanisms to regulate adequate innate immune responses. Recent lines of evidence indicate that the suppressor of cytokine signaling (SOCS) family proteins, originally identified as negative-feedback regulators in cytokine signaling, are involved in the regulation of TLR-mediated immune responses. SOCS1, a member of SOCS family, is strongly induced upon TLR stimulation. Cells lacking SOCS1 are hyperresponsive to TLR stimulation. Thus, SOCS1 is an important regulator for both cytokine and TLR-induced responses. As an immune organ, the liver contains various types of immune cells such as T cells, NK cells, NKT cells, and Kupffer cells and is continuously challenged with gut-derived bacterial and dietary antigens. SOCS1 may be implicated in pathophysiology of the liver. The studies using SOCS1-deficient mice revealed that endogenous SOCS1 is critical for the prevention of liver diseases such as hepatitis, cirrhosis, and cancers. Recent studies on humans suggest that SOCS1 is involved in the development of various liver disorders in humans. Thus, SOCS1 and other SOCS proteins are potential targets for the therapy of human liver diseases. 1. Introduction Proper and coordinated activation of immune signal pathways is required for immune responses, including eradication of invading pathogens. Toll-like receptor (TLR)- and cytokine receptor-mediated signaling are involved in innate and subsequent adoptive immunity. Aberrant and/or sustained activation of immune signal pathways may result in serious disorders such as septic shock, autoimmunity, and cancer. Thus, immune signals must be tightly regulated for preventing overactivated immune responses. A number of regulatory mechanisms on immune signaling pathways have been reported. A family named suppressor of cytokine signaling (SOCS) represents a negative regulator for various cytokine signaling (Table 1) [1]. SOCS proteins play important roles in maintaining organ homeostasis by preventing the harmful cytokine responses in various organs [2]. In this paper, we will focus on SOCS1, a member of SOCS family, which plays a key role in the negative regulation of both cytokine receptor- and TLR-mediated signaling. We will further discuss the importance of SOCS1 in the pathogenesis of liver diseases. Table 1: Inducing factors of SOCS family proteins and suppressed signaling by SOCS family proteins (see [ 1, 3, 4]). 2. Regulation of Immune Signal Pathways by Suppressor of Cytokine Signaling (SOCS) 2.1. Inhibition of Cytokine Signaling by
Application of Laser-Induced Bone Therapy by Carbon Dioxide Laser Irradiation in Implant Therapy
Takahiro Naka,Satoshi Yokose
International Journal of Dentistry , 2012, DOI: 10.1155/2012/409496
Abstract: This study evaluated the application of laser-induced bone therapy (LIBT) to reduce implant healing time in rat tibia. Twenty 10-week-old female Sprague-Dawlay rats were used. The rats received laser irradiation (laser group) or sham operation (control group) on either side of the tibia. Five days after invasion, titanium implants were inserted in proximal tibia. Five, 10, and 20 days after implant placement, tibiae were collected. After taking micro-CT and performing a torque test, the tibiae were decalcified and 8-μm-thick sections were prepared. Specimens were stained with hematoxylin and eosin. Results. Micro-CT images, removal torque values, and histomorphometric analysis data demonstrated a significantly accelerated bone formation in the laser group earlier in the healing process. Conclusion. The use of laser irradiation was effective in promoting bone formation and acquiring osseointegration of titanium implants inserted in rat tibia. LIBT may be suitable for use in implant therapy.
Bench-to-bedside review: Treating acid–base abnormalities in the intensive care unit – the role of renal replacement therapy
Toshio Naka, Rinaldo Bellomo
Critical Care , 2004, DOI: 10.1186/cc2821
Abstract: Acute renal failure (ARF) in the critically ill is still associated with a poor prognosis [1,2]. Metabolic acid–base disorders are particularly common in these patients, especially acidosis. The pathogenesis of such acidosis remains poorly understood because its main cause in ARF patients is not fully understood. However, the nature of this metabolic acidosis is likely multifactorial and probably includes the effect of chloride-rich fluid resuscitation [3] and the accumulation of lactate, phosphate, and unexcreted metabolic acids such as sulfate [4]. This multifactorial metabolic acidosis associated with ARF often leads to acidemia. Furthermore, persistent acidosis has been demonstrated to be an indicator of poor prognosis [5]. The rationale behind the perceived need to correct severe acidosis lies in the potential adverse cellular effects of such metabolic disturbance on myocardial function, likelihood of arrhythmias, and pulmonary vascular tone. However, very few studies [6] have in fact established that clinically significant benefits might arise from the correction of such acidosis.Nonetheless, renal replacement therapy (RRT) such as intermittent hemodialysis (IHD), continuous venovenous hemofiltration (CVVH), continous venovenous hemodailysis, and continuous venovenous hemodiafiltration (CVVHDF) has been applied to the treatment of critically ill patients with ARF to improve fluid overload, uremia, and acid–base disorders. The use of RRT and adjustments in the replacement solutions administered to acidotic critically ill patients with ARF can have a substantial effect on acid–base homeostasis. Furthermore, high-volume hemofiltration (HVHF) may have an even stronger effect on acid–base disorders. Therefore, improving our understanding of the impact of RRT on acid–base disorders and gaining insights into the nature of such disorders and the mechanisms of action of RRT are important.In the present review we explore the acid–base disorders seen in ARF, the effect o
Joint disease caused by defective gp130-mediated STAT signaling
Tetsuji Naka, Tadamitsu Kishimoto
Arthritis Research & Therapy , 2002, DOI: 10.1186/ar400
Abstract: Rheumatoid arthritis (RA) is a major immune-mediated human disease of unknown cause. Nevertheless, cumulative evidence suggests that cytokines are important mediators in its pathology [1]. These substances, especially the so-called proinflammatory cytokines, such as IL-1, tumor necrosis factor-α, and IL-6, play a pivotal role in the pathology of RA. Recently, Ohshima et al. showed that IL-6 is essential for the development of antigen-induced arthritis, an experimental autoimmune arthritis model that resembles RA histologically [2]. Furthermore, results of a recent clinical trial of anti-IL-6-receptor antibody therapy for RA support this idea [3] (reviewed in [4]). However, the molecular mechanisms by which IL-6 is involved in joint destruction in RA have not yet been identified. A detailed study of gp130ΔSTAT/ΔSTAT mice, in which gp130-mediated signal transducer and activator of transcription (STAT) signal was disrupted, showed that lack of STAT-mediated induction of SOCS-1 (suppressor of cytokine signaling-1) accelerates the SHP-2/Ras/Erk signal cascade that would be downregulated by SOCS-1 induction; the acceleration eventually resulted in severe joint disease [5].The IL-6 receptor consists of two molecules: one is an 80-kDa IL-6-binding protein (α chain) and the other is a 130-kDa signal transducer, gp130 (β chain), which is shared by the receptors for other cytokines of the IL-6 family, including IL-11, leukemia inhibitory factor (LIF), cardiotrophin-1, oncostatin M, and ciliary neurotrophic factor. IL-6 signaling is exclusively regulated by gp130, which contains two motifs conserved among the cytokine receptor family, known as Box1 and Box2 (Fig. 1). The membrane-proximal region containing Box1 and Box2 is sufficient for Janus kinase (JAK) to be activated through gp130. gp130 contains six tyrosines in its cytoplasmic region. Tyr-757 is essential for the tyrosine phosphorylation of SHP-2 and subsequent activation of the Erk mitogen-activated protein kinase (MAPK
q-Deformed Bi-Local Fields II
Haruki Toyoda,Shigefumi Naka
Symmetry, Integrability and Geometry : Methods and Applications , 2006,
Abstract: We study a way of q-deformation of the bi-local system, the two particle system bounded by a relativistic harmonic oscillator type of potential, from both points of view of mass spectra and the behavior of scattering amplitudes. In our formulation, the deformation is done so that P^2, the square of center of mass momentum, enters into the deformation parameters of relative coordinates. As a result, the wave equation of the bi-local system becomes nonlinear with respect to P^2; then, the propagator of the bi-local system suffers significant change so as to get a convergent self energy to the second order. The study is also made on the covariant q-deformation in four dimensional spacetime.
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