Quantitative analysis of benign paroxysmal positional vertigo fatigue under canalithiasis conditions

In our daily life, small flows in the semicircular canals (SCCs) of the inner ear displace a sensory structure called the cupula which mediates the transduction of head angular velocities to afferent signals. We consider a dysfunction of the SCCs known as canalithiasis. Under this condition, small debris particles disturb the flow in the SCCs and can cause benign paroxysmal positional vertigo (BPPV), arguably the most common form of vertigo in humans. The diagnosis of BPPV is mainly based on the analysis of typical eye movements (positional nystagmus) following provocative head maneuvers that are known to lead to vertigo in BPPV patients. These eye movements are triggered by the vestibulo-ocular reflex, and their velocity provides an indirect measurement of the cupula displacement. An attenuation of the vertigo and the nystagmus is often observed when the provocative maneuver is repeated. This attenuation is known as BPPV fatigue. It was not quantitatively described so far, and the mechanisms causing it remain unknown. We quantify fatigue by eye velocity measurements and propose a fluid dynamic interpretation of our results based on a computational model for the fluid–particle dynamics of a SCC with canalithiasis. Our model suggests that the particles may not go back to their initial position after a first head maneuver such that a second head maneuver leads to different particle trajectories causing smaller cupula displacements.     

Otx1 and Otx2 activities are required for the normal development of the mouse inner ear

The Otx1 and Otx2 genes are two murine orthologues of the Orthodenticle (Otd) gene in Drosophila. In the developing mouse embryo, both Otx genes are expressed in the rostral head region and in certain sense organs such as the inner ear. Previous studies have shown that mice lacking Otx1 display abnormal patterning of the brain, whereas embryos lacking Otx2 develop without heads. In this study, we examined, at different developmental stages, the inner ears of mice lacking both Otx1 and Otx2 genes. In wild-type inner ears, Otx1, but not Otx2, was expressed in the lateral canal and ampulla, as well as part of the utricle. Ventral to the mid-level of the presumptive utricle, Otx1 and Otx2 were co-expressed, in regions such as the saccule and cochlea. Paint-filled membranous labyrinths of Otx1-/- mutants showed an absence of the lateral semicircular canal, lateral ampulla, utriculosaccular duct and cochleosaccular duct, and a poorly defined hook (the proximal part) of the cochlea. Defects in the shape of the saccule and cochlea were variable in Otx1-/- mice and were much more severe in an Otx1-/-;Otx2(+/)- background. Histological and in situ hybridization experiments of both Otx1-/- and Otx1-/-;Otx2(+/)- mutants revealed that the lateral crista was absent. In addition, the maculae of the utricle and saccule were partially fused. In mutant mice in which both copies of the Otx1 gene were replaced with a human Otx2 cDNA (hOtx2(1)/ hOtx2(1)), most of the defects associated with Otx1-/- mutants were rescued. However, within the inner ear, hOtx2 expression failed to rescue the lateral canal and ampulla phenotypes, and only variable rescues were observed in regions where both Otx1 and Otx2 are normally expressed. These results suggest that both Otx genes play important and differing roles in the morphogenesis of the mouse inner ear and the development of its sensory organs.     

Chemoreception Regulates Chemical Access to Mouse Vomeronasal Organ: Role of Solitary Chemosensory Cells

Controlling stimulus access to sensory organs allows animals to optimize sensory reception and prevent damage. The vomeronasal organ (VNO) detects pheromones and other semiochemicals to regulate innate social and sexual behaviors. This semiochemical detection generally requires the VNO to draw in chemical fluids, such as bodily secretions, which are complex in composition and can be contaminated. Little is known about whether and how chemical constituents are monitored to regulate the fluid access to the VNO. Using transgenic mice and immunolabeling, we found that solitary chemosensory cells (SCCs) reside densely at the entrance duct of the VNO. In this region, most of the intraepithelial trigeminal fibers innervate the SCCs, indicating that SCCs relay sensory information onto the trigeminal fibers. These SCCs express transient receptor potential channel M5 (TRPM5) and the phospholipase C (PLC) β2 signaling pathway. Additionally, the SCCs express choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) for synthesizing and packaging acetylcholine, a potential transmitter. In intracellular Ca²⁺ imaging, the SCCs responded to various chemical stimuli including high concentrations of odorants and bitter compounds. The responses were suppressed significantly by a PLC inhibitor, suggesting involvement of the PLC pathway. Further, we developed a quantitative dye assay to show that the amount of stimulus fluid that entered the VNOs of behaving mice is inversely correlated to the concentration of odorous and bitter substances in the fluid. Genetic knockout and pharmacological inhibition of TRPM5 resulted in larger amounts of bitter compounds entering the VNOs. Our data uncovered that chemoreception of fluid constituents regulates chemical access to the VNO and plays an important role in limiting the access of non-specific irritating and harmful substances. Our results also provide new insight into the emerging role of SCCs in chemoreception and regulation of physiological actions.     

Asymmetric flows of spherical particles in a cylindrical tube

To study the rheological behavior of blood cells in various flow patterns through narrow vessels, we analyzed numerically the motion of blood cells arranged in one row or two rows in tube flow, at low Reynolds numbers. The particles are assumed to be identical rigid spheres placed periodically along the vessel axis at off-axis positions with equal spacings. The flow field of the suspending fluid in a circular cylindrical tube is analyzed by a finite element method applied to the Stokes equations, and the motion of each particle is simultaneously determined by a force-free and torque-free condition. In both cases of single- and two-file arrangements of the particles, their longitudinal and angular velocities are largely affected by the radial position and the axial spacing between neighboring particles. The apparent viscosity of the asymmetric flows is higher than that of the symmetric flow where particles are located on the tube centerline, and this is more pronounced when particles are placed farther from the tube centerline and when the axial distance between neighboring particles is reduced.     

Functional anatomy of the valves in the ambulacral system of sea urchins (Echinodermata,Echinoida)

Summary The water vascular system of sea urchins is examined with special reference to the valves positioned between the radial vessel and the ampullae of the tube feet. The lips of the valve protrude into the ampulla. Thus the valve functions mainly like a check valve that allows the unidirectional flow of fluid towards the ampulla. Each ampulla-tube foot compartment acts as a semi-autonomous hydraulic system. The lumina of the ampulla and the tube foot are lined with myoepithelia except for the interconnecting channels that pierce the ambulacral plate. The contraction of the ampulla results in an increasing hydraulic pressure that protrudes the tube foot, provided that the valve is closed. The retraction of the tube foot results in a backflow of fluid independent of the condition of the valve. The lips of the valve are folds of the hydrocoel epithelium. The pore slit lies in the midline. The perradial faces of the lips are covered with the squamous epithelium of the lateral water vessel. The ampullar faces are specialized parts of the ampulla myoepithelium. Turgescent cells which form incompressible cushions take the place of the support cells. The valve myocytes run parallel to the pore slit and form processes that run along the base of the ampulla and the perradial channel up to the podial retractor muscle. The findings lead to the hypothesis of multiple control of the ampulla-tube foot system: (1) The mutual activity of the ampulla and the tube foot is indirectly controlled by the lateral and podial nerves which release transmitter substances that diffuse through the connective tissue up to the muscle layers. (2) A muscle-to-muscle conduction causes the simultaneous contraction of the ampulla or the podial retractor muscles. (3) The valve muscles are directly controlled by the processes of the valve myocytes which make contact with the podial retractor. In extreme conditions a backflow of hydrocoel fluid towards the radial water vessel occurs.     

Analysis of a high‐throughput cone‐and‐plate apparatus for the application of defined spatiotemporal flow to cultured cells

The shear stresses derived from blood flow regulate many aspects of vascular and immunobiology. In vitro studies on the shear stress‐mediated mechanobiology of endothelial cells have been carried out using systems analogous to the cone‐and‐plate viscometer in which a rotating, low‐angle cone applies fluid shear stress to cells grown on an underlying, flat culture surface. We recently developed a device that could perform high‐throughput studies on shear‐mediated mechanobiology through the rotation of cone‐tipped shafts in a standard 96‐well culture plate. Here, we present a model of the three‐dimensional flow within the culture wells with a rotating, cone‐tipped shaft. Using this model we examined the effects of modifying the design parameters of the system to allow the device to create a variety of flow profiles. We first examined the case of steady‐state flow with the shaft rotating at constant angular velocity. By varying the angular velocity and distance of the cone from the underlying plate we were able to create flow profiles with controlled shear stress gradients in the radial direction within the plate. These findings indicate that both linear and non‐linear spatial distributions in shear stress can be created across the bottom of the culture plate. In the transition and “parallel shaft” regions of the system, the angular velocities needed to provide high levels of physiological shear stress (5 Pa) created intermediate Reynolds number Taylor‐Couette flow. In some cases, this led to the development of a flow regime in which stable helical vortices were created within the well. We also examined the system under oscillatory and pulsatile motion of the shaft and demonstrated minimal time lag between the rotation of the cone and the shear stress on the cell culture surface. Biotechnol. Bioeng. 2013; 110: 1782–1793. © 2013 Wiley Periodicals, Inc.     

Spinal constraint modulates head instantaneous center of rotation and dictates head angular motion

The head is kinematically constrained to the torso through the spine and thus, the spine dictates the amount of output head angular motion expected from an input impact. Here, we investigate the spinal kinematic constraint by analyzing the head instantaneous center of rotation (HICOR) with respect to the torso in head/neck sagittal extension and coronal lateral flexion during mild loads applied to 10 subjects. We found the mean HICOR location was near the C5-C6 intervertebral joint in sagittal extension, and T2-T3 intervertebral joint in coronal lateral flexion. Using the impulse-momentum relationship normalized by subject mass and neck length, we developed a non-dimensional analytical ratio between output angular velocity and input linear impulse as a function of HICOR location. The ratio was 0.65 and 0.50 in sagittal extension and coronal lateral flexion respectively, implying 30% greater angular velocities in sagittal extension given an equivalent impulse. Scaling to subject physiology also predicts larger required impulses given greater subject mass and neck length to achieve equivalent angular velocities, which was observed experimentally. Furthermore, the HICOR has greater motion in sagittal extension than coronal lateral flexion, suggesting the head and spine can be represented with a single inverted pendulum in coronal lateral flexion, but requires a more complex representation in sagittal extension. The upper cervical spine has substantial compliance in sagittal extension, and may be responsible for the complex motion and greater extension angular velocities. In analyzing the HICOR, we can gain intuition regarding the neck’s role in dictating head motion during external loading.     

Some evidence for the ampullary organs in the European cave salamander Proteus anguinus (Urodela,Amphibia)

Summary The multicellular epithelial organs in Proteus anguinus, which Bugnion (1873) assumed to be developing neuromasts, have been analyzed by lightand electron-microscopy. Their fundamental structure consists of single ampullae with sensory and accessory cells with apical parts that extend into the pit of the ampulla, and of a short jelly-filled canal connecting the ampulla pit with the surface of the skin. The organs are located intra-epithelially and are supported by a tiny dermal papilla. The cell elements of sensory epithelium are apically linked together by tight junctions. The free apical surface of the sensory cell bears several hundred densely packed stereocilia-like microvilli whereas the basal surface displays afferent neurosensory junctions with a pronounced round synaptic body. The compact uniform organization of the apical microvillous part shows a hexagonal pattern. A basal body was found in some sensory cells whereas a kinocilium was observed only in a single cell. The accessory cells have their free surface differentiated in a sparsely distributed and frequently-forked microvilli. The canal wall is built of two or three layers of tightly coalescent flat cells bordering on the lumen with branching microvilli. The ultrastructure of the content of the ampulla pit is presented.In the discussion stress is laid on the peculiarities of the natural history of Proteus anguinus that support the view that the morphologically-identified ampullary organs are electroreceptive. The structural characteristics of ampullary receptor cells are dealt with from the viewpoint of functional morphology and in the light of evolutionary hypotheses of ampullary organs.     

Two-Fluid Model of Biofilm Disinfection

We consider a dynamic model of biofilm disinfection in two dimensions. The biofilm is treated as a viscous fluid immersed in a fluid of less viscosity. The bulk fluid moves due to an imposed external parabolic flow. The motion of the fluid is coupled to the biofilm inducing motion of the biofilm. Both the biofilm and the bulk fluid are dominated by viscous forces, hence the Reynolds number is negligible and the appropriate equations are Stokes equations. The governing partial differential equations are recast as boundary integral equations using a version of the Lorenz reciprocal relationship. This allows for robust treatment of the simplified fluid/biofilm motion. The transport of nutrients and antimicrobials, which depends directly on the velocities of the fluid and biofilm, is also included. Disinfection of the bacteria is considered under the assumption that the biofilm growth is overwhelmed by disinfection. Supported by NSF award DMS-0612467.     

Stability of particle motions in a narrow channel flow

Single rows or two rows of identical circular cylinders spaced regularly in a narrow channel flow have been shown to be capable of steady flow provided the cylinders are located at equal lateral positions and with equal spacings in the flow direction. The stability of such steady flows of circular cylinders is studied for periodic perturbations of the particle positions, assuming that every other cylinder is equally perturbed in lateral position and spacing along the channel. This results in two rows which are not symmetrically placed. The suspending fluid is assumed to be an incompressible Newtonian fluid. It is assumed that no external forces or moments act on the cylinders and the effects of inertia forces on the motion of the fluid and the cylinders are negligible. The velocity field of the suspending fluid and the instantaneous velocities of the cylinders are computed by the finite element method. The translational velocities of the cylinders are obtained for a large number of particle positions, from which the trajectories of their relative motion are determined for various initial positions near the regular single-file and two-file arrangements. It is shown that when the initial arrangements of the cylinders are slightly perturbed from the regular (alternating) two-file flows, the trajectories of their relative motions become small closed loops around the regular two-file arrangements. In contrast, such small closed trajectories are not obtained when they start from the arrangements near the regular single-file flows or regular (symmetric) double-file flows, suggesting that these flows are unstable under the conditions examined.     

A model of a radially expanding and contracting lymphangion

The lymphatic system is an extensive vascular network featuring valves and contractile walls that pump interstitial fluid and plasma proteins back to the main circulation. Immune function also relies on the lymphatic system's ability to transport white blood cells. Failure to drain and pump this excess fluid results in edema characterized by fluid retention and swelling of limbs. It is, therefore, important to understand the mechanisms of fluid transport and pumping of lymphatic vessels. Unfortunately, there are very few studies in this area, most of which assume Poiseuille flow conditions. In vivo observations reveal that these vessels contract strongly, with diameter changes of the order of magnitude of the diameter itself over a cycle that lasts typically 2-3s. The radial velocity of the contracting vessel is on the order of the axial fluid velocity, suggesting that modeling flow in these vessels with a Poiseuille model is inappropriate. In this paper, we describe a model of a radially expanding and contracting lymphatic vessel and investigate the validity of assuming Poiseuille flow to estimate wall shear stress, which is presumably important for lymphatic endothelial cell mechanotransduction. Three different wall motions, periodic sinusoidal, skewed sinusoidal and physiologic wall motions, were investigated with steady and unsteady parabolic inlet velocities. Despite high radial velocities resulting from the wall motion, wall shear stress values were within 4% of quasi-static Poiseuille values. Therefore, Poiseuille flow is valid for the estimation of wall shear stress for the majority of the lymphangion contractile cycle.     

The lorenzinian ampullae of Polyodon spathula

Summary Light and electron microscopic observations on the ampullary organs of Polyodon spathula (Chondrostei, Osteichthyes) reveal a sensory epithelium similar to that found in the Lorenzinian ampulla, an electroreceptor found in marine Elasmobranchs.The sensory cells have a very small luminal part provided with a cilium. They are innervated by many nerve endings. Each nerve fibre apparently makes synaptic contact with several sensory cells. The synaptic structure in the sensory cell is composed of a flat sheet, the outermost part of which is surrounded by 3 or 4 annuli of densely staining material. The sheet extends into a protrusion of the sensory cell, and there is a corresponding invagination in the nerve terminal.The conclusion that these organs are electroreceptors, is supported by the finding that the fish responds to the introduction of an iron tube in the aquarium, whereas a wooden rod introduced in the same way causes no response.     

Ultrastructure and physiology of the CO2 sensitive sensillum ampullaceum in the leaf-cutting ant Atta sexdens

The sensilla ampullacea on the apical antennomere of the leaf-cutting ant Atta sexdens were investigated regarding both their responses to CO2 and their ultrastructure. By staining the sensillum during recording, we confirmed that the sensilla ampullacea are responsible for CO2 perception. We showed that the sensory neurons of the sensilla ampullacea are continuously active without adaptation during stimulation with CO2 (test duration: 1 h). This feature should enable ants to assess the absolute CO2 concentration inside their nests. Sensilla ampullacea have been found grouped mainly on the dorso-lateral side of the distal antennal segment. Scanning and transmission electron microscopic investigations revealed that the external pore opens into a chamber which connects to the ampulla via a cuticular duct. We propose protection against evaporation as a possible function of the duct. The ampulla houses a peg which is almost as long as the ampulla and shows cuticular ridges on the external wall. The ridges are separated by furrows with cuticular pores. The peg is innervated by only one sensory neuron with a large soma. Its outer dendritic segment is enveloped by a dendritic sheath up to the middle of the peg. From the middle to the tip numerous dendritic branches (up to 100) completely fill the distal half of the peg. This is the first report of a receptor cell with highly branched dendrites and which probably is tuned to CO2 exclusively.     

The active and passive ciliary motion in the embryo node: A computational fluid dynamics model

The breaking of left–right symmetry in the mammalian embryo is believed to occur in a transient embryonic structure, the node, when cilia create a leftward flow of liquid. The two-cilia hypothesis proposes that the node contains two kinds of primary cilia: motile cilia that rotate autonomously to generate the leftward fluid flow and passive cilia that act as mechano-sensors, responding to flow. While studies support this hypothesis, the mechanism by which the sensory cilia respond to the fluid flow is still unclear. In this paper, we present a computational model of two cilia, one active and one passive. By employing computational fluid dynamics, deformable mesh computational techniques and fluid–structure interaction analysis, and solving the three-dimensional unsteady transport equations, we study the flow pattern produced by the movement of the active cilium and the response of the passive cilium to this flow. Our results reveal that clockwise rotation of the active cilium can generate a counter-clockwise elliptical rotation and overall lateral displacement for its neighboring passive one, of measurable magnitude and consistent pattern. This supports the plausibility of the two-cilia hypothesis and helps quantify the motion pattern for the passive cilium induced by this regional flow.     

Morphogenesis of the inner ear of Rana temporaria (Amphibia,Anura)

Summary Differentiation of the inner ear of Rana temporaria temporaria Linné, 1758 begins with invagination of the epidermis to form the otocyst. The first sensory epithelium to form is the macula communis. Not until this is complete are the semicircular canals produced as protrusions from the otocyst; at the same time the ampullar cristae develop as structures for the detection of rotation, separate from the macula communis. The formation of utricle and saccule, organs for the gravitational sense, occurs by concentric constriction between the superior and inferior parts of the otocyst, dividing the macula communis into two parts. At a time when the utricle and the semicircular canals have completely differentiated, the saccule region of the inner ear is still undergoing morphological development, with the formation first of the two auditory papillae (the basilar and amphibian papillae) and then of the lagena, an evagination of the saccule.Abbreviations aa Anterior ampulla - al Lateral ampulla - c Cartilage - ca Ampullar crista - cc Crus commune - csa Anterior semicircular canal - csl Lateral semicircular canal - csp Posterior semicircular canal - cu Cupula - ed Epidermis - fus Utriculo-saccular foramen - g Ganglion - kc Kinocilium - l Lagena - m Medulla oblongata - mc Macula communis - mes Mesenchyme - ms Macula of the saccule - mu Macula of the utricle - on Organic network - pa Amphibian papilla - pb Basilar papilla - pi Inferior part of otocyst - pm Presumptive medulla oblongata - po Preotolith - ps Superior part of otocyst - raa Anterior acoustic ramus - rl Recess of labyrinth - s Saccule - tm Tectorial membrane - u Utricle - * Perilymphatic space     

An analysis of the flow of a power law fluid due to ciliary motion in an infinite channel

The propulsion mechanics of cilia-induced flow is studied through a mathematical model. The problem of two-dimensional motion of a power law fluid inside a channel with ciliated walls is considered. The characteristics of ciliary systems are determined by the dominance of viscous effects over inertial effects using the long-wavelength approximation. Solutions for the longitudinal, transverse, and resultant velocities are obtained. The pressure gradient and volume flow rate for different values of the power law index are also calculated. The flow properties for the power law fluid are determined as a function of the cilia and metachronal wave velocity. The viscous and power law fluid are compared and discussed graphically.     

On the ampullary organs of the South-American paddle-fish Sorubim lima (Siluroidea,Pimelodidae)

Summary Ampullary organs were found in the epidermis of the paddle-fish Sorubim lima; they are distributed all over the skin surface of the fish but are particularly densely grouped in the head region and on the dorsal surface of the paddle. Histological and electron microscopical observations show that their structure is similar to the type of cutaneous ampullary organs characteristic of other Siluroidea. Composed of a relatively large mucus-filled ampulla, the organ possesses a short and narrow canal which leads to the outer epidermal surface. The wall of the ampulla is formed of several layers of flat epidermal cells. In general four sensory cells, each one surrounded by supporting cells, compose the sensory epithelium at the bottom of the ampulla. The inner surface of the sensory cells in contact with the ampullary mucus bears only microvilli. The contact between the nerve endings and the sensory cells show the characteristic structure of an afferent neuro-sensory junction. Two ampullae are innervated in some cases by the same afferent nerve fibre.The author expresses her gratitude to Dr. Szabo for his scientific advice during her stay in Gif sur Yvette     

Excretion in the house cricket (Acheta domesticus): ultrastructure of the ampulla and ureter

An ultrastructural analysis of the ampulla and ureter of the cricket, Acheta domesticus, is presented. The excretory system of the cricket is unusual in that the 112 Malpighian tubules do not attach directly to the gut, but fuse to form a bladder-like ampulla which is joined to the colon by a muscular ureter. The ampulla consists of two cell types, primary and regenerative. Primary cells secrete large numbers of membrane-bound vesicles into the lumen and also appear to be involved in fluid reabsorption. Regenerative cells are very small and form a layer just beneath the basal lamina of the ampulla. They are believed to differentiate and replace sloughed off primary cells. The ureter is a muscular tube lined with cuticle which connects the ampulla (endoderm) with the colon (ectoderm). The probable origin and significance of the morphological modifications of the excretory system are discussed.     

A mathematical model for the motion of mechanoreceptor hairs in fluid environments.

A differential equation has been derived for the motion of the mechanosensory hairs of animals when they are stimulated by the motion of their fluid environment. Specific solutions of the equation are obtained for three states of fluid flow including steady-state sinusoidal oscillations. The model is specifically applied to crayfish sensilla in an aqueous medium, but the assumptions of the model are also shown to be valid in air for the sensory hairs of insects. The calculations are consistent with available experimental data.