Eye movement control during reading: Fixation measures reflect foveal but not parafoveal processing difficulty.

Explored whether, during natural reading, the difficulty of the upcoming parafoveal word affects eye movement behavior on the currently fixated word. A model in which visual attention is allocated in parallel over both the fixated and the upcoming parafoveal word predicts such an effect, while a sequential attention allocation model, in which attention is directed first to the fixated word and then to the upcoming parafoveal word, does not. An experiment was conducted with 24 college students in which 2 manipulations of parafoveal difficulty were made. Data show that neither the frequency nor the combined length, frequency, and class of the upcoming word affected eye movement behavior on the current word. Findings support the model of eye movement control in reading. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intercellular junctions in the reticular lamina of the organ of Corti

Junctions between the cells in the reticular lamina of the organ of Corti were examined in thin sections and after freeze-fracturing to find a structural basis for the large ionic differences between the endolymph and perilymph. The apices of the cells in the reticular lamina are joined by a band of tight junctions spaced at 140 A intervals. Beneath this apical band the organization of the tight junctions depends on whether they join a supporting cell and a hair cell, or two supporting cells. At hair cell junctions with supporting cells, there is an extensive labyrinth of tight junctions enclosing lengthy, tortuous passages whose walls are composed of either multiple parallel or single junctions. At appositions between two supportinc cells, maculae or fasciae occludentes lie immediately beneath the apical bands of closely spaced tight junctions, near the top of the zonulae adherentia which are characteristic of appositions between supporting cells. The complexes of tight junctions, or zonulae occludentes, between extralaminar supporting cells differ from those in the reticular lamina. The extralaminar cells are joined by a band of four to seven branching, anastomotic tight junctions. Thus, these junctions are like zonulae occludentes in other tissues. The novel organizations of the tight junctions in the reticular lamina, different from those between the extralaminar supporting cells, suggests a special role for these junctions in the reticular lamina. Two sizes of gap junctions link, and presumably couple, supporting cells in the reticular lamina.     

Neurexin is expressed on nerves, but not at nerve terminals, in the electric organ

Neurexins are highly variable transmembrane proteins hypothesized to be nerve terminal-specific cell adhesion molecules. As a test of the hypothesis that neurexin is restricted to the nerve terminal, we examined neurexins in the electric organ of the elasmobranch electric fish. Specific antibodies generated against the intracellular domain of electric fish neurexin were used in immunocytochemical and Western blot analyses of the electromotor neurons that innervate the electric organ. Our results indicate that neurexin is not expressed at electric organ nerve terminals, as expected by the neurexin hypothesis. Instead, neurexin is expressed by electromotor neurons and on myelinated axons. This neurexin has a molecular weight of 140 kDa, consistent with an alpha-neurexin. In addition, we find that perineurial cells of the electromotor nerve also express a neurexin. These cells surround bundles of axons to form a diffusion barrier and are thought to be a special form of fibroblast. The results of the study argue against a universal role for neurexins as nerve terminal-specific proteins but suggest that neurexins are involved in axon-Schwann cell and perineurial cell interactions.     

The Epworth Sleepiness Scale may not reflect objective measures of sleepiness or sleep apnea

OBJECTIVE: To assess the validity of the Epworth Sleepiness Scale score (ES) as a measure of sleepiness among patients suspected or confirmed to have obstructive sleep apnea syndrome. BACKGROUND: The ES is used with increasing frequency as a measure of excessive daytime sleepiness in part because several studies suggested that the ES correlates with mean sleep latency (MSL) on the Multiple Sleep Latency Test and with severity of sleep apnea among patients with that disorder. However, associations identified between the ES and other measures were not strong or consistent. METHODS: The authors used regression models and retrospective data from a relatively large series of 237 patients to restudy how ES relates to MSL, to a simple self-rating of problem sleepiness (available for 141 patients), and to two polysomnographic measures of sleep apnea severity: the number of apneas or hypopneas per hour of sleep and the minimum recorded oxygen saturation. RESULTS: The ES had a statistically significant association with self-rated problem sleepiness but not with MSL or measures of sleep apnea severity. Male gender, adjusted for potential confounding variables, had considerably more influence on the ES than did MSL or measures of sleep apnea severity. CONCLUSIONS: Our data suggest that the subjectively derived ES cannot be used as a surrogate for the objectively determined MSL.     

Terminal dendritic sprouting and reactive synaptogenesis in the postnatal organ of Corti in culture

Synaptogenesis in the organ of Corti between the primary receptors, the inner hair cells, and the peripheral processes of their afferent spiral ganglion neurons in the mouse lasts for 5 days postnatally (Sobkowicz et al. [1986] J. Neurocytol. 15:693-714). The transplantation of the organ into culture at the fifth postnatal day induces a reactive sprouting of dendritic terminals and an extensive formation of new ribbon synapses within 24 hours. This reactive synaptogenesis differs strikingly from the primary synaptogenesis and has been seen thus far only in the inner hair cells. The synaptically engaged neuronal endings sprout a multitude of filopodia that intussuscept the inner hair cells. The filopodial tips contain a heavy electron-dense matter that appears to attract the synaptic ribbons, which form new synaptic contacts with the growing processes. The intensity of the filopodial growth and synaptogenesis subsides in about 3 days; the filopodia undergo resorption, leaving behind fibrous cytoplasmic plaques mostly stored in the supranuclear part of the hair cells. However, occasional filopodial growth and formation of new synaptic connections continued. The data demonstrate that any disruption or disturbance of the initial synaptic contacts between the inner hair cells and their afferent neurons caused by transplantation results in prompt synaptic reacquisition. Furthermore, we suggest that the transitory phase of terminal sprouting and multiribbon synapse formation manifests a trophic dependence that develops postnatally between the synaptic cells.     

Postnatal maturation of the organ of Corti in gerbils: morphology and physiological responses

The organ of Corti, the sensory epithelium of hearing in mammals, matures postnatally in the gerbil. Quantitative analyses of the postnatal development of the organ of Corti, including supporting cells and the basilar membrane, were carried out. The morphological study confirmed that maturation of the sensory cells proceeds with a base-to-apex gradient, with the outer hair cells appearing to mature before the inner hair cells. Maturation of the supporting cells and the basilar membrane commenced first in the middle turn. Expansion of the second row of Deiters' cells began at 6 days after birth in the middle turn, before enlargement of the pillar cell heads at 8 days postnatally. Pillar cell head enlargement continued until 20 days postnatally in the middle turn. The tunnel of Corti and spaces of Nuel appeared first in the middle turn between 8 and 10 days postnatally. The maturation of the basilar membrane involved the thickening of the central hyaline layer and a reduction in the epithelial cells on the tympanic aspect. This process continued until about 20 days after birth. The cochlear microphonic potential, whole nerve action potential, and stimulus frequency otoacoustic emissions were recorded from 12 days after birth onward and related to changes in organ of Corti morphology. The results show that changes in the accessory structures continue throughout the period of onset and development of cochlear responses between 12 and 20 days after birth, and may therefore influence the micromechanical responses of the organ of Corti to acoustic stimuli during this period.     

Suppression of developmental retinal cell death but not of photoreceptor degeneration in Bax-deficient mice

PURPOSE: Bax, a member of the Bcl2 family of cell death regulators, induces cell death by promoting the induction of apoptosis. Bax-deficient mice were examined in this study to determine whether Bax is required for cell death in the developing retina and for pathologic apoptotic photoreceptor degeneration resulting from the rd mutation. METHODS: Retinas from Bax-deficient mice and their wild-type siblings were harvested at postnatal day (P) 7 and processed for TdT-dUTP terminal nick-end labeling (TUNEL) staining, and the number of nuclei containing fragmented DNA were counted. Adult retinas and optic nerves were processed for plastic-embedded 1-microm sections, and the cross-sectional area was determined. The mutant Bax allele was outbred onto the C3H mouse strain, which carries the rd allele. Retinas from these animals were examined histologically at P21 after most of the photoreceptor cell death had occurred. RESULTS: At P7, around the time of peak cell death in the inner nuclear layer (INL), significantly fewer neurons in INL and ganglion cell layer (GCL) were TUNEL positive in Bax-deficient mice than in their wild-type siblings. In adult Bax-deficient mice, the cross-sectional area of the optic nerve was approximately 50% larger than in wild-type siblings, and the total number of retinal ganglion cell axons was increased to 226%. The INL of Bax-deficient mice was thicker than normal. The Bax genotype did not affect the thickness or histologic appearance of the outer nuclear layer in retinas of mice with wild-type or mutant rd alleles. CONCLUSIONS: In the absence of the expression of the Bax gene, there is a profound increase in the survival of retinal ganglion cells that lasts into adulthood. Similarly, death of INL cells is diminished but not completely abolished. The absence of Bax does not, however, protect photoreceptors from naturally occurring cell death or degeneration induced by the rd mutation. This shows that Bax is involved to a variable degree in the control of developmental cell death in the retina and that not all apoptotic retinal cell deaths are controlled by Bax.     

Gap junction change in supporting cells of the organ of Corti with ryanodine and caffeine

It has been demonstrated that the gap junctions of the supporting cells of the organ of Corti are controlled by H+ and Ca2+. Inside these cells there is a tubular structure. It is supposed that this network is endoplasmic reticulum. Calcium release from inside the cells, and the effect of calcium on the gap junctions of these cells, were investigated under whole cell clamping application of ryanodine and caffeine. Membrane capacitance and membrane resistance were calculated, with corrections for changes in whole cell parameters. Ryanodine-treated cells (1 microM-10 mM), caffeine-treated cells (5 mM 500 nM) and A23187-treated cells were uncoupled at their gap junctions. Therefore, Ca2+ plays a role in the uncoupling of the gap junctions in supporting cells of the organ of Corti from inside the cells.     

Self-report measures of prospective memory are reliable but not valid.

Are self-report measures of prospective memory (ProM) reliable and valid? To examine this question, 240 undergraduate student volunteers completed several widely used self-report measures of ProM including the Prospective Memory Questionnaire (PMQ), the Prospective and Retrospective Memory Questionnaire (PRMQ), the Comprehensive Assessment of Prospective Memory (CAPM) questionnaire, self-reports of retrospective memory (RetM), objective measures of ProM and RetM, and measures of involvement in activities and events, memory strategies and aids use, personality and verbal intelligence. The results showed that both convergent and divergent validity of ProM self-reports are poor, even though we assessed ProM using a newly developed, reliable continuous measure. Further analyses showed that a substantial proportion of variability in ProM self-report scores was due to verbal intelligence, personality (conscientiousness, neuroticism), activities and event involvement (busyness), and use of memory strategies and aids. ProM self-reports have adequate reliability, but poor validity and should not be interpreted as reflecting ProM ability. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Postnatal development of the organ of Corti in cats: a light microscopic morphometric study

This study quantitatively characterizes the development of the major morphological features of the organ of Corti during the first 2 weeks postnatal, the period when the cat auditory system makes the transition from being essentially non-functional to having nearly adult-like responses. Four groups of kittens (n = 3) were studied at one day postnatal (P1), P5, P10, P15, and compared to adults. Measurements were made of the organ of Corti at 3 cochlear locations: 20%, 60% and 85% of basilar membrane length from the base cochlear locations which in the adult correspond to best frequencies of approximately 20 kHz, 2 kHz and 500 Hz, respectively. In addition, measurements of basilar membrane length and opening of the tunnel of Corti were made in 20 cochlear specimens from kittens aged P0-P6. Results indicate that: (i) at P0 the basilar membrane has attained adult length, and the tunnel of Corti is open over approximately the basal one-half of the cochlea; (ii) the initial opening of the tunnel of Corti occurs at a site about 4 mm from the cochlear base (best frequency of approximately 25 kHz in the adult cochlea); (iii) the thickness of the tympanic cell layer decreases markedly at the basal 20-kHz location; (iv) the areas of the tunnel of Corti and space of Nuel and the angulation of the inner hair cells (IHC) relative to the basilar membrane all show marked postnatal increases at both the middle and apical locations; (v) IHC are nearly adult-like in length and shape at birth, whereas the OHC (at 2-kHz and 500-Hz locations) undergo marked postnatal changes; (vi) disappearance of the marginal pillars and maturation of the supporting cells are not yet complete by P15.     

L-selectin from human, but not from mouse neutrophils binds directly to E-selectin

L-Selectin on neutrophils as well as inducible E- and P-selectin on endothelium are involved in the recruitment of neutrophils into inflamed tissue. Based on cell attachment assays, L-selectin was suggested to function as a carbohydrate presenting ligand for E- and P-selectin. However, previous affinity isolation experiments with an E-selectin-Ig fusion protein had failed to detect L-selectin among the isolated E-selectin ligands from mouse neutrophils. We show here that L-selectin from human neutrophils, in contrast to mouse neutrophils, can be affinity-isolated as a major ligand from total cell extracts using E-selectin-Ig as affinity probe. Binding of human L-selectin to E-selectin was direct, since purified L-selectin could be reprecipitated with E-selectin-Ig. Recognition of L-selectin was abolished by sialidase-treatment, required Ca2+, and was resistant to treatment with endoglycosidase F. Binding of L-selectin to a P-selectin-Ig fusion protein was not observed. In agreement with the biochemical data, the anti-L-selectin mAb DREG56 inhibited rolling of human neutrophils on immobilized E-selectin-Ig but not on P-selectin-Ig. No such inhibitory effect was seen with the anti-mouse L-selectin mAb MEL14 on mouse neutrophils. Rolling of E-selectin transfectants on purified and immobilized human L-selectin was inhibited by mAb DREG56. We conclude that L-selectin on human neutrophils is a major glycoprotein ligand among very few glycoproteins that can be isolated by an E-selectin affinity matrix. The clear difference between human and mouse L-selectin suggests that E-selectin-binding carbohydrate moieties are attached to different protein scaffolds in different species.     

Pretreatment with pertussis toxin blocks morphine- but not beta-endorphin-induced antinociception in the mouse

We have previously demonstrated that the antinociception induced by morphine and beta-endorphin given intracerebroventricularly (i.c.v.) is mediated by the stimulation of respective mu- and epsilon-opioid receptors. The effects of i.c.v. pretreatment with pertussis toxin on the antinociception induced by morphine and beta-endorphin given i.c.v. were studied in male ICR mice. Antinociception was assessed by the tail-flick and hot-plate tests. Pretreatment with pertussis toxin (0.5 microgram) given i.c.v. 96 h earlier blocks the antinociception induced by i.c.v. administered morphine in both tail-flick and hot-plate tests. The same pretreatment did not affect the antinociception induced by i.c.v. administered beta-endorphin. Our results indicate that morphine-, but not beta-endorphin-induced antinociception is mediated by pertussis toxin sensitive G-proteins.     

The localization of synaptophysin in the organ of Corti of the human as shown by immunoelectron microscopy

Synaptophysin, or p38, a polypeptide of molecular weight 38 kD, is a calcium-binding membrane protein found in synaptic vesicles of neurons and smooth surfaced vesicles of neuroendocrine cells. Six human neonatal and infant temporal bones were fixed in paraformaldehyde and glutaraldehyde, decalcified in EDTA and were than immunoreacted for synaptophysin (ICN Biomedicals) using the avidin-biotin reaction (ABC kit, Vector Labs). The tissue was then prepared for light microscopic surface preparation, radial sections of 5 microns, and serial section electron microscopy. At a light microscopic level, the inner spiral bundle, tunnel spiral bundle, upper tunnel crossing fibers and the base of outer hair cells were stained. At the base of outer hair cells, the immunoreactivity was seen to decrease from the base to the apex and from the first to third outer hair cells. At an electron microscopic level, immunoreactivity at the base of outer hair cells was limited to vesiculated efferent fibers. The degree of immunoreactivity between adjacent efferent fibers varied significantly. Immunoreactive vesiculated endings were also found in the supranuclear region of outer hair cells.     

Ultrastructural localisation of spectrin in sensory and supporting cells of guinea-pig organ of Corti

Spectrin is a cytoskeletal protein found in the cortex of many cell types. It is known to occur in cochlear outer hair cells (OHCs) with previous immunoelectron microscopical studies showing that it is located in the cuticular plate and the cortical lattice. The latter is a network of filaments associated with the lateral plasma membrane that is thought to play a role in OHC motility. Spectrin has also been found in inner hair cells (IHCs) and supporting cells using immunofluorescent techniques, but its ultrastructural distribution in these cells has not yet been described. This has, therefore, been investigated using a monoclonal antibody to alpha-spectrin in conjunction with pre- and post-embedding immunogold labelling for transmission electron microscopy. Labelling was found in a meshwork of filaments beneath the plasma membranes of both IHCs and supporting cells and, in pillar cells, close to microtubule/microfilament arrays. It was also found in association with the stereocilia of OHCs and IHCs and, as expected, in the cortical lattice and cuticular plate of OHCs. Thus, spectrin is a general component of cytoskeletal structures involved in maintaining the specialised cell shapes in the organ of Corti and may contribute to the mechanical properties of all the cell types examined.     

Removal of tissue plasminogen activator does not protect against neuronal degeneration in the cerebellum of the weaver mouse

Tissue plasminogen activator (tPA) is a serine protease that has been shown to be involved in neuronal degeneration. Recently, elevated cerebellar tPA has been reported in a naturally occurring mutant mouse, weaver. Weaver mice suffer extensive degeneration of cerebellar granular neurons during development, leading to severe malformation of the cerebellum as well as abnormal behavior (ataxia). The observations that the developing weaver cerebellum displays a 10-fold increase in tPA activity over wild-type and that a serine protease inhibitor was able to rescue weaver granule cells from premature death in culture suggested that tPA might mediate the death of these mutant neurons. We tested this possibility by introducing the weaver mutation into tPA-deficient mice and comparing the weaver phenotype in the presence or absence of tPA. Analysis at 28 days after birth indicates that tPA-deficient weaver mice are indistinguishable from tPA-containing weaver mice in behavior, cerebellar anatomy, histology, and laminin expression (also reported to be increased in weaver). These results suggest that removal of tPA activity from weaver mice does not protect against neuronal degeneration in the cerebellum and, thus, tPA does not appear to mediate this form of cell death.     

Drosophila engrailed can substitute for mouse Engrailed1 function in mid-hindbrain, but not limb development

The Engrailed-1 gene, En1, a murine homologue of the Drosophila homeobox gene engrailed (en), is required for midbrain and cerebellum development and dorsal/ventral patterning of the limbs. In Drosophila, en is involved in regulating a number of key patterning processes including segmentation of the epidermis. An important question is whether, during evolution, the biochemical properties of En proteins have been conserved, revealing a common underlying molecular mechanism to their diverse developmental activities. To address this question, we have replaced the coding sequences of En1 with Drosophila en. Mice expressing Drosophila en in place of En1 have a near complete rescue of the lethal En1 mutant brain defect and most skeletal abnormalities. In contrast, expression of Drosophila en in the embryonic limbs of En1 mutants does not lead to repression of Wnt7a in the embryonic ventral ectoderm or full rescue of the embryonic dorsal/ventral patterning defects. Furthermore, neither En2 nor en rescue the postnatal limb abnormalities that develop in rare En1 null mutants that survive. These studies demonstrate that the biochemical activity utilized in mouse to mediate brain development has been retained by Engrailed proteins across the phyla, and indicate that during evolution vertebrate En proteins have acquired two unique functions during embryonic and postnatal limb development and that only En1 can function postnatally.     

Facilitation of apoptosis by cyclosporins A and H, but not FK506 in mouse bronchial eosinophils

This study was undertaken to clarify whether or not binding to cyclophilin is a prerequisite for cyclosporin A-induced modulation of apoptotic cell death in eosinophils. Eosinophils were isolated from bronchoalveolar lavage fluid of mice challenged with inhaled allergen after sensitization. Apoptosis was determined by analysing the DNA content. At 72 h, 99% of the cells had died without addition of cytokines, whereas 55-60% of the cells survived in the presence of 10 U/ml recombinant murine interleukin 5 or recombinant murine granulocyte macrophage-colony stimulation factor (GM-CSF). Apoptotic cell death at 72 h in the presence of 10 U/ml interleukin 5 was increased by addition of cyclosporin H, an analogue of cyclosporin A without cyclophilin binding activity, in a concentration-dependent (0.3 to 3 microM) manner. The increase in apoptosis elicited by cyclosporin A and cyclosporin H took place also in the presence of 10 U/ml GM-CSF but to a lesser extent. There was a significant augmentation of apoptosis in eosinophils cultured in the presence of each cytokine for 72 h or longer. Tacrolimus (FK506) failed to augment apoptotic cell death. Thus, it is unlikely that binding of cyclosporin A to cyclophilin accounts for the increased apoptosis induced by cyclosporin A and its analogue in eosinophils. The increase in apoptosis induced by cyclosporin A, but not FK506, in activated eosinophils from the airways may be attributed to the anti-asthmatic effects of cyclosporin A.     

Efferent nerve fibers associated with the outermost supporting cells of the organ of Corti in the guinea pig

In whold-mount preparations of the organ of Corti nerve fibers are sometimes seen peripheral to the third-row outer hair cells where they appear to wander among the Hensen cells. These fibers were studied in the guinea pig by both light and electron microscopy. In the upper second, third and fourth cochlear turns nerve fibers were seen between and on the peripheral side of the third-row Deiters cells as well as in the floor of the outer tunnel space. They were not found in the intercellular spaces between the Hensen cells. These nerve fibers are continuous with the spiral efferent fibers beneath the outer hair cells. Also their ultrastructural and histochemical characteristics indicate that they are efferent neural elements. This identification was confirmed by the finding that they degenerate following interruption of the olivo-cochlear bundle in the brain stem.     

Organization of cell junctions and cytoskeleton in the reticular lamina in normal and ototoxically damaged organ of Corti

The reticular lamina creates an ion barrier, withstands mechanical stress in the organ of Corti and is able to maintain its integrity during and after severe hair cell loss. Tight junctions maintain the ionic gradient whereas adherens junctions and the cytoskeleton are responsible for the integrity and mechanical resistance of tissues. In this study we used immunofluorescence and electron microscopy to examine the distribution of proteins of tight junctions (cingulin), adherens junctions (E-cadherin, alpha- and beta-catenin) and the cytoskeleton (actin, cytokeratin and tubulin) in whole-mounts of the normal and ototoxically damaged organ of Corti. In normal ears the proteins of adherens junctions were found in all cell types of the reticular lamina. We now demonstrate that all cells forming the reticular lamina partially overlap each other organizing extensive cell contacts with a complex three-dimensional shape. During scar formation, the tight junctions as well as adherens junctions between hair and supporting cells appeared in two distinct focal planes, which could help to preserve the ionic barrier and tissue integrity during hair cell degeneration. During scar formation all cytoskeletal structures in the reticular lamina were reorganized in a specific spatio-temporal pattern. We present a three-dimensional model of cell contact organization in the reticular lamina of normal ears and during scar formation.