Biophysics, General

The dynamics of pattern formation and change are studied in a complex, multicomponent system, specifically the arms and legs of human subjects. Previous studies (Kelso & Jeka, in press) have demonstrated novel features in the coordinative dynamics of an arm-leg pair, including: (1) differential stability of coordinative modes produced by limbs moving in the same (S-mode) versus different (D-mode) directions; (2) a slow drift in relative phase preceding transitions from the D- to the S-mode; (3) preferred transition routes between patterns; and (4) spontaneous emergence of non 1:1 frequency- and phase-locked patterns, in addition to periods of relative coordination. These phenomena have been encompassed theoretically in a model of coupled oscillators which includes a symmetry-breaking term to represent the difference in the uncoupled frequencies of the arm and leg (Kelso et al., 1990). To test predictions of the (Kelso et al., 1990) model, the first of two studies was aimed at whether manipulation of the inherent biophysical differences between the arm and leg, through inertial loading, would be reflected in their coordinative dynamics. The results showed that loading the leg led to the highest percentage of: (1) D- to S-mode transitions in the down direction (i.e., with decreasing values of relative phase); and (2) transitions to phase wandering. Loading the arm led to: (1) an approximately equal number of transitions in either the up or down direction; and (2) very few transitions to phase wandering. The conclusion was that adding weight to the arm or leg was influential in minimizing or enhancing the coordinative asymmetry, respectively. A second study used the same loading conditions as Experiment 1 within a perturbation paradigm to study possible differences in relaxation time and perturbation-induced transitions, as additional measures of the asymmetry of the coordinative dynamics. Relaxation time and perturbation-induced transition pathways showed no effects of inertial loading. Pretransition relative phase showed a steady decrease when the leg was loaded and very little drift in the arm load condition. Pretransition relaxation time increased systematically with required frequency and relative phase variability, but only with perturbations in the up direction (i.e., increasing values of relative phase). These effects were consistent with model predictions and showed that asymmetric dynamics characterized the coordinative patterns of anatomically different components.

The effect of simulated body fluid (SBF) on the crystal structure and surface structure properties of Ferrimagnetic Bioglass Ceramics (FBC) as a function of the time of immersion in SBF was studied. The materials examined were prepared with a systematic variation of the composition of the oxides in the system [0.45(CaO, P2O5) (0.52-x)SiO2 xFe2O3 0.03Na2O] and the heat treatment temperature. X-ray powder diffraction (XRD), scanning electron microscopy (SEM) with energy dispersive x-ray spectroscopy (EDX), neutron powder diffraction (NPD) and Rietveld refinement methods were used in our studies. The in vitro experiments demonstrated the bioactivity of the FBC through formation of hydroxyapatite (HAp). It varies with the composition of the FBC, annealing temperature, and time of immersion of the samples in SBF in a non-systematic way. SEM and EDX studies showed that pores appear on the surface of some specimens, while a surface layer of Si, P, and Ca partially covers the Fe, O dendrites of the original samples. Formation and size of pores was determined by the specific processing parameters of the samples. Quantitative phase analysis of the neutron diffraction patterns revealed a phase transition of the calcium phosphate from hexagonal to monoclinic, in weight percentages depended on the composition of the as-prepared FBC and time of immersion in SBF. The weight percentage of the ferrimagnetic phase [Fe3O4] is less affected by immersion in SBF. Inclusion of magnetic scattering of the neutrons in the Rietveld refinement process improved the quality of the fit between calculated and experimental diffraction patterns, resulting in a reduction of the weighted pattern residuals Rwp from 0.15 to 0.07.

The specificity of the conotoxin is one of the attributes that make them a valuable diagnostic tool in the characterization of neuronal mechanisms, or therapeutic agents in medicine. It appears that Nature has provided us with a pharmaceutical tool in the form of Conus peptides. Further studies will only enhance our understanding, and use, of these molecules in medicine and science. The study of three-dimensional structure in relation to the function of cone snail peptides is an area of increasing interest. The venom of a single cone snail can contain as many as 300 different chemical components. Individual cone snail venom components, or conopeptides, can have powerful neurological effects. For many interesting species, not enough venom collected from the natural origin is available for experimental investigations. After a laborious separation procedure, only nanomole quantities of these native conopeptides are able to be obtained. Therefore, several experimental applications, such as NMR spectroscopy, are difficult to carry out using traditional methods. The research was focused on using nanoNMR spectroscopy as an alternative method to the conventional NMR spectroscopy method in order to analyze small quantities of novel peptides with unknown three-dimensional conformational arrangement. The experimental results obtained using the HR-MAS NMR technique, in addition to the use of a 3mm gHCN (with 1.7mm inserts) NMR probes, proved the capability of conformational analysis of different types of natural products at sample levels down to nanomole range. Understanding the interaction between agonist or antagonist ligands and their target receptors, at a molecular level, offer promise for the development of pharmacological therapeutics for the central nervous system. Conopeptides are of great interest as ligands in neuroscience and are valuable leads in drug design, based on their specificity and potency for therapeutically relevant receptors and ion channels. For instance, the compound called Prialt (formerly known as Ziconotide), a synthetic form of a cone snail-derived peptide, is the most powerful painkiller known and has already received the Food and Drug Administration (FDA) approval. The drug is part of a new class known as the N-type calcium channel blockers, which are responsible for transmitting pain signals. Several related cone snail drugs are currently in clinical trials and could eventually be used to treat different diseases such as Alzheimer's, epilepsy and Parkinson's.

One of the most important tasks in biophysics is to understand proteins. It has long been observed that sequence similarity, structural similarity, and functional similarity among proteins are highly correlated. Inspired by this observation, sequence comparison is often employed to retrieve similar/related protein sequences. However, the central issue of assigning statistical significance to the proteins retrieved remains a challenging problem. How a directed polymer/percolation model can shed light in understanding the statistics of global sequence alignments, which is also the fundamental building block for multiple sequence alignment in many multiple alignment applications, is revealed in my thesis. In terms of understanding proteins' specific functionality, it is essential to know how protein sequences determine their unique three dimensional structures and folding kinetics. A careful analysis of the amino acid arrangements in proteins with known structures may provide insights to this issue. In my thesis, I will present a statistical analysis on tertiary contacts to gain more accurate estimates of the preference of amino acid interactions. This analysis reveals an unusually large contact between cysteines, indicating an effective attractive potential among them. The nontrivial role of cysteine-cysteine interactions in protein folding is discussed in my thesis. A new concept termed target-focusing is also introduced.