Adaptability and the integration of computer-based information processing into the dynamics of organizations

The structure of a system influences its adaptability. An important result of adaptability theory is that subsystem independence increases adaptability [Conrad, M., 1983. Adaptability. Plenum Press, New York]. Adaptability is essential in systems that face an uncertain environment such as biological systems and organizations. Modern organizations are the product of human design. And so it is their structure and the effect that it has on their adaptability. In this paper we explore the potential effects of computer-based information processing on the adaptability of organizations. The integration of computer-based processes into the dynamics of the functions they support and the effect it has on subsystem independence are especially relevant to our analysis.     

Role of duplicate genes in robustness against deleterious human mutations

It is now widely recognized that robustness is an inherent property of biological systems [1],[2],[3]. The contribution of close sequence homologs to genetic robustness against null mutations has been previously demonstrated in simple organisms [4],[5]. In this paper we investigate in detail the contribution of gene duplicates to back-up against deleterious human mutations. Our analysis demonstrates that the functional compensation by close homologs may play an important role in human genetic disease. Genes with a 90% sequence identity homolog are about 3 times less likely to harbor known disease mutations compared to genes with remote homologs. Moreover, close duplicates affect the phenotypic consequences of deleterious mutations by making a decrease in life expectancy significantly less likely. We also demonstrate that similarity of expression profiles across tissues significantly increases the likelihood of functional compensation by homologs.     

Characteristics of the vitamin K-dependent carboxylating system in human placenta.

Gamma-carboxyglutamic acid, formed during the post-translational vitamin K-dependent carboxylation of glutamic acid residues in polypeptides has been identified not only in coagulation factors II (prothrombin),, VII, IX and X [1--4], but also in several other plasma proteins [3,5,6] and in protein of bone [7,8] and kidney [9]. In rat liver, carboxylation is mediated through an enzyme system located in the microsomal membrane [10]. The enzyme system requires CO2, O2 and the reduced (hydroquinone) form of the vitamin, as well as a suitable substrate [10,11]. Rat liver microsomes also convert vitamin K1 (phylloquinone) to its stable 2,3-epoxide [12]. Several studies suggest a link between carboxylation and the formation of the epoxide [12--14]. In one of these [14], a survey of rat tissues for vitamin K1 epoxidation revealed that, in addition to liver, this activity was also possessed by kidney, bone, spleen and placenta. In preliminary experiments, vitamin K-dependent carboxylating systems have been found in rat and chick kidney [9], in chick bone [15] and in rat spleen and placenta (unpublished observations). In this communication, we describe some of the basic characteristics of the vitamin K-dependent carboxylating system as found in human placental microsomes.     

A shift in sensory processing that enables the developing human brain to discriminate touch from pain

When and how infants begin to discriminate noxious from innocuous stimuli is a fundamental question in neuroscience [1]. However, little is known about the development of the necessary cortical somatosensory functional prerequisites in the intact human brain. Recent studies of developing brain networks have emphasized the importance of transient spontaneous and evoked neuronal bursting activity in the formation of functional circuits [2, 3]. These neuronal bursts are present during development and precede the onset of sensory functions [4, 5]. Their disappearance and the emergence of more adult-like activity are therefore thought to signal the maturation of functional brain circuitry [2, 4]. Here we show the changing patterns of neuronal activity that underlie the onset of nociception and touch discrimination in the preterm infant. We have conducted noninvasive electroencephalogram (EEG) recording of the brain neuronal activity in response to time-locked touches and clinically essential noxious lances of the heel in infants aged 28-45?weeks gestation. We show a transition in brain response following tactile and noxious stimulation from nonspecific, evenly dispersed neuronal bursts to modality-specific, localized, evoked potentials. The results suggest that specific neural circuits necessary for discrimination between touch and nociception emerge from 35-37?weeks gestation in the human brain.     

Evaluation of the role of the adaptive result in the theory of the functional systems

The fundamental of the theory of the functional systems, i.e., the concept of the useful adaptive result as a universal system-forming factor is considered. It is suggested that the adaptive result is not system-forming in behaviors actualized exclusively due to activity of systems developed earlier. It is argued that positive mutations may serve as the system-forming factor for hereditary determined behavioral forms. In all other cases of goal-directed behavior (except conditioning) the aim of performance as a model of the future result plays the decisive role. Only in conditioning the classical concept of the system-forming role of the adaptive result seems to be undeniable. The refined ideas about the mechanisms of formation of the functional systems may be useful in analysis of a number of animal and human functions (learning, emotional stress, neuroses, etc.).     

Sensorimotor learning configures the human mirror system

Cells in the "mirror system" fire not only when an individual performs an action but also when one observes the same action performed by another agent [1-4]. The mirror system, found in premotor and parietal cortices of human and monkey brains, is thought to provide the foundation for social understanding and to enable the development of theory of mind and language [5-9]. However, it is unclear how mirror neurons acquire their mirror properties -- how they derive the information necessary to match observed with executed actions [10]. We address this by showing that it is possible to manipulate the selectivity of the human mirror system, and thereby make it operate as a countermirror system, by giving participants training to perform one action while observing another. Before this training, participants showed event-related muscle-specific responses to transcranial magnetic stimulation over motor cortex during observation of little- and index-finger movements [11-13]. After training, this normal mirror effect was reversed. These results indicate that the mirror properties of the mirror system are neither wholly innate [14] nor fixed once acquired; instead they develop through sensorimotor learning [15, 16]. Our findings indicate that the human mirror system is, to some extent, both a product and a process of social interaction.     

The Problem of Neuroimmunotherapy of Nervous Diseases

We analyzed the mechanisms of interaction between nervous and immune systems characterized by common principles of organization, common messenger molecules, and regulatory functions significant for the whole organism. Common components of neuroimmunity and nonimmune pathological processes underlie the possibility of their mutual potentiation [1]. Neuroimmune diseases are associated with the formation of cortical, subcortical, and brainstem neuronal ensembles involved in the regulation of immune and endocrine systems [2]. The comparison of these ensembles with neuroimmunological parameters allows us to examine the real mechanisms of pathological processes and to evaluate the efficacy of various kinds of therapy including neuroimmunocorrection by neurotropic drugs.     

一类时滞非自治Lotka-Volterra竞争系统的灭绝性

讨论一类具有离散时滞和连续分布时滞的Lotka-Volterra系统,通过构造Lyapunov函数并引入上下平均的概念,将[3]和[6]的方法结合在一起,得到比[6]种群灭绝条件弱的充分条件,同时把文献[3]的结果推广到了时滞非自治系统上.     

The Arp2/3 complex is essential for the actin-based motility of Listeria monocytogenes.

Actin polymerisation is thought to drive the movement of eukaryotic cells and some intracellular pathogens such as Listeria monocytogenes. The Listeria surface protein ActA synergises with recruited host proteins to induce actin polymerisation, propelling the bacterium through the host cytoplasm [1]. The Arp2/3 complex is one recruited host factor [2] [3]; it is also believed to regulate actin dynamics in lamellipodia [4] [5]. The Arp2/3 complex promotes actin filament nucleation in vitro, which is further enhanced by ActA [6] [7]. The Arp2/3 complex also interacts with members of the Wiskott-Aldrich syndrome protein (WASP) [8] family - Scar1 [9] [10] and WASP itself [11]. We interfered with the targeting of the Arp2/3 complex to Listeria by using carboxy-terminal fragments of Scar1 that bind the Arp2/3 complex [11]. These fragments completely blocked actin tail formation and motility of Listeria, both in mouse brain extract and in Ptk2 cells overexpressing Scar1 constructs. In both systems, Listeria could initiate actin cloud formation, but tail formation was blocked. Full motility in vitro was restored by adding purified Arp2/3 complex. We conclude that the Arp2/3 complex is a host-cell factor essential for the actin-based motility of L. monocytogenes, suggesting that it plays a pivotal role in regulating the actin cytoskeleton.     

Heterarchy in biological systems: a logic-based dynamical model of abstract biological network derived from time-state-scale re-entrant form

Heterarchical structure is important for understanding robustness and evolvability in a wide variety of levels of biological systems. Although many studies emphasize the heterarchical nature of biological systems, only a few computational representations of heterarchy have been created thus far. We propose here the time-state-scale re-entrant form to address the self-referential property derived from setting heterarchical structure. In this paper, we apply the time-state-scale re-entrant form to abstract self-referential modeling for a functional manifestation of biological network presented by [Tsuda, I., Tadaki, K., 1997. A logic-based dynamical theory for a genesis of biological threshold. BioSystems 42, 45-64]. The numerical results of this system show different intermittent phase transitions and power-law distribution of time spent in activating functional manifestation. The Hierarchically separated time-scales obtained from spectrum analysis imply that the reactions at different levels simultaneously appear in a dynamical system. The results verify the mutual inter-relationship between heterarchical structure in biological systems and the self-referential property of computational heterarchical systems.     

The theory of functional systems and purposeful behavior

The role of probability forecasting in the purposive behavior under conditions of subjective uncertainty is considered in terms of the theory of functional systems. Participation of the probability forecasting in the afferent synthesis, goal formation, formation of the acceptor of action result and action program, and, finally, in the action program actualization is substantiated. The model of behavior under conditions of subjective uncertainty is advanced. It includes all the classical elements of the model of behavioral act developed by P.K. Anokhin. In order to take into account the probability aspects of behavior, the role of probability forecasting is emphasized at every stage of the system functioning. In addition to the classical elements, two novel components are introduced. These are the "memory buffer" (results of searching reactions) and the apparatus of probability decisions about changes in the action program. By the memory buffer an apparatus is meant, which gathers and stores the information about the results of many behavioral acts performed during the actualization of the action program. This information is used in the process of making a probability decision as whether to alter or not the action program after each specific behavioral act. Such an approach integrates the probability forecasting and the theory of functional systems. The theory becomes universal, i.e., applicable not only to deterministic but also to probabilistic environments.     

Form and motion coherence activate independent, but not dorsal/ventral segregated, networks in the human brain

There is much evidence in primates' visual processing for distinct mechanisms involved in object recognition and encoding object position and motion, which have been identified with 'ventral' and 'dorsal' streams, respectively, of the extra-striate visual areas [1] [2] [3]. This distinction may yield insights into normal human perception, its development and pathology. Motion coherence sensitivity has been taken as a test of global processing in the dorsal stream [4] [5]. We have proposed an analogous 'form coherence' measure of global processing in the ventral stream [6]. In a functional magnetic resonance imaging (fMRI) experiment, we found that the cortical regions activated by form coherence did not overlap with those activated by motion coherence in the same individuals. Areas differentially activated by form coherence included regions in the middle occipital gyrus, the ventral occipital surface, the intraparietal sulcus, and the temporal lobe. Motion coherence activated areas consistent with those previously identified as V5 and V3a, the ventral occipital surface, the intraparietal sulcus, and temporal structures. Neither form nor motion coherence activated area V1 differentially. Form and motion foci in occipital, parietal, and temporal areas were nearby but showed almost no overlap. These results support the idea that form and motion coherence test distinct functional brain systems, but that these do not necessarily correspond to a gross anatomical separation of dorsal and ventral processing streams.     

Multivalent protein-carbohydrate interactions. A new paradigm for supermolecular assembly and signal transduction

Many biological recognition processes involve the binding and clustering of ligand-receptor complexes and concomitant signal transduction events. Such interactions have recently been observed in human T cells in which binding and cross-linking of specific glycoprotein counter-receptors on the surface of the cells by an endogenous bivalent carbohydrate binding protein (galectin-1) leads to apoptosis [Pace, K. E., et al. (1999) J. Immunol. 163, 3801-3811]. Importantly, different counter-receptors associated with specific phosphatase or kinase activities were shown to form separate clusters on the surface of the cells as a result of galectin-1 binding to the carbohydrate moieties of the respective glycoproteins. This suggests that the unique separation and organization of signaling molecules that results from galectin-1 binding is involved in delivering the signal to die. The ability of galectin-1 to induce the separation of specific glycoprotein receptors was modeled on the basis of molecular and structural studies of the binding of multivalent carbohydrates to lectins that result in the formation of specific two- and three-dimensional cross-linked lattices. These latter studies have been recently highlighted by X-ray crystallographic results showing that a single tetravalent lectin forms distinct cross-linked complexes with four different bivalent oligosaccharides [Olsen, L. R., et al. (1997) Biochemistry 36, 15073-15080]. In this report, binding and cross-linking of multivalent carbohydrates with multivalent lectins is shown to be a new paradigm for supermolecular assembly and signal transduction in biological systems.     

Phenotypic modulations of human umbilical vein endothelial cells and human dermal fibroblasts using two angiogenic assays.

Different angiogenic assays in vitro have helped to define various events underlying angiogenesis. In this report we have compared the phenotypic modifications of human umbilical vein endothelial cells (HUVE cells) and human dermal fibroblasts using Matrigel and collagen gels. Both HUVE cells and human dermal fibroblasts form a network of anastomosing cords that apparently resemble blood capillaries when grown on Matrigel. The whole network was formed by several cellular aggregates joined to each other by cellular cords. Lumen formation was not observed in this angiogenic system. In opposite, considerable differences between HUVE cells and human dermal fibroblasts were observed in the three-dimensional angiogenic assay on collagen gels described by Montesano et al [14]. These results indicate that data obtained with angiogenic systems using Matrigel must be interpreted with caution and that the assay described by Montesano et al [14], is more reliable to describe angiogenesis.     

Serotonin signaling is required for Wnt-dependent GRP specification and leftward flow in Xenopus

In vertebrates, most inner organs are asymmetrically arranged with respect to the main body axis [1]. Symmetry breakage in fish, amphibian, and mammalian embryos depends on cilia-driven leftward flow of extracellular fluid during neurulation [2-5]. Flow induces the asymmetric nodal cascade that governs asymmetric organ morphogenesis and placement [1, 6, 7]. In the frog Xenopus, an alternative laterality-generating mechanism involving asymmetric localization of serotonin at the 32-cell stage has been proposed [8]. However, no functional linkage between this early localization and flow at neurula stage has emerged. Here, we report that serotonin signaling is required for specification of the superficial mesoderm (SM), which gives rise to the ciliated gastrocoel roof plate (GRP) where flow occurs [5, 9]. Flow and asymmetry were lost in embryos in which serotonin signaling was downregulated. Serotonin, which we found uniformly distributed along the main body axes in the early embryo, was required for Wnt signaling, which provides the instructive signal to specify the GRP. Importantly, serotonin was required for Wnt-induced double-axis formation as well. Our data confirm flow as primary mechanism of symmetry breakage and suggest a general role of serotonin as competence factor for Wnt signaling during axis formation in Xenopus.     

The evolution of social cognition: goal familiarity shapes monkeys' action understanding

What is the evolutionary origin of the human ability to understand and predict the behavior of others? Recent studies suggest that human infants' early capacity for understanding others' goal-directed actions relies on nonmentalistic strategies [1-8]. However, there is no consensus about the nature of the mechanisms underpinning these strategies and their evolutionary history. Comparative studies can shed light on these controversial issues. We carried out three preferential looking-time experiments on macaques, modeled on previous work on human infants [1-5], to test whether macaques are sensitive to the functional efficacy of familiar goal-related hand motor acts performed by an experimenter in a given context and to examine to which extent this sensitivity also is present when observing non-goal-related or unusual goal-related motor acts. We demonstrate that macaque monkeys, similar to human infants, do indeed detect action efficacy by gazing longer at less efficient actions. However, they do so only when the observed behavior is directed to a perceptible and familiar goal. Our results show that the direct detection of the functional fitness of action, in relation to goals that have become familiar through previous experience, is the phylogenetic precursor of intentional understanding.     

Spreading speeds as slowest wave speeds for cooperative systems

It is well known that in many scalar models for the spread of a fitter phenotype or species into the territory of a less fit one, the asymptotic spreading speed can be characterized as the lowest speed of a suitable family of traveling waves of the model. Despite a general belief that multi-species (vector) models have the same property, we are unaware of any proof to support this belief. The present work establishes this result for a class of multi-species model of a kind studied by Lui [Biological growth and spread modeled by systems of recursions. I: Mathematical theory, Math. Biosci. 93 (1989) 269] and generalized by the authors [Weinberger et al., Analysis of the linear conjecture for spread in cooperative models, J. Math. Biol. 45 (2002) 183; Lewis et al., Spreading speeds and the linear conjecture for two-species competition models, J. Math. Biol. 45 (2002) 219]. Lui showed the existence of a single spreading speed c(*) for all species. For the systems in the two aforementioned studies by the authors, which include related continuous-time models such as reaction-diffusion systems, as well as some standard competition models, it sometimes happens that different species spread at different rates, so that there are a slowest speed c(*) and a fastest speed c(f)(*). It is shown here that, for a large class of such multi-species systems, the slowest spreading speed c(*) is always characterized as the slowest speed of a class of traveling wave solutions.     

The systems organization of human functions: the theoretical aspects

On the basis of the theory of functional systems, suggested by P. K. Anokhin, leading principals of system organization of human functions are regarded. General characteristics of functional systems are stated. Some peculiarities of intrasystem and intersystem organization of functional systems of human organism are discovered. The role of functional systems in organization of normal human live activity as well as under psychoemotional stress and pathology is shown. System principals of compensation of disordered functions during rehabilitation of persons undergone stresses and ecologically unfavorable loads are considered.     

Olfactory neurons are interdependent in maintaining axonal projections

In mice, individual olfactory neurons express one of the thousand distinct olfactory receptor genes [1] [2] [3]. Neurons that express a given receptor converge on distinct loci in the olfactory bulb to form structures called glomeruli [4] [5] [6]. The olfactory receptor is involved in an instructive manner in this axonal convergence [6] [7] but little is known about the mechanisms involved in maintaining convergence. We have previously created a transgenic olfactory receptor locus that functions independently of the endogenous loci [8]. Here, we show that, although the projections of neurons expressing this ectopic transgenic olfactory receptor always converge in newborn mice, surprisingly, in adult mice, convergence is not always maintained. Moreover, in adult mice there is a positive correlation between the number of neurons expressing the transgenic receptor and the probability of maintaining convergence. These observations, taken together with the variability observed in wild-type [4] [6] and genetically manipulated mice ([6] and our unpublished observations), suggest that olfactory neurons require the presence of other similar axons to maintain a glomerulus. We call this phenomenon interdependence.