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Biomedical subjects

E M Wright

Publications and source records attributed to E M Wright.

At least 19 recordsLinked to original sources
PubMed2007

Active sugar transport in health and disease.

Secondary active glucose transport occurs by at least four members of the SLC5 gene family. This review considers the structure and function of two premier members, SGLT1 and SGLT2, and their role in intestinal glucose absorption and renal glucose reabsorption. Genetics disorders of SGLTs include Glucose-Galactose Malabsorption, and Familial Renal Glucosuria. SGLT1 plays a central role in Oral Rehydration Therapy used so effectively to treat secretory diarrhoea such as cholera. Increasing attention is being focused on SGLTs as drug targets for the therapy of diabetes.

Biological Transport, Active↗
PubMed2006

Conical electron tomography of a chemical synapse: vesicles docked to the active zone are hemi-fused.

We have used thin sectioning and conical electron tomography to determine the three-dimensional structure of synaptic vesicles that were associated (docked) at release sites of the presynaptic membrane, called active-zones. Vesicles docked at the active zone occupied a strategic location: they formed regions of contact with the plasma membrane on one side and with that of one or more vesicles located deeper within the presynaptic terminal on the other side. The region of contact with the active zone measured approximately 15 nm in diameter ( approximately 2% of the vesicle's surface) and contained a smaller approximately 6 nm region where the proximal leaflets merged (hemi-fused). Hemi-fusion was only observed on the side of vesicles in contact with the active zone; at the side of contact between neighboring vesicles, the membranes were not hemi-fused. Approximately three-fourths of the docked vesicles contained hemi-fused regions. Vesicles fully fused to the active zone (exhibiting pores that appeared as interruptions of a single membrane) were less frequently observed ( approximately 1 of 10 hemi-fused vesicles). In conclusion, our observations in cortical synapses strengthen the hypothesis that hemi-fusion is a stable intermediary that precedes full fusion and release.

Animals↗
PubMed2006

Observation of bistability and hysteresis in optical binding of two dielectric spheres.

Using a dual-beam fiber optic trap, we have experimentally observed bistability and hysteresis in the equilibrium separations of a pair of optically bound dielectric spheres in one dimension. These observations are in agreement with our coupled system model in which the dielectric spheres modify the field propagation, and the field self-consistently determines the optical forces on the spheres. Our results reveal hitherto unsuspected complexity in the coupled light-sphere system.

Journal Article↗
PubMed2005

Static and dynamic properties of trapped fermionic Tonks-Girardeau gases.

We investigate some static and dynamic properties of harmonically trapped fermionic Tonks-Girardeau gases in tight de Broglie waveguides with attractive p-wave interactions induced by a Feshbach resonance. An exact solution for the one-body density matrix is analyzed in terms of its natural orbitals, with the surprising result that for odd, but not for even, numbers of fermions the maximally occupied orbital coincides with the ground harmonic oscillator orbital. A dynamical consequence of this is that when the interactions are turned off the on-axis density remains a maximum for an odd number of fermions, whereas a minimum develops for an even number.

Journal Article↗
PubMed2005

Photoluminescence and terahertz emission from femtosecond laser-induced plasma channels.

Luminescence as a mechanism for terahertz emission from femtosecond laser-induced plasmas is studied. By using a fully microscopic theory, Coulomb scattering between electrons and ions is shown to lead to luminescence even for a spatially homogeneous plasma. The spectral features introduced by the rod geometry of laser-induced plasma channels in air are discussed on the basis of a generalized mode-function analysis.

Journal Article↗
PubMed2005

Kinetics of the reverse mode of the Na+/glucose cotransporter.

This study investigates the reverse mode of the Na(+)/glucose cotransporter (SGLT1). In giant excised inside-out membrane patches from Xenopus laevis oocytes expressing rabbit SGLT1, application of alpha-methyl-D: -glucopyranoside (alphaMDG) to the cytoplasmic solution induced an outward current from cytosolic to external membrane surface. The outward current was Na(+)- and sugar-dependent, and was blocked by phlorizin, a specific inhibitor of SGLT1. The current-voltage relationship saturated at positive membrane voltages (30-50 mV), and approached zero at -150 mV. The half-maximal concentration for alphaMDG-evoked outward current (K(0.5) (alphaMDG)) was 35 mM (at 0 mV). In comparison, K(0.5) (alphaMDG) for forward sugar transport was 0.15 mM (at 0 mV). K(0.5) (Na) was similar for forward and reverse transport ( approximately 35 mM at 0 mV). Specificity of SGLT1 for reverse transport was: alphaMDG (1.0) > D: -galactose (0.84) > 3-O-methyl-glucose (0.55) > D: -glucose (0.38), whereas for forward transport, specificity was: alphaMDG approximately D: -glucose approximately D: -galactose > 3-O-methyl-glucose. Thus there is an asymmetry in sugar kinetics and specificity between forward and reverse modes. Computer simulations showed that a 6-state kinetic model for SGLT1 can account for Na(+)/sugar cotransport and its voltage dependence in both the forward and reverse modes at saturating sodium concentrations. Our data indicate that under physiological conditions, the transporter is poised to accumulate sugar efficiently in the enterocyte.

Animals↗
PubMed2005

Conical tomography II: A method for the study of cellular organelles in thin sections.

We have used conical electron tomography in order to reconstruct neuronal organelles in thin sections of plastic embedded rat somato-sensory cortical tissue. The conical tilt series were collected at a 55 degrees tilt and at 5 degrees rotations, aligned using gold particles as fiduciary markers, and reconstructed using the weighted back projection algorithm. After a refinement process based on projection matching, the 3D maps showed the "unit membrane pattern" along the entire reconstructed volume. This pattern is indicative of the bilayer arrangement of phospholipids in biological membranes. Based on Fourier correlation methods as well as the visualization of the "unit membrane" pattern, we estimated resolutions of approximately 4 nm. To illustrate the prospective advantages of conical tomography, we segmented "coated" vesicles in the reconstructed volumes. These vesicles were comprised of a central core enclosing a small lumen, and a protein "coating" extending into the cytoplasm. The "coated" vesicle was attached to the plasma membrane through a complex structure shaped as an arch where the ends are attached to the membrane and the crook is connected to the vesicle. We concluded that conical electron tomography of thin-sectioned specimens provides a powerful experimental approach for studying thin-sectioned neuronal organelles at resolution levels of approximately 4 nm.

Animals↗
PubMed2004

Dynamic nonlinear X waves for femtosecond pulse propagation in water.

Recent experiments involving femtosecond pulses in water displayed long-distance propagation analogous to that reported in air. We verify this phenomenon numerically and show that the propagation is dynamic as opposed to self-guided. Furthermore, we demonstrate that the propagation can be interpreted as being due to dynamic nonlinear X waves whose robustness and role in long-distance propagation follows from the interplay between nonlinearity and chromatic dispersion.

Journal Article↗
PubMed2004

Optically bound microscopic particles in one dimension.

Counterpropagating light fields have the ability to create self-organized one-dimensional optically bound arrays of microscopic particles, where the light fields adapt to the particle locations and vice versa. We develop a theoretical model to describe this situation and show good agreement with recent experimental data [Phys. Rev. Lett. 89, 128301 (2002)] for two and three particles, if the scattering force is assumed to dominate the axial trapping of the particles. The extension of these ideas to two- and three-dimensional optically bound states is also discussed.

Journal Article↗
PubMed2003

Physical factors limiting the spectral extent and band gap dependence of supercontinuum generation.

Based on simulations of femtosecond pulse propagation in water we elucidate the physical factors that limit the attainable spectral extent of supercontinuum generation in bulk media. In contrast to the standard scenario, where arrest of self-focusing collapse by multiphoton absorption and plasma defocusing are viewed as imposing a limit to supercontinuum broadening, we show that linear chromatic dispersion also plays a major role. This insight provides an intuitive explanation of the observed band gap dependence of the attainable supercontinuum generation in condensed media.

Journal Article↗
PubMed2002

Presteady-state and steady-state kinetics and turnover rate of the mouse gamma-aminobutyric acid transporter (mGAT3).

We expressed mouse gamma-aminobutyric acid (GABA) transporter (mGAT3) in Xenopus laevis oocytes and examined its steady-state and presteady-state kinetics and turnover rate by using tracer flux and electrophysiological methods. In oocytes expressing mGAT3, GABA evoked a Na+-dependent and Cl(-)-facilitated inward current. The dependence on Na+ was absolute, whereas that for Cl(-) was not. At a membrane potential of -50 mV, the half-maximal concentrations for Na+, Cl(-), and GABA were 14 mM, 5 mM, and 3 microM. The Hill coefficient for GABA activation and Cl(-) enhancement of the inward current was 1, and that for Na+ activation was > or =2. The GABA-evoked inward current was directly proportional to GABA influx (2.2 +/- 0.1 charges/GABA) into cells, indicating that under these conditions, there is tight ion/GABA coupling in the transport cycle. In response to step changes in the membrane voltage and in the absence of GABA, mGAT3 exhibited presteady-state current transients (charge movements). The charge-voltage (Q-V) relation was fitted with a single Boltzmann function. The voltage at half-maximal charge (V(0.5)) was +25 mV, and the effective valence of the moveable charge (zdelta) was 1.6. In contrast to the ON transients, which relaxed with a time constant of < or =30 msec, the OFF transients had a time constant of 1.1 sec. Reduction in external Na+ ([Na+]o) and Cl(-) ([Cl(-)]o) concentrations shifted the Q-V relationship to negative membrane potentials. At zero [Na+]o (106 mM Cl(-)), no mGAT3-mediated transients were observed, and at zero [Cl(-)]o (100 mM Na+), the charge movements decreased to approximately 30% of the maximal charge (Q(max)). GABA led to the elimination of charge movements. The half-maximal concentrations for Na+ activation, Cl(-) enhancement, and GABA elimination of the charge movements were 48 mM, 19 mM, and 5 mM, respectively. Q(max) and I(max) obtained in the same cells yielded the mGAT3 turnover rate, 1.7 sec(-1) at -50 mV. The low turnover rate of mGAT3 may be due to the slow return of the empty transporter from the internal to the external membrane surface.

Animals↗
PubMed2002

Interference of a thermal tonks gas on a ring.

A nonzero temperature generalization of the Fermi-Bose mapping theorem is used to study the exact quantum statistical dynamics of a one-dimensional gas of impenetrable bosons on a ring. We investigate the interference produced when an initially trapped gas localized on one side of the ring is released, split via an optical-dipole grating, and recombined on the other side of the ring. Nonzero temperature is shown not to be a limitation to obtaining high visibility fringes.

Journal Article↗
PubMed2002

Crossover from one to three dimensions for a gas of hard-core bosons.

We develop a variational theory of the crossover from the one-dimensional (1D) regime to the 3D regime for ultracold Bose gases in thin waveguides. Within the 1D regime we map out the parameter space for fermionization, which may span the full 1D regime for suitable transverse confinement.

Journal Article↗
PubMed2002

Functional expression of the Vibrio parahaemolyticus Na+/galactose (vSGLT) cotransporter in Xenopus laevis oocytes.

We have successfully expressed a bacterial cotransporter in a functional form in the Xenopus laevis oocyte expression system. The goals were to compare the kinetics and selectivity of the cotransporter expressed in oocytes with those obtained in bacteria and in proteoliposomes, and to determine if it is possible to measure the electrical properties of the bacterial cotransporter expressed in oocytes. The Vibrio parahaemolyticus Na+/galactose cotransporter (vSGLT) expressed in oocytes has functional properties that are similar to those expressed in bacteria and those of the purified cotransporter reconstituted into liposomes. vSGLT is a Na+-dependent transporter that is saturable with Na+ (K(0.5)=17 mM) and D-galactose (K(0.5)=237 microM) and is sensitive to both D-fucose and phlorizin. In addition, vSGLT in oocytes shows a sugar specificity in the order of D-galactose >D-fucose > D-glucose, distinguishing it from the animal members of the Na+/glucose cotransporter family. The level of transport by vSGLT in oocytes is lower overall (V(max) approximately 10 pmol/oocyte/hour) compared to other plant and animal cotransporters (V(max) approximately 1000 pmol/oocyte/hour). The low level of expression does not permit us to carry out electrophysiological studies of the bacterial cotransporter. This study shows the potential and unique advantages of utilizing a eukaryotic oocyte expression system to study bacterial cotransporters.

Animals↗
PubMed2002

A ligand-dependent conformational change of the Na+/galactose cotransporter of Vibrio parahaemolyticus, monitored by tryptophan fluorescence.

Purification and reconstitution of the active Vibrio parahaemolyticus Na+/galactose transporter (vSGLT) enables us to do protein chemistry studies on a representative member of this class of membrane transporters. By measuring intrinsic tryptophan (Trp) fluorescence, conformational changes on the binding of substrates could be investigated. Trp fluorescence increased by 6% on the addition of saturating levels of both Na+ and D-galactose, with a K0.5 for D-galactose of 0.6 mM. No change was seen on the addition of Na+ alone or by adding D-galactose in the presence of K+. The Trp fluorescence could be quenched by acrylamide, but not by Cs+or I?. In the presence of Na+ or K+ alone, of Na+ or K+ and D-galactose, of Na+ and L-glucose, or in the absence of ligands, the fluorescence quenches by acrylamide were similar. This indicated that the tryptophan exposure to acrylamide was unchanged in the presence or absence of ligands. No shifts in lem maximum were observed. To find the Trp responsible for the change in fluorescence, Trp 448 in transmembrane helix 11 in the putative sugar-binding pocket was mutated. It was found that W448F showed a similar change in Trp fluorescence upon the addition of D-galactose in the presence of Na+. We conclude that the Trp fluorescence properties of the purified and reconstituted Na+/galactose cotransporter are selectively changed by the transported substrates Na+ and D-galactose, but it is not the Trp (W448) in the sugar translocation pathway that is involved.

Calcium-Binding Proteins↗
PubMed2002

Inhibition of gap junction hemichannels by chloride channel blockers.

Electrophysiological methods were used to assess the effect of chloride-channel blockers on the macroscopic and microscopic currents of mouse connexin50 (Cx50) and rat connexin46 (Cx46) hemichannels expressed in Xenopus laevis oocytes. Oocytes were voltage-clamped at -50 mV and hemichannel currents (ICx50 or ICx46) were activated by lowering the extracellular Ca2+ concentration ([Ca2+]o) from 5 mM to 10 microM. Ion-replacement experiments suggested that ICx50 is carried primarily (>95%) by monovalent cations (PK : PNa : PCl = 1.0 : 0.74 : 0.05). ICx50 was inhibited by 18beta-glycyrrhetinic acid (apparent Ki, 2 microM), gadolinium (3 microM), flufenamic acid (3 microM), niflumic acid (11 microM), NPPB (15 microM), diphenyl-2-carboxylate (26 microM), and octanol (177 microM). With the exception of octanol, niflumic acid, and diphenyl-2-carboxylate, the above agents also inhibited ICx46. Anthracene-9-carboxylate, furosemide, DIDS, SITS, IAA-94, and tamoxifen had no inhibitory effect on either ICx50 or ICx46. The kinetics of ICx50 inhibition were not altered at widely different [Ca2+]o (10-500 microM), suggesting that drug-hemichannel interaction does not involve the Ca2+ binding site. In excised membrane patches, application of flufenamic acid or octanol to the extracellular surface of Cx50 hemichannels reduced single channel-open probability without altering the single-channel conductance, but application to the cytoplasmic surface had no effect on the channels. We conclude that some chloride-channel blockers inhibit lens-connexin hemichannels by acting on a site accessible only from the extracellular space, and that drug-hemichannel interaction involves a high-affinity site other than the Ca2+ binding site.

Animals↗
PubMed2001

Generation of electromagnetic pulses from plasma channels induced by femtosecond light strings.

We present a model that elucidates the physics underlying the generation of an electromagnetic pulse from a femtosecond laser induced plasma channel. The radiation pressure force from the laser pulse spatially separates the ionized electrons from the heavier ions and the induced dipole moment subsequently oscillates at the plasma frequency and radiates an electromagnetic pulse.

Journal Article↗