Herbimycin A suppresses NF-κB activation and tyrosine phosphorylation of JAK2 and the subsequent induction of nitric oxide synthase in C6 glioma cells

AbstractHerbimycin A, a potent tyrosine kinase inhibitor, suppressed nitric oxide synthase (NOS) induced by lipopolysaccharide (LPS) and interferon-γ (IFN-γ) in C6 glial cells. LPS activated NF-κB, and this effect was inhibited by pretreatment with herbimycin A. In addition, IFN-γ activated the tyrosine protein kinase, JAK2, and tyrosine-phosphorylation by itself was also inhibited by herbimycin A. These results suggest that herbimycin A suppresses iNOS induction by inhibition of both NF-κB activation caused by LPS, and tyrosine-phosphorylation of JAK2 caused by IFN-γ in C6 glioma cells

Intermittent control with ankle, hip, and mixed strategies during quiet standing: A theoretical proposal based on a double inverted pendulum model

Abstract Human upright posture, as a mechanical system, is characterized by an instability of saddle type, involving both stable and unstable dynamic modes. The brain stabilizes such system by generating active joint torques, according to a time-delayed neural feedback control. What is still unsolved is a clear understanding of the control strategies and the control mechanisms that are used by the central nervous system in order to stabilize the unstable posture in a robust way while maintaining flexibility. Most studies in this direction have been limited to the single inverted pendulum model, which is useful for formalizing fundamental mechanical aspects but insufficient for addressing more general issues concerning neural control strategies. Here we consider a double inverted pendulum model in the sagittal plane with small passive viscoelasticity at the ankle and hip joints. Despite difficulties in stabilizing the double pendulum model in the presence of the large feedback delay, we show that robust and flexible stabilization of the upright posture can be established by an intermittent control mechanism that achieves the goal of stabilizing the body posture according to a "divide and conquer strategy", which switches among different controllers in different parts of the state space of the double inverted pendulum. Remarkably, it is shown that a global, robust stability is achieved even if the individual controllers are unstable and the information exploited for switching from one controller to another is severely delayed, as it happens in biological reality. Moreover, the intermittent controller can automatically resolve coordination among multiple active torques associated with the muscle synergy, leading to the emergence of distinct temporally coordinated active torque patterns, referred to as the intermittent ankle, hip, and mixed strategies during quiet standing, depending on the passive elasticity at the hip joint

Intermittent Feedback-Control Strategy for Stabilizing Inverted Pendulum on Manually Controlled Cart as Analogy to Human Stick Balancing

The stabilization of an inverted pendulum on a manually controlled cart (cart-inverted-pendulum; CIP) in an upright position, which is analogous to balancing a stick on a fingertip, is considered in order to investigate how the human central nervous system (CNS) stabilizes unstable dynamics due to mechanical instability and time delays in neural feedback control. We explore the possibility that a type of intermittent time-delayed feedback control, which has been proposed for human postural control during quiet standing, is also a promising strategy for the CIP task and stick balancing on a fingertip. Such a strategy hypothesizes that the CNS exploits transient contracting dynamics along a stable manifold of a saddle-type unstable upright equilibrium of the inverted pendulum in the absence of control by inactivating neural feedback control intermittently for compensating delay-induced instability. To this end, the motions of a CIP stabilized by human subjects were experimentally acquired, and computational models of the system were employed to characterize the experimental behaviors. We first confirmed fat-tailed non-Gaussian temporal fluctuation in the acceleration distribution of the pendulum, as well as the power-law distributions of corrective cart movements for skilled subjects, which was previously reported for stick balancing. We then showed that the experimental behaviors could be better described by the models with an intermittent delayed feedback controller than by those with the conventional continuous delayed feedback controller, suggesting that the human CNS stabilizes the upright posture of the pendulum by utilizing the intermittent delayed feedback-control strategy