Computational analysis of the tryptophan cation radical energetics in peroxidase Compound I.

Three well-characterized heme peroxidases (cytochrome c peroxidase = CCP, ascorbate peroxidase = APX, and Leishmania major peroxidase = LMP) all have a Trp residue tucked under the heme stacked against the proximal His heme ligand. The reaction of peroxidases with H2O2 to give Compound I results in the oxidation of this Trp to a cationic radical in CCP and LMP but not in APX. Considerable experimental data indicate that the local electrostatic environment controls whether this Trp or the porphyrin is oxidized in Compound I. Attempts have been made to place the differences between these peroxidases on a quantitative basis using computational methods. These efforts have been somewhat limited by the approximations required owing to the computational cost of using fully solvated atomistic models with well-developed forcefields. This now has changed with available GPU computing power and the associated development of software. Here we employ thermodynamic integration and multistate Bennett acceptance ratio methods to help fine-tune our understanding on the energetic differences in Trp radical stabilization in all three peroxidases. These results indicate that the local solvent structure near the redox active Trp plays a significant role in stabilization of the cationic Trp radical.

The neural correlates of an expanded functional field of view.

The size of the functional field of view (FFOV) predicts driving safety in older adults ( Owsley et al., 1998), and practice-related changes in the FFOV may transfer to driving safety ( Roenker, Cissell, Ball, Wadley, & Edwards, 2003). We used functional magnetic resonance imaging (fMRI) and behavioral measures to examine how practice with the FFOV task changes older adults' attentional function. Behavioral data collected outside of the MRI revealed that participants in the training group showed larger improvements across conditions than did those in the control group. fMRI data revealed training-related changes in activation in a number of brain regions. In the right precentral gyrus and right inferior frontal gyrus, increases in activation between fMRI sessions correlated positively with increases in accuracy between behavioral sessions. Practice with the FFOV task improves older adults' attentional function by increasing their recruitment of regions traditionally associated with orienting visual attention.

Aerobic exercise training increases brain volume in aging humans.

BACKGROUND: The present study examined whether aerobic fitness training of older humans can increase brain volume in regions associated with age-related decline in both brain structure and cognition. METHODS: Fifty-nine healthy but sedentary community-dwelling volunteers, aged 60-79 years, participated in the 6-month randomized clinical trial. Half of the older adults served in the aerobic training group, the other half of the older adults participated in the toning and stretching control group. Twenty young adults served as controls for the magnetic resonance imaging (MRI), and did not participate in the exercise intervention. High spatial resolution estimates of gray and white matter volume, derived from 3D spoiled gradient recalled acquisition MRI images, were collected before and after the 6-month fitness intervention. Estimates of maximal oxygen uptake (VO2) were also obtained. RESULTS: Significant increases in brain volume, in both gray and white matter regions, were found as a function of fitness training for the older adults who participated in the aerobic fitness training but not for the older adults who participated in the stretching and toning (nonaerobic) control group. As predicted, no significant changes in either gray or white matter volume were detected for our younger participants. CONCLUSIONS: These results suggest that cardiovascular fitness is associated with the sparing of brain tissue in aging humans. Furthermore, these results suggest a strong biological basis for the role of aerobic fitness in maintaining and enhancing central nervous system health and cognitive functioning in older adults.