Skeletal model reduction

FIGURE 12. Stereo diagram of the complete fimiarate reductase complex. The FAD-binding subunit is at the top, the iron-sulfur subunit is in the center and die two membrane anchoring subunits that provide die binding sites for two molecules of menaquinone are at the bottom. In this molecule electron h ansfer occiffs from menaquinone at die bottom to FAD at die top during reduction of fumarate by menaquinone. Skeletal models of two molecules of menaquinone, a 3Fe-4S, a 4Fe-4S, a 2Fe-2S, an FAD molecule and one molecule of oxalate are included. 

Fig. 13.1 Cytoprotective action of adenosine in a quantitative model of mouse hindlimb ischemia and reperfusion (I/R) injury. Adult wild type mice were injected with (a) sterile vehicle (0.1% DMSO in phosphate-buffered saline, pH 7.4) or various adenosine receptor agonists (b, c) or antagonist (d, f). (a) Following ischemia and reperfusion, skeletal muscle showed a significant uptake of Evans Blue dye (EBD) in vehicle-treated mice (first part of (a), representative of 7 mice). The contra-lateral leg not subjected to ischemia-reperfusion showed virtually no EBD uptake. In the second part of (a), the same section was stained with rabbit polyclonal anti-skeletal muscle actin antibodies followed by staining with goat anti-rabbit IgG conjugated with FITC. (b) The nonselective adenosine agonist R-PIA caused a large reduction in the EBD-stained area (see both first and second parts to this figure, representative of six mice)...

In the search for agents to increase bone formation through bone morphogenetic proteins, 3-hydroxymethyl-4-glutaryl CoA reductase inhibitors (statins) were discovered to increase bone density in animal models. Interest in the potential skeletal benefits of statins was heightened by the discovery that bisphosphonates may also affect cholesterol biosynthesis, but at a different step than statins. Although observational studies have linked statin use with decreased fracture risk, a large case-control study did not demonstrate reduction in fracture risk for statin-treated patients. A meta-analysis casts doubt on a protective effect of statins (odds ratio for hip fracture, 0.87 95% Cl 0.48 to 1.58). 02... 

The observed proton transfer times of the order of 50 fs have already been discussed in earlier work with respect to the importance of skeletal vibrations [16-18, 46[. It was proposed that a reduction in the distance between the proton donor and the acceptor results in a decrease in the energetic barrier between the enol-and the keto-form. At times when the barrier is suppressed the proton can tunnel or jump from its enol position to the keto site. In the case of HBO it was suggested that, in particular, the in-plane bending vibration modulates the donor-acceptor distance and thereby enables the proton movement [17]. This model was then applied to MS and to 2-(2 -hydroxyphenyl)-5-pheny]oxazole [18, 46]. However, due to insufficient time resolution of these experiments it was not possible to give experimental evidence for this model. 

W.H. Akeson, Reduction of skeletal muscle necrosis using intermittent hyperbaric oxygen in a model compartment syndrome, J Bone Joint Surg. 65A 656(1983). 

Tomlin, A.S., Tur yi, T. Mechanism reduction to skeletal form and species lumping. In Battin-Leclerc, F., Blurock, E., Simmie, J. (eds.) Development of Detailed Chemical Kinetic Models for Cleaner Combustion, pp. 447-466. Springer, Heidelberg (2013b)... 

---