Oxygen Pathway Modeling Estimates High Reactive Oxygen Species Production above the Highest Permanent Human Habitation

The production of reactive oxygen species (ROS) from the inner mitochondrial membrane is one of many fundamental processes governing the balance between health and disease. It is well known that ROS are necessary signaling molecules in gene expression, yet when expressed at high levels, ROS may cause oxidative stress and cell damage. Both hypoxia and hyperoxia may alter ROS production by changing mitochondrial Po ₂ (). Because depends on the balance between O₂ transport and utilization, we formulated an integrative mathematical model of O₂ transport and utilization in skeletal muscle to predict conditions to cause abnormally high ROS generation. Simulations using data from healthy subjects during maximal exercise at sea level reveal little mitochondrial ROS production. However, altitude triggers high mitochondrial ROS production in muscle regions with high metabolic capacity but limited O₂ delivery. This altitude roughly coincides with the highest location of permanent human habitation. Above 25,000 ft., more than 90% of exercising muscle is predicted to produce abnormally high levels of ROS, corresponding to the “death zone” in mountaineering.     

Mathematical model study of megakaryocytopoiesis. 1. The simulation model, cell steady-state distribution and the number of divisions in a proliferating population

A method of simulation has been proposed for studying megakaryocytopoiesis. A model has been developed which takes into account the age structure of cell population, the stochasticity of their maturation, and the principles of megakaryocytopoiesis regulation (known from the experiments). The mean number of divisions in a proliferating pool has been determined, as well as the duration of development of the cells with a positive acetylcholine esterase reaction.     

Megakaryocytopoiesis studied in a mathematical model. 3. Regulation of cell differentiation in immune thrombocytopenia

Simulation experiments have shown that just after antiplatelet serum of rabbit blood is introduced into mice the transit time of early proliferating precursors of the megakaryocytes is reduced by about 17 h, the transit time for megakaryoblasts increases, and within 24 h after the treatment the transit time for mature megakaryocytes is reduced b about 17 h. The data obtained confirmed our earlier hypothesis on correlation between the duration of proliferative period and the mean size of megakaryocytes.     

Preparation,properties and potential applications of exopolysaccharides from bacteria of the genera <Emphasis Type="Italic">Xanthobacter</Emphasis> and <Emphasis Type="Italic">Ancylobater</Emphasis>

Two new bacterial biopolymers (exopolysaccharides), ancylan and xylophilan, have been isolated and characterized. The optimal parameters for ancylan and xylophilan production under laboratory conditions were selected. Their physicochemical properties and effects on microorganisms (bacteria, fungi, and ciliates) were studied. The results suggest the potential application of these new exopolysaccharides in medicine and veterinary science.     

Quantitative evaluation of radiation damage to thrombocytopoiesis

From the comparison of the results of model and experimental kinetics of thrombocytopoiesis the following parameters have been quantitatively estimated: (1) the percentage of cells killed during the interphase (interphase death) and (2) the duration of the mitosis delay and the abortive rise. There was a 1.3-1.5-fold and 2-3-fold nonspecific and postirradiation, respectively, decrease in the megacaryocyte maturation time. The transit time of the committed megacaryocyte precursors was reduced due to death of premature precursors and survival of mature forms.     

Individual optimization: Mechanisms shaping the optimal reaction norm

In general, optimal reaction norms in heterogeneous populations can be obtained only by iterative numerical procedures (McNamara, 1991; Kawecki and Stearns, 1993). We consider two particular, but biologically plausible and analytically tractable cases of individual optimization to gain insight into the mechanisms which shape the optimal reaction norm of fecundity in relation to an environmental variable or an individual trait. In the first case, we assume that the quality of the environment (e.g. food abundance) or the quality of the individual (e.g. body size) is fixed during its entire life; it may also be a heritable individual trait. In the second case, individual quality is assumed to change randomly such that the probability distribution of quality in the next year is the same for the parent and for her offspring. For these two cases, we obtain analytical expressions for the shape of the optimal reaction norm, which are heuristically interpretable in terms of underlying selective mechanisms. It is shown that better quality may reduce the optimal fecundity. This outcome is particularly likely if better quality increases a fecundity-independent factor of parental survival in a long-lived species with fixed quality. This revised version was published online in July 2006 with corrections to the Cover Date.     

Megakaryocytopoiesis studied in a mathematical model. 4. Regulation of cell flow in a transit population

The role of cells capable of formation of megakaryocytic colonies (CFUm) in regulation of thrombocytopoiesis was studied using a simulation model of megakaryocytopoiesis. The CFUm were shown to be the least differentiated cells involved in regulation of megakaryocytopoiesis in mice upon immune thrombocytopenia and after intravenous injection of hydroxyurea. A correlation was found between the CFUm population productivity and the number of cells in a transit population of the megakaryocytic line which makes it possible to reproduce experimental kinetics in the model. The duration of cell development from CFUm to megakaryocytes is about 3 days.