The aim of this paper is to compare various methods for the quantification of metabolic pathways dynamics. A Yates-Pardee metabolic pathway with enzyme organization, i.e. with spatial localization of the enzymes in a specific cellular compartment, was studied using: (i) the classical Henri-Michaelis-Menten (HMM) equations, (ii) linearization of the HMM equations in the vicinity of a steady state (linearized formalism), and (iii) Biochemical Systems Theory formalism (BST formalism). It is shown that transient solutions computed via either the (...) linearized formalism or the BST formalism can greatly differ from transient solutions computed with the HMM equations. However, in the studied example, results remain qualitatively the same for the three formalisms. This suggests that the study of the topology of the system may give useful insights into the metabolic pathways dynamics. (shrink)

This paper examines three exemplary theories of living organization with respect to their common feature of defining life in terms of metabolic closure: autopoiesis, systems, and chemoton theory. Metabolic closure is broadly understood to denote the property of organized chemical systems that each component necessary for the maintenance of the system is produced from within the system itself, except for an input of energy. It is argued that two of the theories considered—autopoiesis and systems—participate in a hylomorphist (...) pattern of thinking which separates the “form” of the living system from its “matter.” The analysis and critique of hylomorphism found in the work of the philosopher Gilbert Simondon is then applied to these two theories, and on the basis of this critique it is argued that the chemoton model offers a superior theory of minimal life which overcomes many of the problems associated with the other two. Throughout, the relationship between hylomorphism and the understanding of living things as machines is explored. The paper concludes by considering how hylomorphism as a background ontology for theories of life fundamentally influences the way life is defined. (shrink)

The goal of synthetic biology is to create artificial organisms. To achieve this it is essential to understand what life is. Metabolism-replacement systems, or (M, R)-systems, constitute a theory of life developed by Robert Rosen, characterized in the statement that organisms are closed to efficient causation, which means that they must themselves produce all the catalysts they need. This theory overlaps in part with other current theories, including autopoiesis, the chemoton, and autocatalytic sets, all of them invoking some idea of (...) closure. A simple model of an (M, R)-system has been implemented in the computer, and behaves in ways that may shed light on the requirements for a prebiotic self-organizing system. In addition to a trivial steady state in which nothing happens, it can establish a non-trivial steady state in which all intermediates have finite concentrations, with their rates of degradation balanced by their rates of synthesis. The system can be regenerated from the set of food components plus a single intermediate, and maintain itself in that state indefinitely, despite continuous degradation. At the very low compartment volumes that may have existed in prebiotic conditions, for example in cavities in minerals, or in micelles formed by simple amphiphiles, statistical fluctuations in the numbers of molecules need to be taken into account. With the stochastic approach there is no non-trivial steady state in strict mathematical terms, because the system will always collapse to the trivial state after sufficient time. However, the average time before collapse is so long for volumes greater than $10^{-19}\;{\textsc{l}}$ (much smaller than the volume of the order of $10^{-15}\;{\textsc{l}}$ for a typical bacterial cell) that for practical purposes the self-maintaining state of non-null concentrations becomes significant, recalling the situation of bistability that is observed in deterministic analysis. In turn, there exists a minimum size below which the self-organizing system cannot maintain itself on chemically relevant time scales. The value of the critical volume depends on the particular concentrations and rate constants assumed, but the principle could apply generally. (shrink)

The aim of this paper is to provide a theoretical framework to understand how multicellular systems realize functionally integrated physiological entities by organizing their intercellular space. From a perspective centered on physiology and integration, biological systems are often characterized as organized in such a way that they realize metabolic self-production and self-maintenance. The existence and activity of their components rely on the network they realize and on the continuous management of the exchange of matter and energy with their environment. (...) One of the virtues of the organismic approach focused on organization is that it can provide an understanding of how biological systems are functionally integrated into coherent wholes. Organismic frameworks have been primarily developed by focusing on unicellular life. Multicellularity, however, presents additional challenges to our understanding of biological systems, related to how cells are capable to live together in higher-order entities, in such a way that some of their features and behaviors are constrained and controlled by the system they realize. Whereas most accounts of multicellularity focus on cell differentiation and increase in size as the main elements to understand biological systems at this level of organization, we argue that these factors are insufficient to provide an understanding of how cells are physically and functionally integrated in a coherent system. In this paper, we provide a new theoretical framework to understand multicellularity, capable to overcome these issues. Our thesis is that one of the fundamental theoretical principles to understand multicellularity, which is missing or underdeveloped in current accounts, is the functional organization of the intercellular space. In our view, the capability to be organized in space plays a central role in this context, as it enables (and allows to exploit all the implications of) cell differentiation and increase in size, and even specialized functions such as immunity. We argue that the extracellular matrix plays a crucial active role in this respect, as an evolutionary ancient and specific (non-cellular) control subsystem that contributes as a key actor to the functional specification of the multicellular space and to modulate cell fate and behavior. We also analyze how multicellular systems exert control upon internal movement and communication. Finally, we show how the organization of space is involved in some of the failures of multicellular organization, such as aging and cancer. (shrink)

The premise of biological modularity is an ontological claim that appears to come out of practice. We understand that the biological world is modular because we can manipulate different parts of organisms in ways that would only work if there were discrete parts that were interchangeable. This is the foundation of the BioBrick assembly method widely used in synthetic biology. It is one of a number of methods that allows practitioners to construct and reconstruct biological pathways and devices using DNA (...) libraries of standardized parts with known functions. In this paper, we investigate how the practice of synthetic biology reconfigures biological understanding of the key concepts of modularity and evolvability. We illustrate how this practice approach takes engineering knowledge and uses it to try to understand biological organization by showing how the construction of functional parts and processes can be used in synthetic experimental evolution. We introduce a new approach within synthetic biology that uses the premise of a parts-based ontology together with that of organismal self-organization to optimize orthogonal metabolic pathways in E. coli. We then use this and other examples to help characterize semisynthetic categories of modularity, parthood, and evolvability within the discipline. (shrink)

Let us start by some general definitions of the concept of complexity. We take a complex system to be one composed by a large number of parts, and whose properties are not fully explained by an understanding of its components parts. Studies of complex systems recognized the importance of “wholeness”, defined as problems of organization (and of regulation), phenomena non resolvable into local events, dynamics interactions in the difference of behaviour of parts when isolated or in higher configuration, etc., (...) in short, systems of various orders (or levels) not understandable by investigation of their respective parts in isolation. In a complex system it is essential to distinguish between ‘global’ and ‘local’ properties. Theoretical physicists in the last two decades have discovered that the collective behaviour of a macro-system, i.e. a system composed of many objects, does not change qualitatively when the behaviour of single components are modified slightly. Conversely, it has been also found that the behaviour of single components does change when the overall behaviour of the system is modified. There are many universal classes which describe the collective behaviour of the system, and each class has its own characteristics; the universal classes do not change when we perturb the system. The most interesting and rewarding work consists in finding these universal classes and in spelling out their properties. This conception has been followed in studies done in the last twenty years on second order phase transitions. The objective, which has been mostly achieved, was to classify all possible types of phase transitions in different universality classes and to compute the parameters that control the behaviour of the system near the transition (or critical or bifurcation) point as a function of the universality class. This point of view is not very different from the one expressed by Thom in the introduction of Structural Stability and Morphogenesis (1975). It differs from Thom’s program because there is no a priori idea of the mathematical framework which should be used. Indeed Thom considers only a restricted class of models (ordinary differential equations in low dimensional spaces) while we do not have any prejudice regarding which models should be accepted. One of the most interesting and surprising results obtained by studying complex systems is the possibility of classifying the configurations of the system taxonomically. It is well-known that a well founded taxonomy is possible only if the objects we want to classify have some unique properties, i.e. species may be introduced in an objective way only if it is impossible to go continuously from one specie to another; in a more mathematical language, we say that objects must have the property of ultrametricity. More precisely, it was discovered that there are conditions under which a class of complex systems may only exist in configurations that have the ultrametricity property and consequently they can be classified in a hierarchical way. Indeed, it has been found that only this ultrametricity property is shared by the near-optimal solutions of many optimization problems of complex functions, i.e. corrugated landscapes in Kauffman’s language. These results are derived from the study of spin glass model, but they have wider implications. It is possible that the kind of structures that arise in these cases is present in many other apparently unrelated problems. Before to go on with our considerations, we have to pick in mind two main complementary ideas about complexity. (i) According to the prevalent and usual point of view, the essence of complex systems lies in the emergence of complex structures from the non-linear interaction of many simple elements that obey simple rules. Typically, these rules consist of 0–1 alternatives selected in response to the input received, as in many prototypes like cellular automata, Boolean networks, spin systems, etc. Quite intricate patterns and structures can occur in such systems. However, what can be also said is that these are toy systems, and the systems occurring in reality rather consist of elements that individually are quite complex themselves. (ii) So, this bring a new aspect that seems essential and indispensable to the emergence and functioning of complex systems, namely the coordination of individual agents or elements that themselves are complex at their own scale of operation. This coordination dramatically reduces the degree of freedom of those participating agents. Even the constituents of molecules, i.e. the atoms, are rather complicated conglomerations of subatomic particles, perhaps ultimately excitations of patterns of superstrings. Genes, the elementary biochemical coding units, are very complex macromolecular strings, as are the metabolic units, the proteins. Neurons, the basic elements of cognitive networks, themselves are cells. In those mentioned and in other complex systems, it is an important feature that the potential complexity of the behaviour of the individual agents gets dramatically simplified through the global interactions within the system. The individual degrees of freedom are drastically reduced, or, in a more formal terminology, the factual space of the system is much smaller than the product of the state space of the individual elements. That is one key aspect. The other one is that on this basis, that is utilizing the coordination between the activities of its members, the system then becomes able to develop and express a coherent structure at a higher level, that is, an emergent behaviour (and emergent properties) that transcends what each element is individually capable of. (shrink)

In this chapter we offer a critical analysis of organizational models about the process of origins of life and, thereby, a reflection about life itself (understood in a general, minimal sense). We begin by demarcating the idea of organization as an explanatory construct, linking it to the complex relationships and transformations that the material parts of (proto-)biological systems establish to maintain themselves under non-equilibrium dynamic conditions. The diverse ways in which this basic idea has been applied within the prebiotic (...) field are then reviewed in relative detail. We distinguish between “network” and “protocell” approaches, discussing their specific implications and explaining the greater relevance of the latter in the current state of affairs. Despite the key role that such organizational approaches play (and should keep playing) to advance on the problem of primordial biogenesis, the second half of our contribution is devoted to argue that they must be combined with other explanatory accounts, which go beyond the physiology of any single (proto-)organism. With that aim, we underline the fundamental differences between the autonomous, metabolic dynamics that individual (proto-)cells perform and the evolutionary and ecological dynamics that take place in a collective and trans-generational dimension. Apart from obvious gaps in the characteristic temporal and spatial scales involved, the corresponding causal and interactive regimes also reveal themselves as neatly distinct, what is reflected in the unpaired functional integration and the agent behavior displayed by biological individuals. Nevertheless, any living organism (and life in a wider, general sense) derives from the deep interweaving of those two phenomenological domains: namely, the “individual-metabolic” and the “collective-evolutionary” domains. At the end of the chapter, we propose the principle of dynamical decoupling as the core idea to develop a more comprehensive theoretical framework to understand how this intricate, causally asymmetric connection must be articulated during the actual process of biogenesis (as it happened here on Earth or anywhere else in the universe), so that life’s minimal complexity threshold is reached. (shrink)

The metabolic organization of both normal and malignant prostate cellular phenotypes involves some unusual and surprising features. In particular, both conditions exhibit ratios of NADH/NAD+ and NADPH/NADP+ charactersitic of high oxidative states despite a chronic shortage of O2 in both conditions. In this paper, we observe that, in prostate cancer cells, the oxidizing power of the fatty acid synthesis (FAS) pathway is so large that redox is stabilized more favorably (more oxidized) than in normal prostate cells. This FAS‐facilitated (...) redox improvement occurs despite the fact that malignant cells are more O2 limited and therefore express more hypoxia inducible factor 1 (HIF1) and express hypoxia‐regulated genes more robustly. This unusual metabolic situation clearly separates direct regulatory effects of redox balance from secondary effects of hypoxia per se. The physiological significance of the FAS pathway is thus the harnessing of its oxidizing power for improving redox balance despite conditions of more extreme hypoxia. Similar hypoxia defense strategies are found in animal species that are unusually tolerant to oxygen lack. Our hypothesis is that the metabolic organization in the “low zinc, low citrate” phenotype reflects an hypoxia‐defense adaptation geared toward redox balance, with prostate cancer cells being relatively more oxidized, even if more hypoxic, than normal prostate cells. Recognition and understanding of these redox balancing and hypoxia defense functions may lead to new intervention strategies by developing new intracellular targets for prostate cancer therapy. BioEssays 24:749–757, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

This book is a selection of papers from a conference which took place at the University of Keele in July 1982. The conference was an extraordinarily enjoyable one, and we would like to take this opportunity of thanking all participants for helping to make it so. The conference was intended to allow scholars working on different aspects of symbolic behaviour to compare findings, to look for common ground, and to identify differences between the various areas. We hope that it was (...) successful in these aims: the assiduous reader may judge for himself. Several themes emerged during the course of the conference. Some of these were: 1. There is a distinction to be made between those symbol systems which attempt, more or less directly, to represent a state of affairs in the world (e. g. language, drawing, map and navigational skill) and those in which the representational function is complemented, if not overshadowed, by properties of the symbol system itself, and the systematic inter-relations that symbols can have to one another (e. g. music, mathematics). The distinction is not absolute, for the nature of all symbolic skills is, in part, a function of the structure of the symbolic system employed. Nonetheless, this distinction helps us to understand some common acquisition difficulties, such as that experienced in mathematics, where mental manipulation of symbols can go awry if a child assumes too close a correspondence between mathematical symbols and the world they represent. 2. (shrink)

In this article, we propose some fundamental requirements for the appearance of adaptivity. We argue that a basic metabolic organization, taken in its minimal sense, may provide the conceptual framework for naturalizing the origin of teleology and normative functionality as it appears in living systems. However, adaptivity also requires the emergence of a regulatory subsystem, which implies a certain form of dynamic decoupling within a globally integrated, autonomous system. Thus, we analyze several forms of minimal adaptivity, including the (...) special case of motility. We go on to explain how an open-ended complexity growth of motility-based adaptive agency, namely, behavior, requires the appearance of the nervous system. Finally, we discuss some implications of these ideas for embodied robotics. (shrink)

Diffusion theory explains in physical terms how materials move through a medium, e.g. water or a biological fluid. There are strong and widely acknowledged grounds for doubting the applicability of this theory in biology, although it continues to be accepted almost uncritically and taught as a basis of both biology and medicine. Our principal aim is to explore how this situation arose and has been allowed to continue seemingly unchallenged for more than 150 years. The main shortcomings of diffusion theory (...) will be briefly reviewed to show that the entrenchment of this theory in the corpus of biological knowledge needs to be explained, especially as there are equally valid historical grounds for presuming that bulk fluid movement powered by the energy of cell metabolism plays a prominent note in the transport of molecules in the living body. First, the theory's evolution, notably from its origins in connection with the mechanistic materialist philosophy of mid nineteenth century physiology, is discussed. Following this, the entrenchment of the theory in twentieth century biology is analyzed in relation to three situations: the mechanism of oxygen transport between air and mammalian tissues; the structure and function of cell membranes; and the nature of the intermediary metabolism, with its implicit presumptions about the intracellular organization and the movement of molecules within it. In our final section, we consider several historically based alternatives to diffusion theory, all of which have their precursors in nineteenth and twentieth century philosophy of science. (shrink)

The logic of genetic discovery has changed little over time, but the focus of biology is shifting from simple genotype–phenotype relationships to complex metabolic, physiological, developmental, and behavioral traits. In light of this, the traditional reductionist view of individual genes as privileged difference‐making causes of phenotypes is re‐examined. The scope and nature of genetic effects in complex regulatory systems, in which dynamics are driven by regulatory feedback and hierarchical interactions across levels of organization are considered. This review argues (...) that it is appropriate to treat genes as specific actual difference‐makers for the molecular regulation of gene expression. However, they are often neither stable, proportional, nor specific as causes of the overall dynamic behavior of regulatory networks. Dynamical models, properly formulated and validated, provide the tools to probe cause‐and‐effect relationships in complex biological systems, allowing to go beyond the limitations of genetic reductionism to gain an integrative understanding of the causal processes underlying complex phenotypes. (shrink)

The search for a systems‐level picture of metabolism as a web of molecular interactions provides a paradigmatic example of how the methods used to characterize a system can bias the interpretation of its functional meaning. Metabolic maps have been analyzed using novel techniques from network theory, revealing some non‐trivial, functionally relevant properties. These include a small‐world structure and hierarchical modularity. However, as discussed here, some of these properties might actually result from an inappropriate way of defining network interactions. Starting (...) from the so‐called bipartite organization of metabolism, where the two meaningful subsets (reactions and metabolites) are considered, most current works use only one of the subsets by means of so‐called graph projections. Unfortunately, projected graphs often ignore relevant biological and chemical constraints, thus leading to statistical artifacts. Some of these drawbacks and alternative approaches need to be properly addressed. (shrink)

We critique the organizational account of biological functions by showing how its basis in the closure of constraints fails to be objective. While the account treats constraints as objective features of physical systems, the number and relationship of potential constraints are subject to potentially arbitrary redescription by investigators. For example, we show that self-maintaining systems such as candle flames can realize closure on a more thorough analysis of the case, contradicting the claim that these “simple” systems lack functional organization. (...) This also raises problems for Moreno and Mossio’s associated theory of biological autonomy, which asserts that living beings are distinguished by their possession of a closed system of constraints that channel and regulate their metabolic processes. (shrink)

Most conceptual models of the organization of the cardiovascular system begin with the premise that the nervous system regulates the metabolic and nonmetabolic reflex adjustments of the circulation. These models assume that all the neurally mediated responses of the circulation are reactive, i.e., reflexes elicited by adequate stimuli. This target article suggests that the responses of the circulation are conditional in three senses. First, as Sherrington argued, reflexes are conditional in that they never operate in a vacuum but (...) in a context together with other reflexes. Guided by functional utility, they interact rather than add. Second, as Pavlov argued, stimuli acquire meanings as a result of experience. This notion of stimulus effect plus the Sherringtonian notion of conditionality suggest that association is one of the ways stimuli eliciting cardiovascular reflexes acquire their meanings and thus their relative strengths. Finally, as Skinner and others have argued, operants are responses that act upon the environment to obtain consequences – that is, stimuli. As operants, cardiovascular responses fulfill a major biological need, functioning proactively. The cardiovascular response is an integral component of the animal's behavior regardless of whether it is an elicited reflex or the eliciting stimulus acquired its properties as a result of the genetic inheritance of the animal or through experience, or the cardiovascular response is emitted in anticipation of an environmental consequence. The main theses of this essay are: (1) behavior is an integrated set of responses and the circulation is one of the response systems comprising behavior; (2) behavior is, in part, determined by its functional significance within a context; (3) the contextual factors operative at the time of the behavior have a major role in determining which of the set of possible responses will determine the final act, that is, which behavior will be the effective response and which other behaviors will be concomitants. (shrink)

In this short contribution we explore the historical roots of recent synthetic approaches in biology and try to assess their real potential, as well as identify future hurdles or the reasons behind some of the main difficulties they currently face. We suggest that part of these difficulties might not be just the result of our present lack of adequate technical skills or understanding, but could spring directly from the nature of the biological phenomenon itself. In particular, if life is conceived (...) as autonomy in open-ended evolution, which would help to explain the highly complex and dynamic organization of the simplest known organisms (i.e., genetically-instructed cellular metabolisms), external synthetic implementations of such systems, or interventions on them, are bound to interfere with some of their characteristic transformation processes, both at the ontogenetic and phylogenetic scales. In any case, this will prove very revealing and productive, technologically and scientifically speaking, since the knowledge gathered from those implementations/interventions will be extremely valuable in establishing our capacities and limitations to fully comprehend, utilize, and expand the living domain as we know it today. (shrink)

Life is a self-maintaining process based on metabolism. Something is said to be alive when it exhibits organization and is actively involved in its own continued existence through carrying out metabolic processes. A life is a spatio-temporally restricted event, which continues while the life processes are occurring in a particular chunk of matter (or, arguably, when they are temporally suspended, but can be restarted at any moment), even though there is continuous replacement of parts. Life is organized in (...) discrete packages, particular cells and multicellular organisms with differing degrees of individuality. Biological species, too, have been shown to be individuals, and not classes, as these collections of organisms are spatio-temporally localized, restricted, continuous, and somewhat cohesive entities, with a definite beginning and end. Assuming that all life on Earth has a common origin, all living organisms, cells, and tissues descending from this origin exhibit continuity of the life processes at the cellular level, as well as many of the features that define the individual character of species: spatio-temporal localization and restriction, continuity, historicity, and cohesiveness. Therefore, life on Earth is an ontological individual. Independent origins of life will have produced other such individuals. These provisionally called ‘life-individuals’ constitute a category of organization of life which has seldom been recognized. The discovery of at least one independent life-individual would go a long way toward the project of the universality of biology. (shrink)

This paper reinforces the current consensus against the applicability of the selected effect theory of function in ecology. It does so by presenting an argument which, in contrast with the usual argument invoked in support of this consensus, is not based on claims about whether ecosystems are customary units of natural selection. Instead, the argument developed here is based on observations about the use of the function concept in functional ecology, and more specifically, research into the relationship between biodiversity and (...) ecosystem functioning. It is argued that a selected effect account of ecological functions is made implausible by the fact that it would conflict with important aspects of the understanding of function and ecosystem functional organization which underpins functional ecology’s research program. Specifically, it would conflict with (1) Functional ecology’s adoption of a context-based understanding of function and its aim to study the functional equivalence between phylogenetically-divergent organisms; (2) Functional ecology’s attribution to ecosystems of a lower degree of part-whole integration than the one found in paradigm individual organisms; and (3) Functional ecology’s adoption of a physiological or metabolic perspective on ecosystems rather than an evolutionary one. (shrink)

Revonsuo argues that current brain imaging methods do not allow us to ‘discover’ consciousness. While all observational methods in science have limitations, consciousness is such a massive and pervasive phenomenon that we cannot fail to observe its effects at every level of brain organization: molecular, cellular, electrical, anatomical, metabolic, and even the ‘higher levels of electrophysiological organization that are crucial for the empirical discovery and theoretical explanation of consciousness’ . Indeed, the first major discovery in that respect (...) was Hans Berger's finding that scalp EEG is massively different between waking and deep sleep, already seven decades ago. We now have perhaps a dozen sophisticated methods for monitoring consciousness-related activity at multiple levels of brain observation. Theoretical progress has come quite rapidly. Recently, E.R. John and colleagues have made fundamental findings using Quantitative EEG, showing consistent brainwide changes as a result of several types of general anaesthetics . John has proposed a neuronal ‘field theory’ to account for those results. Another promising new method involves frequency-tagging of competing stimuli, allowing us to follow the activity of billions of neurons synchronized to particular conscious stimuli, always compared to very similar unconscious input . A fundamental theoretical account of such results has been provided by Tononi & Edelman . Such results and theory are in broad agreement with the cognitive theory proposed by Baars. (shrink)

Darwinian evolution can be simply stated: natural selection of inherited variations increasing differential reproduction. However, formulated thus, links with biochemistry, cell biology, ecology, and population dynamics remain unclear. To understand interactive contributions of chance and selection, higher levels of biological organization (e.g., endosymbiosis), complexities of competing selection forces, and emerging biological novelties (such as eukaryotes or meiotic sex), we must analyze actual examples. Focusing on mitochondria, I will illuminate how biology makes sense of life's evolution, and the concepts involved. (...) First, looking at the bacterium – mitochondrion transition: merging with an archaeon, it lost its independence, but played a decisive role in eukaryogenesis, as an extremely efficient aerobic ATP generator and internal ROS source. Second, surveying later mitochondrion adaptations and diversifications illustrates concepts such as constructive neutral evolution, dynamic interactions between endosymbionts and hosts, the contingency of life histories, and metabolic reprogramming. Without oxygen, mitochondria disappear; with (intermittent) oxygen diversification occurs in highly complex ways, especially upon (temporary) phototrophic substrate supply. These expositions show the Darwinian model to be a highly fruitful paradigm. (shrink)

In this paper we review and argue for the relevance of the concept of open-ended evolution in biological theory. Defining it as a process in which a set of chemical systems bring about an unlimited variety of equivalent systems that are not subject to any pre-determined upper bound of organizational complexity, we explain why only a special type of self-constructing, autonomous systems can actually implement it. We further argue that this capacity derives from the ‘dynamic decoupling’ (in its minimal or (...) most basic sense: the phenotype–genotype decoupling) by means of which a radically new way of material organization (minimal living organization) is achieved, allowing for the long-term sustenance of systems whose individual-metabolic and collective-historical pathways become thereafter deeply intertwined. (shrink)

Cognition in living entities—and their social groupings or institutional artifacts—is necessarily as complicated as their embedding environments, which, for humans, includes a particularly rich cultural milieu. The asymptotic limit theorems of information and control theories permit construction of a new class of empirical ‘regression-like’ statistical models for cognitive developmental processes, their dynamics, and modes of dysfunction. Such models may, as have their simpler analogs, prove useful in the study and re-mediation of cognitive failure at and across the scales and levels (...) of organization that constitute and drive the phenomena of life. These new models particularly focus on the roles of sociocultural environment and stress, in a large sense, as both trigger for the failure of the regulation of bio-cognition and as ‘riverbanks’ determining the channels of pathology, with implications across life-course developmental trajectories. We examine the effects of an embedding cultural milieu and its socioeconomic implementations using the ‘lenses’ of metabolic optimization, control system theory, and an extension of symmetry-breaking appropriate to information systems. A central implication is that most, if not all, human developmental disorders are fundamentally culture-bound syndromes. This has deep implications for both individual treatment and public health policy. (shrink)

Scale-free network models describe many natural and social phenomena. In particular, networks of interacting components of a living cell were shown to possess scale-free properties. A recent study(1) compares the system-level properties of metabolic and information networks in 43 archaeal, bacterial and eukaryal species and claims that the scale-free organization of these networks is more conserved during evolution than their content. BioEssays 24:105–109, 2002. Published 2002 Wiley Periodicals, Inc.

The vast majority (> 95%) of single-gene mutations in yeast affect not only the expression of the mutant gene, but also the expression of many other genes. These data suggest the presence of a previously uncharacterized ‘gene expression network’—a set of interactions between genes which dictate gene expression in the native cell environment. Here, we quantitatively analyze the gene expression network revealed by microarray expression data from 273 different yeast gene deletion mutants.(1) We find that gene expression interactions form a (...) robust, error-tolerant ‘scale-free’ network, similar to metabolic pathways(2) and artificial networks such as power grids and the internet.(3-5) Because the connectivity between genes in the gene expression network is unevenly distributed, a scale-free organization helps make organisms resistant to the deleterious effects of mutation, and is thus highly adaptive. The existence of a gene expression network poses practical considerations for the study of gene function, since most mutant phenotypes are the result of changes in the expression of many genes. Using principles of scale-free network topology, we propose that fragmenting the gene expression network via ‘genome-engineering’ may be a viable and practical approach to isolating gene function. BioEssays 24:267–274, 2002. © 2002 Wiley Periodicals, Inc.; DOI 10.1002/bies.10054. (shrink)

After more than a century of research on glycolysis, we have detailed descriptions of its molecular organization, but despite this wealth of knowledge, linking the enzyme properties to metabolic pathway behavior remains challenging. These challenges arise from multi‐layered regulation and the context and time dependence of component functions. However, when viewed as a system that functions according to the principles of supply and demand, a simplifying theoretical framework can be applied to study its regulation logic and to assess (...) the coherence of experimental interpretations. These principles are universally applicable, as they emphasize the common metabolic tasks of glycolysis: the provision of free‐energy carriers, and precursors for biosynthesis and stress‐related compounds. Here we will review the regulation of multi‐tasking by glycolysis and consider how an understanding of this central metabolic pathway can be pursued using general principles, rather than focusing on the biochemical details of constituent components. (shrink)

The subject of the presentation was to reveal the main components of the views of Rev. Włodzimierz Sedlak (31.10.1911-17.02.1993) concerning the origin of life. The development of these views passed through the following stages: 1) the theory of silicic life forms (1959-1967) which he labeled \"the theory of siliconides\", 2) the bioelectronic model of abiogenesis (1967-1988), and 3) speculations about electromagnetic biogenesis. The basic claims of the theory of silicic life forms are the following: (a) silicon is an essential component (...) of biosystems and fulfils significant roles in phylogenetically older forms of life; (b) the previous essential role of silicon in the organization of life has been reduced in higher organisms to the role of a microelement; (c) the attempts at the reconstruction of the chemical evolution of life should be undertaken, to extend it beyond the organic compounds of carbon, namely to those containing silicon and forming the most primitive forms of life on the Earth; (d) hypothetic silicic organisms made up the most primitive life on the Earth.. The main theses of bioelectronic model of abiogenesis are the following: (a) there exists the coupling between chemical reactions and electronic processes in organisms (he calls it \"the quantum seam of life\"); photons act as a coupling factor between these two classes of processes; (b) the existence the such coupling makes the generation and duration of the plasma state of particles possible in all metabolizing parts of the organism; (c) there exists bioplasma - a new state of matter - that is characteristic for living organisms only; (d) the first act of the creation of the chemical-electronic coupling is to be regarded as equivalent with biogenesis: (e) bioplasma existed well before the macroscopic organic morphological structures were formed and functioned already when the life was based on aluminosilicates. Sedlak\'s speculation on the electromagnetic biogenesis implies that the evolution of biosphere began with the moment of birth of light, i.e. in one of the earliest phases of existence of Universe. God, identified by him with the Light, created life, possessing the luminous nature. Life never altered its electromagnetic foundation: either at any new stage, or at a new level of organization, or when the first human being was created. It seems that Sedlak\'s works can be valuable for the present and future investigations aimed at the reconstruction of biogenesis. Although they are undervalued now, they should be regarded as containing many valuable intuitions. They deserve a thorough analysis and - where it is possible - empirical testing of implications drawn from them. (shrink)

In this article I suggest how we might conceptualize some kind of artificial consciousness as an ultimate development of Artificial Life. This entity will be embodied in some sort of constructed (biological or non-biological) body. The contention is that consciousness within self-organized entities is not only possible but inevitable. The basic sensory and interactive processes by which an organism operates within an environment are such as to be the basic processes that are necessary for consciousness. I then look at likely (...) criteria for consciousness, and point to an architecture of the cognitive which maps onto the physiological layer, the brain. While evolutionary algorithms and neural nets will be at the heart of the production of artificial intelligences there is a particular architectural organization that may be necessary in the production of conscious artefacts. This involves the operations of multiple layers of feedback loops in the anatomy of the brain, in the social construction of the contents of consciousness and in particular in the self-regulation necessary for the continued operation of metabolically organized systems. Finally I make some comments on the ethics of such a procedure. (shrink)

In this paper I suggest how we might conceptualize some kind of artificial consciousness as an ultimate development of Artificial Life. This entity will be embodied in some sort of constructed (biological or non-biological) body. The contention is that consciousness within self-organized entities is not only possible but inevitable. The basic sensory and interactive processes by which an organism operates within an environment are such as to be the basic processes that are necessary for consciousness. I then look at likely (...) criteria for consciousness, and point to an architecture of the cognitive which maps onto the physiological layer, the brain. While evolutionary algorithms and neural nets will be at the heart of the production of artificial intelligences there is a particular architectural organization that may be necessary in the production of conscious artefacts. This involves the operations of multiple layers of feedback loops in the anatomy of the brain, in the social construction of the contents of consciousness and in particular in the self-regulation necessary for the continued operation of metabolically organized systems. Finally I make some comments on the ethics of such a procedure. (shrink)

The cognitive and behavioral functions of the frontal lobes have been of great interest to neuroscientists, neurologists, psychologists and psychiatrists. Recent technical advances have made it possible to trace their neuroanatomical connections more precisely and to conduct evoked potential and neuroimaging studies in patients. This book presents a broad and authoritative synthesis of research progress in this field. It encompasses neuroanatomical studies; experiments involving temporal organization and working memory tasks in non-human primates; clinical studies of patients following frontal lobe (...) excisions for intractable epilepsy; metabolic imaging in schizophrenia and affective disorder; neurobehavioral studies of patients with dementia, frontal lobe tumors, and head injuries; magnetic resonance imaging methods for studying human frontal lobe anatomy; theoretical approaches to describing frontal lobe functions; and rehabilitation of patients with frontal lobe damage including their core problem of diminished awareness. Written by a distinguished group of neuroscientists, psychologists and clinicians, Frontal Lobe Function and Dysfunction provides the best current source of information on this region of the brain and its role in cognition, behavior and clinical disorders. (shrink)

The coronavirus disease-2019 pandemic impacted the lives of children and adolescents, leading to many changes in their routines, especially in education. Face-to-face physical education classes during COVID-19 were affected in organization, possibly conditioning students' participation, motivation, and learning. In the extreme conditions of the coronavirus, it may be assumed that daily physical activity became much less than before, partly because students are learning outside the school environment and PE lessons taught using remote forms do not fulfill their purpose. The (...) aim of the study was to assess the pupil's perception of inclusion in school education during the remote learning caused by the COVID-19 pandemic and to compare the results with the control group. Moreover, the physical activity of respondents during social isolation due to the coronavirus was examined. The sample consisted of 111 pupils of both genders, aged 14–21 years. The Perceptions of Inclusion Questionnaire was used to measure the perception of inclusion in school education. The structure of the participants' physical activity was examined using the International Physical Activity Questionnaire-Long Form for adolescents. It was observed that the pupils' gender did not differentiate their perception of inclusion in school education. It was proved that respondents participating in research during the COVID-19 pandemic obtained statistically significantly lower results in the case of “emotional wellbeing in school” but a higher mean was observed in relation to “social relationships with other pupils” than the control group. Girls achieved a higher mean in the case of walk Metabolic Equivalent of Task than boys. In addition, it was observed that the recommendation of vigorous physical activities was achieved by 37.78% of boys and 34.85% of girls. In turn, 69.70% of female pupils and 77.78% of male respondents met the recommendations for medium physical activities. It was also noted that 87.88% of girls and 86.67% of boys participating in the research achieved the recommendation for total physical activities. The analysis showed negligible and low positive correlations between examined variables. (shrink)

How should we conceptualize direct action against climate change? Although direct action is an increasingly significant tactic by the global climate movement, we lack understanding how direct action contributes to the systemic change necessary for addressing the crisis. Drawing upon critical theories of climate change as a crisis in the social reproduction of the metabolic relations between humans and nature in capitalism, I conceptualize direct action as attempts to intervene directly in the organization of the social metabolism, towards (...) reorganizing these relations in a more socially just and ecologically sustainable manner. My framework thus expands and clarifies the scope and potential of direct action as a means of confronting the capitalist climate crisis, as evidenced by Greta Thunberg’s school strike for climate. (shrink)

Whipple disease is a rare, infectious, disease first described from a single case by Whipple in 1907. As well as characterising the clinical and pathological features of the condition, Whipple made two suggestions regarding its aetiology. These were either than the disease was caused by an infectious agent, or that it was of metabolic origin. As the disease is now thought to be caused by infection with the bacterium Tropheryma whipplei, historical reviews of the history of the disease typically (...) mention only the first of these suggestions. In this paper, we therefore revisit Whipple’s other theory. We argue that a diverse and often successful research programme was developed around this mechanism of disease causation which gave rise to many useful findings on the condition. In the later parts of this article, we then turn to discuss the surprising neglect of this period of Whipple disease research in the current literature, and conclude by offering a brief reconstruction of this early history suitable for use in a technical context. (shrink)

When an agent can not recognize, immediately, the implausible part of new information received, she will usually first expand her belief state by the new information, and then she may encounter some belief conflicts, and find the implausible information based on her criteria to consolidate her belief state. This process indicates a new kind of non-prioritized multiple revision, called metabolic revision. I give some axiomatic postulates for metabolic revision and propose two functional constructions for it, namely kernel (...) class='Hi'>metabolic revision and partial meet metabolic revision, with respect to which the representation theorems are proved. I also compare metabolic revision with some related works in the literature, including semi-revision, merging with integrity constraints, evaluation, and evaluative multiple revision. (shrink)

The reprogramming of metabolism has been identified as one of the hallmarks of cancer. It is becoming more and more frequent to connect other diseases with metabolic reprogramming. This article aims to argue that metabolic reprogramming is not driven by disease but instead is the main hallmark of metabolism, based on its dynamic behavior that allows it to continuously adapt to changes in the internal and external conditions.

I consider the case of the “simplest” living beings—bacteria—and examine how their embodied activity constitutes an organism/environment interaction, out of which emerges the possibility of learning from an environment. I suggest that this mutual co-emergence of organism and environment implies a panbiotic educational interaction that is at once the condition for, and achievement of, all living beings. Learning and being learned from are entangled in varied ways throughout the biosphere. Education is not an exclusively human project, it is part of (...) the ancient evolutionary process of elaborating and diversifying the relational possibilities inherent in metabolism that has brought forth our diverse and flourishing world.ed from context, “education” appears as a set of ways in which humans actively engage and take responsibility for the learning outcomes of relationships with each other. Insofar as we consider this distinction absolute rather than a performed construct to be assessed by its consequences, we blind ourselves to the educative dimension of other species as well as our many miseducative engagements with them. If learning processes are inherent and constitutive of ecological communities, education theorists should devote their pedagogical sensitivities and insights to the crucial challenge of developing educative sustainable human–nature relations. (shrink)

The definition of metabolic syndrome has been, and still is, extremely controversial. My purpose is not to give a solution to the associated debate but to argue that the controversy is at least partially due to the different ‘causal content’ of the various definitions: their theoretical validity and practical utility can be evaluated by reconstructing or making explicit the underlying causal structure. I will therefore propose to distinguish the alternative definitions according to the kinds of causal content they carry: (...) definitions grounded on associations, definitions presupposing a causal model built upon statistical associations, and definitions grounded on underlying mechanisms. I suggest that analysing definitions according to their causal content can be helpful in evaluating alternative definitions of some diseases. I want to show how the controversy over MetS suggests a distinction among three kinds of definitions based on how explicitly they characterise the syndrome in causal terms, and on the type of causality involved. I will call ‘type 1 definitions’ those definitions that are purely associative; ‘type 2 definitions’ the definitions based on statistical associations, plus generic medical and causal knowledge; and ‘type 3 definitions’ the definitions based on mechanisms. These kinds of definitions, although different, can be related to each other. A definition with more specific causal content may be useful in the evaluation of definitions characterised by a lower degree of causal specificity. Moreover, the identification of the type of causality involved is of help to constitute a good criterion for choosing among different definitions of a pathological entity. In section I introduce the controversy about MetS, in section I propose some remarks about medical definitions and their ‘causal import’, and in section I suggest that the different attitudes towards the definition of MetS are relevant to evaluate their explicative power. (shrink)

In the flowering of Red-Green Thought over the past two decades, metabolic rift thinking is surely one of its most colorful varieties. The metabolic rift has captured the imagination of critical environmental scholars, becoming a shorthand for capitalism’s troubled relations in the web of life. This article pursues an entwined critique and reconstruction: of metabolic rift thinking and the possibilities for a post-Cartesian perspective on historical change, the world-ecology conversation. Far from dismissing metabolic rift thinking, my (...) intention is to affirm its dialectical core. At stake is not merely the mode of explanation within environmental sociology. The impasse of metabolic rift thinking is suggestive of wider problems across the environmental social sciences, now confronted by a double challenge. One of course is the widespread—and reasonable—sense of urgency to evolve modes of thought appropriate to an era of deepening biospheric instability. The second is the widely recognized—but inadequately internalized—understanding that humans are part of nature. (shrink)

Introduction -- Organization, society and politics -- An Aristotelian perspective -- The politics -- The public good -- The rhetoric -- Talk and texts -- The Nichomachean ethics -- Decision making and ethics -- The Poetics -- Bolshevism to ballet in three steps -- What is "public interest"?: a case study -- Where do we go from here?

Many kinds of multifunctional regulatory proteins have been identified that perform distinct biochemical functions in the nucleus, the cytoplasm, or both. Here we describe the recent discovery by Hall et al. (2004)1 of a new type of multifunctional protein: a metabolic enzyme that doubles as a transcription factor. This enzyme, Arg5,6, functions as a catalytic enzyme in ornithine biosynthesis and also binds and regulates the promoters of nuclear and mitochondrial genes. It may also regulate precursor mRNA metabolism. We discuss (...) how proteins that serve as both metabolic enzymes and transcription factors might have evolved. BioEssays 27:467–471, 2005. © 2005 Wiley Periodicals, Inc. (shrink)