Molecular events

The essential weakness of the correlation approach is that it lacks a linkage to molecular events. A correlation is not a cause-effect relationship. Nevertheless, with sufficient weight of evidence it becomes reasonable to seek an underlying... 

The molecular events of contraction are powered by the ATPase activity of myosin. Much of our present understanding of this reaction and its dependence on actin can be traced to several key discoveries by Albert Szent-Gyorgyi at the University of Szeged in Hungary in the early 1940s. Szent-Gyorgyi showed that solution viscosity is dramatically increased when solutions of myosin and actin are mixed. Increased viscosity is a manifestation of the formation of an actomyosin complex. 

Although blood pressure control follows Ohm s law and seems to be simple, it underlies a complex circuit of interrelated systems. Hence, numerous physiologic systems that have pleiotropic effects and interact in complex fashion have been found to modulate blood pressure. Because of their number and complexity it is beyond the scope of the current account to cover all mechanisms and feedback circuits involved in blood pressure control. Rather, an overview of the clinically most relevant ones is presented. These systems include the heart, the blood vessels, the extracellular volume, the kidneys, the nervous system, a variety of humoral factors, and molecular events at the cellular level. They are intertwined to maintain adequate tissue perfusion and nutrition. Normal blood pressure control can be related to cardiac output and the total peripheral resistance. The stroke volume and the heart rate determine cardiac output. Each cycle of cardiac contraction propels a bolus of about 70 ml blood into the systemic arterial system. As one example of the interaction of these multiple systems, the stroke volume is dependent in part on intravascular volume regulated by the kidneys as well as on myocardial contractility. The latter is, in turn, a complex function involving sympathetic and parasympathetic control of heart rate intrinsic activity of the cardiac conduction system complex membrane transport and cellular events requiring influx of calcium, which lead to myocardial fibre shortening and relaxation and affects the humoral substances (e.g., catecholamines) in stimulation heart rate and myocardial fibre tension. 

In the case of liganded NRs, ligand binding is the first and ciucial molecular event that switches the function of these transcription factors from inactive to active state by inducing a conformational change in the LBD of the receptor (Fig. 1). This specific conformation allows the second step of NR activation that corresponds to the recruitment of coregulatoiy complexes, which contain chromatin-modifying enzymes required for transcription. The transcriptional coactivators are very diverse and have expanded to more than hundred in number. These include the pi 60 family of proteins,... 

In kinetic theory, the macroscopic quantities are found as averages over the motion of many molecules each molecular event is assumed to take place over a microscopic time interval, so that a measurement that is made over a macroscopic time interval involves many molecules. The kinetic-description is, therefore, a probabilistic one in that assumptions are made about the motion of one molecule and the results of this motion are averaged over all of the molecules of the gas, giving proper weight to the probability that the various molecules of the gas can have the assumed motion. 

An elementary reaction is a molecular event. Thus, its rate is proportional to the concentrations of the species entering the reaction itself. Consider the combination of two methyl radicals, Eq. (1-7). This elementary reaction, occurs at a rate that is proportional to [CH3]2. Given the elementary reaction in Eq. (1-7), its rate can be written as a particular derivative, Eq. (1-8). 

The rate law for a reaction is a window into the changes that take place at the molecular level in the course of the reaction. Knowing how those changes take place provides answers to many important questions. For example, what controls the rate of formation of the DNA double helix from its individual strands What molecular events convert ozone into oxygen or turn a mixture of fuel and air into carbon dioxide and water when it ignites in an engine ... 

Johnson, M.K. (1992). Molecular events in delayed neuropathy Experimental aspects of neuropathy target esterase. In B. Ballantyne and T.C. Marrs, (1992). Clinical and Experimental Toxicology of Organophosphates and Carbamates 90-113. 

To date, this system provides the best understanding of the molecular events involved in gene regulation. 

Birch and coworkers studied the time-intensity interrelationships for the sweetness of sucrose and thaumatin, and proposed three thematically different processes (see Fig. 47). In mechanism (1), the sweet stimuli approach the ion-channel, triggering site on the taste-cell membrane, where they bind, open the ion-channel (ionophore), and cause a flow of sodium and potassium ions into, or out of, the cell. Such a mechanism would correspond to a single molecular event, and would thus account for both time and intensity of response, the intensity of response being dependent on the ion flux achieved while the stimulus molecule binds to the ionophore. 

Atoms, ions, and molecules rearrange and recombine during chemical reactions. These processes usually do not occur all at once. Instead, each reaction consists of a sequence of molecular events called a reaction mechanism. 

A mechanism is a description of the actual molecular events that occur during a chemical reaction. Each such event is an elementary reaction. Elementary reactions involve one, two, or occasionally three reactant molecules or atoms. In other words, elementary reactions can be unimolecular, bimolecular, or termolecular. A typical mechanism consists of a sequence of elementary reactions. Although an overall reaction describes the starting materials and final products, it usually is not elementary because it does not represent the individual steps by which the reaction occurs. 

Fluorescent probes are divided in two categories, i.e., intrinsic and extrinsic probes. Tryptophan is the most widely used intrinsic probe. The absorption spectrum, centered at 280 nm, displays two overlapping absorbance transitions. In contrast, the fluorescence emission spectrum is broad and is characterized by a large Stokes shift, which varies with the polarity of the environment. The fluorescence emission peak is at about 350 nm in water but the peak shifts to about 315 nm in nonpolar media, such as within the hydrophobic core of folded proteins. Vitamin A, located in milk fat globules, may be used as an intrinsic probe to follow, for example, the changes of triglyceride physical state as a function of temperature [20]. Extrinsic probes are used to characterize molecular events when intrinsic fluorophores are absent or are so numerous that the interpretation of the data becomes ambiguous. Extrinsic probes may also be used to obtain additional or complementary information from a specific macromolecular domain or from an oil water interface. 

Razzaque MS, Taguchi T. Pulmonary fibrosis Cellular and molecular events. 

De Levie, R., Electrochemical observation of single molecular events, AE, 13, 1 (1985). 

The concepts of intrinsic activity and efficacy just outlined are purely descriptive, without reference to mechanism. We turn now to how differences in efficacy might be explained in terms of the molecular events that underlie receptor activation, and we begin by considering some of the experimental evidence that has provided remarkably direct evidence of the nature of these events. 

INSIGHTS INTO N-N AND 0-0 BONDS FORMATION MOLECULAR EVENTS... 

This chapter treats the descriptions of the molecular events that lead to the kinetic phenomena that one observes in the laboratory. These events are referred to as the mechanism of the reaction. The chapter begins with definitions of the various terms that are basic to the concept of reaction mechanisms, indicates how elementary events may be combined to yield a description that is consistent with observed macroscopic phenomena, and discusses some of the techniques that may be used to elucidate the mechanism of a reaction. Finally, two basic molecular theories of chemical kinetics are discussed—the kinetic theory of gases and the transition state theory. The determination of a reaction mechanism is a much more complex problem than that of obtaining an accurate rate expression, and the well-educated chemical engineer should have a knowledge of and an appreciation for some of the techniques used in such studies. 

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