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IPRS, Inc.
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The Magnesium Project - Basic Research
Basic Research We have identified a significant opportunity in furthering our understanding of the role of cations in metabolism and homeostasis. Homeostasis is that collection of interdependent reactions and systems that make the difference between being healthy, pain free and feeling good or being run-down, ailing or suffering from acute illnesses, pain and vulnerable to infections. The level of magnesium ions is critical to hundreds of enzymatic reactions in the body and is known to be involved in many diseases, yet its regulation and regulating entities are not well known. Animals, Humans, Plants and Microbes All living organisms have numerous metabolic pathways and similar regulatory mechanisms involved in assuring survival. Thus we find Mg-activated enzymes and pathways in micro-organisms, plants, and all the animals including humans. Research in each organism can provide useful insights in possible mechanisms used by others. Regulatory Systems There are many components to living organisms that contribute to the growth and maintenance of the organism. Since the initial concept of homeostasis was articulated many decades ago, we have come to see that there is an elaborate system of receptors that monitor the environment and communicate via signaling pathways changes for the better or worse. There are elaborate biochemical systems and pathways to respond to signals. Means of response may be mechanical, chemical or electrical. Chemical responses may include the initiation of synthesis of a series of proteins, enzymes or other biological materials or structures that help preserve the integrity of the organism. Homeostatic mechanisms for electrolytes include specialized hormones, tissue specific receptors, specialized channels and active transport mechanisms. Protein kinases are involved in the transfer of phosphates in over five hundred biochemical reactions; most of which are activated by magnesium (Mg++) ions or to a lesser extent calcium (Ca++) ions. The regulation of calcium is a complex process that impacts many systems and disease process. Complex Systems Behavior Often one sees intricate cascades of reactions complete with positive or negative feedback loops. Biological systems may exhibit behaviors analogous to electronic circuits including oscillations, overshoot and damping effects. One may also gain insights from various modeling schemes such as neural networks. One may often observe counter-intuitive behaviors. An example of the graphical representation of the elements of a complex biological system is given by the Calcium Regulatory System. In the diagram the top portion shows feedback loops and the lower portion shows the various sites of action of the regulatory hormone and other potential factors of influence that are still being defined. Modeling and Hypothesis Building/Testing Development of models can be a valuable tool in understanding how complex systems behave. Mathematical models can help in formulating and testing certain hypotheses. Does the data support a hypothesis or negate it (Null hypothesis)? Using mathematical constructs one can also run statistical tests on how well a model predicts or represents the behavior of the actual system. Scientific Discovery Process The scientific discovery process may be a long and arduous gradual process and in other cases it advances by chance discoveries or sudden inspirations. The Edisonian approach is to eliminate all the things that don't work until you find the one that does. Theoreticians argue that working from basic principles is a more efficient process; yet, sometimes the theory and our ability to represent it in a mathematical or even logical scheme is limited. Modern science is often a blend of these two approaches. The view of IPRS is that both have merit; but that as greater complexity is discovered in the biological world, one needs better models and better analytical tools to aid in guiding the discovery process. To that end, we strive to develop useful models and to encourage others to do the same. Assertions, Qualifications & Testing One of the tools to increase our odds of discovering truly innovative solutions is to scan the literature for statements (assertions) about the relationships between different entities or data. Is the relationship one that is casual or causal? Is it one that is statistically significant? Can it be represented by a mathematical or logical statement? Can it be readily tested? Is it consistent with other data or other understandings of the system under investigation? At IPRS we are in the process of cataloguing assertions and relationships between various components of systems relating to magnesium metabolism and regulation. ------------------------------------
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