Theoretical generalizations

This essay aims to define the origin, expansion, and evolution of living matter. The first formations, identified as remains, fossils, traces etc. of life are almost as old as the Earth itself. During four billion years, life on the Earth has continuously existed and been implemented in the range of conditions, ensuring the liquid state of water. During the entire period of life existence, its evolution was proceeding with the tendency of multidirectionality, after each catastrophe tending to the diversity and vastness of distribution, and all the currently living species, regardless of their complexity, have the same evolutionary age. The property of reproductive surplus (multiplication) is inherent in all the living matter. The reproduction of all the living matter is implemented via the “development” – a process of continuous occurrence of something new that did not exist in the previous moment in the reproduced individual at each specific moment of time with the tendency towards the reproduction of a “copy”. In its fundamental basis, Life is based on a programme, its material support is implemented and exists not in the field of causative-consecutive events, but in the field of programmed-causative-consecutive events. This predetermines the “biology laws”, the behaviour of the material constituent of Life at each time period, and the future of the material constituent of life

Summary

The use of MSCs as a therapeutic agent is proven to be highly successful in many cases. However, the effects obtained are often temporary, and not leading to complete recovery. The reasons of such phenomenon are discussed in the article and the concept of “triggering effects” of MSCs is substantiated. The effect consists of the fact, that signal molecules, secreted by MSCs after administration, on one hand reduce the cell damage severity, supports and heals the cells. And on the other hand, MSCs induce mobilization and activation of the own (resident) stem cells, which replace the damaged cells. The realization of the therapeutic effect depends on the presence or absence of genetically determined disorders.

Summary

The problem of chronic diseases is analyzed from the perspective of general biology. We develop and substantiate the idea that the chronic diseases are an evolutionary mechanism of cleansing the population and the species of its mutational load. This is achieved by keeping self-restoration systems of a chronically damaged organism in the off-state, unlike in the ‘permissible’ self-restoration triggered by the acute damage. Evolutionary, chronic diseases serve as a somatic marker for the accelerated elimination of their carriers.

The review briefly describes the history of prediction and discovery of mesenchymal stem cells (MSCs). The evolution of our views on the nature, functions, and status of MSCs in the organism is presented. We propose that MSCs represent transient states of different cells. The MSCs are involved in tissue repair by programmed replacement of the dying or dead cells). They also induce o renewal of specialized differentiated cells by action of specific signal molecules). MSCs might also participate in the continuous renewal of an organism during its lifetime.

Монография посвящена концепции информационного пространства Биосферы. Представлены и анализируются многочисленные литературные данные о наличии, распространении, вариантах образования, путях переносов материального носителя генетической информации и формах его пребывания в природе вне организмов. Обсуждаются необычные следствия из развиваемых представлений и ставится вопрос о переоценке, переосмысливанию ряда устоявшихся понятий. Изложение материала выполнено в живом стиле, а текст обильно иллюстрирован. Монография рассчитана на широкий круг биологов и тех, кто интересуется биологией.

The present article analyzes the problem of «origin»by the example of respiration. The «origin» implies the system of molecular sensor and affecting signal, which start the chain (cascade) of molecular conversions, leading to the phenotypic changes. As «origin» the most studied elements of the cascade are chosen: molecular oxygen, PHD and HIF protein families and molecules interacting directly with them. The alternative and additional systems are also considered. The important point of the whole regulation is the absence of signaling systems for increasing molecular oxygen concentration (above necessary, i. e. hyperoxia) in the cell.

The present article analyzes the problem of «origin»by the example of respiration. The «origin» implies the system of molecular sensor and affecting signal, which start the chain (cascade) of molecular conversions, leading to the phenotypic changes. As «origin» the most studied elements of the cascade are chosen: molecular oxygen, PHD and HIF protein families and molecules interacting directly with them. The alternative and additional systems are also considered. The important point of the whole regulation is the absence of signaling systems for increasing molecular oxygen concentration (above necessary, i. e. hyperoxia) in the cell.

Summary

The idea about intracellular transport of metabolic products is presented considering two constituents. The first was described in general in the previous publication. It justified the thesis that cell metabolism is localized and realized not on the fixed structures but on the vigorously and steadily moving («prowling») microvesicles. In the current paper we have shown that an addition of tetrazolium (MTT) to mesenchymal stem cells (MSC) leads to the cumulation of formazan on the surface of actively moving vesicles. This process was time-tracked and shown in dynamics. As formazan is a metabolite product, its formation on the vesicles is an experimental confirmation of the metabolic processes on these moving structures. The second constituent is presented as a hypothesis that is based on the literature data on the intracellular electrical potentials and the calculations of their possible involvement in precision transport of metabolic products.

Summary

The article raises the problems of intracellular spatial and temporal organization of metabolism, signaling, and energy supply of these processes. To provide cell functions, the enzymes of metabolic chains, molecules of signaling pathways, and macroergs (as units of molecular interactions, accompanied by energy consumption) should find their partners and get their precise spatial relationship. The current views are based on ideas of compartmentalization of all processes as local sites of cellular matrix membrane, where specific stages of different metabolic cycles take place. The assembly of complexes of macromolecules in the number and combinations, required for their adequate functioning in the space of a cell, is generally described as intracellular transport of vesicles, implemented by mobile elements of cytoskeleton. Inside the vesicle there is «effective load» – macromolecules. The membranes of these vesicles fuse with specific sites of the matrix membranes and therefore relocate macromolecules. Neither calculations nor assumptions allow explaining precise formation of enzymatic chains, their interaction, signaling, etc. on this basis. Such transport of macromolecules (inside vesicles) enables solving other tasks. The concept of search-and-address systems in the form of space-scanning micro vesicles is proposed and well-grounded for purposes of searching for partners, forming chains and complexes, and building compartments. The micro vesicles collect corresponding chains of enzymes, signaling, and ensure the interactions on their surface. These micro vesicles are exactly those compartments, which provide for both precision of processes and their relationship. Keywords: metabolism, cell, compartmentalization, vesicle, transport of macromolecules, precision of processes

Summary

The published experimental data on functional differences in organization and functioning of genetic materials between eukaryotes and prokaryotes have been analyzed. A new conception of both specific status of prokaryotic genome and uncertainty of the cell definition has been proposed. It is based on the information about multitude and diversity of the channels for horizontal gene transfers, taking into account the fertility characteristics, and the facts of formation of some bodies less than 0,2 µm in size under different conditions. The question is: what are the forms which cannot be cultivated in laboratory and at the same time prevail in natural substrates?

Summary

The conceptions of mutations are analyzed. The literature data that are not consistent with the existent ideas about mutations are presented. The statement about physiological ambiguity of mutations and their biological role is formulated, according to which the mutations in soma perform a regulatory role, therefore, they are a normal component of biological processes, controlled by an organism. Once uncontrolled, mutations in soma lead to oncogenesis. As for a germ route, mutations provide the elimination of their carriers through cascade integral processes, thus realizing the function of purification. Being out of control and not resulting in elimination of their carriers, the mutations are realized into the whole range of hereditary pathologies – from a latency form («mutational load») to a bright manifestation.

Our "Shagreen leather" is our problem. And we have to solve it
Biopolym. Cell. 2003;19(2):113-132.http://dx.doi.org/10.7124/bc.000644

One of the main problems to be solved by modern biology is disclosing a complex of mechanisms determining absolute reliability of both the restriction of any organism (including human) lifetime, and the existence of practically immortal life (if taken as a continuous chain of unconditionally mortal generations). A planned series of four publications is aimed at the formulation of basic ideas to develop the problem conception. The essentials allowing to regard a cell as a typical (though very complex and perfect) molecular machine, and an organism – as a self-organizing system of such molecular machines, are analyzed in the first publication.

Our "Shagreen leather" is our problem. And we have to solve it. 2. The united space of organism
Biopolym. Cell. 2003;19(4):328-349.http://dx.doi.org/10.7124/bc.000665

Organism is a special, unified in itself formation consisting of a very large amount of different cells. The problem of an such unification is being analyzed. Thesis about some united organism space is being advanced and substantiated. Such space consists of the following combined spaces: uninterruptedly opened regulatory-metabolic, uninterruptedly closed regulatory-metabolic, rotary, architectural and dynamic. The peculiarities of such a combination and consequences following for the examining problem are being discussed.

Our "Shagreen leather" is our problem. And we have to solve it. 3. A missing link
Biopolym. Cell. 2003;19(6):473-491.http://dx.doi.org/10.7124/bc.000678

The idea that genomes of multi-cellular organisms, including human, are not informatively isolated but united into a common informational space is being developed. Such unification is performed through formation of out-chromosomal DNA, its release from cells, absorption by other cells (or direct transfer from cell to cell) and further selective inclusion into their genomes. The common informational space of organism is a special and exceptionally effective mechanism of the resistance to mutational pressure.

Our shagreen leather is our problem, and we have to solve it. 4. «Shagreenity» that makes our skin shagreen
Biopolym. Cell. 2004;20(4):267-289.http://dx.doi.org/10.7124/bc.0006B0

The principal differences between the «living» and «non-living», are discussed taking into account the specific features of life, the «living» and an organism. In this aspect, the «living» differs from the «non-living» by the existence of information transferred from one carrier to another. While in the «non-living» its information is inseparable from the carrier, in the «living» all the material carriers get destroyed and disappear countless times, but the information and the only information) is transferred endlessly. However, the providing system is necessary for the information to be re-written. Because the «living» (in contrast to the «non-living» again, but this time in relation to a functional characteristic) differs by self-assembly, self-creation of the alike to itself out of the «unlike», the separable information of the «living» includes in itself all the information concerning «self» processes. Conceptually, the life is the way of the information existence, not in a general sense, but meaning the information aimed at the reconstruction of the systems serving for this information, for supplying every «self» process and the interactions with environment, as well as the programs for correct switching on all the systems. To correct the mistakes in the organism information system (written in DNA as its material carrier), a standard is needed. The information of an individual, being informationally closed system, is the standard by itself. However, like any closed system, an organism and its information standard inevitably degrade. In generations such informationally closed system becomes informationally open and moreover, in case of Biosphere - self-complicating (being formally closed).

Our «Shagreen leather» is our problem. We have to solve it ourselves. 5. Forerunner
Biopolym. Cell. 2005;21(3):230-249.http://dx.doi.org/10.7124/bc.0006ED

The problem of biological time and its difference from physical time (i. e. reversibility) is under discussion. Some issues of the problem usually identified as «struggle with aging» are under analysis. The possibilities of regenerative medicine are evaluated in connection with this question. The mechanism of purification (though not radical, but sufficiently effective) from the mutations accumulated in stem cells has been investigated. In the frame of the conception being developed the anabiosis and its incompatibility with the contemporary view of life are discussed. «The split of biological time» is being defined as a movement to a new level of knowledge.

Our shagreen leather is our problem. And we have to solve it. 6. Paying back.
Biopolym. Cell. 2005;21(6):485-514.http://dx.doi.org/10.7124/bc.00070E

The problem of spatial and temporal organization of metabolic cycles in a cell is being analyzed. The unsolved questions are emphasized and the variants for their solution are suggested. The total amount of intermediate products as well as their removal from the active centers of metabolic cycle enzymes are being evaluated in view of the ideas under consideration. The removal of metabolytes is believed to be a result of the macromolecular damage. The age-related changes are explained taking into account this suggestion along with peculiarities of the mutative process.

Our «Shagreen leather» is our problem, and we are the ones to solve it. 7. The change of paradigm. First steps
Biopolym. Cell. 2006;22(4):251-275.http://dx.doi.org/10.7124/bc.000738

The problem of Timeliness of scientific and technological achievements is brought up for discussion. Existence of more sophisticated mechanisms rather than the real implementation of a new idea, development, and even prototype is being postulated in order for this novelty to enter life and everyday routine. As for our “shagreen leather” problem under consideration, Timeliness is conditioned by Mankind passing into the new system of his existence called the Noosphere. And this fact predetermines the inevitability of its solving. The notion of biological time is analyzed on the grounds of its difference from physical one. The last, though, still not resolved fundamental restriction on the way to the biological time control, i.e. heterochronous incompatibility, is highlighted. The reality of the beginning of the individual’s parting in biological time with his subsequent heterochronous compatibility was also marked to have passed into practice, in the form of cord blood preserving and storing in liquid nitrogen (i.e. at the condition, when the biological time is stopped) with its subsequent usage as autologous material for tissue and organ reconstruction (“regenerative medicine”) for a young, adult and old organism to be. Possible ways of heterochronous material usage and expected establishment of the new “age regulating” trend in medicine are analyzed.

The concept presented is confirmed by both direct experiments on the genetic markers transfer and microscopic observations. The authors formulate an idea that there is a universal informational space of the organism, created due to the DNA release within the lifetime of cells without destroying their genomes (and DNA absorption, complementing the mutations) or due to the addressed transfer of genetic material by specialized cells.

Questions concerning a wide group of the organism vital activity waste formed and transformed in tissues are discussed. The definition of this waste, named as "garbage", is given. This designation is complementary to the term "scavenger receptor", the receptor through which the absorption of this group of vital activity garbage takes place. On the basis of analysis of "garbage" formation and utilization, possible pathological processes in the organism are considered, and the existence of a separate pathology form named «scavenger-syndrome», is postulated.

The non-traditional ideas about the possible evolution of the infections (mainly, viral), and its mechanisms are discussed and analysed in the review. The formation of Noosphere as a self-sufficient system, alternative to Biosphere caused the explosive (as for the scope and the rate) viral evolution. The discrepancy between the rate of viral variability and the rise of new infections is noted which suggests the «indefinition of infections». The acceleration and direction of the evolution of the infections (mainly, viral) a forecasted. The condition about the «ranges» of the infections' evolution is proved and the criteria for such «ranges» are formulated. The beginning of pure Noosphere contribution into the evolution of the infections is noted.

The problem of oncogenesis from the point of view of molecular genetics is analyzed. The special attention is paid to the genome instability as the main reason of the malignant cells growth. It is pointed out that the genome instability provides the material for the selection. An immune control system destroys everything what it can destroy. But at the same time it creates the «own» tumor for each patient, which is not recognized by the immune control system as a harmful one.

The ideas about viruses as tools for transduction of the genetic information in tlie biosphere that provide unity of all living beings in global scale have been developed in this article. According to these ideas, tlie previous and modern meaning of notion «virus», as an infectious basis that evokes pathologic events, does not correspond to new facts and should be radically reconsidered.

Биологические пьезо-эффекты как следствие механохимических процессов и возможный механизм клеточной гравиовосприимчивости / В. А. Кордюм ; Международный центр научной культуры "Всемирная лаборатория". Украинское отделение. - К. : [б.в.], 1997. - 134 с.

Книга- перевертыш.- На рус. и англ. яз.

И тогда я сел писать эту книгу : (не совсем обычные представления о генетике человека) / В. А. Кордюм ; Украинское отделение Всемирной лаборатории. - К. : [б.в.], 1993. - 247 с. - ISBN 0233-7657

The whole complex of investigations is described that allows to run the way from the idea to experimental realization of a fundamental possibility of gene therapy and its application to mass pathologies on the sample of insulin-dependent diabetes and atherosclerosis. The search and analysis were performed of such regulatory elements that would permit an expression irrespective of the state of a general cell regulation. Expression of the implanted gene material is shown on cells of different tissues and different organisms and also in vivo (both the model gene of β-galactosidase Escherichia coli and insulin- and apolipoprotein high density Al-coding genes related to above stated pathologies). It is concluded that the results obtained in the culture outside the organisms shouldn't be extrapolated on the animals, i. e. on the organism's level. The expression of recombinant molecules is shown to be ambiguous and depend on gene's surroundings and the type of recipient cells. Both in the culture and in the organism the individual cell heterogeneity is observed in the quantitative characteristics of the expression of gene implanted from outside. Besides, an individual organism and age heterogeneity with regard to the expression of the exogenous gene is reported. The conclusion is made about the necessity to individualize gene therapy of mass pathologies.

We are putting forward and giving ground the statement according to which accepted and the only possible model of human civilisation for visible future (providing stabilization of the population growth with minimum child-birth), is incompatable with human biology in part of his genome and should lead to gene degeneration. Taking into consideration mutogenic influence of environment and practical stabilization of population growth, in developed countries they came closely to gene degeneration or in some regions it is possibly going on. Disorders of genome, which already have occured could be corrected only by gene therapy. So, its wide development is inevitable if we have enough time to realise it.

The possibilities of gene therapy for treatment of basic mass human pathologies such as atherosclerosis, malignant neoplasms, infectious diseases and diabetes have been analysed. The gene therapy is subdivided into two basic trends: 1) repair of gene defect; 2) gene compensation of function. The first trend is based on the precision replacement of a defective gene or its fragments and requires obligatory knowledge of lesion details. It is mostly implied in terms of gene therapy but refers almost exclusively to classic hereditary diseases caused by defects in gene structure. The second trend provides for the introduction of gene which should compensate for the reduced or generally altered function under specific regulation. In this case the knowledge of the specific gene defect responsible for the pathology is not obligatory. Since mass pathologies are mostly due to the defects caused by unknown damages in the expression regulation of the intact structural gene, they can be repaired via compensation of gene function. The general scheme of gene therapy of basic mass pathologies and the concrete variants for its elucidation have been proposed. Recent publications on gene therapy of basic mass pathologies have been reviewed.

A range of problems comprising the notion «gene therapy» in the broad and narrow sense has been analyzed. In the broad sense this field of research includes the following components: gene surgery, gene therapy itself; gene prophylaxis, gene diagnosis, gene vaccination, «gene antihumanism», gene engineering of gametogenesis, gametes and zygotes and prenatal gene engineering. Taking into account the components and the range of problems solved by them, the full definition of the field of research has been suggested as well. In its full meaning gene therapy signifies genome identification per individuum followed by correction of hereditary cell apparatus of the whole organism or its separate tissues, elimination of diseases inherent in the patient and prevention of appearance of any novel pathologies with time and in accordance with desire (or in case of need) reconstruction (in human cells) of novel genetic information ensuring the emergence of potentially different phenotypes up to those completely absent in nature in the living and future generations.

Кордюм В.А Эволюция и Биосфера. Киев. Наукова Думка 1982 г.
В монографии анализируется современное (1982 г.) состояние эволюционной теории. Подробно рассматриваются последние достижения в изучении переноса генетической информации у живых организмов. На основании обширного литературного материала и собственных данных произведена количественная оценка информационного окружения и, поступления в различные живые существа по конкретным информационным каналам материального носителя наследственности. Демонстрируется универсальность разбираемого процесса, который имеет место не только у прокариотов, но и у организмов с дифференцированным ядром. Развиваются представления о том, что для более правильной оценки эволюционных событий должна быть введена информационная составляющая эволюции.

Для биологов, селекционеров, преподавателей и студентов биологических факультетов.