Many technical solutions are bio-inspired. Octopus-inspired robotic arms belong to continuum robots which are used in minimally invasive surgery or for technical system restoration in areas difficult-to-access. Continuum robot missions are bounded with their motions, whereby the motion of the robots is controlled by humans via wireless communication. In case of a lost connection, robot autonomy is required. Distributed control and distributed decision-making mechanisms based on artificial intelligence approaches can be a promising solution to achieve autonomy of technical systems and to increase their resilience. However these methods are not well investigated yet. Octopuses are the living example of natural distributed intelligence but their learning and decision-making mechanisms are also not fully investigated and understood yet. Our major interest is investigating mechanisms of Distributed Artificial Intelligence as a basis for improving resilience of complex systems. We decided to use a physical continuum robot prototype that is able to perform some basic movements for our research. The idea is to research how a technical system can be empowered to combine movements into sequences of motions by itself. For the experimental investigations a suitable physical prototype has to be selected, its motion control has to be implemented and automated. In this paper, we give an overview combining different fields of research, such as Distributed Artificial Intelligence and continuum robots based on 98 publications. We provide a detailed description of the basic motion control models of continuum robots based on the literature reviewed, discuss different aspects of autonomy and give an overview of physical prototypes of continuum robots.
Adenosine triphosphate (ATP) is well-known as a universal source of energy in living cells. Less known is that this molecule has a variety of important signaling functions: it activates a variety of specific metabotropic (P2Y) and ionotropic (P2X) receptors in neuronal and non-neuronal cell membranes. So, a wide variety of signaling functions well fits the ubiquitous presence of ATP in the tissues. Even more ubiquitous are protons. Apart from the unspecific interaction of protons with any protein, many physiological processes are affected by protons acting on specific ionotropic receptors—acid-sensing ion channels (ASICs). Both protons (acidification) and ATP are locally elevated in various pathological states. Using these fundamentally important molecules as agonists, ASICs and P2X receptors signal a variety of major brain pathologies. Here we briefly outline the physiological roles of ASICs and P2X receptors, focusing on the brain pathologies involving these receptors.
Acid-sensing ion channels (ASICs) play a key role in the perception and response to extracellular acidification changes. These proton-gated cation channels are critical for neuronal functions, like learning and memory, fear, mechanosensation and internal adjustments like synaptic plasticity. Moreover, they play a key role in neuronal degeneration, ischemic neuronal injury, seizure termination, pain-sensing, etc. Functional ASICs are homo or heterotrimers formed with (ASIC1–ASIC3) homologous subunits. ASIC1a, a major ASIC isoform in the central nervous system (CNS), possesses an acidic pocket in the extracellular region, which is a key regulator of channel gating. Growing data suggest that ASIC1a channels are a potential therapeutic target for treating a variety of neurological disorders, including stroke, epilepsy and pain. Many studies were aimed at identifying allosteric modulators of ASIC channels. However, the regulation of ASICs remains poorly understood. Using all available crystal structures, which correspond to different functional states of ASIC1, and a molecular dynamics simulation (MD) protocol, we analyzed the process of channel inactivation. Then we applied a molecular docking procedure to predict the protein conformation suitable for the amiloride binding. To confirm the effect of its sole active blocker against the ASIC1 state transition route we studied the complex with another MD simulation run. Further experiments evaluated various compounds in the Enamine library that emerge with a detectable ASIC inhibitory activity. We performed a detailed analysis of the structural basis of ASIC1a inhibition by amiloride, using a combination of in silico approaches to visualize its interaction with the ion pore in the open state. An artificial activation (otherwise, expansion of the central pore) causes a complex modification of the channel structure, namely its transmembrane domain. The output protein conformations were used as a set of docking models, suitable for a high-throughput virtual screening of the Enamine chemical library. The outcome of the virtual screening was confirmed by electrophysiological assays with the best results shown for three hit compounds.
8 January 2024 in Frontiers in Cellular Neuroscience
The issue of pain management is one of the key challenges in modern medicine. Among the methods of pain relief, pharmacotherapy plays a significant role, relying on the use of a wide range of analgesic agents. Modern pharmacology necessitates the development of innovative pain-relief drugs that are more effective, non-toxic, safe for health, and convenient to use. The process of developing new pharmaceuticals includes stages of design, synthesis, and testing of molecules. Analysis of experimental data obtained during the study of pain-relieving agents provides better insights into the molecular mechanisms of pain. Various research methods are employed for a detailed study of analgesic effects and the molecular mechanisms underlying nociceptive sensitivity. These approaches include testing the effects of analgesic agents on nociceptive responses induced by chemical, thermal, and mechanical stimuli. Fundamental, screening and applied research requires researchers to maintain maximum objectivity in obtaining results, taking into account all factors that may influence their recording and interpretation. This study aims to describe the most commonly used methods in research laboratories for testing skin nociceptive sensitivity. These include electrophysiological studies of the soma of cultured neurons in vitro, recordings of afferent activity in vivo and ex vivo, and methods for studying pain behavior in animals. The study also includes a list and analysis of factors to consider when interpreting experimental data in pharmacological research, aiding in selecting an appropriate methodological approach for investigating the chosen mechanism of sensory sensitivity.