Mind-body problem : does complexity exist objectively?

Complexity and related phenomena exist as at least as “objective” and primary aspects/elements of the world as matter, space, and time. On the other hand, space, time, and matter become more and more subjective in modern physics. Complexity causes “something new” to emerge at the level of the whole complex system, which is not present at the level of the elements of this system and cannot be fully reduced to the interactions between these elements. This fact concerns both simple systems, such as atoms composed of a nucleus and electrons or (macro)molecules composed of atoms, as well as very complex systems such as living individuals built of (macro)molecules, organelles, cells, and organs, and conscious brains composed of networks of neurons. In other words, the dynamic complexity consisting of a special concrete spatiotemporal organisation of matter/ energy is as real as space, time, and matter themselves. Therefore, one can speak about the “objective” existence of such a “subjective” phenomenon as (self-)consciousness. The last phenomenon constitutes an aspect, epiphenomenon, or “by-product” of the functional complexity of the (part of the) neural network in the human brain. Self-)consciousness is equivalent to a certain kind of such complexity and must emerge as a necessary aspect of an appropriately organised dynamic neural network. Therefore, for instance, zombies cannot exist or are even nonsensical. Each dynamic state of the neural network underling self-consciousness is univocally related to one psychic state, and inversely. It is postulated that the mind-body problem can be explained/resolved by a special kind of complexity, which consists of recurrent self-reference, directing on itself the “cognitive centre” in the neural network in the human brain

Philosophy of conceptual network

The article formulates the philosophy of a conceptual network and defines a concept as a unit of meaning. According to the proposed idea, the substance of our mind (subjective psyche) is constituted by a conceptual network which is composed of continuous concepts which have meanings through connotation. The conceptual network is an epiphenomenon of the neural network that is based on a dynamic structure of a complex of neurons interconnected in a functional way. Language is a secondary phenomenon in relation to the conceptual network: the words of language correspond to the best-distinguished concepts, and their meaning is determined by their conceptual “lining”. The conceptual networks of logic, mathematics and, especially, philosophy are not perfectly determined and specified. The “Absolute Truth” not only does not exist, but in fact it does not have any sense. Self-) consciousness emerged as a result of recurrent self-reference of the neural/conceptual network

Mechanisms underlying extremely fast muscle V˙O2 on-kinetics in humans.

The time constant of the primary phase of pulmonary V˙O2 on-kinetics (τp ), which reflects muscle V˙O2 kinetics during moderate-intensity exercise, is about 30 s in young healthy untrained individuals, while it can be as low as 8 s in endurance-trained athletes. We aimed to determine the intramuscular factors that enable very low values of t0.63 to be achieved (analogous to τp , t0.63 is the time to reach 63% of the V˙O2 amplitude). A computer model of oxidative phosphorylation (OXPHOS) in skeletal muscle was used. Muscle t0.63 was near-linearly proportional to the difference in phosphocreatine (PCr) concentration between rest and work (ΔPCr). Of the two main factors that determine t0.63 , a huge increase in either OXPHOS activity (six- to eightfold) or each-step activation (ESA) of OXPHOS intensity (>3-fold) was needed to reduce muscle t0.63 from the reference value of 29 s (selected to represent young untrained subjects) to below 10 s (observed in athletes) when altered separately. On the other hand, the effect of a simultaneous increase of both OXPHOS activity and ESA intensity required only a twofold elevation of each to decrease t0.63 below 10 s. Of note, the dependence of t0.63 on OXPHOS activity and ESA intensity is hyperbolic, meaning that in trained individuals a large increase in OXPHOS activity and ESA intensity are required to elicit a small reduction in τp . In summary, we postulate that the synergistic action of elevated OXPHOS activity and ESA intensity is responsible for extremely low τp (t0.63 ) observed in highly endurance-trained athletes

Regulation of oxidative phosphorylation is different in electrically- and cortically-stimulated skeletal muscle

A computer model of the skeletal muscle bioenergetic system was used to study the regulation of oxidative phosphorylation (OXPHOS) in electrically-stimulated and cortically-stimulated skeletal muscle. Two types of the dependence of the intensity of each-step activation (ESA) of OXPHOS complexes on ATP usage activity were tested: power-type dependence and saturating-type dependence. The dependence of muscle oxygen consumption ([Formula: see text]), phosphocreatine (PCr), cytosolic ADP, ATP, inorganic phosphate (Pi), pH and τp (characteristic transition time) of the principal component of the muscle [Formula: see text] on-kinetics on the ATP usage activity was simulated for both types of the ESA intensity-ATP usage activity dependence. Computer simulations involving the power-type dependence predict system properties that agree well with experimental data for electrically-stimulated muscle. On the other hand, model predictions for the saturating-type dependence in the presence of the 'additional' ATP usage (postulated previously to underlie the slow component of the VO2 on-kinetics) reproduce well system properties encountered in human skeletal muscle during voluntary exercise. It is postulated that the difference between the regulation and kinetic properties of the system in electrically- and cortically-stimulated muscle is mostly due to the different muscle fibers recruitment pattern. In the former, all fiber types are recruited in parallel already at low power output (PO) values, while in the latter type I fibers (with higher ESA intensity) are stimulated at low PO values, while type II fibers (especially type II b and IIx fibers) with low ESA intensity are recruited predominantly at high PO values

Mechanisms of attenuation of pulmonary V'O_{2} slow component in humans after prolonged endurance training

In this study we have examined the effect of prolonged endurance training program on the pulmonary oxygen uptake (V'O2 ) kinetics during heavy-intensity cycling-exercise and its impact on maximal cycling and running performance. Twelve healthy, physically active men (mean\ub1SD: age 22.33\ub11.44 years, V'O2peak 3198\ub1458 mL \ub7 min-1 ) performed an endurance training composed mainly of moderate-intensity cycling, lasting 20 weeks. Training resulted in a decrease (by 3c5%, P = 0.027) in V'O2 during prior low-intensity exercise (20 W) and in shortening of \u3c4 p of the V'O2 on-kinetics (30.1\ub15.9 s vs. 25.4\ub11.5 s, P = 0.007) during subsequent heavy-intensity cycling. This was accompanied by a decrease of the slow component of V'O2 on-kinetics by 49% (P = 0.001) and a decrease in the end-exercise V'O2 by 3c5% (P = 0.005). An increase (P = 0.02) in the vascular endothelial growth factor receptor 2 mRNA level and a tendency (P = 0.06) to higher capillary-to-fiber ratio in the vastus lateralis muscle were found after training (n = 11). No significant effect of training on the V'O2peak was found (P = 0.12). However, the power output reached at the lactate threshold increased by 19% (P = 0.01). The power output obtained at the V'O2peak increased by 14% (P = 0.003) and the time of 1,500-m performance decreased by 5% (P = 0.001). Computer modeling of the skeletal muscle bioenergetic system suggests that the training-induced decrease in the slow component of V'O2 on-kinetics found in the present study is mainly caused by two factors: an intensification of the each-step activation (ESA) of oxidative phosphorylation (OXPHOS) complexes after training and decrease in the "additional" ATP usage rising gradually during heavy-intensity exercise

Philosophical Basis and Some Historical Aspects of Systems Biology: From Hegel to Noble - Applications for Bioenergetic Research

We live in times of paradigmatic changes for the biological sciences. Reductionism, that for the last six decades has been the philosophical basis of biochemistry and molecular biology, is being displaced by Systems Biology, which favors the study of integrated systems. Historically, Systems Biology - defined as the higher level analysis of complex biological systems - was pioneered by Claude Bernard in physiology, Norbert Wiener with the development of cybernetics, and Erwin Schrödinger in his thermodynamic approach to the living. Systems Biology applies methods inspired by cybernetics, network analysis, and non-equilibrium dynamics of open systems. These developments follow very precisely the dialectical principles of development from thesis to antithesis to synthesis discovered by Hegel. Systems Biology opens new perspectives for studies of the integrated processes of energy metabolism in different cells. These integrated systems acquire new, system-level properties due to interaction of cellular components, such as metabolic compartmentation, channeling and functional coupling mechanisms, which are central for regulation of the energy fluxes. State of the art of these studies in the new area of Molecular System Bioenergetics is analyzed

Application of the Principles of Systems Biology and Wiener’s Cybernetics for Analysis of Regulation of Energy Fluxes in Muscle Cells in Vivo

The mechanisms of regulation of respiration and energy fluxes in the cells are analyzed based on the concepts of systems biology, non-equilibrium steady state kinetics and applications of Wiener’s cybernetic principles of feedback regulation. Under physiological conditions cardiac function is governed by the Frank-Starling law and the main metabolic characteristic of cardiac muscle cells is metabolic homeostasis, when both workload and respiration rate can be changed manifold at constant intracellular level of phosphocreatine and ATP in the cells. This is not observed in skeletal muscles. Controversies in theoretical explanations of these observations are analyzed. Experimental studies of permeabilized fibers from human skeletal muscle vastus lateralis and adult rat cardiomyocytes showed that the respiration rate is always an apparent hyperbolic but not a sigmoid function of ADP concentration. It is our conclusion that realistic explanations of regulation of energy fluxes in muscle cells require systemic approaches including application of the feedback theory of Wiener’s cybernetics in combination with detailed experimental research. Such an analysis reveals the importance of limited permeability of mitochondrial outer membrane for ADP due to interactions of mitochondria with cytoskeleton resulting in quasi-linear dependence of respiration rate on amplitude of cyclic changes in cytoplasmic ADP concentrations. The system of compartmentalized creatine kinase (CK) isoenzymes functionally coupled to ANT and ATPases, and mitochondrial-cytoskeletal interactions separate energy fluxes (mass and energy transfer) from signalling (information transfer) within dissipative metabolic structures – intracellular energetic units (ICEU). Due to the non-equilibrium state of CK reactions, intracellular ATP utilization and mitochondrial ATP regeneration are interconnected by the PCr flux from mitochondria. The feedback regulation of respiration occurring via cyclic fluctuations of cytosolic ADP, Pi and Cr/PCr ensures metabolic stability necessary for normal function of cardiac cells