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Yuri K. Shestopaloff

Publications and source records attributed to Yuri K. Shestopaloff.

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Metabolic Allometric Scaling of Unicellular Organisms as a Product of Selection Guided by Optimization of Nutrients Distribution in Food Chains

One of the major characteristics of living organisms is metabolic rate, which is the amount of energy produced per unit of time. When the mass of organisms increases, the metabolic rate also increases (usually as a power function of mass), but usually slower than mass. This effect is called metabolic allometric scaling. Its causes are considered unknown. The effect has important implications for individual and population organismal development. It was shown in the first part of this study, presented in a separate paper, that in the case of multicellular organisms, this effect is a consequence of natural selection and optimization of nutrient distribution between the species of a food chain, sharing resources of a common habitat. Here, in the second part that studies unicellular organisms, we discover that the same principle of natural selection guided by optimization of nutrient distribution between the species of a food chain defines also metabolic allometric scaling of unicellular organisms. To find that, we consider the metabolic properties of Amoeba proteus, fission yeast Schizosaccharomyces pombe, Escherichia coli, Bacillus subtilis, Staphylococcus. The sharing of nutrients is optimized in such a way that bigger microorganisms have progressively bigger nutrient influx per unit of surface. This evolutionary arrangement secures the stability of a food chain by providing certain metabolic advantages for bigger organisms. Accounting for this regular increase of nutrient influx with mass increase, we obtained allometric exponents and their ranges close to experimental values, thus proving that metabolic allometric scaling of both multicellular and unicellular organisms is defined by the same fundamental evolutionary principle of optimized sharing of nutrients between the species of a food chain.

q-bio.OT

Metabolic allometric scaling of multicellular organisms as a product of evolutionary development and optimization of food chains

Production of energy is a foundation of life. Metabolic rate of organisms (amount of energy produced per unit time) generally increases slower than organisms' mass, which has important implications for life organization. This phenomenon, when considered across different taxa, is called interspecific allometric scaling. Its origin has puzzled scientists for many decades, and still is considered unknown. In this paper we posit that natural selection, as determined by evolutionary pressures, leads to distribution of resources, and accordingly energy, within a food chain, which is optimal from the perspective of stability of the food chain, when each species has sufficient amount of resources for continuous reproduction, but not too much to jeopardize existence of other species. Metabolic allometric scaling is then a quantitative representation of this optimal distribution. Taking locomotion and the primary mechanism for distribution of energy, we developed a biomechanical model to find energy expenditures, considering limb length, skeleton mass and speed. Using the interspecific allometric exponents for these three measures and substituting into the locomotion-derived model for energy expenditure, we calculated allometric exponents for mammals, reptiles, fish and birds, and compared these values with allometric exponents derived from experimental observations. The calculated allometric exponents were nearly identical to experimentally observed exponents for mammals, and very close for fish, reptiles and the basal metabolic rate of birds. The main result of the study is that the metabolic allometric scaling is a function of a mechanism of optimal energy distribution between the species of a food chain. This optimized sharing of common resources provides stability of a food chain for a given habitat and is guided by evolutionary pressures and natural selection.

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Physical mechanisms influencing life origin and development. Physical-biochemical paradigm of Life

The present view of biological phenomena is based on a biochemical paradigm that development of living organisms is defined by information stored in a molecular form as some genetic code. However, new discoveries indicate that biological phenomena cannot be confined to a biochemical realm alone, but are also influenced by physical mechanisms. These mechanisms work at cellular, organ and whole organism spatial levels. They impose uniquely defined constraints on distribution of nutrients between biomass synthesis and maintenance of existing biomass, thus influencing the composition of biochemical reactions, their successive change and irreversibility during the organismal life cycle. Mathematically, such a growth mechanism is represented by a growth equation. Using this equation, we introduce growth models, show their adequacy to experimental data, and discover two types of division mechanisms, examining growth of unicellular organisms Amoeba, S. pombe, E. coli, B. subtilis, Staphylococcus. Also, on the basis of the growth equation, we find different metabolic characteristics of these organisms. For instance, it was shown that in logarithmic coordinates the values of their metabolic allometric exponents are located on a straight line. This fact has important implications with regard to evolutionary process of organisms within a food chain, considered as a single system. High adequateness of obtained results to experimental data, from different perspectives, as well as excellent compliance with previously proven more particular knowledge, and with general criteria for validation of scientific truths, proves validity of the introduced general growth mechanism and the growth equation. Taken together, the obtained results set solid grounds for introduction of a more comprehensive physical-biochemical paradigm of Life origin, development and evolution.

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New reconstruction and data processing methods for regression and interpolation analysis of multidimensional big data

The problems of computational data processing involving regression, interpolation, reconstruction and imputation for multidimensional big datasets are becoming more important these days, because of the availability of data and their widely spread usage in business, technological, scientific and other applications. The existing methods often have limitations, which either do not allow, or make it difficult to accomplish many data processing tasks. The problems usually relate to algorithm accuracy, applicability, performance (computational and algorithmic), demands for computational resources, both in terms of power and memory, and difficulty working with high dimensions. Here, we propose a new concept and introduce two methods, which use local area predictors (input data) for finding outcomes. One method uses the gradient based approach, while the second one employs an introduced family of smooth approximating functions. The new methods are free from many drawbacks of existing approaches. They are practical, have very wide range of applicability, provide high accuracy, excellent computational performance, fit for parallel computing, and very well suited for processing high dimension big data. The methods also provide multidimensional outcome, when needed. We present numerical examples of up to one hundred dimensions, and report in detail performance characteristics and various properties of new methods.

stat.ME

Interspecific allometric scaling of unicellular organisms as an evolutionary process of food chain creation

Metabolism of living organisms is a foundation of life. The metabolic rate (energy production per unit time) increases slower than organisms' mass. When this phenomenon is considered across different species, it is called interspecific allometric scaling, whose causes are unknown. We argue that the cause of interspecific allometric scaling is the total effect of physiological and adaptation mechanisms inherent to organisms composing a food chain. Together, the workings of these mechanisms are united by a primary goal of any living creature - its successful reproduction. This primary necessity of each organism and of the entire food chain is that common denominator, to which all organisms adjust their metabolic rates. In this article, we consider unicellular organisms, while the second paper studies multicellular organisms and the entire concept in more detail. Here, using the proposed concepts and experimentally verified growth models of five different unicellular organisms, we obtain close to experimental findings values of allometric exponents of 0.757 for the end of growth and 0.853 for the beginning of growth. These results comply with experimental observations and prove our theory that the requirement of successful reproduction within the food chain is an important factor shaping interspecific allometric scaling.

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Why cells grow and divide? General growth mechanism and how it defines cells' growth, reproduction and metabolic properties

We consider a general growth mechanism, which acts at cellular level and above (organs, systems and whole organisms). Using its mathematical representation, the growth equation, we study the growth and division mechanisms of amoeba and fission yeast Schizosaccharomyces pombe. We show how this mechanism, together with biomolecular machinery, governs growth and reproduction of cells, and these organisms in particular. This mechanism provides revealing answers to fundamental questions of biology, like why cells grow and divide, why and when cells' growth stops. It also sheds light on questions like why and how life originated and developed. Solving the growth equation, we obtain analytical expression for the growth curve of fission yeast as a function of geometrical characteristics and nutrient influxes for RNA and protein synthesis, and compare the computed growth curves with 85 experiments. Statistical evaluation shows that these growth curves correspond to experimental data significantly better than all previous approximations. Also, using the general growth mechanism, we show how metabolic characteristics of cells, their size and evolutionary traits relate, considering fission yeast. In particular, we found that fission yeast S. pombe consumes about 16-18 times more nutrients for maintenance needs than for biomass synthesis.

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A Method for Modeling Growth of Organs and Transplants Based on the General Growth Law: Application to the Liver in Dogs and Humans

Understanding biological phenomena requires a systemic approach that incorporates different mechanisms acting on different spatial and temporal scales, since in organisms the workings of all components, such as organelles, cells, and organs interrelate. This inherent interdependency between diverse biological mechanisms, both on the same and on different scales, provides the functioning of an organism capable of maintaining homeostasis and physiological stability through numerous feedback loops. Thus, developing models of organisms and their constituents should be done within the overall systemic context of the studied phenomena. We introduce such a method for modeling growth and regeneration of livers at the organ scale, considering it a part of the overall multi-scale biochemical and biophysical processes of an organism. Our method is based on the earlier discovered general growth law, postulating that any biological growth process comprises a uniquely defined distribution of nutritional resources between maintenance needs and biomass production. Based on this law, we introduce a liver growth model that allows to accurately predicting the growth of liver transplants in dogs and liver grafts in humans. Using this model, we find quantitative growth characteristics, such as the time point when the transition period after surgery is over and the liver resumes normal growth, rates at which hepatocytes are involved in proliferation, etc. We then use the model to determine and quantify otherwise unobservable metabolic properties of livers.

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Method for finding metabolic properties based on the general growth law. Liver examples. A General framework for biological modeling

We propose a method for finding metabolic parameters of cells, organs and whole organisms, which is based on the earlier discovered general growth law. Based on the obtained results and analysis of available biological models, we propose a general framework for modeling biological phenomena and discuss how it can be used in Virtual Liver Network project. The foundational idea of the study is that growth of cells, organs, systems and whole organisms, besides biomolecular machinery, is influenced by biophysical mechanisms acting at different scale levels. In particular, the general growth law uniquely defines distribution of nutritional resources between maintenance needs and biomass synthesis at each phase of growth and at each scale level. We exemplify the approach considering metabolic properties of growing human and dog livers and liver transplants. A procedure for verification of obtained results has been introduced too. We found that two examined dogs have high metabolic rates consuming about 0.62 and 1 gram of nutrients per cubic centimeter of liver per day, and verified this using the proposed verification procedure. We also evaluated consumption rate of nutrients in human livers, determining it to be about 0.088 gram of nutrients per cubic centimeter of liver per day for males, and about 0.098 for females. This noticeable difference can be explained by evolutionary development, which required females to have greater liver processing capacity to support pregnancy. We also found how much nutrients go to biomass synthesis and maintenance at each phase of liver and liver transplant growth. Obtained results demonstrate that the proposed approach can be used for finding metabolic characteristics of cells, organs, and whole organisms, which can further serve as important inputs for many applications in biology (protein expression), biotechnology (synthesis of substances), and medicine.

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Predicting growth and finding biomass production using the general growth mechanism

First, we briefly describe the general growth mechanism, which governs the growth of living organisms, and its mathematical representation, the growth equation. Using the growth equation, we compute growth curve for S. cerevisiae and show that it corresponds to available experimental data. Then, we propose a new method for finding amount of synthesized biomass without complicated stoichiometric computations and apply this method to evaluation of biomass production by S. cerevisiae. We found that obtained results are very close to values obtained by methods of metabolic flux analysis. Since methods of metabolic flux analysis require finding produced biomass, which is one of the most important parameters affecting stoichiometric models, a priori knowledge of produced biomass can significantly improve methods of metabolic flux analysis in many aspects, which we also discuss. Besides, based on the general growth mechanism, we considered evolutionary development of S. cerevisiae and found that it is a more ancient organism than S. pombe and is apparently its direct predecessor.

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