Association-induction hypothesis

Ling, G. N. (1962). A Physical Theory of the Living State The Association-Induction Hypothesis. Blaisdell, Waltham, MA. 

Ling, G. N. (1979). The polarized multilayer theory of cell water according to the association-induction hypothesis. In Cell-Associated Water (Drost-Hansen, W Clegg, J. S., eds.), pp. 261-269, Academic Press, New York. 

The association-induction hypothesis was in its early days known as Ling s fixed-charge hypothesis. In years following, the theory has evolved. The newer version plus results of more than 30 years of experimental testing are presented in a book called In Search of the Physical Basis of Life (Gilbert N. Ling, Plenum Press, 1984). The following is a brief sketch of the key features of the AI hypothesis. 

G. N. Ling, The Cellular Resting and Action Potentials Interpretation Based on the Association-Induction Hypothesis, Physiol. Ghent. Phys. 14, 47 (1982). 

Utilising a reversion assay in Salmonella enterica, Prieto et al reported an increased frequency of point mutations following bile-salt exposure. Mutations were predominantly nucleotide substitutions (GC to AT transitions) and -1 frameshift mutations.The frameshifts were dependent on SOS induction and linked to the activity of DinB polymerase (Pol IV). The authors proposed that the GC to AT transitions stimulated by bile, could have arisen from oxidative processes giving rise to oxidised cytosine residues. Consistent with this hypothesis, the authors demonstrated that strains of S. enterica-lacking enzymes required for base-excision repair (endonuclease III and exonuclease IV) and the removal of oxidised bases, demonstrated increased bile-acid sensitivity compared with competent strains. In another study using E. coli, resistance to the DNA-damaging effects of bile was associated with Dam-directed mismatch repair, a pathway also involved with the repair of oxidative DNA lesions. ... 

Body iron level and iron depletion play an important role in the gender differences seen in death from cardiac disease. There is a better correlation with heart disease mortality in iron levels compared with levels of cholesterol (5). It was found that risk of coronary heart disease (6) and carotid atherosclerosis (7) is associated with increased iron stores. However, impaired endothelium-derived nitric oxide activity may be without overt atherosclerosis in patients with risk factors and may be associated with the presence of atherosclerosis (4). Thus, endothelial dysfunction related to iron activity not only may be an early marker for cardiovascular risk but also may contribute to the pathogenesis of atherosclerosis (2) by the stimulation of low-density lipoproteins (LDL) and membrane lipid peroxidation (I) and may be a key to the understanding of early mechanism in the development of atheroma (7,8). Nakayama et al. (9) showed the role of heme oxygenase induction in the modulation of macrophage activation in atherosclerosis. However, Howes et al. (10) concludes that at the moment, the available evidence on iron hypothesis remains circumstantial. Moreover, Kiechl et al. (7) showed that the adverse effect of iron is hypercholesterolemia, In patients... 

Johnson, C. R., Muir, D. G., and Reysenbach, A. L., Characteristic bacteria associated with surfaces of coralline algae a hypothesis for bacterial induction of marine invertebrate larvae, Mar. Ecol. Prog. Ser., 74, 281, 1991. 

Another central element of the Grishko hypothesis is the upregulation of inducible nitric oxide synthase (iNOS). Since the induction of iNOS is often associated with extensive nitric oxide formation, it is commonly a toxic event. However, nitric oxide formation is not detrimental in all cell types. Dimmeler et al. (1997) found that nitric oxide protects human endothelial cells against angiotensin II-mediated apoptosis. A key variable appears to be the amount of nitric oxide produced. In the cardiomyocyte, sufficient levels of nitric oxide are generated to cause the formation of toxic levels of peroxynitrite, while in endothelial cells, ROS, rather than reactive nitrogen species, appear to be the toxic mediators of apoptosis. 

Some experimental information consistent with our hypothesis exists. V. Vonka and co-workers at the Institute of Sera and Vaccines in Prague, were able to induce up to 300% increase in the number of Epstein Barr virus (an oncogenic Herpes type virus) positive cells in a culture of Burkitt lymphoma cells (EB 3) by treatment with d,y-dichlorodi am mi ncpl ati num( 11). The induction of the new, virus-associated antigens was monitored both by an indirect immunofluorescence test for the coat proteins of the virus appearing at the cell surface, and by the visualization of virus-like particles in the treated cells by electron microscopy. 

The induction period is shortened by adding prehydrated CjS (013), but additions of lime or CH, including that formed from CjS, are variously reported to be ineffective (013,B67) or to lengthen it, though shortening it with cement (Ull). In cement mixes, additions of pfa or some other finely divided materials accelerate hydration after the first day, apparently by acting as nucleation sites for C-S-H (Section 9.3.3). Additions of reactive silica markedly accelerate hydration (S53). Most of this evidence supports hypothesis 3 and tells against hypothesis 4. Hypothesis 3 does not exclude hypothesis 1, as the breakdown of a protective layer could be associated with formation of a new product. 

In 1954, the book by Professor B.N. Tarusov "Principles of Biological Effects of Radioactive Emissions" was published [1] the book made a great impression on me. The author, an outstanding Soviet biophysicist. Head of the Biophysics Department at the Faculty of Biology of the Moscow State University, put forward a hypothesis that the development of radiation-induced disease is associated with the induction of ramified chain reaction of oxidation of fats of cellular shells (membranes), the oxidation products are very toxic for the cell. 

Chronic treatment with phenobarbital, phenytoin, and carbamazepine is associated with reduced serum folate concentrations. Although megaloblastic anemia is rare, macrocytic changes in red cells are common in these patients. The fact that serum folate is not reduced by valproate and zonisamide, which do not induce liver enzymes, is consistent with the hypothesis that enzyme induction plays a role in the pathogenesis of folate deficiency (99). 

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