The origin of membranes

The physicochemical conditions of the environment in which life arose are discussed, along with the appearance of protocells, their membranous envelope and the subsequent appearance of plasma membranes. The hypothesis that the first cells originated in reservoirs where potassium and magnesium salts (necessary for protein synthesis and thus for the formation of a cellular membrane) dominated, is substantiated. This was followed by adaptation of these cells to an external ocean-like environment, where sodium salts were prevalent. This stage of evolution required a plasma membrane capable of providing ion asymmetry between the cell’s cytoplasm and the external environment. At this stage of evolution in the predecessors of animals, the process of removal of sodium ions and accumulation of potassium ions began functioning in the plasma membrane. The problem of multicellular organisms was solved differently by animals and plants: animals developed a system of the extracellular fluids that provided stable physicochemical conditions on the external surface of the plasma membrane. Sodium ions were the stimulus for the formation of the polar cell, where sodium channels are situated on one side of the plasma membrane, and sodium pumps on the other, allowing the development of the absorption, excretion and breathing functions. The formation of fluids of the internal environment enabled the development of homeostasis and facilitated the biological progress of the animal kingdom.     

Cells in the system of multicelular organism from positions of non-linear dynamics

The organism physiological systems forming a hierarchic network with mutual dependence and subordination can be considered as systems with non-linear dynamics including positive and negative feedbacks. In the course of evolution there occurred selection of robust, flexible, modular systems capable for adaptive self-organization by non-linear interaction of components, which leads to formation of the ordered in space and time robust and plastic organization of the whole. Cells of multicellular organisms are capable for coordinated “social” behavior with formation of ordered cell assemblies, which provides a possibility of morphological and functional variability correlating with manifestations of the large spectrum of adaptive reactions. The multicellular organism is the multilevel system with hierarchy of numerous subsystems capable for adaptive self-organization; disturbance of their homeostasis can lead to pathological changes. The healthy organism regulates homeostasis, self-renewal, differentiation, and apoptosis of cells serving its parts and construction blocks by preserving its integrity and controlling behavior of cells. The systemic approach taking into account biological regularities of the appearance and development of functions in evolution of multicellular organisms opens new possibilities for diagnostics and treatment of many diseases.     

From quantum to integrative physiology

Physiology studies the functions of different organs, systems and how they maintain the integrity of organisms. Nervous and endocrine systems react to stimulus, causality plays a key role in their activities. Physical and chemical conditions of fluids in the internal environment serve as a background and an active modulator for regulatory influences. Autacoid formation is in many respects based on probable events. It has been proved, that during the formation of regulatory systems in cell evolution the appearance of regulatory molecules was based on statistical probability of quantum events: sporadical appearance in cells during metabolism of peptides, lipids, hydrolysis of larger molecules on fragments, quanta, which received physiological activity in the form of function regulators. These processes in their adapted, according to Darwin's mechanism of natural selection, value were recorded into the genome since synthesis readings of the polypeptides were fixed. The formation of multicellular organisms was promoted by the arise of regulatory systems and their integration under the supervision of the nervous system.     

An integrative model of evolutionary covariance: a symposium on body shape in fishes

A major direction of current and future biological research is to understand how multiple, interacting functional systems coordinate in producing a body that works. This understanding is complicated by the fact that organisms need to work well in multiple environments, with both predictable and unpredictable environmental perturbations. Furthermore, organismal design reflects a history of past environments and not a plan for future environments. How complex, interacting functional systems evolve, then, is a truly grand challenge. In accepting the challenge, an integrative model of evolutionary covariance is developed. The model combines quantitative genetics, functional morphology/physiology, and functional ecology. The model is used to convene scientists ranging from geneticists, to physiologists, to ecologists, to engineers to facilitate the emergence of body shape in fishes as a model system for understanding how complex, interacting functional systems develop and evolve. Body shape of fish is a complex morphology that (1) results from many developmental paths and (2) functions in many different behaviors. Understanding the coordination and evolution of the many paths from genes to body shape, body shape to function, and function to a working fish body in a dynamic environment is now possible given new technologies from genetics to engineering and new theoretical models that integrate the different levels of biological organization (from genes to ecology).     

Functional evolution: origin and problems

In the article the history of comparative and evolutionary physiology since the early XIX is given. The most substantial methods of evolutionary physiology are described. In the mid-50ies Orbely put forward the suggestion concerning two tasks facing evolutionary physiology, namely the study of evolution of functions and functional evolution. In the present work attention is given to the principles underlying evolution of functions on different levels of physiological systems. The main aspects of functional evolution are discussed.     

Structural and regulatory evolution of cellular electrophysiological systems

SUMMARY Cellular electrophysiological systems, like developmental systems, appear to evolve primarily by means of regulatory evolution. It is suggested that electrophysiological systems share two key features with developmental systems that account for this dependence on regulatory evolution. For both systems, structural evolution has the potential to create significant problems of pleiotropy and both systems are predominantly computational in nature. It is concluded that the relative balance of physical and computational tasks that a biological system has to perform, combined with the probability that these tasks may have to change significantly during the course of evolution, will be major factors in determining the relative mix of regulatory and structural evolution that is observed for a given system. Physiological systems that directly interface with the environment will almost always perform some low-level physical task. In the majority of cases this will require evolution of protein function in order for the tasks themselves to evolve. For complex physiological systems a large fraction of their function will be devoted to high-level control functions that are predominantly computational in nature. In most cases regulatory evolution will be sufficient in order for these computational tasks to evolve.     

A zonal model of cortical functions

A model of cortical functions is developed with the object of simulating the observed behavior of individual neurons organized in unit circuits and functional systems of the cerebellum, the cerebrum and the hippocampal formation. The neuronal model is capable of representing refractory and potentiated states, as well as the firing and lowest resting states. The unit circuits of each system consist of all common types of cells with known synaptic connections. In the cerebral system these unit circuits are interconnected to form columns as well as zones. A new discrete neural network equation, which takes account of interactions with the extracellular field, is proposed to simulate electrical activity in these circuits. A coherent theory of cortical activity and functions is derived that accounts for many of the observed phenomena, including those associated with the development of long-term potentiation and sequential memory. Three appendices are devoted to the theory of extracellular interactions, the derivation of non-linear network equations, and a computer program to simulate learning in the cortex.     

Coevolution of physiological systems

Coevolution is the interaction in the process of evolution of different species that are closely related biologically but do not exchange genetic information. In this paper, we address the problem of coevolution of the whole organism’s physiological systems as a process of the interrelated development of structure and function as well as their regulatory systems during the formation of living organisms. We consider the coevolution of osmoregulation and the nitrogen metabolism type, systemic and individual coevolutionary strategies of cell volume regulation in poikiloosmotic and homoiosmotic animals, coevolution of effectory organs and endocrine factors in the development of water–salt homeostasis, co-involvement of neurohypophyseal nonapeptides and glucagon-like peptide-1 in the regulation of the renal function aimed at stabilizing physico-chemical parameters of extracellular fluids which make up the internal environment of the organism.     

EMERGENCE OF TEMPLATE-AND-SEQUENCE-DIRECTED (TSD) SYNTHESES: I. A BIO-GEOCHEMICAL MODEL

A biogeochemical model for the evolution of template-and-sequence-directed (TSD) syntheses of biological templates (proto-RNAs) and catalysts (peptides) is described. A fluctuating environment characterized by hydrating (cool) and dehydrating (warm) phases with cycles of consecutive organic reactions, as well as a constant supply of the polymeric building blocks is assumed. The scenario starts with the catalyzed formation of a primordial population of small random peptides, based on the relatively-ineffective mineral catalysts. The resulting peptides initiate a catalytic takeover process, during which the catalytic functions are gradually taken over by peptides. The evolution of TSD peptides is based on a combination of Lahavs (1991) co-evolution and Möller and Janssen's (1990) specific recognition sites hypotheses. During the emergence of TSD systems the fraction of TSD peptides and proto-RNA constituents rises from almost insignificance to dominance in a TSD Reactions Takeover. The TSD system is characterized by autocatalysis, positive feedback loops and a primordial genetic code. The model is the basis for a computer program (Part II of present series).     

A family of acid-sensing ion channels from the zebrafish: widespread expression in the central nervous system suggests a conserved role in neuronal communication

Acid-sensing ion channels (ASICs) are excitatory receptors for extracellular H(+). Proposed functions include synaptic transmission, peripheral perception of pain, and mechanosensation. Despite the physiological importance of these functions, the precise role of ASICs has not yet been established. In order to increase our understanding of the physiological role and basic structure-function relationships of ASICs, we report here the cloning of six new ASICs from the zebrafish (zASICs). zASICs possess the basic functional properties of mammalian ASICs: activation by extracellular H(+), Na(+) selectivity, and block by micromolar concentrations of amiloride. The zasic genes are broadly expressed in the central nervous system, whereas expression in the peripheral nervous system is scarce. This pattern suggests a predominant role for zASICs in neuronal communication. Our results suggest a conserved function for receptors of extracellular H(+) in the central nervous system of vertebrates.     

蛋白质组研究中细胞质膜的纯化和纯度鉴定研究进展

细胞质膜是构成细胞对外界环境的屏障和细胞内外环境交流的界面,镶嵌或连接于其中的蛋白质参与细胞/细胞以及细胞/细胞外基质的识别、信号的接受和跨膜传导、细胞内外物质的转运;此外,质膜蛋白质在药物研发中也起着非常重要的作用,在现有的药靶中质膜蛋白质占70%.因此质膜蛋白质组学研究成为亚细胞蛋白质组学研究的热点.然而在质膜蛋白质组学的研究中,由于很难获得高纯度的质膜样品,因此这一领域的研究具有很大的挑战性.现主要对质膜及其微区结构的纯化方法和质膜纯度的评价标准作扼要的介绍.     

Archean Iron-Based Metabolism Analysis and the Photoferrotrophy-Driven Hypothesis of Microbial Magnetotaxis Origin

Despite its biological and geological significance, the origin of microbial magnetosome biomineralization, as well as the evolution of magnetotaxis, is still not well understood. Recently, the origin of magnetotaxis has been proposed to already exist in the Archean Eon. However, the Archean environment was fully anoxic. Therefore, what was the reason for the evolution of magnetotaxis in the anoxic Archean ocean and what mechanism could lead to the formation of single domain-sized magnetite nanoparticles that are a necessary condition of magnetotaxis functionality? Since the genetically controlled magnetosomes formation is extremely energetically demanding, in this review, we analyze Archean anoxic iron-based metabolism and we delineate the alternative possibilities of non-genetically controlled magnetosomes precursor origin as a necessary condition of magnetotaxis emergence. We show that coupling of anoxygenic photosynthesis with ferrous iron as an electron donor, with anaerobic respiration with ferric iron as an electron acceptor, provided sufficient material for non-genetically controlled magnetite formation. The co-evolution of cyanobacteria is suggested as the possible environmental pressure responsible for the emergence of Archean magnetotaxis. In accordance with the hypothesis of the reactive oxygen species-protective function of the first magnetosomes, we show that the formation of single domain-sized magnetite nanoparticles did not have to be initially connected with magnetotaxis origin, neither had to be genetically controlled nor intracellular. Instead, it could result from the long-lasting ambient pressure of metabolically produced extracellular iron oxide minerals in photoferrotrophs together with the emergence of local oxygen oases. The presence of oxygen could favor cells with the ability to navigate into oxic-anoxic transition zones since the oxygen was entirely toxic to Archean life. This evolutionary advantageous trait could finally result in a niche construction origin of genes responsible for intracellular magnetosome formation, which have remained preserved until today.     

外泌体：探究微生物感染机制的新视角

外泌体是细胞外囊泡的一种,由多囊泡体和细胞膜融合后释放到细胞外。外泌体能递送有功能的分子,包括蛋白质、脂质和核酸给受体细胞,参与细胞间通讯,影响细胞的各种生理与病理功能。近年来,越来越多研究发现,外泌体在病原微生物感染性疾病发病机制中也发挥重要作用。在慢性感染中,外泌体能传播感染性蛋白质和病毒RNA,并改变未感染细胞的功能。同时,这些具有极强免疫原性的蛋白质可向免疫系统递送病原信息,激活免疫系统。本文就外泌体在慢性病原体感染中的相关研究进展进行综述。研究这些机制,可为慢性感染的诊断和治疗提供新的思路。     

Peptides derived from the extracellular loop of receptors: structure, mechanisms of action and application in physiology and medicine

One of the main tasks of the peptide strategy, a new direction in modern biochemistry and physiology, is the creation of selective and effective regulators of hormonal signaling systems on the basis of the peptides corresponding to functionally important regions of signal proteins. At the last years the greatest interest is connected with peptides, derivatives of the extracellular loops of receptors of the serpentine type. With these peptides the molecular basis of interaction between receptors and their ligands are studied, the new approaches for construction and testing of highly selective agonists and antagonists are developed, the etiology and pathogenesis of diseases of human and animals induced by autoimmune reactions to the extracellular loops of receptors are investigated. It is shown that peptides corresponding to the extracellular loops of the receptors and the specific antibodies to them are capable to regulate the activity of hormonal signaling systems in vitro and in vivo and can be considered as functional probes for studying of physiological functions in the norm and pathology. In the review the data obtained during the last years concerning the structures, functions, mechanisms of action and practical application ofpeptides, derivatives of the extracellular loops of serpentine type receptors, are summarized and analyzed. The prospective of their use in fundamental biology and practical medicine are discussed.     

Cellular immunosenescence in adult male crickets, Gryllus assimilis

Ecological immunity studies in invertebrates, particularly insects, have generated new insights into trade-offs between immune functions and other physiological parameters. These studies document physiologically directed reallocations of immune costs to other high-cost areas of physiology. Immunosenescence, recognized as the age-related deterioration of immune functions, is another mechanism of radically altering immune systems. We investigated the hypothesis that aging brings on immunosenescence in adult males of the cricket, Gryllus assimilis. Our data show that the intensity of melanotic nodule formation decreased with adult age from after 3-week post-adult emergence. Circulating hemocyte populations similarly decreased from about 5,000 hemocytes/μl hemolymph to about 1,000 hemocytes/μl hemolymph. The numbers of damaged hemocytes in circulation increased from less than 10% at 1-week post-adult emergence to approximately 60% by 3-week post-adult emergence. The composition of hemocyte types changed with age, with increasing proportions of granulocytes and decreasing proportions of plasmatocytes. The declines in nodule formation were not linked to the adult age of sexual behaviors, which begin shortly after entering adulthood in this species. We infer that age-related senescence, rather than cost reallocations, may account for observed declines in various parameters of immune functions in insects, as seen in other animals.     

Integrons: natural tools for bacterial genome evolution

Integrons were first identified as the primary mechanism for antibiotic resistance gene capture and dissemination among Gram-negative bacteria. More recently, their role in genome evolution has been extended with the discovery of larger integron structures, the super-integrons, as genuine components of the genomes of many species throughout the gamma-proteobacterial radiation. The functional platforms of these integrons appear to be sedentary, whereas their gene cassette contents are highly variable. Nevertheless, the gene cassettes for which an activity has been experimentally demonstrated encode proteins related to simple adaptive functions and their recruitment is seen as providing the bacterial host with a selective advantage. The widespread occurrence of the integron system among Gram-negative bacteria is discussed, with special focus on the super-integrons. Some of the adaptive functions encoded by these genes are also reviewed, and implications of integron-mediated genome evolution in the emergence of novel bacterial species are highlighted.     

On the Classification and Evolution of Protein Modules

Our efforts to classify the functional units of many proteins, the modules, are reviewed. The data from the sequencing projects for various model organisms are extremely helpful in deducing the evolution of proteins and modules. For example, a dramatic increase of modular proteins can be observed from yeast to C. elegans in accordance with new protein functions that had to be introduced in multicellular organisms. Our sequence characterization of modules relies on sensitive similarity search algorithms and the collection of multiple sequence alignments for each module. To trace the evolution of modules and to further automate the classification, we have developed a sequence and a module alerting system that checks newly arriving sequence data for the presence of already classified modules. Using these systems, we were able to identify an unexpected similarity between extracellular C1Q modules with bacterial proteins.     

Architecture of physiological functions: the same basis but new aspects

The principles of physiological functions formulated by J. Barckroft (constancy of the internal medium, reserves, any adaptation as an integration, principle of antagonism, doubling of mechanisms) are compared with principles of modern physiology. The place and role of physiology in the life sciences are discussed. The necessity of taking into consideration 4 level of regulation of functions (the nervous system, hormones, autacoids, physicochemical factors of the extracellular fluid) is substantiated, as well as the necessity of identification of 4 levels of organization of physiological systems. The main role of the water-salt homeostasis in maintaining the cell volume is suggested. Significance of various types of receptors and second messengers in regulation and modulation of functions is shown.     

Adaptivity of social systems: the problem for scientific research

The notion of adaptive evolution of social systems as of a real process of selection of the properties of such systems implies group selection. But strong evidences of effective group selection seem impossible, at least in vertebrates. However, understanding the origin of social systems adaptivity based on individual selection is difficult, as well, without analyzing the proximal mechanisms of the formation of such systems. I suppose that social systems change due to changes of individual features that underlie the proximal mechanisms of the system formation. These features are the characteristics of neurophysiological and hormonal regulatory mechanisms. They are strongly associated with intrinsic biochemical processes and are coded in the genome. Thus, the evolution of social systems is the evolution of their proximal mechanisms. At the same time, the specificity of neurophysiological and hormonal regulation determines not only social interactions, but also the individual behaviour of animals. The most important characteristics of life history, such as the regime of activity, foraging strategy, etc., are strongly affected by the same regulatory mechanisms. This view is useful for understanding the relations combining many features into an integrated and adaptive species-specific life form. I suppose that such forms emerged as evolutionary consequences of changes in regulatory mechanisms adaptive to specific environment. Thus, we have as substantial reasons to discuss adaptations of social systems to ecological features as to discuss ecological features adapted to particular social systems. The species-specificity of regulatory mechanisms is probably based on different kinds of evolutionary choice between the rapidity and the perfection of adaptation, between flexibility and stability, and between sensibility and resistibility. I think that this choice depends largely on the predictability of the environment. The less predictable it is, the more it increases the selective value of sensibility, flexibility, and rapidity of evolution. On the contrary, stable and predictable environment stimulates less rapid but more perfect adaptations. Such choices consolidate in the genome during evolution as specific features of neurophysiological and hormonal regulation systems. These specific features, in their turn, determine ecological, behavioural, and physiological species-specificity. From this point of view, evolutionary changes in social systems can be readily perceived as consequences of the selection of individuals, promoting optimal properties under particular conditional features of regulation systems. The boundary condition for this model is the absence of specificity of the characteristics of regulation systems to different forms of stress. This condition needs to be considered closely.     

Stress chaperone GRP-78 functions in mineralized matrix formation

Mineralized matrix formation is a well orchestrated event requiring several players. Glucose-regulated protein-78 (GRP-78) is an endoplasmic reticulum chaperone protein that has been implicated in functional roles ranging from involvement in cancer biology to serving as a receptor for viruses. In the present study we explored the role of GRP-78 in mineralized matrix formation. Differential expression of GRP-78 mRNA and protein was observed upon in vitro differentiation of primary mouse calvarial cells. An interesting observation was that GRP-78 was identified in the secretome of these cells and in the bone matrix, suggesting an extracellular function during matrix formation. In vitro nucleation experiments under physiological concentrations of calcium and phosphate ions indicated that GRP-78 can induce the formation of calcium phosphate polymorphs by itself, when bound to immobilized type I collagen and on demineralized collagen wafers. We provide evidence that GRP-78 can bind to DMP1 and type I collagen independent of each other in a simulated extracellular environment. Furthermore, we demonstrate the cell surface localization of GRP-78 and provide evidence that it functions as a receptor for DMP1 endocytosis in pre-osteoblasts and primary calvarial cells. Overall, this study represents a paradigm shift in the biological function of GRP-78.