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Aminoglycoside antibiotics and the sensory hair cells of inner ear and lateral line system in the Atlantic cod, Gadus morhua: effects on fish hearing threshold

Aminoglycoside antibiotics and the sensory hair cells of inner ear and lateral line system in the Atlantic cod, Gadus morhua: effects on fish hearing threshold

AMINOGLYCOSIDE ANTIBIOTICS AND THE SENSORY HAIR CELLS OF INNER EAR IN THE ATLANTIC COD, Gadus morhua: EFFECTS ON FISH HEARING THRESHOLD Faucher, K. 1 , Aas-Hansen, Ø. 2 , Damsgård, B. 2 , Bégout, M.L. 3 , Fuhr, T. 4 , Laukli, E. 1 , Stenklev, N.C. 1 AIMS OF THE STUDY: to investigate: a) the potential involvement of the fish lateral line system in hearing at 250 Hz, b) the consequences of the inner ear inactivation on hearing at 250 Hz and c) the possible regeneration of the inner ear hair cells in the Atlantic cod (Gadus morhua).

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Clonal Expansion of Lgr5-Positive Cells from Mammalian Cochlea and High-Purity Generation of Sensory Hair Cells

Clonal Expansion of Lgr5-Positive Cells from Mammalian Cochlea and High-Purity Generation of Sensory Hair Cells

the gut, these cells were Wnt responsive and could be stimulated to divide and differentiate to some extent by forced activation of Wnt signaling ( Shi et al., 2013 ), even though the postnatal mammalian cochlea is normally quiescent. Further, although these previous studies showed Wnt stimulation could induce di- vision in Lgr5+ cells, the limited potential for propagation and conversion to hair cells suggested that other pathways might be required to increase the stem cell capacity of Lgr5+ cells in the cochlea. Here, we show that Lgr5+ cells from the inner ear can also be extensively expanded with a GSK3b inhibitor to acti- vate the Wnt signaling pathway combined with an HDAC inhibi- tor to activate Notch signaling. When provided with additional cues, specifically, 2-phospho-L-ascorbic acid, which was previ- ously shown to facilitate induced pluripotent stem cell (iPSC) generation ( Esteban et al., 2010 ), and the TGF-b inhibitor 616452, which regulates cell senescence ( Hua and Thompson, 2001 ), neonatal cells could be passaged and clonal colonies of adult murine, primate, and human progenitor cells could be generated ( Figures 6 A, 6E, and 6F). Differentiating these cells by simultaneously activating Wnt and inhibiting Notch enabled conversion of progenitor cells into high purity populations of hair cells. Moreover, treatment of cochlear tissue with small mol- ecules to simultaneously activate Wnt and Notch led to upregu- lation of Lgr5 in all supporting cells and increased numbers of Lgr5+ cells and hair cells ( Figure 7 ). The increase in hair cell num- ber was achieved even in cochlear tissue that had been depleted of hair cells by exposure to an aminoglycoside antibiotic. The ef- fect of this drug combination on the cochlea suggests that small molecules activating Wnt and Notch could be useful as a therapeutic option to restore hair cells without loss of the sup- porting cells, which are important for cochlear homeostasis and mechanics.
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Mechanical Frequency Tuning by Sensory Hair Cells, the Receptors and Amplifiers of the Inner Ear

Mechanical Frequency Tuning by Sensory Hair Cells, the Receptors and Amplifiers of the Inner Ear

deviates from linear, Hookean behavior over the narrow range of positions in which the channels’ open probability changes significantly. For large negative or positive stimuli, the curve's slope K ∞ = K GS + K SP is the sum of the stiffness contributions K GS from the grating springs and K SP from the stereociliary pivots. The slope declines for intermediate values and can even become negative if the gating force is sufficiently great. Under force-clamp conditions (thin horizontal line), this behavior destabilizes the bundle’s position X = X 0 at which P o = 0.5 (open circle) and the bundle becomes bistable, residing at either of two stable fixed points (solid circles). (d) The hair bundle's stiffness as a function of displacement is given by the slope of the preceding curve. The reduction of stiffness associated with channel opening and closing—the gating compliance—can reduce the stiffness until it becomes negative (dashed line). (e) An effective mechanical description of the hair bundle depicts a channel (pink) that opens or closes through distance D under the influence of tension in a gating spring of stiffness K GS (maroon). An external force F displaces the bundle a distance X by acting on the gating-spring stiffness K GS as well as on the stereociliary-pivot stiffness K SP (green) and the bundle's viscous drag of coefficient λ (brown). Active force feedback on the bundle’s displacement may proceed through two adaptation mechanisms that are not mutually exclusive. In the motor model, myosin molecules (red) move a distance X a to restore force balance between the motors’ stall force F a and tension in the gating spring; the velocity of motion Ẋ a is inversely related to the friction coefficient λ a (gray). In the Ca 2+ -reclosure model, Ca 2+ that enters the
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Damage and functional recovery of the Atlantic cod (Gadus morhua) inner ear hair cells following local injection of gentamicin

Damage and functional recovery of the Atlantic cod (Gadus morhua) inner ear hair cells following local injection of gentamicin

Introduction As in birds, fish inner ear hair cells have the ability to regenerate after damage by noise or ototoxic drugs (Lombarte et al, 1993; Scholik & Yan, 2002; Smith et al, 2006). This capacity for regeneration has led to increased interest in fish models for investigations on hair cell regeneration with the goal of a possible translation into mammalian hair cell research. Amino- glycoside antibiotics are commonly used for damage of sensory hair cells in the fish lateral line system (Kaus, 1987; Song et al, 1995; Harris et al, 2003; Santos et al, 2006) and inner ear (Matsuura et al, 1971; Yan et al, 1991; Lombarte et al, 1993). In the past, intramuscular (Yan et al, 1991; Lombarte et al, 1993) or intravenous (Faucher et al, 2008) gentamicin injections have been used to study sensory hair cell regeneration in fish. However, systemic administration of aminoglycosides may be accompanied by unwanted side-effects, like nephrotoxicity and subsequent mortality of study animals. Matsuura et al (1971) used intrasaccular kanamycin and streptomycin injections into the goldfish (Carassius auratus) inner ear, and our group has recently demonstrated that local injection of gentamicin directly into the inner ear sacculus is an efficient method to obtain inner ear damage without undue side effects in the
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Blood, urine, and hair kinetic analysis following an acute lead intoxication

Blood, urine, and hair kinetic analysis following an acute lead intoxication

Moreover, urinary lead excretion is a good marker for recent lead exposure and for patients who underwent chelation therapy. In this case report, we had the opportunity to analyze on many urine samples, more than in other case reports (4,14). Furthermore, δ-aminolevulinic acid (ALA) excretion and δ- aminolevulinic acid dehydratase (ALA-D) enzymatic activity are also good markers for recent exposition but may fluctuate and are less reliable. Hair analysis could also reflect a lead in- toxication (15,16), but no one has yet evaluated the hair ex- cretion three months after exposition. In our case, the lead levels were between 2 and 5 ng/mg of hair at the moment of in- toxication. These concentrations are usual in the general pop- ulation and demonstrate that the patient was non-exposed to lead before. Three months later, no peak of lead excretion was observed in the different 1-cm pieces of hair, especially in the section corresponding to the moment of intoxication and the lead values were also included between 2 and 5 ng/mg of hair. The chelation therapy performed early after the intoxication can therefore explain these results.
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Spinal sensory circuits in motion

Spinal sensory circuits in motion

14. Woo S-H, Ranade S, Weyer AD, Dubin AE, Baba Y, Qiu Z, Petrus M, Miyamoto T, Reddy K, Lumpkin EA, et al.: Piezo2 is required for Merkel-cell mechanotransduction. Nature 2014, 509:622–626. *15. Ranade SS, Woo S-H, Dubin AE, Moshourab RA, Wetzel C, Petrus M, Mathur J, Bégay V, Coste B, Mainquist J, et al.: Piezo2 is the major transducer of mechanical forces for touch sensation in mice. Nature 2014, 516:121–125. This study is the last in a list that puts Piezo2 in the center of touch sensation in vertebrates. Eliminating Piezo2 from Merkel cells and sensory neurons lead to an almost complete loss of touch sensitivity.
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en fr Functional characterisation of the mechano-electrical transduction complex of the auditory hair cells Caractérisation fonctionnelle du complexe de transduction mécano-électrique des cellules ciliées du système auditif

Gene therapy as a cure for Usher syndrome? In the gene therapy project I participated in, although there was a spectacular restoration of the vestibular function in Ush1g -/- mice, hearing restoration was only partial. This raises the question of whether the viral injection was done early enough. If an injection were done at an embryonic stage, would the hearing restoration be increased? It is essential such a hypothesis be tested, as the timing of the viral injection is a crucial factor if we were to apply the method to Ush2a ΔTM/ΔTM mice. If we were to test virally mediated gene therapy on Ush2a ΔTM/ΔTM mice, the initial hypothesis is that P3 would be too late an age to inject animals and hope for good auditory restoration, as ankle links are already well established at this age, and the effects of the absence of the long b-isoform of usherin could already be felt by the developing hair bundle. Although it is true for all USH genes, when it comes to USH2 proteins such as usherin for example, it is essential the virus be injected as early as possible, as USH2 proteins make part of a transient structure in the cochlea, i.e. the ankle link complex, that only exists between P2 and P9. Although difficult to carry out, in utero injections could provide a solution to the time constraints related to the use of virally mediated gene therapy to treat Usher syndrome in mice.
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Does spatial attention modulate sensory memory?

Does spatial attention modulate sensory memory?

We expected significant attentional effects in both sensory memories and working memory in both experiments. Moreover, we predicted that endogenous attention would mostly improve the efficiency of working memory, on the basis of the shared dependency on fronto- parietal networks of endogenous attention and working memory maintenance [ 22 ] while exogenous attention would mainly facilitate sensory memories, given its prominent effect on sensory regions [ 23 ]. In agreement with these predictions, we observed that selective spatial attention, independently of the mode (endogenous or exogenous) by which it was distributed during the encoding phase, reliably affected accuracy in both sensory memory (iconic and fragile) and working memory. However, the nature of the attentional effect on the three mem- ory stores varied depending on the way by which attention was spatially allocated. In the first experiment, consistent with our predictions, we observed that when attention was endoge- nously oriented, the effect of attention on accuracy varied across the 3 memory stages, with attentional benefits increasing from working to fragile and from fragile to iconic memory, and attentional costs being similar for the three memory stages. On the other hand, in Experiment 2, when attention was automatically and exogenously captured by non-predictive peripheral cues, it produced similar modulatory effects (i.e. similar benefits and similar costs) on the three memory stores. This differential attentional modulation between the two experiments was likely due to a different data pattern at valid locations, which was characterized by pretty identical accuracy for the three memory types in Experiment 1, and by a significantly higher performance in iconic than in working memory, in Experiment 2.
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A new scenario for the evolutionary origin of hair, feather, and avian scales.: Origin of hair, feather and avian scales

A new scenario for the evolutionary origin of hair, feather, and avian scales.: Origin of hair, feather and avian scales

22 Like in birds, the dorsal/ventral orientation of the limb bud depends on Engrailed-1 expression in the ventral ectoderm. In mice, the expression of En-1 in the presumptive palmar/plantar ectoderm is required for eccrine gland development (Loomis et al. 1996): the loss of En-1 expression in the palmar/plantar ectoderm causes a sweat gland-hair metaplasia. A sweat gland- hair metaplasia occurs in two other experiments: 1-when Noggin, a BMP antagonist, is over expressed in the plantar epidermis (Fig. 5 A, B) (Plikus et al. 2004), or 2-when beta-catenin is over expressed in mouse embryo epidermis (Fig.5 D, D’) (Nähri et al. 2008). Likewise, recent experiments (Mayer et al. 2008) showed the conversion of the mammary gland nipple into hair-bearing skin by lowering BMP activity. Beta-catenin is the major factor in the initiation of feather morphogenesis (Noramly et al. 1999. Widelitz et al. 2000) and plays a similar role during mammalian skin morphogenesis, for both adult (Gat et al. 1998), and embryo (Nähri et al. 2008). The laboratory of I. Thesleff recently showed that the expression of stabilized beta-catenin results in accelerated and supplementary formation of hair placodes in the hairy and glabrous fields in transgenic mice embryo (Fig 5 B-C’), as well as the abutting of hair pegs. Reversely, mice whose Wnt/beta-catenin pathways are inhibited do not form mammary glands, hairs or teeth (Andl et al. 2002; van Genderen et al.1994; for a review on mammary gland, see Velmatt et al. 2003).
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Caspases, the enemy within, and their role in oxidative stress-induced apoptosis of inner ear sensory cells

Caspases, the enemy within, and their role in oxidative stress-induced apoptosis of inner ear sensory cells

Application of a pancaspase inhibitor should be local or if administered in a systemic application it should be of a very short duration because apoptosis is an important process by which the body eliminates cells that could be dangerous to the overall health of the individual. Caspases have already been suggested as treatment targets in both stroke and in neurodegenative diseases of the central nervous system (25). Because to inner ear tissues are accessible via the round window membrane and the round window membrane is already being used to deliver some drugs to the inner ear (26) there may be an application for a broad acting pancaspase inhibitor delivered via this local route of administration in the treatment of inner ear disorders and trauma that involves the generation of oxidative stress and apoptotic death of inner ear sensory cells (27) (e.g.
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Divergence among arabica coffee genotypes for sensory quality.

Divergence among arabica coffee genotypes for sensory quality.

Evaluated characteristics Sensory analysis of the beverage was performed by two tasters per sample (repetition), using the Cup of Excellence (CoE) methodology, enhanced by the Brazilian Specialty Coffee Association (BSCA, 2014). The following attributes, rated in numeric values, were assessed: clean cup, sweetness (SWE), acidity (ACI), body (BOD), flavor (FLA), aftertaste (AFT), balance, overall and final score (FSC). Genotypes that presented more than 80 points in the final score were classified as Specialty Coffees. Each sample considered the average score among the tasters. The data related to beverage were obtained from beans which passed through a ≥16 size sieve. In genotypes that stood out with regards to sensory quality we evaluated the average sieve size (ASS) and the peaberry percentage (PBE). The first was obtained by the ratio between the sum of the mass of flat beans retained in each sieve (19, 18 , 17 , 16 , 15 and 14/64ths of an inch) multiplied by the respective sieve number, divided by the total mass of beans (Krug, 1940). The second was determined by the summed percentages of peaberries retained in the 11, 10 and 9 sieve sizes. The bean shape and size was evaluated considering a processed sample of 300 grams.
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Sensory Arts and Design

Sensory Arts and Design

L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignemen[r]

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Computational hair quality categorization in lower magnifications

Computational hair quality categorization in lower magnifications

[6] Hadjur, C., Daty, G., Madry, G. and Corcuff, P., " Cosmetic assessment of the human hair by confocal microscopy, " Scanning, 24, 59–64 (2002). [7] Kuzuhara, A., " Analysis of structural changes in permanent waved human hair using Raman spectroscopy, " Biopolymers, 85, 274–283 (2007).

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Hair mercury levels in Amazonian populations: spatial distribution and trends

Hair mercury levels in Amazonian populations: spatial distribution and trends

ner in all the studies. Each research team chose their indi- cators according to their objectives, so this measure can be found in grams per day, percentage of meals composed by fish, meals per week or per day and/or times per week. No matter which indicator for fish consumption the authors chose, there was always a positive relation between fish consumption and hair mercury levels [19,46,47,49,64,75,76]. Most of these study sites are usu- ally small and traditional riverside villages, some of them Amerindian reservations, without the proper roads con- necting them to larger villages and cities. It is possible to hypothesize that this situation makes those populations more dependent on fish as source of protein intake. In spite of those considerations, some populations with high fish consumption showed hair mercury levels below 10 μg/g, even if there was a significant relation with fish consumption frequency [55-57,59,78,79]. In those partic- ular six studies, it is important to consider the different geographical and socio-economic situation those popula- tions are in: three of those studies were conducted in the Andean piedmont Amazonian regions, the two Ecuado- rian studies [55,56] and one of the Bolivian studies [57]. Also, those populations are not solely dependent on fish because they are also farmers or hunters, even if fish remains the most important source of nutrients. The Bolivian population of Cachuela Esperanza, located near the Brazilian border, consumes large amounts of fish (10 fish meals per week), but only during the dry season, pre- ferring game meat during the rainy season, which lasts from October to April [57].
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Sensory reweighting in controls and stroke patients

Sensory reweighting in controls and stroke patients

also been suggested that using various non-linear and linear measures of static postural control fluctuations can predict the likelihood of subsequent injury (Cavanaugh et al, 2005) and the occurrence of stepping strategies (Hasson 2008). As expected, stroke patients were more unstable in the present study than the control group. We found no significant correlation between stability of standing posture and responses to sensory stimulation, either for control or for stroke patients when the groups were studied separately. However, we found two exceptions to that rule for the C2/opto composite score in controls (p=0.01), and for PF/ opto score in stoke patients (p=0.02) i.e the trunk and the CoP displacements during optokinetic stimulation were greater for the more stable group at rest. Furthermore, polling the control and stroke patient data revealed a relationship between
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News Application Adaptation based on User Sensory Profile

News Application Adaptation based on User Sensory Profile

Dunn’s Model of Sensory Processing [4] is a four-quadrant model that mea- sures our responses to everyday sensory experiences. The model was conceptual- ized on the relationship between the neurological threshold (low and high), and behavioral response (accordance and counteract). In this research, we analyze only the visual and auditory sensory processing categories corresponding to all four quadrants: Sensation Avoiding (low neurological threshold and counteract), Sensory Sensitivity (low neurological threshold and accordance), Sensation Seek- ing (high neurological threshold and counteract), and Low Registration (high neurological threshold and accordance). The visual and auditory sensory pro- cessing categories have been chosen as they are better suited for an interaction between a robot and a user.
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Analog VLSI circuits for inertial sensory systems

Analog VLSI circuits for inertial sensory systems

Figure 2.13 shows the transistor level implementation of the final offset-compensated demodulator. Out+ and Out.) is not lowpass filtered and goes to the offset compen[r]

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Analog VLSI circuits for inertial sensory systems

Analog VLSI circuits for inertial sensory systems

It shows the output signal waveforms (i.e. V+ and V.) of the whole vibration sensor of figure 2.28, which incorporates the new closed-loop front-end bandpass amplifi[r]

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Mecanisms underlying sensory interactions and complex perceptions

Mecanisms underlying sensory interactions and complex perceptions

PART 2: Perceptual multi-sensory interactions The role of congruency on perceptual interaction has been widely investigated in solution between sensory stimuli and mainly odorant and tastant. Congruency between two stimuli results from repeated consumption of food containing these stimuli in combination. Congruency is therefore strongly related to the level of familiarity for these paired stimuli. To our knowledge, the impact of familiarity at an upper level, i.e. induced by the overall product, has never been investigated. Similarly, the exploration of perceptual interactions on product description was widely studied with experienced assessors using an analytical approach, generally a conventional sensory profiling where subjects are trained to evaluate independently each sensory attribute. Such a strategy can reduce the impact of perceptual interactions on perception. Results from a trained panel were never compared with a more synthetical procedure closer to how consumers apprehend foods during everyday consumption, i.e. considering perception as a whole without dissociating each sensory dimension. For improving basic knowledge about perceptual interaction mechanisms but also to explore perceptual interactions in a more realistic environment in terms of product and evaluation procedure, we investigated in PART 2.1.1: 1) the impact of existing products differing in familiarity on olfactory and taste interactions at psychophysics level and neural level by functional Magnetic Resonance Imagery (fMRI); and 2) the effect of two evaluation methodologies encouraging attentional strategy during tasting (sensory profiling using trained assessors) or synthetical strategy (sorting task with consumers) on description of coffee aroma.
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The design of a combination room heater and hair dryer

The design of a combination room heater and hair dryer

No definite data could be found on design of nozzles operat- ing at subsonic speeds such as would be encountered in a hair dryer, It was suggested that any smooth curve connecting the in- let and outlet areas of the nozzle would prove adequate, and that the shape of the curve would be largely dependent on the appear-

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