Humans possess three main phenotypes of Hp, designated Hp 1-1, Hp 2-1, and Hp 2-2. These variants exhibit diverse structural configurations and have been reported to be functionally nonequivalent. We have investigated the functional and redox properties of Hb-Hp complexes prepared using 123 commercially fractionated Hp and found that all forms exhibit similar behavior. The rate of Hb dimer binding to Hp occurs with bimolecular rate constants of similar to 0.9 mu M-1 s(-1), irrespective of the type of Hp assayed. Although Hp binding does accelerate the observed rate of HbO(2) autoxidation by dissociating Hb tetramers into dimers, the rate observed for
these bound dimers is three- to fourfold slower than that of Hb dimers free in
solution. Co-incubation of ferric Hb with any form of Hp inhibits heme loss to below VX-680 cell line detectable levels. Intrinsic selleck kinase inhibitor redox potentials (E-1/2) of the ferric/ferrous pair of each Hb-Hp complex are similar, varying from +54 to +59 mV (vs NHE), and are essentially the same as reported by us previously for Hb-Hp complexes prepared from unfractionated Hp. All Hb-Hp complexes generate similar high amounts of ferryl Hb after exposure to hydrogen peroxide. Electron paramagnetic resonance data indicate that the yields of protein-based radicals during this process are approximately 4 to 5% and are unaffected by the variant of Hp assayed. These data indicate that the Hp fractions Vorinostat order examined are equivalent to one another with respect to Hb binding and associated stability and redox properties and that this result should be taken into account in the design of phenotype-specific
Hp therapeutics aimed at countering Hb-mediated vascular disease.”
“DNA profile interpretation has benefitted from recent improvements that use semi-continuous or fully continuous methods to interpret information within an electropherogram. These methods are likelihood ratio based and currently require that a number of contributors be assigned prior to analysis. Often there is ambiguity in the choice of number of contributors, and an analyst is left with the task of determining what they believe to be the most probable number. The choice can be particularly important when the difference between two possible contributor numbers means the difference between excluding a person of interest as being a possible contributor, and producing a statistic that favours their inclusion. Presenting both options in a court of law places the decision with the court. We demonstrate here an MCMC method of correctly weighting analyses of DNA profile data spanning a range of contributors. We explore the theoretical behaviour of such a weight and demonstrate these theories using practical examples. We also highlight the issues with omitting this weight term from the LR calculation when considering different numbers of contributors in the one calculation. (C) 2014 Elsevier Ireland Ltd. All rights reserved.