An intrinsic compartmentalization code for peripheral membrane proteins in photoreceptor neurons.

In neurons, peripheral membrane proteins are enriched in subcellular compartments, where they play key roles, including transducing and transmitting information. However, little is known about the mechanisms underlying their compartmentalization. To explore the roles of hydrophobic and electrostatic interactions, we engineered probes consisting of lipidation motifs attached to fluorescent proteins by variously charged linkers and expressed them in rod photoreceptors.

Modeling solute reactivity in a phreatic solution conduit penetrating a karst aquifer.

A two-dimensional model for solute migration, transformation, and deposition in a phreatic solution conduit penetrating a karst aquifer is presented in which the solute is anthropogenic to the natural system. Transformation of a reacting solute in a solution conduit has generally been accepted as likely occurring but actual physical measurements and mathematical analyses of the suspected process have been generally minimally investigated, primarily because of the logistical difficulties and complexities associated with solute transport through solution conduits. The model demonstrates how a reacting solute might decay or be transformed to a product solute some of which then migrates via radial dispersion to the conduit wall where it may become adsorbed.

Methadone Recycling Sustains Drug Reservoir in Tissue.

We hypothesize that there is a tissue store of methadone content in humans that is not directly accessible, but is quantifiable. Further, we hypothesize the mechanism by which methadone content is sustained in tissue stores involves methadone uptake, storage, and release from tissue depots in the body (recycling). Accordingly, we hypothesize that such tissue stores, in part, determine plasma methadone levels.

In silico ordinary differential equation/partial differential equation hemodialysis model estimates methadone removal during dialysis.

Background: There is a need to have a model to study methadone's losses during hemodialysis to provide informed methadone dose recommendations for the practitioner.

Aim: To build a one-dimensional (1-D), hollow-fiber geometry, ordinary differential equation (ODE) and partial differential equation (PDE) countercurrent hemodialyzer model (ODE/PDE model).

Methodology: We conducted a cross-sectional study in silico that evaluated eleven hemodialysis patients.

CYP2D6 phenotype-specific codeine population pharmacokinetics.

Codeine's metabolic fate in the body is complex, and detailed quantitative knowledge of it, and that of its metabolites is lacking among prescribers. We aimed to develop a codeine pharmacokinetic pathway model for codeine and its metabolites that incorporates the effects of genetic polymorphisms. We studied the phenotype-specific time courses of plasma codeine, codeine-6-glucoronide, morphine, morphine-3-glucoronide, and morphine-6-glucoronide.

ODE/PDE analysis of corneal curvature.

The starting point for this paper is a nonlinear, two-point boundary value ordinary differential equation (BVODE) that defines corneal curvature according to a static force balance. A numerical solution to the BVODE is computed by first converting the BVODE to a parabolic partial differential equation (PDE) by adding an initial value (t, pseudo-time) derivative to the BVODE. A numerical solution to the PDE is then computed by the method of lines (MOL) with the calculation proceeding to a sufficiently large value of t such that the derivative in t reduces to essentially zero.

Oxycodone recycling: a novel hypothesis of opioid tolerance development in humans.

We hypothesize that oxycodone (OC) recycling promotes sustained synaptic OC content, which prolongs OC's exposure to local μ-opioid receptors (μORs). In that way, OC recycling gives rise to OC tolerance in humans. To pilot test our hypothesis, we developed a whole-body OC mass transport tolerance recovery model.

A transit compartment model unmasks OxyContin's reflective pharmacokinetics from urine measurements in humans.

The absorption pattern of orally administered OxyContin (OXC) reflected in urine indicates that its appearance into systemic circulation undergoes transit absorption delays. The authors developed an OXC transit-delay compartment model that identified a new source of oxycodone hydrochloride (OC): the rate of appearance of OC due to OXC tablet dissolution in transit through the gastrointestinal (GI) tract (R(a)(GI)), which is due to disintegration of OXC's AcroContin delivery system. R(a)(GI) is independent of the biphasic dissolution and release of OC from the delivery system.

Organ-specific microcirculatory mass transport of oxycodone in humans: clinical implications for therapeutic use.

Objectives: To begin to address the problem of heterogeneity of distribution of oxycodone (OC) in humans, we developed an organ-specific microcirculatory capillary-tissue exchange 2-compartment model for studying regional OC mass transport.

Materials And Methods: The model was developed in silico. It quantifies OC's organ-specific mass transport rates, clearances and recycling, and it considers the effects of blood flow on OC's convective and diffusive transport.

Impact of signaling microcompartment geometry on GPCR dynamics in live retinal photoreceptors.

G protein-coupled receptor (GPCR) cascades rely on membrane protein diffusion for signaling and are generally found in spatially constrained subcellular microcompartments. How the geometry of these microcompartments impacts cascade activities, however, is not understood, primarily because of the inability of current live cell-imaging technologies to resolve these small structures. Here, we examine the dynamics of the GPCR rhodopsin within discrete signaling microcompartments of live photoreceptors using a novel high resolution approach.

Diffusion of a soluble protein, photoactivatable GFP, through a sensory cilium.

Transport of proteins to and from cilia is crucial for normal cell function and survival, and interruption of transport has been implicated in degenerative and neoplastic diseases. It has been hypothesized that the ciliary axoneme and structures adjacent to and including the basal bodies of cilia impose selective barriers to the movement of proteins into and out of the cilium. To examine this hypothesis, using confocal and multiphoton microscopy we determined the mobility of the highly soluble photoactivatable green fluorescent protein (PAGFP) in the connecting cilium (CC) of live Xenopus retinal rod photoreceptors, and in the contiguous subcellular compartments bridged by the CC, the inner segment (IS) and the outer segment (OS).

Light-driven translocation of signaling proteins in vertebrate photoreceptors.

The dynamic localization of proteins within cells is often determined by environmental stimuli. In retinal photoreceptors, light exposure results in the massive translocation of three key signal transduction proteins, transducin, arrestin and recoverin, into and out of the outer segment compartment where phototransduction takes place. This phenomenon has rapidly taken the center stage of photoreceptor cell biology, thanks to the introduction of new quantitative and transgenic approaches.