A numerical model for the oxygenation of blood in lung capillaries--effect of nth order one-step kinetics of oxygen uptake by haemoglobin

A numerical model is described for the oxygenation of blood in lung capillaries by considering the transport mechanisms of molecular diffusion, convection and the facilitated diffusion due to the presence of haemoglobin. In order to represent the oxygen dissociation curve accurately in the model, the nth order one-step kinetics of oxygen uptake by haemoglobin has been used. The resulting system of coupled, non-linear partial differential equations is solved numerically. It is shown that the blood is required to traverse a larger distance in the capillary before becoming fully oxygenated with nth order one-step kinetics in comparison to first-order one-step kinetics.     

Effects of Genetic and Environmental Factors on Trait Network Predictions From Quantitative Trait Locus Data

The use of high-throughput genomic techniques to map gene expression quantitative trait loci has spurred the development of path analysis approaches for predicting functional networks linking genes and natural trait variation. The goal of this study was to test whether potentially confounding factors, including effects of common environment and genes not included in path models, affect predictions of cause–effect relationships among traits generated by QTL path analyses. Structural equation modeling (SEM) was used to test simple QTL-trait networks under different regulatory scenarios involving direct and indirect effects. SEM identified the correct models under simple scenarios, but when common-environment effects were simulated in conjunction with direct QTL effects on traits, they were poorly distinguished from indirect effects, leading to false support for indirect models. Application of SEM to loblolly pine QTL data provided support for biologically plausible a priori hypotheses of QTL mechanisms affecting height and diameter growth. However, some biologically implausible models were also well supported. The results emphasize the need to include any available functional information, including predictions for genetic and environmental correlations, to develop plausible models if biologically useful trait network predictions are to be made.     

Exponential Megapriming PCR (EMP) Cloning—Seamless DNA Insertion into Any Target Plasmid without Sequence Constraints

We present a fast, reliable and inexpensive restriction-free cloning method for seamless DNA insertion into any plasmid without sequence limitation. Exponential megapriming PCR (EMP) cloning requires two consecutive PCR steps and can be carried out in one day. We show that EMP cloning has a higher efficiency than restriction-free (RF) cloning, especially for long inserts above 2.5 kb. EMP further enables simultaneous cloning of multiple inserts.     

Anti-insulin antibody structure and conformation. I. Molecular modeling and mechanics of an insulin antibody.

A knowledge-based three-dimensional model of an anti-insulin antibody, 125, was constructed using the structures of conserved residues found in other known crystallographic immunoglobulins. Molecular modeling and mechanics were done with the 125 amino acid sequences using QUANTA and CHARMm on a Silicon Graphics 4D70GT workstation. A minimal model was made by scaffolding using crystallography coordinates of the antibody HyHEL-5, because it had the highest amino acid sequence homology with 125 (84% light chain, 65% heavy chain). The three hypervariable loop turns that are longer in 125 than in HyHEL-5 (L1, L3, and H3) were modeled separately and incorporated into the HyHEL-5 structure; then other amino acid substitutions were made and torsions optimized. The 125 model maintains all the structural attributes of an antibody and the structures conserved in known antibodies. Although there are many polar amino acids (especially serines) in this site, the overall van der Waals surface shape is determined by positions of aromatic side chains. Based on this model, it is suggested that hydrogen bonding may be key in the interaction between the human insulin A chain loop antigenic epitope and 125.