The first aim of simulation in virtual environment is to help biologists to have a better understanding of the simulated system. The cost of such simulation is significantly reduced compared to that of in vivo simulation. However, the inherent complexity of biological system makes it hard to simulate these systems on non-parallel architectures: models might be made of sub-models and take several scales into account; the number of simulated entities may be quite large. Today, graphics cards are used for (...) general purpose computing which has been made easier thanks to frameworks like CUDA or OpenCL. Parallelization of models may however not be easy: parallel computer programing skills are often required; several hardware architectures may be used to execute models. In this paper, we present the software architecture we built in order to implement various models able to simulate multi-cellular system. This architecture is modular and it implements data structures adapted for graphics processing units architectures. It allows efficient simulation of biological mechanisms. (shrink)

Ranging from miniaturized biological robots to organoids, multi-cellular engineered living systems (M-CELS) pose complex ethical and societal challenges. Some of these challenges, such as how to best distribute risks and benefits, are likely to arise in the development of any new technology. Other challenges arise specifically because of the particular characteristics of M-CELS. For example, as an engineered living system becomes increasingly complex, it may provoke societal debate about its moral considerability, perhaps necessitating protection from harm or recognition (...) of positive moral and legal rights, particularly if derived from cells of human origin. The use of emergence-based principles in M-CELS development may also create unique challenges, making the technology difficult to fully control or predict in the laboratory as well as in applied medical or environmental settings. In response to these challenges, we argue that the M-CELS community has an obligation to systematically address the ethical and societal aspects of research and to seek input from and accountability to a broad range of stakeholders and publics. As a newly developing field, M-CELS has a significant opportunity to integrate ethically responsible norms and standards into its research and development practices from the start. With the aim of seizing this opportunity, we identify two general kinds of salient ethical issues arising from M-CELS research, and then present a set of commitments to and strategies for addressing these issues. If adopted, these commitments and strategies would help define M-CELS as not only an innovative field, but also as a model for responsible research and engineering. (shrink)

Central nervous system (CNS)Abbreviations: CNS=central nervous system; PNS=peripheral nervous system; MS=multiple sclerosis; MBP=myelin basic protein; MHC=major histocompatibility complex; EAE=experimental allergic encephalomyelitis; O‐2A=oligodendrocyte‐type 2 astrocyte; GC=galactocerebroside; GFAP=glial fibrillary acidic protein; FGF=fibroblast growth factor; IGF1=insulin‐like growth factor. regeneration is a subject of great interest, particularly in diseases causing a dramatic loss of neurons. However, some CNS diseases do not affect neurons but damage other cells, such as the myelin‐forming cells — called oligodendrocytes — which are also crucial to the harmonious function of (...) the nervous system. Diseases in which oligodendrocytes and myelin are attacked can cause devastating neurological dysfunction which is sometimes followed by recovery and myelin repair or remyelination. The question of the regeneration potential of oligodendrocytes in experimental and human demyelinating diseases such as multiple sclerosis has been debated for a long time. Present evidence suggests that oligodendrocyte precursor cells persist in the adult CNS and that oligodendrocyte regeneration can occur but may be limited by ongoing disease processes. Here we will briefly review recent advances which have broadened our understanding of the cellular and molecular events of CNS remyelination. (shrink)

It is argued that once biological systems reach a certain level of complexity, mechanistic explanations provide an inadequate account of many relevant phenomena. In this article, I evaluate such claims with respect to a representative programme in systems biological research: the study of regulatory networks within single-celled organisms. I argue that these networks are amenable to mechanistic philosophy without need to appeal to some alternate form of explanation. In particular, I claim that we can understand the mathematical modelling (...) techniques of systems biologists as part of a broader practice of constructing and evaluating mechanism schemas. This argument is elaborated by considering the case of bacterial chemotactic networks, where some research has been interpreted as explaining phenomena by means of abstract design principles. (shrink)

In some recent papers (G. ‘t Hooft and others), it has been argued that quantum mechanics can arise from classical cellular automata. Nonetheless, G. Shpenkov has proved that the classical wave equation makes it possible to derive a periodic table of elements, which is very close to Mendeleyev’s one, and describe also other phenomena related to the structure of molecules. Hence the classical wave equation complements Schrödinger’s equation, which implies the appearance of a cellular automaton molecular model starting (...) from classical wave equation. The other studies show that the microworld is constituted as a tessellation of primary topological balls. The tessellattice becomes the origin of a submicrospic mechanics in which a quantum system is subdivided to two subsystems: the particle and its inerton cloud, which appears due to the interaction of the moving particle with oncoming cells of the tessellattice. The particle and its inerton cloud periodically change the momentum and hence move like a wave. The new approach allows us to correlate the Klein-Gordon equation with the deformation coat that is formed in the tessellatice around the particle. The submicroscopic approach shows that the source of any type of wave movements including the Klein-Gordon, Schrödinger, and classical wave equations is hidden in the tessellattice and its basic exciations – inertons, carriers of mass and inert properies of matter. We also discuss possible correspondence with Konrad Zuse’s calculating space. (shrink)

The sodium cotransport systems comprise an important group of transport proteins which are involved in the transport of a variety of organic and inorganic solutes across the cellular membrane of animal cells. These systems play a central role in a wide variety of cellular and biochemical processes. We summarize here the current state of knowledge regarding the variety, structure and regulation of this important group of membrane proteins.

Novel cellular therapy techniques promise to cure many haematology patients refractory to other treatment modalities. These therapies are intensive and require referral to and care from specialised providers. In the USA, this pool of providers is not expanding at a rate necessary to meet expected demand; therefore, access scarcity appears forthcoming and is likely to be widespread. To maintain fair access to these scarce and curative therapies, we must prospectively create a just and practical system to distribute care. In (...) this article, we first review previously implemented medical product and personnel allocation systems, examining their applicability to cellular therapy provider shortages to demonstrate that this problem requires a novel approach. We then present an innovative system for allocating cellular therapy access, which accounts for the constraints of distribution during real-world oncology practice by using a combination of the following principles: maximising life-years per personnel time, youngest and robust first, sickest first, first come/first served and instrumental value. We conclude with justifications for the incorporation of these principles and the omission of others, discuss how access can be distributed using this combination, consider cost and review fundamental factors necessary for the practical implementation and maintenance of this system. (shrink)

Selective protein degradation maintains cellular homeostasis, but this process is disrupted in many diseases. Targeted protein degradation (TPD) approaches, built upon existing cellular mechanisms, are promising methods for therapeutically regulating protein levels. Here, we review the diverse palette of tools that are now available for doing so throughout the gene expression pathway and in specific cellular compartments. These include methods for directly removing targeted proteins via the ubiquitin proteasome system with proteolysis targeting chimeras (PROTACs) or dephosphorylation targeting (...) chimeras (DEPTACs). Similar effects can also be achieved through the lysosomal system with autophagy‐targeting chimeras (AUTACs), autophagosome tethering compounds (ATTECs), and lysosome targeting chimeras (LYTACs). Other methods act upstream to degrade RNAs (ribonuclease targeting chimeras; RIBOTACs) or transcription factors (transcription factor targeting chimeras; TRAFTACs), offering control throughout the gene expression process. We highlight the evolution and function of these methods and discuss their clinical implications in diverse disease contexts. (shrink)

The controversy of neuroanatomy on the principal structure of the nervous systems, which took place at the end of the nineteenth century, is described. Two groups of scientists are identified: one that favoured the idea of a discrete cellular organization of the nervous tissue, and one that favoured a syncytial organization. These two interpretations arose from different histological techniques that produced conflicting pictures of the organization of the nervous tissue. In an experimental reexamination of the techniques used at (...) the end of the nineteenth century, the present study concerns the impact of these different histological procedures on the controversy about the principle nature of the nervous tissue. This controversy could not be resolved by neuroanatomy itself until the 1950s when electron microscopy was introduced into neurobiology. Thus, in a critical period of the conceptual development of neurosciences, neuroanatomy failed to establish a proper base for an interpretation of the functional morphology of nervous tissues. (shrink)

Cellular automata (henceforth: CA) are discrete, abstract computational systems that have proved useful both as general models of complexity and as more specific representations of non-linear dynamics in a variety of scientific fields. Firstly, CA are (typically) spatially and temporally discrete: they are composed of a finite or denumerable set of homogeneous, simple units, the atoms or cells. At each time unit, the cells instantiate one of a finite set of states. They evolve in parallel at discrete time (...) steps, following state update functions or dynamical transition rules: the update of a cell state obtains by taking into account the states of cells in its local neighborhood (there are, therefore, no actions at a distance). Secondly, CA are abstract, as they can be specified in purely mathematical terms and implemented in physical structures. Thirdly, CA are computational systems: they can compute functions and solve algorithmic problems. Despite functioning in a different way from traditional, Turing machine-like devices, CA with suitable rules can emulate a universal Turing machine, and therefore compute, given Turing's Thesis, anything computable.... (shrink)

Feedback loops have been identified in a variety of regulatory systems and organisms. While feedback loops of the same type (negative or positive) tend to have properties in common, they can play distinctively diverse roles in different regulatory systems, where they can affect virulence in a pathogenic bacterium, maturation patterns of vertebrate oocytes and transitions through cell cycle phases in eukaryotic cells. This review focuses on the properties and functions of positive feedback in biological systems, including bistability, (...) hysteresis and activation surges. BioEssays 30:542–555, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

We present a distributed control modeling approach for an automated manufacturing system based on the dynamics of one-dimensional cellular automata. This is inspired by the fact that both cellular automata and manufacturing systems are discrete dynamical systems where local interactions given among their elements can lead to complex dynamics, despite the simple rules governing such interactions. The cellular automaton model developed in this study focuses on two states of the resources of a manufacturing system, namely, (...) busy or idle. However, the interaction among the resources such as whether they are shared at different stages of the manufacturing process determines the global dynamics of the system. A procedure is shown to obtain the local evolution rule of the automaton based on the relationships among the resources and the material flow through the manufacturing process. The resulting distributed control of the manufacturing system appears to be heterarchical, and the evolution of the cellular automaton exhibits a Class II behavior for some given disordered initial conditions. (shrink)

Morphogenesis is a key process in developmental biology. An important issue is the understanding of the generation of shape and cellular organisation in tissues. Despite of their great diversity, morphogenetic processes share common features. This work is an attempt to describe this diversity using the same formalism based on a cellular description. Tissue is seen as a multi-cellular system whose behaviour is the result of all constitutive cells dynamics. Morphogenesis is then considered as a spatiotemporal organization of (...) cells activities. We show how this formalism relies on Reaction–Diffusion/Positional Information approach and how it permits to generalize its modelling possibilities. Three quite different applications for concrete morphogenetic processes are presented. The first one is a model for epithelial invagination, the second is a model of cellular differentiation by local cell–cell signalling. The last example is the secondary radial growth of conifer trees. From the mathematical point of view, different modelling tools are used according to the specificity of each process. (shrink)

This book presents the deterministic view of quantum mechanics developed by Nobel Laureate Gerard 't Hooft. Dissatisfied with the uncomfortable gaps in the way conventional quantum mechanics meshes with the classical world, 't Hooft has revived the old hidden variable ideas, but now in a much more systematic way than usual. In this, quantum mechanics is viewed as a tool rather than a theory. The book presents examples of models that are classical in essence, but can be analysed by the (...) use of quantum techniques, and argues that even the Standard Model, together with gravitational interactions, might be viewed as a quantum mechanical approach to analysing a system that could be classical at its core. He shows how this approach, even though it is based on hidden variables, can be plausibly reconciled with Bell's theorem, and how the usual objections voiced against the idea of 'superdeterminism' can be overcome, at least in principle. This framework elegantly explains - and automatically cures - the problems of the wave function collapse and the measurement problem. Even the existence of an "arrow of time" can perhaps be explained in a more elegant way than usual. As well as reviewing the author's earlier work in the field, the book also contains many new observations and calculations. It provides stimulating reading for all physicists working on the foundations of quantum theory. (shrink)

Depression might be associated with accelerated cellular aging. However, does this result in an irreversible state or is the body able to slow down or recover from such a process? Telomeres are DNA‐protein complexes that protect the ends of chromosomes and generally shorten with age; and therefore index cellular aging. The majority of studies indicate that persons with depression have shorter leukocyte telomeres than similarly aged non‐depressed persons, which may contribute to the observed unfavorable somatic health outcomes in (...) the depressed population. Some small‐scale preliminary studies raise the possibility that behavioral or pharmacological interventions may either slow down or else reverse this accelerated telomere shortening, possibly through increasing the activity of the telomere‐lengthening enzyme telomerase. This paper covers the current state of evidence in the relationship between depression and the telomere‐telomerase system and debates whether depression‐related cellular aging should be considered a reversible process or permanent damage. (shrink)

The study of cellular senescence and proliferative lifespan is becoming increasingly important because of the promises of autologous cell therapy, the need for model systems for tissue disease and the implication of senescent cell phenotypes in organismal disease states such as sarcopenia, diabetes and various cancers, among others. Here, we explain the concepts of proliferative cellular lifespan and cellular senescence, and we present factors that have been shown to mediate cellular lifespan positively or negatively. We (...) review much recent literature and present potential molecular mechanisms by which lifespan mediation occurs, drawing from the fields of telomere biology, metabolism, NAD+ and sirtuin biology, growth factor signaling and oxygen and antioxidants. We conclude that cellular lifespan and senescence are complex concepts that are governed by multiple independent and interdependent pathways, and that greater understanding of these pathways, their interactions and their convergence upon specific cellular phenotypes may lead to viable therapies for tissue regeneration and treatment of age‐related pathologies, which are caused by or exacerbated by senescent cells in vivo. (shrink)

The establishment of a functional vascular system requires multiple complex steps throughout embryogenesis, from endothelial cell (EC) specification to vascular patterning into venous and arterial hierarchies. Following the initial assembly of ECs into a network of cord‐like structures, vascular expansion and remodeling occur rapidly through morphogenetic events including vessel sprouting, fusion, and pruning. In addition, vascular morphogenesis encompasses the process of lumen formation, critical for the transformation of cords into perfusable vascular tubes. Studies in mouse, zebrafish, frog, and human endothelial (...) cells have begun to outline the cellular and molecular requirements underlying lumen formation. Although the lumen can be generated through diverse mechanisms, the coordinated participation of multiple conserved molecules including transcription factors, small GTPases, and adhesion and polarity proteins remains a fundamental principle, leading us closer to a more thorough understanding of this complex event. (shrink)

The capacity of cells and organisms to respond to external stimuli and to maintain stability in order to survive decreases progressively during ageing. The mitogenic and stimulatory effects of growth factors, hormones and other agents are reduced significantly during cellular ageing. The sensitivity of ageing cells to toxic agents including antibiotics, phorbol esters, radiations and heat shock increases. This failure of homeostasis during cellular ageing does not appear to be due to any quantitative and qualitative defects in the (...) receptor systems. Instead, metabolic defects in the pathways of macromolecular synthesis may be the basis of altered cellular responsiveness during ageing. (shrink)

The molecular cloning of new neuroactive growth factors and their receptors has greatly enhanced our understanding of important interactions among receptors and singnaling molecules. These studies have begun to illuminate some of the mechanisms that allow for specificity in neuronal signaling. Model cell systems, such as the PC‐12 pheochromocytoma cell line, express receptors for these different neurotirophic factors, leading to comparisons of signaling pathways for these factors. Upon binding their ligands, these receptors undergo phosphorylation on tyrosine residues, which directs (...) their interaction with signaling proteins containing src homology (SH2) domains, sequences that mediate associations with tyrosine‐phosphorylated proteins. These SH2 proteins translate the tyrosine kinase activity of receptors into downstream events that result in the specific cellular response. Investigations such as these have revealed that molecular specificity in signaling pathways may arise from combinatorial diversity in interactions between receptors and key regulatory proteins. (shrink)

Oxycholesterols (OS) are formed from cholesterol or its immediate precursors by enzymatic or free radical action in vivo, or they may be derived from food. OS exhibit a wide spectrum of biological activities. In OS cytotoxicity, several mechanisms seem to be involved: e.g. inhibition of HMG‐CoA reductase activity, antiproliferative action, apoptosis induction, replacement of cholesterol by OS in membranes followed by changes in cellular membrane structure and functionality, and immune system functions alteration. Furthermore, OS may be mutagenic and carcinogenic (...) and may serve as intracellular signaling or regulatory molecules. Here we review OS cellular activities with special attention to the cytotoxic action in vivo and in vitro using experimental models. BioEssays 28: 387–398, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Recent successes of systems biology clarified that biological functionality is multilevel. We point out that this fact makes it necessary to revise popular views about macromolecular functions and distinguish between local, physico-chemical and global, biological functions. Our analysis shows that physico-chemical functions are merely tools of biological functionality. This result sheds new light on the origin of cellular life, indicating that in evolutionary history, assignment of biological functions to cellular ingredients plays a crucial role. In this wider (...) picture, even if aggregation of chance mutations of replicator molecules and spontaneously self-assembled proteins led to the formation of a system identical with a living cell in all physical respects but devoid of biological functions, it would remain an inanimate physical system, a pseudo-cell or a zombie-cell but not a viable cell. In the origin of life scenarios, a fundamental circularity arises, since if cells are the minimal units of life, it is apparent that assignments of cellular functions require the presence of cells and vice versa. Resolution of this dilemma requires distinguishing between physico-chemical and biological symbols as well as between physico-chemical and biological information. Our analysis of the concepts of symbol, rule and code suggests that they all rely implicitly on biological laws or principles. We show that the problem is how to establish physico-chemically arbitrary rules assigning biological functions without the presence of living organisms. We propose a solution to that problem with the help of a generalized action principle and biological harnessing of quantum uncertainties. By our proposal, biology is an autonomous science having its own fundamental principle. The biological principle ought not to be regarded as an emergent phenomenon. It can guide chemical evolution towards the biological one, progressively assigning greater complexity and functionality to macromolecules and systems of macromolecules at all levels of organization. This solution explains some perplexing facts and posits a new context for thinking about the problems of the origin of life and mind. (shrink)

This article reviews recent findings that bear on the mechanism(s) of tumor‐specific Lyt‐1+2− T cell‐mediated tumor eradication in vivo A tumor‐immune Lyt‐1+2− T cell subset has been identified which is distinct from T cells mediating in vitro cytotoxicity (Lyt‐1+2+/1−2+). The Lyt‐1+2− cells have a crucial role in rejecting tumor cells when adoptively transferred into T cell‐deprived B cell mice. This indicates that Lyt‐1+2− T cells do not necessarily require recruitment of the host's cytotoxic T cell precursors for implementation of in (...) vivo immunity. Instead, this T cell subset exerts its anti‐tumor effect in collaboration with macrophages as shown with an in vivo tumor cell culture system utilizing a diffusion chamber. A pathway of Lyt‐1+2− T cell‐macrophage interaction leading to tumor cell killing is discussed in terms of its probable relevance to the eradication of tumor cell masses consisting of tumor cells expressing quantitatively and/or qualitatively different tumor antigens. (shrink)

In this paper I explore the question of how artificial life might be used to get a handle on philosophical issues concerning the mind-body problem. I focus on questions concerning what the physical precursors were to the earliest evolved versions of intelligent life. I discuss how cellular automata might constitute an experimental platform for the exploration of such issues, since cellular automata offer a unified framework for the modeling of physical, biological, and psychological processes. I discuss what it (...) would take to implement in a cellular automaton the evolutionary emergence of cognition from non-cognitive artificial organisms. I review work on the artificial evolution of minimally cognitive organisms and discuss how such projects might be translated into cellular automata simulations. (shrink)

Age‐related and cancer‐related epigenomic modifications have been associated with enhanced cell‐to‐cell gene expression variability that characterizes increased cellular stochasticity. Since gene expression variability appears to be highly reduced by—and epigenetic and phenotypic stability acquired through—direct or long‐range cellular interactions during cell differentiation, we propose a common origin for aging and cancer in the failure to control cellular stochasticity by cell–cell interactions. Tissue‐disruption‐induced cellular stochasticity associated with epigenetic drift would be at the origin of organ dysfunction because (...) of an increase in phenotypic variation among cells, ultimately leading to cell death and organ failure through a loss of coordination in cellular functions, and eventually to cancerization. We propose mechanistic research perspectives to corroborate this hypothesis and explore its evolutionary consequences, highlighting a positive correlation between the median age of mass loss onset (a proxy for the onset of organ aging) and the median age at cancer diagnosis. (shrink)

From its genesis in the 1960s, the focus of inquiry in neuroscience has been on the cellular and molecular processes underlying neural activity. In this pursuit neuroscience has been enormously successful. Like any successful scientific inquiry, initial successes have raised new questions that inspire ongoing research. While there is still much that is not known about the molecular processes in brains, a great deal of very important knowledge has been secured, especially in the last 50 years. It has also (...) attracted the attention of a number of philosophers, some of whom have viewed it as evidence for a ruthlessly reductionistic program that will eventually explain how mental processes are performed in the brain in purely molecular terms. As neuroscience developed, however, there emerged a smaller group of researchers who focused on systems, behavioral, and cognitive neuroscience. These investigators have also made impressive advances in the last 50 years and they have been the focus of an even larger group of philosophers, who have appealed to systems level understanding of the brain as providing the appropriate point of connection to the information processing accounts advanced in psychology. (shrink)

Constructivist biosemiotics foundations imply the first-person basis of cognition. CBF are developed by the biology of cognition, relational biology, enactive approach, ecology of mind, second order cybernetics, genetic epistemology, gestalt, ecological perception and affordances, and active inference by minimization of free energy. CBF reject the idea of an objective independent reality to be represented by information processing in order to be the fittest. CBF assumes that perception is the behavioral configuration of an object and objects are tokens for eigen-behaviors. Cognition (...) takes place in the organism-environment structural coupling during the ontogeny and phylogeny of all biological unities including unicellular organisms. Therefore, if exogenous DNA particles are just tokens for the cell signalling eigen-behaviors, if there is no ‘information’ in the DNA sequence, how can we explain that the same virus or trans- sequence is associated with a similar phenotype? We call this ‘exogenomic problem’. With this basic example, but sufficiently generic to the whole biological world, we agree respectively with Autopoiesis, -system, and Gaia theory: i) ‘Information, code and meaning’ in the DNA sequence belong to the domain of the observer’s description. ii) Genetic ‘information’ is not a program or algorithmic software in DNA sequence. Rather it is a microphysical observable mode of eigen-behaviors in biological unities. iii) The transfer and acquisition of DNA particles is a biospheric phenomenon that maintains its homeorhesis, symbiotic and biosemiotic entailment. Based on the theoretical and experimental results of these theories, it is concluded that genetic ‘information’ is not a genomic sequence, nor any kind of information, but for the cell DNA must embody physical forcing. Genetic characters are the effects and not the cause of phenotype and DNA particles do not ‘use or manipulate’ cellular metabolism. Rather, any cellular configuration change that occurred before or during DNA perturbation is determined on the basis of the cellular standpoint. (shrink)

Animals use their chemosensory systems to detect and discriminate among chemical cues in the environment. Remarkable progress has recently been made in our knowledge of the molecular and cellular basis of chemosensory perception in insects, based largely on studies in Drosophila. This progress has been possible due to the identification of gene families for olfactory and gustatory receptors, the use of electro‐physiological recording techniques on sensory neurons, the multitude of genetic manipulations that are available in this species, and (...) insights from several insect model systems. Recent studies show that the superfamily of chemoreceptor proteins represent the essential elements in chemosensory coding, endowing chemosensory neurons with their abilities to respond to specific sets of odorants, tastants or pheromones. Investigating how insects detect chemicals in their environment can show us how receptor protein structures relate to ligand binding, how nervous systems process complex information, and how chemosensory systems and genes evolve. BioEssays 28:23–34, 2006. © 2005 Wiley Periodicals, Inc. (shrink)

More than one researcher is currently proposing that the notion of information become an important element for defining living systems as well as for explaining conditions that make their origins possible. During the pre-biotic era, the type of compounds encountered would mainly have been very simple in nature and might have been immersed in the natural dynamic of the physical world and in processes of self-organization. It is furthermore quite possible that they formed a relationship between and among certain (...) types of processes that here we are specifically proposing as central for the emergence of cell organization. Consequently, an important initial step towards constructing a theory of biological information is to ask ourselves the question: how do biological systems process information? In this way, we will be contributing to the proposals of this paper where we seek to identify general principles that govern biological computing and that deal with biosemiotic approaches as they are defended in naturalistic normative terms. (shrink)

The data on the cellular mechanism of LTD that is presented in four target articles is synthesized into a new model of Purkinje cell plasticity. This model attempts to address credit assignment problems that are crucial in learning systems. Intracellular signal transduction mechanisms may provide the mechanism for a 3-factor learning rule and a trace mechanism. The latter may permit delayed information about motor error to modify the prior synaptic events that caused the error. This model may help (...) to focus future cellular studies on issues that are particularly critical for a computationally viable concept of cerebellar plasticity, [CRÉPEL et al.; HOUK et al.; KANO; LINDEN; VINCENT]. (shrink)

A conscious moment occurs when an individual is in a state of awareness of one’s self and the external environment. The human brain has been extensively studied to understand the phenomena of human thought and behavior in the context of consciousness. Consciousness has always been linked to the nervous system but there are several studies that have recorded conscious behaviours in organisms without nerve cells. This paper hypothesizes that quantum energy generated consciousness emerges in each and every living cell and (...) traverses by means of electromagnetic radiation; an oldest form of energy that exist in the cosmos and which utilizes the cellular structures to flow by means of a coherent, invisible, powerful, recyclable process; a connection with the cosmic energy bridge. (shrink)

First isolated in the fly and now characterised in vertebrates, the Slit proteins have emerged as pivotal components controlling the guidance of axonal growth cones and the directional migration of neuronal precursors. As well as extensive expression during development of the central nervous system (CNS), the Slit proteins exhibit a striking array of expression sites in non-neuronal tissues, including the urogenital system, limb primordia and developing eye. Zebrafish Slit has been shown to mediate mesodermal migration during gastrulation, while Drosophila slit (...) guides the migration of mesodermal cells during myogenesis. This suggests that the actions of these secreted molecules are not simply confined to the sphere of CNS development, but rather act in a more general fashion during development and throughout the lifetime of an organism. This review focuses on the non-neuronal activities of Slit proteins, highlighting a common role for the Slit family in cellular migration. (shrink)

Lattice-gas cellular automaton (LGCA) and lattice Boltzmann (LB) models are promising models for studying emergent behaviour of transport and interaction processes in biological systems. In this chapter, we will emphasise the use of LGCA/LB models and the derivation and analysis of LGCA models ranging from the classical example dynamics of fluid flow to clotting phenomena in cerebral aneurysms and the invasion of tumour cells.

Dimorphism in the yeast Candida albicans provides an unusually simple model system for investigating the mechanisms which regulate cellular differentiation, or cell divergence. Under the regime of pH‐regulated dimorphism, it has been demonstrated that the programs of protein synthesis accompanying bud and hypha formation are strikingly similar. Instead of dramatic differences in the repertoire of gene products possessed by bud‐ and hypha‐forming cells, subtle temporal, spatial and quantitative differences in the same architectural events appear to be basic to the (...) genesis of alternative phenotypes. This emerging story of phenotypic regulation does not exclude differential gene expression, but rather de‐emphasizes its role and underscores other mechanisms which are not generally considered. (shrink)

The concept of cell, more than any other biological concept, has been modelled on three powerful metaphors: in a morphological perspective, the cell has been defined Baustein, the brick or elementary unit of the body; from the physiological point of view, it has been associated to a chemical laboratory and finally, in a systemic view, it has been compared to the citizen of the cellular state. The pathologist Rudolf Virchow and the zoologist Ernst Haeckel showed the philosophical and aesthetic (...) potential of the latter metaphor, opening two different perspectives on a crucial problem in the science of living: the problem of the definition of biological individual. (shrink)

Teleological variations of non-deterministic processes are defined. The immediate past of a system defines the state from which the ordinary (non-teleological) dynamical law governing the system derives different possible present states. For every possible present state, again a number of possible states for the next time step can be defined, and so on. After k time steps, a selection criterion is applied. The present state leading to the selected state after k time steps is taken to be the effective present (...) state. Hence, the present state of a system is defined by its past in the sense that the past determines the possible states that are to be considered, and by its future in the sense that the selection of a possible future state determines the effective present state. A system that obeys this type of teleological dynamics may have significantly better performance than its non-teleological counterpart. The basic reason is that evolutions that are less optimal for the present time step, but which lead to a higher optimality after k time steps, may be preferred. This abstract concept of teleology is implemented for two concrete systems. First, it is applied to a general method for function approximation and classification problems. The method at issue treats all problems handled by conventional connectionism, and is suited for information with inner structure also. Second, it is applied to a dynamics in which forms of maximal homogeneity have to be produced. The relevance of the latter dynamics for generative art is illustrated. The teleology is `deep' in the sense that it is situated at the cellular level, in contradistinction with the teleology that is usually met in cognitive contexts, and which refers to macroscopic processes such as making plans. It is conjectured that deep level teleology is useful for machines, even though the issue if natural systems use this teleology is left open. (shrink)

Cellular circadian clocks represent ancient anticipatory systems which co‐evolved with the first cells to safeguard their survival. Cyanobacteria represent one of the most ancient cells, having essentially invented photosynthesis together with redox‐based cellular circadian clocks some 2.7 billion years ago. Bioelectricity phenomena, based on redox homeostasis associated electron transfers in membranes and within protein complexes inserted in excitable membranes, play important roles, not only in the cellular circadian clocks and in anesthetics‐sensitive cellular sentience (awareness of (...) environment), but also in the coupling of single cells into tissues and organs of unitary multicellular organisms. This integration of cellular circadian clocks with cellular basis of sentience is an essential feature of the cognitive CBC‐Clock basis of cellular life. (shrink)

Causal Bayes nets (CBNs) can be used to model causal relationships up to whole mechanisms. Though modelling mechanisms with CBNs comes with many advantages, CBNs might fail to adequately represent some biological mechanisms because—as Kaiser (2016) pointed out—they have problems with capturing relevant spatial and structural information. In this paper we propose a hybrid approach for modelling mechanisms that combines CBNs and cellular automata. Our approach can incorporate spatial and structural information while, at the same time, it comes with (...) all the merits of a CBN representation of mechanisms. (shrink)

Cellular circuits have positive and negative feedback loops that allow them to respond properly to noisy external stimuli. It is intriguing that such feedback loops exist in many cases in a particular form of coupled positive and negative feedback loops with different time delays. As a result of our mathematical simulations and investigations into various experimental evidences, we found that such coupled feedback circuits can rapidly turn on a reaction to a proper stimulus, robustly maintain its status, and immediately (...) turn off the reaction when the stimulus disappears. In other words, coupled feedback loops enable cellular systems to produce perfect responses to noisy stimuli with respect to signal duration and amplitude. This suggests that coupled positive and negative feedback loops form essential signal transduction motifs in cellular signaling systems. BioEssays 29: 85–90, 2007. © 2006 Wiley Periodicals, Inc. (shrink)

Evolutionary systems biology (ESB) is a rapidly growing integrative approach that has the core aim of generating mechanistic and evolutionary understanding of genotype‐phenotype relationships at multiple levels. ESB's more specific objectives include extending knowledge gained from model organisms to non‐model organisms, predicting the effects of mutations, and defining the core network structures and dynamics that have evolved to cause particular intracellular and intercellular responses. By combining mathematical, molecular, and cellular approaches to evolution, ESB adds new insights and methods (...) to the modern evolutionary synthesis, and offers ways in which to enhance its explanatory and predictive capacities. This combination of prediction and explanation marks ESB out as a research manifesto that goes further than its two contributing fields. Here, we summarize ESB via an analysis of characteristic research examples and exploratory questions, while also making a case for why these integrative efforts are worth pursuing. (shrink)

In Amerindian ontologies, hallucinations or visions, rather than being dismissed as delusions or symbolic constructs, are recognized as means of perceptual access to physical reality. Lowland South American shamans claim to be able to diagnose and treat infectious diseases, and to assess the status of wildlife resources through interactions with pathogenic agents perceived in visions. This essay examines some perceptual capabilities that shamans might be employing to explore their physical reality. The structure of the eye affords a form of microscopy (...) of retinal structures and of objects flowing within them, including cells and microbial agents during systemic infection. Lowland South American shamanic practices involve optical and physiological conditions that optimize entoptic microscopy. Images of those visions display the characteristic features of shadow formation, confirming their microscopic origin. This phenomenological access to the microscopic world and similarities with the panorama depicted by current microbiology indicate the commensurability of these forms of knowledge. (shrink)

Cells are cognitive entities possessing great computational power. DNA serves as a multivalent information storage medium for these computations at various time scales. Information is stored in sequences, epigenetic modifications, and rapidly changing nucleoprotein complexes. Because DNA must operate through complexes formed with other molecules in the cell, genome functions are inherently interactive and involve two-way communication with various cellular compartments. Both coding sequences and repetitive sequences contribute to the hierarchical systemic organization of the genome. By virtue of nucleoprotein (...) complexes, epigenetic modifications, and natural genetic engineering activities, the genome can serve as a read-write storage system. An interactive informatic conceptualization of the genome allows us to understand the functional importance of DNA that does not code for protein or RNA structure, clarifies the essential multidirectional and systemic nature of genomic information transfer, and emphasizes the need to investigate how cellular computation operates in reproduction and evolution. (shrink)

This paper investigates the stochastically exponential stability of reaction-diffusion impulsive stochastic cellular neural networks. The reaction-diffusion pulse stochastic system model characterizes the complexity of practical engineering and brings about mathematical difficulties, too. However, the difficulties have been overcome by constructing a new contraction mapping and an appropriate distance on a product space which is guaranteed to be a complete space. This is the first time to employ the fixed point theorem to derive the stability criterion of reaction-diffusion impulsive stochastic (...) CNN with distributed time delays. Finally, an example is provided to illustrate the effectiveness of the proposed methods. (shrink)

The majority of G protein-coupled receptors (GPCRs) self-assemble in the form dimeric/oligomeric complexes along the plasma membrane. Due to the molecular interactions they participate, GPCRs can potentially provide the framework for discriminating a wide variety of intercellular signals, as based on some kind of combinatorial receptor codes. GPCRs can in fact transduce signals from the external milieu by modifying the activity of such intracellular proteins as adenylyl cyclases, phospholipases and ion channels via interactions with specific G-proteins. However, in spite of (...) the number of cell functions they can actually control, both GPCRs and their associated signal transduction pathways are extremely well conserved, for only a few alleles with null or minor functional alterations have so far been found. This would seem to suggest that, beside a mechanism for DNA repairing, there must be another level of quality control that may help maintaining GPCRs rather stable throughout evolution. We propose here receptor oligomerization to be a basic molecular mechanism controlling GPCRs redundancy in many different cell types, and the plasma membrane as the first hierarchical cell structure at which selective categorical sensing may occur. Categorical sensing can be seen as the cellular capacity for identifying and ordering complex patterns of mixed signals out of a contextual matrix, i.e., the recognition of meaningful patterns out of ubiquitous signals. In this context, redundancy and degeneracy may appear as the required feature to integrate the cell system into functional units of progressively higher hierarchical levels. (shrink)

Consciousness has always been linked to the nervous system or rather the brain, but there recorded conscious behaviors in organisms without nerve cells have changed the perspective of consciousness. A living cell is a blend of resonant frequencies, due to degrees of freedom that make it vibrate as a harmonic oscillator supporting the progression of vibrations as waves in and out of the system; to the neighboring cells, to the body, to other bodies and ultimately to the Universe; all of (...) which connects. Quantum generated consciousness is energy; emerges in each and every living cell and traverses by means of resonating vibrations; which utilizes the cellular structures to flow by means of a coherent, obscured, robust, recoverable process. (shrink)