Molecular initiating event

However, the most important driving force for performing in vitro toxicity studies is a scientific one if one wishes to study the toxicity mechanisms of action of a compound, it is no longer appropriate to rely on the apical endpoints for toxicity that are the commonly measured parameters in an animal study. A focus on these mechanisms, in relation to the events following the molecular initiating event, eventually leading to an adverse outcome gives... 

Ellison CM, Enoch SJ, Cronin MT (2011) A review of the use of in silico methods to predict the chemistry of molecular initiating events related to drug toxicity. Expert Opin Drug Metab Toxicol 7 1481-1495... 

MIE molecular initiating event ROS reactive oxygen species... 

The theories that attempt to describe the initial event in sweet-taste stimulation will be discussed, as will some of the practical attempts to isolate sweet-receptor molecules. Relevant, behavioral data will be examined, particularly where the effects of molecular structure on behavior responses are being evaluated. 

That the initial event of taste stimulation takes place on the cell surface of the taste receptor is now universally accepted. In addition, accumulated evidence strongly suggests that taste-bud stimulation is extracellular in nature. For example, (1) the sweet-taste response is both rapid and reversible, (2) the intensely sweet proteins monellin" and thaumatin could not possibly penetrate the cell, because of their size, and (3) miraculin, the taste-modifying glycoprotein, having a molecular weight of 44,000 would also be too large to penetrate the taste cell. ... 

Fig. 11.6. Diagram depicting desorption ionization (MALDI, FAB or SIMS). The operating principles of the three techniques are similar. The initiating event is exposure of the analyte to a beam of photons, atoms or ions. In order to prevent damage to the fragile analyte molecules and enhance the conversion of the involatile molecules into gas-phase ions, a matrix is employed. For MALDI, the matrix compounds are UV absorbing compounds such as hydroxycinnamic acid. The most commonly used FAB matrix was glycerol and ammonium chloride was employed by some investigators in SIMS experiments (although at low ion beam fluxes molecular species could be effectively ionized for many analytes with minimal evidence of damage by the primary ion beam).

The initial event is the binding of ferri-heme to hemopexin in the plasma, which induces a conformational change in the protein and enables high-affinity molecular recognition by cells expressing the... 

Because the process of development of the embryo and then the fetus is a complex series of events, it is clear that many different mechanisms may cause the disruption that underlies the teratogenic effects of foreign compounds. In many cases, the initiating events probably occur at the subcellular or molecular level in the embryo, but may be only detectable as malformations or cell death. 

One such theory considers the statistical accumulation of molecular fracture events, in a plane perpendicular to the applied stress, for an assembly of chains under equal initial stress. Once a small number (say 3 or 4) adjacent chains have broken, the probability of further adjacent fractures increases rapidly and the process moves into a thermal propagation phase. Typical results as cited by Kausch and De Vries are shown in Fig. 3. 

Generation of the A-ehloroamide from HA was later confirmed also by means of ESR [254] it was shown that this product degrades under the generation of an A-centered radical that subsequently isomerizes into a carbon-centered radical located in the pyranose ring. This represents the initial event for the reduction of the molecular mass of the HA chain. 

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