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Biomedical subjects

K R Wilson

Publications and source records attributed to K R Wilson.

16 recordsLinked to original sources

Overview of endogenous and synthetic melanocortin peptides.

The melanocortin system consists of five seven-transmembrane spanning G-protein coupled (GPCRs) receptors (MC1R-MC5R), the endogenous agonists a-, B- and melanocyte stimulating hormone (MSH), adrenocorticotropic hormone (ACTH), and the endogenous antagonists Agouti and Agouti-related protein (AGRP). Melanocortin agonists are involved in the regulation of feeding behavior and weight omeostasis in mammals. Structure-activity relationships (SAR) have been performed on the endogenous melanocortin receptor agonists and antagonists that have identified ligand amino acid residues implicated as important for receptor binding and stimulation. Knowledge of putative ligand-receptor interactions may help to design molecules as therapeutic agents for the treatment of physiological diseases.

Agouti Signaling Protein↗

pH dependence of the electronic structure of glycine.

The carbon, nitrogen, and oxygen K-edge spectra were measured for aqueous solutions of glycine by total electron yield near-edge X-ray absorption fine structure (TEY NEXAFS) spectroscopy. The bulk solution pH was systematically varied while maintaining a constant amino acid concentration. Spectra were assigned through comparisons with both previous studies and ab initio computed spectra of isolated glycine molecules and hydrated glycine clusters. Nitrogen K-edge solution spectra recorded at low and moderate pH are nearly identical to those of solid glycine, whereas basic solution spectra strongly resemble those of the gas phase. The carbon 1s --> pi*(C=O) transition exhibits a 0.2 eV red shift at high pH due to the deprotonation of the amine terminus. This deprotonation also effects a 1.4 eV red shift in the nitrogen K-edge at high pH. Two sharp preedge features at 401.3 and 402.5 eV are also observed at high pH. These resonances, previously observed in the vapor-phase ISEELS spectrum of glycine, have been reassigned as transitions to sigma* bound states. The observation of these peaks indicates that the amine moiety is in an acceptor-only hydrogen bond configuration at high pH. At low pH, the oxygen 1s --> pi*(C=O) transition exhibits a 0.25-eV red shift due to the protonation of the carboxylic acid terminus. These spectral differences indicate that the variations in electronic structure observed in the NEXAFS spectra are determined by the internal charge state and hydration environment of the molecule in solution.

Glycine↗

Interpersonal variability in dependent personality.

The interpersonal circumplex (IPC) was recommended as a personality trait dimensional model with good potential to identify the phenomenological scope of personality disorders whose core dysfunction involves maladaptive expression of interpersonal traits. The IPC was then applied to the reconceptualization of dependent personality and dependent personality disorder. In Study 1, Pincus and Gurtman's (1995) three interpersonal vectors of dependency were validated via factor analyses conducted on two large samples (N = 921; N = 472) and a reliable self-report measure, the 3 Vector Dependency Inventory (3VDI) was constructed. In Study 2, two samples (N = 103; N = 122) of individuals identified as predominantly endorsing submissive dependence, exploitable dependence, or love dependence, or who were low in aspects of dependency were compared via ANOVA and chi-square analyses on parental representations, adult attachment styles, loneliness, and pathological attachment. Submissive dependence was associated with higher scores on maladaptive constructs (fearful attachment, pathological attachment, and loneliness) and was also associated with lower parental affiliation and higher maternal control. Love dependence was associated with lower scores on maladaptive constructs and higher scores on secure attachment and parental affiliation. Variability in dependent phenomenology was related to its three component traits. Multiple perspectives on integrating love dependence, exploitable dependence, and submissive dependence into a reconceptualization of dependent personality disorder were articulated.

Adult↗

Anharmonic lattice dynamics in germanium measured with ultrafast x-ray diffraction.

Damping of impulsively generated coherent acoustic oscillations in a femtosecond laser-heated thin germanium film is measured as a function of fluence by means of ultrafast x-ray diffraction. By simultaneously measuring picosecond strain dynamics in the film and in the unexcited silicon substrate, we separate anharmonic damping from acoustic transmission through the buried interface. The measured damping rate and its dependence on the calculated temperature of the thermal bath is consistent with estimated four-body, elastic dephasing times (T2) for 7-GHz longitudinal acoustic phonons in germanium.

Journal Article↗

Regulation of protein mobility in cell membranes: a dynamic corral model.

We analyze a two-state stochastic corral model for regulation of protein diffusion in a cell membrane. This model could mimic control of protein transport in the membrane by the cytoskeleton. The dynamic corral acts as a gate which when open permits an otherwise trapped protein to escape to a neighboring corral in the cytoskeletal network. We solve for the escape rate over a wide range of parameters of the model, and compare these results with Monte Carlo simulations. Upon introducing measured values of the model parameters for Band 3 in erythrocyte membranes, we are able to estimate the value for one unknown parameter, the average rate at which the corral closes. The ratio of calculated closing rate to measured opening rate is roughly 100:1, consistent with a gating mechanism whereby protein mobility is regulated by dissociation and reassociation of segments of the cytoskeletal network.

Cell Membrane↗

Lateral diffusion of membrane proteins in the presence of static and dynamic corrals: suggestions for appropriate observables.

We consider the possibility of inferring the nature of cytoskeletal interaction with transmembrane proteins via optical experiments such as single-particle tracking (SPT) and near-field scanning optical microscopy (NSOM). In particular, we demonstrate that it may be possible to differentiate between static and dynamic barriers to diffusion by examining the time-dependent variance and higher moments of protein population inside cytoskeletal "corrals." Simulations modeling Band 3 diffusion on the surface of erythrocytes provide a concrete demonstration that these statistical tools might prove useful in the study of biological systems.

Anion Exchange Protein 1, Erythrocyte↗

Two-photon image correlation spectroscopy and image cross-correlation spectroscopy.

We introduce two-photon image correlation spectroscopy (ICS) using a video rate capable multiphoton microscope. We demonstrate how video rate two-photon microscopic imaging and image correlation analysis may be combined to measure molecular transport properties over ranges typical of biomolecules in membrane environments. Using two-photon ICS, we measured diffusion coefficients as large as 10(-8) cm2 s(-1) that matched theoretical predictions for samples of fluorescent microspheres suspended in aqueous sucrose solutions. We also show the sensitivity of the method for measuring microscopic flow using analogous test samples. We demonstrate explicitly the advantages of the image correlation approach for measurement of correlation functions with high signal-to-noise in relatively short time periods and discuss situations when these methods represent improvements over non-imaging fluorescence correlation spectroscopy. We present the first demonstration of two-photon image cross-correlation spectroscopy where we simultaneously excite (via two-photon absorption) non-identical fluorophores with a single pulsed laser. We also demonstrate cellular application of two-photon ICS for measurements of slow diffusion of green fluorescent protein/adhesion receptor constructs within the basal membrane of live CHO fibroblast cells.

Animals↗

Detection of nonthermal melting by ultrafast X-ray diffraction.

Using ultrafast, time-resolved, 1.54 angstrom x-ray diffraction, thermal and ultrafast nonthermal melting of germanium, involving passage through nonequilibrium extreme states of matter, was observed. Such ultrafast, optical-pump, x-ray diffraction probe measurements provide a way to study many other transient processes in physics, chemistry, and biology, including direct observation of the atomic motion by which many solid-state processes and chemical and biochemical reactions take place.

Biochemistry↗

Fast space-filling molecular graphics using dynamic partitioning among parallel processors.

We present a novel algorithm for the efficient generation of high-quality space-filling molecular graphics that is particularly appropriate for the creation of the large number of images needed in the animation of molecular dynamics. Each atom of the molecule is represented by a sphere of an appropriate radius, and the image of the sphere is constructed pixel-by-pixel using a generalization of the lighting model proposed by Porter (Comp. Graphics 1978, 12, 282). The edges of the spheres are antialiased, and intersections between spheres are handled through a simple blending algorithm that provides very smooth edges. We have implemented this algorithm on a multiprocessor computer using a procedure that dynamically repartitions the effort among the processors based on the CPU time used by each processor to create the previous image. This dynamic reallocation among processors automatically maximizes efficiency in the face of both the changing nature of the image from frame to frame and the shifting demands of the other programs running simultaneously on the same processors. We present data showing the efficiency of this multiprocessing algorithm as the number of processors is increased. The combination of the graphics and multiprocessor algorithms allows the fast generation of many high-quality images.

Algorithms↗

The anterior tibial vessels and their role in epiphyseal and diaphyseal transfer of the fibula: experimental study and clinical applications.

The blood supply to the fibula from the anterior tibial and peroneal arteries was investigated in 66 fresh cadaver limbs by India ink injection and radiographic studies. These studies revealed a reliable blood supply to the proximal epiphysis and the proximal two-thirds of the diaphysis of the fibula from the anterior tibial artery. Although the peroneal artery provided the dominant supply to the shaft of the bone, its contribution to the head of the fibula was scanty. The cutaneous supply of each vessel was defined and correlated with the territories of the other vessels supplying the leg. The vascular anatomy of the leg was examined in 100 clinical angiograms, revealing 21 limbs with anomalies. This reinforces the case for preoperative angiogram studies where transfer of the fibula is contemplated. The technique of harvesting the proximal growth plate and the shaft of the fibula on the anterior tibial vessels alone is described and illustrated with two successful clinical cases, each followed for 4 years. The growth rate of the transferred epiphysis averaged 1 cm per year.

Blood Vessels↗

Possible allosteric significance of water structures in proteins.

In recent theoretical molecular dynamics studies of ion solvation and transport through the model peptide ionophore, gramicidin A, it has been observed that the waters forming a linear single file within the channel have solvation and dynamic properties quite different from those found in bulk water. Strongly correlated motions among the interior single file column of waters persist over 20 A. A speculation is entertained that related water structures could provide a mechanism for long range enzymatic allosteric effects as an alternative to chemical action at a distance propagated through the protein itself. Two possible specific mechanisms are discussed, hydraulic and "proton wire". As a further control mechanism, the possibility is considered of modulating the allosteric effect though protein motion to open or close the channel thus producing a "valve" in the hydraulic line or a "switch" in the proton wire.

Allosteric Regulation↗

Structure and dynamics of ion transport through gramicidin A.

Molecular dynamics calculations in which all atoms were allowed to move were performed on a water-filled ion channel of the polypeptide dimer gramicidin A (approximately 600 atoms total) in the head-to-head Urry model conformation. Comparisons were made among nine simulations in which four different ions (lithium, sodium, potassium, and cesium) were each placed at two different locations in the channel as well as a reference simulation with only water present. Each simulation lasted for 5 ps and was carried out at approximately 300 K. The structure and dynamics of the peptide and interior waters were found to depend strongly on the ion tested and upon its location along the pore. Speculations on the solution and diffusion of ions in gramicidin are offered based on the observations in our model that smaller ions tended to lie off axis and to distort the positions of the carbonyl oxygens more to achieve proper solvation and that the monomer-monomer junction was more distortable than the center of the monomer. With the potential energy surface used, the unique properties of the linear chain of interior water molecules were found to be important for optimal solvation of the various ions. Strongly correlated motions persisting over 25 A among the waters in the interior single-file column were observed.

Cations↗

Regulation of 25-hydroxy-vitamin D-1 alpha-hydroxylase in chick isolated renal tubules: effects of prostaglandin E2, frusemide and acetylsalicylic acid.

1. Isolated renal tubules were prepared from vitamin D-deficient chicks. The effects of added prostaglandin E2 (PGE2) and agents which modify prostaglandin metabolism on the metabolism of 25-hydroxy-vitamin D3 were studied. 2. Frusemide (0.1 mmol/l) raised the prostaglandin E (PGE) content of the tubule incubation medium; it significantly increased 1,25-dihydroxy-vitamin D3 [1,25-(OH)2D3] production from 25-hydroxy-vitamin D3 [25-(OH)D3] and significantly inhibited the net production of 24,25-dihydroxy-vitamin D3 [24,25-(OH)2D3]. 3. Acetylsalicylic acid (aspirin; 0.1 mmol/l) decreased the PGE content of the tubule incubation medium and significantly inhibited 1,25-(OH)2D3 production. 4. In the presence of 1,25-(OH)2D3, 4 h exposure of tubules from vitamin D-deficient chicks to concentrations of PGE2 between 2.8 X 10(-6) and 2.8 X 10(-8) mol/l significantly enhanced 1,25-(OH)2D3 production. 5. It is concluded that, in view of the effects of modulation of endogenous prostaglandin levels by frusemide in aspirin, and the stimulatory effect of exogenous PGE2, prostaglandins should be considered potential regulators of the renal 25-hydroxy-vitamin D-1 alpha-hydroxylase [25-(OH)D-1 alpha-hydroxylase] enzyme.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗