Animal models and conserved processes

Background

The concept of conserved processes presents unique opportunities for using nonhuman animal models in biomedical research. However, the concept must be examined in the context that humans and nonhuman animals are evolved, complex, adaptive systems. Given that nonhuman animals are examples of living systems that are differently complex from humans, what does the existence of a conserved gene or process imply for inter-species extrapolation?

Methods

We surveyed the literature including philosophy of science, biological complexity, conserved processes, evolutionary biology, comparative medicine, anti-neoplastic agents, inhalational anesthetics, and drug development journals in order to determine the value of nonhuman animal models when studying conserved processes.

Results

Evolution through natural selection has employed components and processes both to produce the same outcomes among species but also to generate different functions and traits. Many genes and processes are conserved, but new combinations of these processes or different regulation of the genes involved in these processes have resulted in unique organisms. Further, there is a hierarchy of organization in complex living systems. At some levels, the components are simple systems that can be analyzed by mathematics or the physical sciences, while at other levels the system cannot be fully analyzed by reducing it to a physical system. The study of complex living systems must alternate between focusing on the parts and examining the intact whole organism while taking into account the connections between the two. Systems biology aims for this holism. We examined the actions of inhalational anesthetic agents and anti-neoplastic agents in order to address what the characteristics of complex living systems imply for inter-species extrapolation of traits and responses related to conserved processes.

Conclusion

We conclude that even the presence of conserved processes is insufficient for inter-species extrapolation when the trait or response being studied is located at higher levels of organization, is in a different module, or is influenced by other modules. However, when the examination of the conserved process occurs at the same level of organization or in the same module, and hence is subject to study solely by reductionism, then extrapolation is possible.     

Structures closed into cycles in globular proteins

Different types of structures closed into cycles are widespread at all the levels of structural organization of proteins. β-Hairpins, triple-stranded β-sheets, and βαβ-units represent simple structural motifs closed into cycles by systems of hydrogen bonds. Secondary closing of these simple motifs into larger cycles by means of different superhelices, split β-hairpins, or SS-bridges results in formation of complex structural motifs such as abcd-units, φ-motifs, five- and seven-segment α/β-motifs, etc. At the level of tertiary structure many proteins and domains fold into structures closed into cylinders. Apparently, closing the motifs and domains into cycles and cylinders results in formation of more cooperative and stable structures as compared with open ones, and this may be the reason for high frequencies of occurrence of the motifs in proteins.     

Multiform wave organization of neurophysiological processes-universal “language” of human brain in realization of informational-controlling functions

The paper summarizes literature data and results of many-year Laboratory studies disclosing principles of the multiform spatial-time organization of differing by rates of neurophysiologic brain processes as the universal “language” of its informational-controlling functions. There are considered current concepts of electrogenesis and physiological significance of ratios of gradual changes of biopotentials and impulse activity of neurons considered in studies of cerebral mechanisms of regulation of normal and pathological states, and organization of human psychic activity. Put forward and argumented are concepts of the probability principle of hierarchical organization of differing by rates of neurophysiologic processes brain zones, structures, and areas in formation of the brain systems participating in provision of the higher psychic functions and states. It is proposed to discuss the concept of the brain as the “swimming,” many-contour, neurodynamic informational-controlling suprasystem with universal, hierarchically organized neurodynamic structures—”functional organs” by A.A. Ukhtomskii (1978), of which formation provides large informational brain capacity and a wide specter of adaptive possibilities of the human organism.     

Autopoiesis 40 years Later. A Review and a Reformulation

The concept of autopoiesis was proposed 40 years ago as a definition of a living being, with the aim of providing a unifying concept for biology. The concept has also been extended to the theory of knowledge and to different areas of the social and behavioral sciences. Given some ambiguities of the original definitions of autopoiesis, the concept has been criticized and has been interpreted in diverse and even contradictory ways, which has prevented its integration into the biological sciences where it originated. Here I present a critical review and conceptual analysis of the definition of autopoiesis, and propose a new definition that is more precise, clear, and concise than the original ones. I argue that the difficulty in understanding the term lies in its refined conceptual subtlety and not, as has been claimed by some authors, because it is a vacuous, trivial or very complex concept. I also relate the concept of autopoiesis to the concepts of closed systems, boundaries, homeostasis, self-reproduction, causal circularity, organization and multicellularity. I show that under my proposed definition the concept of a molecular autopoietic system is a good demarcation criterion of a living being, allowing its general integration into the biological sciences and enhancing its interdisciplinary use.     

Marine Ecosystems as Complex Adaptive Systems: Emergent Patterns,Critical Transitions,and Public Goods

Complex adaptive systems provide a unified framework for explaining ecosystem phenomena. In the past 20 years, complex adaptive systems have been sharpened from an abstract concept into a series of tools that can be used to solve concrete problems. These advances have been led by the development of new techniques for coupling ecological and evolutionary dynamics, for integrating dynamics across multiple scales of organization, and for using data to infer the complex interactions among different components of ecological systems. Focusing on the development and usage of these new methods, we discuss how they have led to an improved understanding of three universal features of complex adaptive systems, emergent patterns; tipping points and critical phenomena; and cooperative behavior. We restrict our attention primarily to marine ecosystems, which provide numerous successful examples of the application of complex adaptive systems. Many of these are currently undergoing dramatic changes due to anthropogenic perturbations, and we take the opportunity to discuss how complex adaptive systems can be used to improve the management of public goods and to better preserve critical ecosystem services.     

Longevity control in fungi and other organisms. The conception of scales

The review deals mainly with gerontological processes that occur on the cellular-colonial level of organization in fungi and cellular-tissular level in other organisms. Aging and anti-aging mechanisms operating on these levels of organization can be considered as common ones for all living things. Fungi, as an object with tissular-like organization of thallus, afford a broad spectrum of possibilities as to solving the tasks of general gerontological import. Three basic (chronological, replicative, and cell-suicidal) and several auxiliary mechanisms of aging are singled out, the classification is given of stochastic aging factors accumulating in cells. It is shown that in complex multi-cellular organisms, aging and anti-aging mechanisms operate on the level of interactions between tissues, though in the base of their actions lie the aforesaid conservative basic mechanisms. Preliminary generalized conception of aging--the conception of scales--is put forward that is founded on the model of balanced and non-balanced counteractions between stressful impacts and various mechanisms of aging and anti-aging with different extent of genetic preprogramming. The importance is reaffirmed of mycological gerontology contribution to broadening of inferences on aging nature.     

Adaptation as a manifestation of informational connections in living systems

The problem of adaptation of living systems in terms of the concept of informational communications is considered. The informational communication means the qualitative evaluation of information and determines correspondence of living systems to concrete conditions of life during interaction of these living systems to the source of the information. The system of the wholeorganism regulatory chemical communication is the main functional basis for the informational communication. Due to it, the transformation of the information signal in biological systems is performed, which results in their adequate response according to this information. The existence of living systems and their adaptation are determined by peculiarities of functioning of elements of their regulatory systems according to the character of the informational communication.     

Verbal morphology in Murrinh-Patha: evidence for templates

If questions concerning affix ordering are among the central ones in morphological theory, then languages with templatic morphology appear to provide the least interesting answer, since in these languages affix order must be simply stipulated in the form of arbitrary position classes. For this reason, much recent research into templatic morphology has attempted to show that affix order in such languages is in fact governed by underlying semantic or syntactic principles. The most fully articulated position in this respect is that of Rice (Morpheme order and semantic scope, Cambridge University Press, Cambridge, 2000), who provides a comprehensive analysis of morpheme order across the Athapaskan languages and argues that it is largely determined by universal principles of semantic (and syntactic) scope. If these principles of word formation are truly universal, we should expect to find evidence for them in all similarly ‘templatic’ systems, including the head-marking languages of Australia. In this context, I discuss the order of verbal affixes in Murrinh-Patha and show that these data cannot be adequately accounted for by syntactic or semantic accounts of affix ordering, but rather provide strong support for the existence of templatic organization in morphological systems.     

Functionally referential signals: A promising paradigm whose time has passed

Finding the evolutionary origins of human language in the communication systems of our closest living relatives has, for the last several decades, been a major goal of many in the field of animal communication generally and primate communication specifically. 1 - 4 The so‐called “functionally referential” signals have long been considered promising in this regard, with apparent parallels with the semantic communication that characterizes language. The once‐prominent idea that functionally referential signals are word‐like, in that they are arbitrary sounds that refer to phenomena external to the caller, has largely been abandoned. 5 However, the idea that these signals may offer the strongest link between primate communication and human language remains widespread, primarily due to the fact the behavior of receivers indicates that such signals enable them to make very specific inferences about their physical or social environment. Here we review the concept of functional reference and discuss modern perspectives that indicate that, although the sophistication of receivers provides some continuity between nonhuman primate and human cognition, this continuity is not unique to functionally referential signals. In fact, because functionally referential signals are, by definition, produced only in specific contexts, receivers are less dependent on the integration of contextual cues with signal features to determine an appropriate response. The processing of functionally referential signals is therefore likely to entail simpler cognitive operations than does that of less context‐specific signals. While studies of functional reference have been important in highlighting the relatively sophisticated processes that underlie receiver behavior, we believe that the continued focus on context‐specific calls detracts from the potentially more complex processes underlying responses to more unspecific calls. In this sense, we argue that the concept of functional reference, while historically important for the field, has outlived its usefulness and become a red herring in the pursuit of the links between primate communication and human language. © 2012 Wiley Periodicals, Inc.     

Nitric Oxide Cycle in Mammals and the Cyclicity Principle

This paper continues a series of reports considering nitric oxide (NO) and its cyclic conversions in mammals. Numerous facts are summarized with the goal of developing a general concept that would allow the statement of the multiple effects of NO on various systems of living organisms in the form of a short and comprehensive law. The current state of biological aspects of NO research is analyzed in term of elucidation of possible role of these studies in the system of biological sciences. The general concept is based on a notion on cyclic conversions of NO and its metabolites. NO cycles in living organisms and nitrogen turnover in the biosphere and also the Bethe nitrogen–carbon cycle in star matter are considered. A hypothesis that the cyclic organization of processes in living organisms and the biosphere reflects the evolution of life is proposed: the development of physiological functions and metabolism are suggested to be closely related to space and evolution of the Earth as a planet of the Solar System.     

Representation of living forms

The living forms represented in this paper are sets of parts that spontaneously increase in organization. Their organizations are measured by an information-theoretic function derived from the work of Boltzmann and Shannon. We briefly review its derivation in the context of the troubled role of mathematics in biology, and then define the function. We illustrate its nature by measuring the 22 different organizations of a set of eight things; and we facilitate its use by defining the parameters that determine an amount of organization. The measure is then applied to show that the organization of limb pairs on free-living arthropods, based on data given by Cisne, confirms a pattern of increasing organization in their evolution from the Cambrian era to the present. Further applications measure the changes in organizations of ideal (theoretical) life forms, and contrasting changes in inanimate systems. Our main results represent the reproduction of unicellular organisms, and the formation of hierarchies, as processes of increasing organization.     

Minireviews: Exploring the Basic Ecological Unit: Ecosystem-like Concepts in Traditional Societies

Ancient conceptualizations of ecosystems exist in several Amerindian, Asia-Pacific, European, and African cultures. The rediscovery by scientists of ecosystem-like concepts among traditional peoples has been important in the appreciation of traditional ecological knowledge among ecologists, anthropologists, and interdisciplinary scholars. Two key characteristics of these systems are that (a) the unit of nature is often defined in terms of a geographical boundary, such as a watershed, and (b) abiotic components, plants, animals, and humans within this unit are considered to be interlinked. Many traditional ecological knowledge systems are compatible with the emerging view of ecosystems as unpredictable and uncontrollable, and of ecosystem processes as nonlinear, multiequilibrium, and full of surprises. Traditional knowledge may complement scientific knowledge by providing practical experience in living within ecosystems and responding to ecosystem change. However, the “language” of traditional ecology is different from the scientific and usually includes metaphorical imagery and spiritual expression, signifying differences in context, motive, and conceptual underpinnings. Received 28 April 1998; accepted 9 July 1998.     

Principles of self-generation and self-maintenance

Living systems are characterized as self-generating and self-maintaining systems. This type of characterization allows integration of a wide variety of detailed knowledge in biology.The paper clarifies general notions such as processes, systems, and interactions. Basic properties of self-generating systems, i.e. systems which produce their own parts and hence themselves, are discussed and exemplified. This makes possible a clear distinction between living beings and ordinary machines. Stronger conditions are summarized under the concept of self-maintenance as an almost unique character of living systems. Finally, we discuss the far-reaching consequences that the principles of self-generation and self-maintenance have for the organization, structure, function, and evolution of single- and multi-cellular organisms.     

Meaning-making in the immune system

Meaning-making is the process by which a system responds to an indeterminate signal. This article focuses on meaning-making in living systems. It proposes several guidelines for studying the process of meaning-making in living systems in general, and in the immune system in particular. Drawing on a general framework for studying meaning-making in living systems, I suggest three basic organizing concepts for studying meaning-making-variability of the signal, context markers, and transgradience. Those concepts present a radical alternative to the information-processing approach that governs biological research and may shed new light on biological processes.     

Topology and life: In search of general mathematical principles in biology and sociology

Mathematical biology has hitherto emphasized the quantitative, metric aspects of the physical manifestations of life, but has neglected the relational or positional aspects, which are of paramount importance in biology. Although, for example, the processes of locomotion, ingestion, and digestion in a human are much more complex than in a protozoan, the general relations between these processes are the same in all organisms. To a set of very complicated digestive functions of a higher animal there correspond a few simple functions in a protozoan. In other words, the more complicated processes in higher organisms can be mapped on the simpler corresponding processes in the lower ones. If any scientific study of this aspect of biology is to be possible at all, there must exist some regularity in such mappings. We are, therefore, led to the following principle: If the relations between various biological functions of an organism are represented geometrically in an appropriate topological space or by an appropriate topological complex, then the spaces or complexes representing different organisms must be obtainable by a proper transformation from one or very fewprimordial spaces or complexes. The appropriate representation of the relations between the different biological functions of an organism appears to be a one-dimensional complex, or graph, which represents the “organization chart” of the organism. The problem then is to find a proper transformation which derives from this graph the graphs of all possible higher organisms. Both a primordial graph and a transformation are suggested and discussed. Theorems are derived which show that the basic principle of mapping and the transformation have a predictive value and are verifiable experimentally. These considerations are extended to relations within animal and human societies and thus indicate the reason for the similarities between some aspects of societies and organisms. It is finally suggested that the relation between physics and biology may lie on a different plane from the one hitherto considered. While physical phenomena are the manifestations of the metric properties of the four-dimensional universe, biological phenomena may perhaps reflect some local topological properties of that universe.     

Self-organization of populations of polistine wasps (Hymenoptera,Vespidae, Polistinae)

In a natural population of Polistes dominulus (Christ) in the Black Sea Biosphere Reserve, Ukraine, the fluctuations of the number of nests founded were monitored in 1992–2008; the variations in the spatial and ethological structure of populations as well as in the colony organization patterns were examined. The highest indices of foundress fecundity (daily egg production, the foundress longevity after emergence of worker), colony productivity (the number of adults reared, the intensity of repeated cell use) and the efficiency of colony functioning (the degree of worker specialization and the mode of loyal or aggressive relationships between individuals) were characteristic of the population growth phase. In contrast, low indices were recorded during the peak and the decline phases. Transition to a more complicated social organization is favored by the self-organization process that accelerates the appearance of such interrelated features as a complex communication system, worker specialization, and their ability to perform complicated tasks. The study is focused on spatio-temporal processes in the population, using the body melanin patterns as markers of the social roles of foundresses. The changes observed in the population phenotypic structure are considered from the viewpoint of autowave processes. Analysis of the functional and numerical response of paper wasp parasitoids to changes in the host population density has shown that the regulating effect becomes noticeable only under such a concurrence of the life cycles of the parasitoid and the host when the larvae of the first cohort of workers become infested. The application of the concept of self-organized criticality used to describe complex systems with developed fluctuations results in a better understanding of population regulation in resocial insects.