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Sample records for auditory signals requires

  1. Auditory signal design for automatic number plate recognition system

    NARCIS (Netherlands)

    Heydra, C.G.; Jansen, R.J.; Van Egmond, R.

    2014-01-01

    This paper focuses on the design of an auditory signal for the Automatic Number Plate Recognition system of Dutch national police. The auditory signal is designed to alert police officers of suspicious cars in their proximity, communicating priority level and location of the suspicious car and takin

  2. Auditory display of knee-joint vibration signals

    Science.gov (United States)

    Krishnan, Sridhar; Rangayyan, Rangaraj M.; Bell, G. Douglas; Frank, Cyril B.

    2001-12-01

    Sounds generated due to rubbing of knee-joint surfaces may lead to a potential tool for noninvasive assessment of articular cartilage degeneration. In the work reported in the present paper, an attempt is made to perform computer-assisted auscultation of knee joints by auditory display (AD) of vibration signals (also known as vibroarthrographic or VAG signals) emitted during active movement of the leg. Two types of AD methods are considered: audification and sonification. In audification, the VAG signals are scaled in time and frequency using a time-frequency distribution to facilitate aural analysis. In sonification, the instantaneous mean frequency and envelope of the VAG signals are derived and used to synthesize sounds that are expected to facilitate more accurate diagnosis than the original signals by improving their aural quality. Auditory classification experiments were performed by two orthopedic surgeons with 37 VAG signals including 19 normal and 18 abnormal cases. Sensitivity values (correct detection of abnormality) of 31%, 44%, and 83%, and overall classification accuracies of 53%, 40%, and 57% were obtained with the direct playback, audification, and sonification methods, respectively. The corresponding d' scores were estimated to be 1.10, -0.36, and 0.55. The high sensitivity of the sonification method indicates that the technique could lead to improved detection of knee-joint abnormalities; however, additional work is required to improve its specificity and achieve better overall performance.

  3. A virtual auditory environment for investigating the auditory signal processing of realistic sounds

    DEFF Research Database (Denmark)

    Favrot, Sylvain Emmanuel

    A loudspeaker-based virtual auditory environment (VAE) has been developed to provide a realistic versatile research environment for investigating the auditory signal processing in real environments, i.e., considering multiple sound sources and room reverberation. The VAE allows a full control of...... the acoustic scenario in order to systematically study the auditory processing of reverberant sounds. It is based on the ODEON software, which is state-of-the-art software for room acoustic simulations developed at Acoustic Technology, DTU. First, a MATLAB interface to the ODEON software has been...

  4. Auditory Signal Processing in Communication: Perception and Performance of Vocal Sounds

    Science.gov (United States)

    Prather, Jonathan F.

    2013-01-01

    Learning and maintaining the sounds we use in vocal communication require accurate perception of the sounds we hear performed by others and feedback-dependent imitation of those sounds to produce our own vocalizations. Understanding how the central nervous system integrates auditory and vocal-motor information to enable communication is a fundamental goal of systems neuroscience, and insights into the mechanisms of those processes will profoundly enhance clinical therapies for communication disorders. Gaining the high-resolution insight necessary to define the circuits and cellular mechanisms underlying human vocal communication is presently impractical. Songbirds are the best animal model of human speech, and this review highlights recent insights into the neural basis of auditory perception and feedback-dependent imitation in those animals. Neural correlates of song perception are present in auditory areas, and those correlates are preserved in the auditory responses of downstream neurons that are also active when the bird sings. Initial tests indicate that singing-related activity in those downstream neurons is associated with vocal-motor performance as opposed to the bird simply hearing itself sing. Therefore, action potentials related to auditory perception and action potentials related to vocal performance are co-localized in individual neurons. Conceptual models of song learning involve comparison of vocal commands and the associated auditory feedback to compute an error signal that is used to guide refinement of subsequent song performances, yet the sites of that comparison remain unknown. Convergence of sensory and motor activity onto individual neurons points to a possible mechanism through which auditory and vocal-motor signals may be linked to enable learning and maintenance of the sounds used in vocal communication. PMID:23827717

  5. A computational model of human auditory signal processing and perception

    DEFF Research Database (Denmark)

    Jepsen, Morten Løve; Ewert, Stephan D.; Dau, Torsten

    2008-01-01

    A model of computational auditory signal-processing and perception that accounts for various aspects of simultaneous and nonsimultaneous masking in human listeners is presented. The model is based on the modulation filterbank model described by Dau et al. [J. Acoust. Soc. Am. 102, 2892 (1997......)] but includes major changes at the peripheral and more central stages of processing. The model contains outer- and middle-ear transformations, a nonlinear basilar-membrane processing stage, a hair-cell transduction stage, a squaring expansion, an adaptation stage, a 150-Hz lowpass modulation filter, a bandpass...... modulation filterbank, a constant-variance internal noise, and an optimal detector stage. The model was evaluated in experimental conditions that reflect, to a different degree, effects of compression as well as spectral and temporal resolution in auditory processing. The experiments include intensity...

  6. A hardware model of the auditory periphery to transduce acoustic signals into neural activity

    Directory of Open Access Journals (Sweden)

    Takashi eTateno

    2013-11-01

    Full Text Available To improve the performance of cochlear implants, we have integrated a microdevice into a model of the auditory periphery with the goal of creating a microprocessor. We constructed an artificial peripheral auditory system using a hybrid model in which polyvinylidene difluoride was used as a piezoelectric sensor to convert mechanical stimuli into electric signals. To produce frequency selectivity, the slit on a stainless steel base plate was designed such that the local resonance frequency of the membrane over the slit reflected the transfer function. In the acoustic sensor, electric signals were generated based on the piezoelectric effect from local stress in the membrane. The electrodes on the resonating plate produced relatively large electric output signals. The signals were fed into a computer model that mimicked some functions of inner hair cells, inner hair cell–auditory nerve synapses, and auditory nerve fibers. In general, the responses of the model to pure-tone burst and complex stimuli accurately represented the discharge rates of high-spontaneous-rate auditory nerve fibers across a range of frequencies greater than 1 kHz and middle to high sound pressure levels. Thus, the model provides a tool to understand information processing in the peripheral auditory system and a basic design for connecting artificial acoustic sensors to the peripheral auditory nervous system. Finally, we discuss the need for stimulus control with an appropriate model of the auditory periphery based on auditory brainstem responses that were electrically evoked by different temporal pulse patterns with the same pulse number.

  7. Neural interactions in unilateral colliculus and between bilateral colliculi modulate auditory signal processing

    Science.gov (United States)

    Mei, Hui-Xian; Cheng, Liang; Chen, Qi-Cai

    2013-01-01

    In the auditory pathway, the inferior colliculus (IC) is a major center for temporal and spectral integration of auditory information. There are widespread neural interactions in unilateral (one) IC and between bilateral (two) ICs that could modulate auditory signal processing such as the amplitude and frequency selectivity of IC neurons. These neural interactions are either inhibitory or excitatory, and are mostly mediated by γ-aminobutyric acid (GABA) and glutamate, respectively. However, the majority of interactions are inhibitory while excitatory interactions are in the minority. Such unbalanced properties between excitatory and inhibitory projections have an important role in the formation of unilateral auditory dominance and sound location, and the neural interaction in one IC and between two ICs provide an adjustable and plastic modulation pattern for auditory signal processing. PMID:23626523

  8. Neural interactions in unilateral colliculus and between bilateral colliculi modulate auditory signal processing.

    Science.gov (United States)

    Mei, Hui-Xian; Cheng, Liang; Chen, Qi-Cai

    2013-01-01

    In the auditory pathway, the inferior colliculus (IC) is a major center for temporal and spectral integration of auditory information. There are widespread neural interactions in unilateral (one) IC and between bilateral (two) ICs that could modulate auditory signal processing such as the amplitude and frequency selectivity of IC neurons. These neural interactions are either inhibitory or excitatory, and are mostly mediated by γ-aminobutyric acid (GABA) and glutamate, respectively. However, the majority of interactions are inhibitory while excitatory interactions are in the minority. Such unbalanced properties between excitatory and inhibitory projections have an important role in the formation of unilateral auditory dominance and sound location, and the neural interaction in one IC and between two ICs provide an adjustable and plastic modulation pattern for auditory signal processing.

  9. Instantaneous and Frequency-Warped Signal Processing Techniques for Auditory Source Separation.

    Science.gov (United States)

    Wang, Avery Li-Chun

    which require a small fraction of the computational power of conventional FIR implementations. This design strategy is based on truncated and stabilized IIR filters. These signal-processing methods have been applied to the problem of auditory source separation, resulting in voice separation from complex music that is significantly better than previous results at far lower computational cost.

  10. Speech motor learning changes the neural response to both auditory and somatosensory signals

    Science.gov (United States)

    Ito, Takayuki; Coppola, Joshua H.; Ostry, David J.

    2016-01-01

    In the present paper, we present evidence for the idea that speech motor learning is accompanied by changes to the neural coding of both auditory and somatosensory stimuli. Participants in our experiments undergo adaptation to altered auditory feedback, an experimental model of speech motor learning which like visuo-motor adaptation in limb movement, requires that participants change their speech movements and associated somatosensory inputs to correct for systematic real-time changes to auditory feedback. We measure the sensory effects of adaptation by examining changes to auditory and somatosensory event-related responses. We find that adaptation results in progressive changes to speech acoustical outputs that serve to correct for the perturbation. We also observe changes in both auditory and somatosensory event-related responses that are correlated with the magnitude of adaptation. These results indicate that sensory change occurs in conjunction with the processes involved in speech motor adaptation. PMID:27181603

  11. A virtual auditory environment for investigating the auditory signal processing of realistic sounds

    DEFF Research Database (Denmark)

    Favrot, Sylvain Emmanuel; Buchholz, Jörg

    2008-01-01

    reverberation. The environment is based on the ODEON room acoustic simulation software to render the acoustical scene. ODEON outputs are processed using a combination of different order Ambisonic techniques to calculate multichannel room impulse responses (mRIR). Auralization is then obtained by the convolution....... Throughout the VAE development, special care was taken in order to achieve a realistic auditory percept and to avoid “artifacts” such as unnatural coloration. The performance of the VAE has been evaluated and optimized on a 29 loudspeaker setup using both objective and subjective measurement techniques....

  12. Temporal Integration of Auditory Stimulation and Binocular Disparity Signals

    Directory of Open Access Journals (Sweden)

    Marina Zannoli

    2011-10-01

    Full Text Available Several studies using visual objects defined by luminance have reported that the auditory event must be presented 30 to 40 ms after the visual stimulus to perceive audiovisual synchrony. In the present study, we used visual objects defined only by their binocular disparity. We measured the optimal latency between visual and auditory stimuli for the perception of synchrony using a method introduced by Moutoussis & Zeki (1997. Visual stimuli were defined either by luminance and disparity or by disparity only. They moved either back and forth between 6 and 12 arcmin or from left to right at a constant disparity of 9 arcmin. This visual modulation was presented together with an amplitude-modulated 500 Hz tone. Both modulations were sinusoidal (frequency: 0.7 Hz. We found no difference between 2D and 3D motion for luminance stimuli: a 40 ms auditory lag was necessary for perceived synchrony. Surprisingly, even though stereopsis is often thought to be slow, we found a similar optimal latency in the disparity 3D motion condition (55 ms. However, when participants had to judge simultaneity for disparity 2D motion stimuli, it led to larger latencies (170 ms, suggesting that stereo motion detectors are poorly suited to track 2D motion.

  13. Bilateral collicular interaction: modulation of auditory signal processing in frequency domain.

    Science.gov (United States)

    Cheng, L; Mei, H-X; Tang, J; Fu, Z-Y; Jen, P H-S; Chen, Q-C

    2013-04-01

    In the ascending auditory pathway, the inferior colliculus (IC) receives and integrates excitatory and inhibitory inputs from a variety of lower auditory nuclei, intrinsic projections within the IC, contralateral IC through the commissure of the IC and the auditory cortex. All these connections make the IC a major center for subcortical temporal and spectral integration of auditory information. In this study, we examine bilateral collicular interaction in the modulation of frequency-domain signal processing of mice using electrophysiological recording and focal electrical stimulation. Focal electrical stimulation of neurons in one IC produces widespread inhibition and focused facilitation of responses of neurons in the other IC. This bilateral collicular interaction decreases the response magnitude and lengthens the response latency of inhibited IC neurons but produces an opposite effect on the response of facilitated IC neurons. In the frequency domain, the focal electrical stimulation of one IC sharpens or expands the frequency tuning curves (FTCs) of neurons in the other IC to improve frequency sensitivity and the frequency response range. The focal electrical stimulation also produces a shift in the best frequency (BF) of modulated IC (ICMdu) neurons toward that of electrically stimulated IC (ICES) neurons. The degree of bilateral collicular interaction is dependent upon the difference in the BF between the ICES neurons and ICMdu neurons. These data suggest that bilateral collicular interaction is a part of dynamic acoustic signal processing that adjusts and improves signal processing as well as reorganizes collicular representation of signal parameters according to the acoustic experience.

  14. Differential maturation of brain signal complexity in the human auditory and visual system

    Directory of Open Access Journals (Sweden)

    Sarah Lippe

    2009-11-01

    Full Text Available Brain development carries with it a large number of structural changes at the local level which impact on the functional interactions of distributed neuronal networks for perceptual processing. Such changes enhance information processing capacity, which can be indexed by estimation of neural signal complexity. Here, we show that during development, EEG signal complexity increases from one month to 5 years of age in response to auditory and visual stimulation. However, the rates of change in complexity were not equivalent for the two responses. Infants’ signal complexity for the visual condition was greater than auditory signal complexity, whereas adults showed the same level of complexity to both types of stimuli. The differential rates of complexity change may reflect a combination of innate and experiential factors on the structure and function of the two sensory systems.

  15. Temporally selective processing of communication signals by auditory midbrain neurons

    DEFF Research Database (Denmark)

    Elliott, Taffeta M; Christensen-Dalsgaard, Jakob; Kelley, Darcy B

    2011-01-01

    Perception of the temporal structure of acoustic signals contributes critically to vocal signaling. In the aquatic clawed frog Xenopus laevis, calls differ primarily in the temporal parameter of click rate, which conveys sexual identity and reproductive state. We show here that an ensemble of aud...

  16. Effect of noise on reaction time for auditory signals

    Directory of Open Access Journals (Sweden)

    M.S. Prakash Rao

    1958-10-01

    Full Text Available The effect of noise on the time taken to react to pure tone signals was studied. The reaction time was found to increase with rise in the level of noise. Individual differences become more prominent at the higher noise levels. Greater fluctuation in the same individual was also observed with increase in the noise level.

  17. Increased Signal Complexity Improves the Breadth of Generalization in Auditory Perceptual Learning

    OpenAIRE

    Brown, David J.; Proulx, Michael J.

    2013-01-01

    Perceptual learning can be specific to a trained stimulus or optimally generalized to novel stimuli with the breadth of generalization being imperative for how we structure perceptual training programs. Adapting an established auditory interval discrimination paradigm to utilise complex signals, we trained human adults on a standard interval for either 2, 4, or 10 days. We then tested the standard, alternate frequency, interval, and stereo input conditions to evaluate the rapidity of specifi...

  18. Coordinated Eph-ephrin signaling guides migration and axon targeting in the avian auditory system

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    Allen-Sharpley Michelle R

    2012-08-01

    Full Text Available Abstract Background In the avian sound localization circuit, nucleus magnocellularis (NM projects bilaterally to nucleus laminaris (NL, with ipsilateral and contralateral NM axon branches directed to dorsal and ventral NL dendrites, respectively. We previously showed that the Eph receptor EphB2 is expressed in NL neuropil and NM axons during development. Here we tested whether EphB2 contributes to NM-NL circuit formation. Results We found that misexpression of EphB2 in embryonic NM precursors significantly increased the number of axon targeting errors from NM to contralateral NL in a cell-autonomous manner when forward signaling was impaired. We also tested the effects of inhibiting forward signaling of different Eph receptor subclasses by injecting soluble unclustered Fc-fusion proteins at stages when NM axons are approaching their NL target. Again we found an increase in axon targeting errors compared to controls when forward signaling was impaired, an effect that was significantly increased when both Eph receptor subclasses were inhibited together. In addition to axon targeting errors, we also observed morphological abnormalities of the auditory nuclei when EphB2 forward signaling was increased by E2 transfection, and when Eph-ephrin forward signaling was inhibited by E6-E8 injection of Eph receptor fusion proteins. Conclusions These data suggest that EphB signaling has distinct functions in axon guidance and morphogenesis. The results provide evidence that multiple Eph receptors work synergistically in the formation of precise auditory circuitry.

  19. Valid cues for auditory or somatosensory targets affect their perception: a signal detection approach.

    Science.gov (United States)

    Van Hulle, Lore; Van Damme, Stefaan; Crombez, Geert

    2013-01-01

    We investigated the effects of focusing attention towards auditory or somatosensory stimuli on perceptual sensitivity and response bias using a signal detection task. Participants (N = 44) performed an unspeeded detection task in which weak (individually calibrated) somatosensory or auditory stimuli were delivered. The focus of attention was manipulated by the presentation of a visual cue at the start of each trial. The visual cue consisted of the word "warmth" or the word "tone". This word cue was predictive of the corresponding target on two-thirds of the trials. As hypothesised, the results showed that cueing attention to a specific sensory modality resulted in a higher perceptual sensitivity for validly cued targets than for invalidly cued targets, as well as in a more liberal response criterion for reporting stimuli in the valid modality than in the invalid modality. The value of this experimental paradigm for investigating excessive attentional focus or hypervigilance in various non-clinical and clinical populations is discussed.

  20. Bilateral Collicular Interaction: Modulation of Auditory Signal Processing in Amplitude Domain

    Science.gov (United States)

    Fu, Zi-Ying; Wang, Xin; Jen, Philip H.-S.; Chen, Qi-Cai

    2012-01-01

    In the ascending auditory pathway, the inferior colliculus (IC) receives and integrates excitatory and inhibitory inputs from many lower auditory nuclei, intrinsic projections within the IC, contralateral IC through the commissure of the IC and from the auditory cortex. All these connections make the IC a major center for subcortical temporal and spectral integration of auditory information. In this study, we examine bilateral collicular interaction in modulating amplitude-domain signal processing using electrophysiological recording, acoustic and focal electrical stimulation. Focal electrical stimulation of one (ipsilateral) IC produces widespread inhibition (61.6%) and focused facilitation (9.1%) of responses of neurons in the other (contralateral) IC, while 29.3% of the neurons were not affected. Bilateral collicular interaction produces a decrease in the response magnitude and an increase in the response latency of inhibited IC neurons but produces opposite effects on the response of facilitated IC neurons. These two groups of neurons are not separately located and are tonotopically organized within the IC. The modulation effect is most effective at low sound level and is dependent upon the interval between the acoustic and electric stimuli. The focal electrical stimulation of the ipsilateral IC compresses or expands the rate-level functions of contralateral IC neurons. The focal electrical stimulation also produces a shift in the minimum threshold and dynamic range of contralateral IC neurons for as long as 150 minutes. The degree of bilateral collicular interaction is dependent upon the difference in the best frequency between the electrically stimulated IC neurons and modulated IC neurons. These data suggest that bilateral collicular interaction mainly changes the ratio between excitation and inhibition during signal processing so as to sharpen the amplitude sensitivity of IC neurons. Bilateral interaction may be also involved in acoustic

  1. Neural Processing of Auditory Signals and Modular Neural Control for Sound Tropism of Walking Machines

    Directory of Open Access Journals (Sweden)

    Hubert Roth

    2008-11-01

    Full Text Available The specialized hairs and slit sensillae of spiders (Cupiennius salei can sense the airflow and auditory signals in a low-frequency range. They provide the sensor information for reactive behavior, like e.g. capturing a prey. In analogy, in this paper a setup is described where two microphones and a neural preprocessing system together with a modular neural controller are used to generate a sound tropism of a four-legged walking machine. The neural preprocessing network is acting as a low-pass filter and it is followed by a network which discerns between signals coming from the left or the right. The parameters of these networks are optimized by an evolutionary algorithm. In addition, a simple modular neural controller then generates the desired different walking patterns such that the machine walks straight, then turns towards a switched-on sound source, and then stops near to it.

  2. The afferent signaling complex: Regulation of type I spiral ganglion neuron responses in the auditory periphery.

    Science.gov (United States)

    Reijntjes, Daniël O J; Pyott, Sonja J

    2016-06-01

    The spiral ganglion neurons (SGNs) are the first action potential generating neurons in the auditory pathway. The type I SGNs contact the sensory inner hair cells via their peripheral dendrites and relay auditory information to the brainstem via their central axon fibers. Individual afferent fibers show differences in response properties that are essential for normal hearing. The mechanisms that give rise to the heterogeneity of afferent responses are very poorly understood but are likely already in place at the peripheral dendrites where synapses are formed and action potentials are generated. To identify these molecular mechanisms, this review synthesizes a variety of literature and comprehensively outlines the cellular and molecular components positioned to regulate SGN afferent dendrite excitability, especially following glutamate release. These components include 1) proteins of the SGN postsynapses and neighboring supporting cells that together shape glutamatergic signaling, 2) the ion channels and transporters that determine the intrinsic excitability of the SGN afferent dendrites, and 3) the neurotransmitter receptors that extrinsically modify this excitability via synaptic input from the lateral olivocochlear efferents. This cellular and molecular machinery, together with presynaptic specializations of the inner hair cells, can be collectively referred to as the type I afferent signaling complex. As this review underscores, interactions of this signaling complex determine excitability of the SGN afferent dendrites and the afferent fiber responses. Moreover, this complex establishes the environmental milieu critical for the development and maintenance of the SGN afferent dendrites and synapses. Motivated by these important functions, this review also indicates areas of future research to elucidate the contributions of the afferent signaling complex to both normal hearing and also hearing loss. PMID:27018296

  3. Calcium Signaling Is Required for Erythroid Enucleation.

    Science.gov (United States)

    Wölwer, Christina B; Pase, Luke B; Russell, Sarah M; Humbert, Patrick O

    2016-01-01

    Although erythroid enucleation, the property of erythroblasts to expel their nucleus, has been known for 7ore than a century, surprisingly little is known regarding the molecular mechanisms governing this unique developmental process. Here we show that similar to cytokinesis, nuclear extrusion requires intracellular calcium signaling and signal transduction through the calmodulin (CaM) pathway. However, in contrast to cytokinesis we found that orthochromatic erythroblasts require uptake of extracellular calcium to enucleate. Together these functional studies highlight a critical role for calcium signaling in the regulation of erythroid enucleation.

  4. Calcium Signaling Is Required for Erythroid Enucleation.

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    Christina B Wölwer

    Full Text Available Although erythroid enucleation, the property of erythroblasts to expel their nucleus, has been known for 7ore than a century, surprisingly little is known regarding the molecular mechanisms governing this unique developmental process. Here we show that similar to cytokinesis, nuclear extrusion requires intracellular calcium signaling and signal transduction through the calmodulin (CaM pathway. However, in contrast to cytokinesis we found that orthochromatic erythroblasts require uptake of extracellular calcium to enucleate. Together these functional studies highlight a critical role for calcium signaling in the regulation of erythroid enucleation.

  5. Calcium Signaling Is Required for Erythroid Enucleation

    Science.gov (United States)

    Russell, Sarah M.; Humbert, Patrick O.

    2016-01-01

    Although erythroid enucleation, the property of erythroblasts to expel their nucleus, has been known for 7ore than a century, surprisingly little is known regarding the molecular mechanisms governing this unique developmental process. Here we show that similar to cytokinesis, nuclear extrusion requires intracellular calcium signaling and signal transduction through the calmodulin (CaM) pathway. However, in contrast to cytokinesis we found that orthochromatic erythroblasts require uptake of extracellular calcium to enucleate. Together these functional studies highlight a critical role for calcium signaling in the regulation of erythroid enucleation. PMID:26731108

  6. Hear no evil: The effect of auditory warning signals on avian innate avoidance, learned avoidance and memory

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    Emma C. SIDDALL, Nicola M. MARPLES

    2011-04-01

    Full Text Available Many aposematic insect species advertise their toxicity to potential predators using olfactory and auditory signals, in addition to visual signals, to produce a multimodal warning display. The olfactory signals in these displays may have interesting effects, such as eliciting innate avoidance against novel colored prey, or improving learning and memory of defended prey. However, little is known about the effects of such ancillary signals when they are auditory rather than olfactory. The few studies that have investigated this question have provided conflicting results. The current study sought to clarify and extend understanding of the effects of prey auditory signals on avian predator responses. The domestic chick Gallus gallus domesticus was used as a model avian predator to examine how the defensive buzzing sound of a bumblebee Bombus terrestris affected the chick’s innate avoidance behavior, and the learning and memory of prey avoidance. The results demonstrate that the buzzing sound had no effect on the predator’s responses to unpalatable aposematically colored crumbs, suggesting that the agitated buzzing of B. terrestris may provide no additional protection from avian predators [Current Zoology 57 (2: 197–207, 2011].

  7. Hear no evil:The effect of auditory warning signals on avian innate avoidance,learned avoidance and memory

    Institute of Scientific and Technical Information of China (English)

    Emma C.SIDDALL; Nicola M.MARPLES

    2011-01-01

    Many aposematic insect species advertise their toxicity to potential predators using olfactory and auditory signals,in addition to visual signals,to produce a multimodal warning display.The olfactory signals in these displays may have interesting effects,such as eliciting innate avoidance against novel colored prey,or improving learning and memory of defended prey.However,little is known about the effects of such ancillary signals when they are auditory rather than olfactory.The few studies that have investigated this question have provided confficting results.The current study sought to clarify and extend understanding of the effects of prey auditory signals on avian predator responses.The domestic chick Gallus gallus domesticus was used as a model avian predator to examine how the defensive buzzing sound of a bumblebee Bombus terrestris affected the chick's innate avoidance behavior,and the learning and memory of prey avoidance.The resuits demonstrate that the buzzing sound had no effect on the predator's responses to unpalalable aposematically colored crumbs,suggesting that the agitated buzzing of B.terrestris may provide no additional protection from avian predators.

  8. Increased Signal Complexity Improves the Breadth of Generalization in Auditory Perceptual Learning

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    David J. Brown

    2013-01-01

    Full Text Available Perceptual learning can be specific to a trained stimulus or optimally generalized to novel stimuli with the breadth of generalization being imperative for how we structure perceptual training programs. Adapting an established auditory interval discrimination paradigm to utilise complex signals, we trained human adults on a standard interval for either 2, 4, or 10 days. We then tested the standard, alternate frequency, interval, and stereo input conditions to evaluate the rapidity of specific learning and breadth of generalization over the time course. In comparison with previous research using simple stimuli, the speed of perceptual learning and breadth of generalization were more rapid and greater in magnitude, including novel generalization to an alternate temporal interval within stimulus type. We also investigated the long term maintenance of learning and found that specific and generalized learning was maintained over 3 and 6 months. We discuss these findings regarding stimulus complexity in perceptual learning and how they can inform the development of effective training protocols.

  9. To modulate and be modulated: estrogenic influences on auditory processing of communication signals within a socio-neuro-endocrine framework.

    Science.gov (United States)

    Yoder, Kathleen M; Vicario, David S

    2012-02-01

    Gonadal hormones modulate behavioral responses to sexual stimuli, and communication signals can also modulate circulating hormone levels. In several species, these combined effects appear to underlie a two-way interaction between circulating gonadal hormones and behavioral responses to socially salient stimuli. Recent work in songbirds has shown that manipulating local estradiol levels in the auditory forebrain produces physiological changes that affect discrimination of conspecific vocalizations and can affect behavior. These studies provide new evidence that estrogens can directly alter auditory processing and indirectly alter the behavioral response to a stimulus. These studies show that: 1) Local estradiol action within an auditory area is necessary for socially relevant sounds to induce normal physiological responses in the brains of both sexes; 2) These physiological effects occur much more quickly than predicted by the classical time-frame for genomic effects; 3) Estradiol action within the auditory forebrain enables behavioral discrimination among socially relevant sounds in males; and 4) Estradiol is produced locally in the male brain during exposure to particular social interactions. The accumulating evidence suggests a socio-neuro-endocrinology framework in which estradiol is essential to auditory processing, is increased by a socially relevant stimulus, acts rapidly to shape perception of subsequent stimuli experienced during social interactions, and modulates behavioral responses to these stimuli. Brain estrogens are likely to function similarly in both songbird sexes because aromatase and estrogen receptors are present in both male and female forebrain. Estrogenic modulation of perception in songbirds and perhaps other animals could fine-tune male advertising signals and female ability to discriminate them, facilitating mate selection by modulating behaviors. PMID:22201281

  10. Representation of Reward Feedback in Primate Auditory Cortex

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    Michael eBrosch

    2011-02-01

    Full Text Available It is well established that auditory cortex is plastic on different time scales and that this plasticity is driven by the reinforcement that is used to motivate subjects to learn or to perform an auditory task. Motivated by these findings, we study in detail properties of neuronal firing in auditory cortex that is related to reward feedback. We recorded from the auditory cortex of two monkeys while they were performing an auditory categorization task. Monkeys listened to a sequence of tones and had to signal when the frequency of adjacent tones stepped in downward direction, irrespective of the tone frequency and step size. Correct identifications were rewarded with either a large or a small amount of water. The size of reward depended on the monkeys' performance in the previous trial: it was large after a correct trial and small after an incorrect trial. The rewards served to maintain task performance. During task performance we found three successive periods of neuronal firing in auditory cortex that reflected (1 the reward expectancy for each trial, (2 the reward size received and (3 the mismatch between the expected and delivered reward. These results, together with control experiments suggest that auditory cortex receives reward feedback that could be used to adapt auditory cortex to task requirements. Additionally, the results presented here extend previous observations of non-auditory roles of auditory cortex and shows that auditory cortex is even more cognitively influenced than lately recognized.

  11. Representation of reward feedback in primate auditory cortex.

    Science.gov (United States)

    Brosch, Michael; Selezneva, Elena; Scheich, Henning

    2011-01-01

    It is well established that auditory cortex is plastic on different time scales and that this plasticity is driven by the reinforcement that is used to motivate subjects to learn or to perform an auditory task. Motivated by these findings, we study in detail properties of neuronal firing in auditory cortex that is related to reward feedback. We recorded from the auditory cortex of two monkeys while they were performing an auditory categorization task. Monkeys listened to a sequence of tones and had to signal when the frequency of adjacent tones stepped in downward direction, irrespective of the tone frequency and step size. Correct identifications were rewarded with either a large or a small amount of water. The size of reward depended on the monkeys' performance in the previous trial: it was large after a correct trial and small after an incorrect trial. The rewards served to maintain task performance. During task performance we found three successive periods of neuronal firing in auditory cortex that reflected (1) the reward expectancy for each trial, (2) the reward-size received, and (3) the mismatch between the expected and delivered reward. These results, together with control experiments suggest that auditory cortex receives reward feedback that could be used to adapt auditory cortex to task requirements. Additionally, the results presented here extend previous observations of non-auditory roles of auditory cortex and shows that auditory cortex is even more cognitively influenced than lately recognized.

  12. Retrosplenial Cortex Is Required for the Retrieval of Remote Memory for Auditory Cues

    Science.gov (United States)

    Todd, Travis P.; Mehlman, Max L.; Keene, Christopher S.; DeAngeli, Nicole E.; Bucci, David J.

    2016-01-01

    The retrosplenial cortex (RSC) has a well-established role in contextual and spatial learning and memory, consistent with its known connectivity with visuo-spatial association areas. In contrast, RSC appears to have little involvement with delay fear conditioning to an auditory cue. However, all previous studies have examined the contribution of…

  13. Habituation of Auditory Steady State Responses Evoked by Amplitude-Modulated Acoustic Signals in Rats

    Science.gov (United States)

    Prado-Gutierrez, Pavel; Castro-Fariñas, Anisleidy; Morgado-Rodriguez, Lisbet; Velarde-Reyes, Ernesto; Martínez, Agustín D.; Martínez-Montes, Eduardo

    2015-01-01

    Generation of the auditory steady state responses (ASSR) is commonly explained by the linear combination of random background noise activity and the stationary response. Based on this model, the decrease of amplitude that occurs over the sequential averaging of epochs of the raw data has been exclusively linked to the cancelation of noise. Nevertheless, this behavior might also reflect the non-stationary response of the ASSR generators. We tested this hypothesis by characterizing the ASSR time course in rats with different auditory maturational stages. ASSR were evoked by 8-kHz tones of different supra-threshold intensities, modulated in amplitude at 115 Hz. Results show that the ASSR amplitude habituated to the sustained stimulation and that dishabituation occurred when deviant stimuli were presented. ASSR habituation increased as animals became adults, suggesting that the ability to filter acoustic stimuli with no-relevant temporal information increased with age. Results are discussed in terms of the current model of the ASSR generation and analysis procedures. They might have implications for audiometric tests designed to assess hearing in subjects who cannot provide reliable results in the psychophysical trials. PMID:26557360

  14. ROS signalling – Specificity is required

    DEFF Research Database (Denmark)

    Møller, Ian Max; Sweetlove, Lee J

    2011-01-01

    The production of reactive oxygen species (ROS) increases in plants under stress. ROS can damage cellular components, but they can also act in signal transduction to help the cell counteract the oxidative damage in the stressed compartment. H2O2 may induce a general stress response, but it does not...

  15. Auditory Display

    DEFF Research Database (Denmark)

    volume. The conference's topics include auditory exploration of data via sonification and audification; real time monitoring of multivariate date; sound in immersive interfaces and teleoperation; perceptual issues in auditory display; sound in generalized computer interfaces; technologies supporting...... auditory display creation; data handling for auditory display systems; applications of auditory display....

  16. Diet-Induced Obesity Exacerbates Auditory Degeneration via Hypoxia, Inflammation, and Apoptosis Signaling Pathways in CD/1 Mice

    Science.gov (United States)

    Hwang, Juen-Haur; Hsu, Chuan-Jen; Yu, Wei-Hsuan; Liu, Tien-Chen; Yang, Wei-Shiung

    2013-01-01

    The aim of this study was to investigate the mechanisms of diet-induced obesity on hearing degeneration in CD/1 mice. Sixty 4-week-old male CD/1 mice were randomly and equally divided into 2 groups. For 16 weeks, the diet-induced obesity (DIO) group was fed a high fat diet and the control group was fed a standard diet of 13.43 % kcal fat. The morphometry, biochemistry, auditory brainstem response thresholds, omental fat, and histopathology of the cochlea were compared between the beginning and end of the study (4 vs. 20 weeks old). The results show that the body weight, fasting plasma triglyceride concentrations, and omental fat weight were higher in the DIO group than in the control group at the end of experiment. The auditory brainstem response thresholds at high frequencies were significantly elevated in the DIO group compared to those of the control group. Histology studies showed that, compared to the control group, the DIO group had blood vessels with smaller diameters and thicker walls in the stria vascularis at the middle and basal turns of the cochlea. The cell densities in the spiral ganglion and spiral ligament at the basal turn of the cochlea were significantly lower in the DIO group. Immunohistochemical staining showed that hypoxia-induced factor 1 (HIF-1), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-κB), caspase 3, poly(ADP-ribose) polymerase-1, and apoptosis inducing factor were all significantly more dense in the spiral ganglion and spiral ligament at the basal turn of cochlea in the DIO group. Our results suggest that diet-induced obesity exacerbates hearing degeneration via increased hypoxia, inflammatory responses, and cell loss in the spiral ganglion and spiral ligament and is associated with the activation of both caspase-dependent and -independent apoptosis signaling pathways in CD/1 mice. PMID:23637762

  17. Diet-induced obesity exacerbates auditory degeneration via hypoxia, inflammation, and apoptosis signaling pathways in CD/1 mice.

    Directory of Open Access Journals (Sweden)

    Juen-Haur Hwang

    Full Text Available The aim of this study was to investigate the mechanisms of diet-induced obesity on hearing degeneration in CD/1 mice. Sixty 4-week-old male CD/1 mice were randomly and equally divided into 2 groups. For 16 weeks, the diet-induced obesity (DIO group was fed a high fat diet and the control group was fed a standard diet of 13.43 % kcal fat. The morphometry, biochemistry, auditory brainstem response thresholds, omental fat, and histopathology of the cochlea were compared between the beginning and end of the study (4 vs. 20 weeks old. The results show that the body weight, fasting plasma triglyceride concentrations, and omental fat weight were higher in the DIO group than in the control group at the end of experiment. The auditory brainstem response thresholds at high frequencies were significantly elevated in the DIO group compared to those of the control group. Histology studies showed that, compared to the control group, the DIO group had blood vessels with smaller diameters and thicker walls in the stria vascularis at the middle and basal turns of the cochlea. The cell densities in the spiral ganglion and spiral ligament at the basal turn of the cochlea were significantly lower in the DIO group. Immunohistochemical staining showed that hypoxia-induced factor 1 (HIF-1, tumor necrosis factor alpha (TNF-α, nuclear factor kappa B (NF-κB, caspase 3, poly(ADP-ribose polymerase-1, and apoptosis inducing factor were all significantly more dense in the spiral ganglion and spiral ligament at the basal turn of cochlea in the DIO group. Our results suggest that diet-induced obesity exacerbates hearing degeneration via increased hypoxia, inflammatory responses, and cell loss in the spiral ganglion and spiral ligament and is associated with the activation of both caspase-dependent and -independent apoptosis signaling pathways in CD/1 mice.

  18. Synaptic Plasticity and NO-cGMP-PKG Signaling Coordinately Regulate ERK-Driven Gene Expression in the Lateral Amygdala and in the Auditory Thalamus Following Pavlovian Fear Conditioning

    Science.gov (United States)

    Ota, Kristie T.; Monsey, Melissa S.; Wu, Melissa S.; Young, Grace J.; Schafe, Glenn E.

    2010-01-01

    We have recently hypothesized that NO-cGMP-PKG signaling in the lateral nucleus of the amygdala (LA) during auditory fear conditioning coordinately regulates ERK-driven transcriptional changes in both auditory thalamic (MGm/PIN) and LA neurons that serve to promote pre- and postsynaptic alterations at thalamo-LA synapses, respectively. In the…

  19. Auditory Processing Disorders

    Science.gov (United States)

    Auditory Processing Disorders Auditory processing disorders (APDs) are referred to by many names: central auditory processing disorders , auditory perceptual disorders , and central auditory disorders . APDs ...

  20. Neural processing of auditory signals and modular neural control for sound tropism of walking machines

    DEFF Research Database (Denmark)

    Manoonpong, Poramate; Pasemann, Frank; Fischer, Joern;

    2005-01-01

    . The parameters of these networks are optimized by an evolutionary algorithm. In addition, a simple modular neural controller then generates the desired different walking patterns such that the machine walks straight, then turns towards a switched-on sound source, and then stops near to it....... and a neural preprocessing system together with a modular neural controller are used to generate a sound tropism of a four-legged walking machine. The neural preprocessing network is acting as a low-pass filter and it is followed by a network which discerns between signals coming from the left or the right...

  1. Primate Auditory Recognition Memory Performance Varies With Sound Type

    OpenAIRE

    Chi-Wing, Ng; Bethany, Plakke; Amy, Poremba

    2009-01-01

    Neural correlates of auditory processing, including for species-specific vocalizations that convey biological and ethological significance (e.g. social status, kinship, environment),have been identified in a wide variety of areas including the temporal and frontal cortices. However, few studies elucidate how non-human primates interact with these vocalization signals when they are challenged by tasks requiring auditory discrimination, recognition, and/or memory. The present study employs a de...

  2. Potyviruses differ in their requirement for TOR signalling.

    Science.gov (United States)

    Ouibrahim, Laurence; Rubio, Ana Giner; Moretti, André; Montané, Marie-Hélène; Menand, Benoît; Meyer, Christian; Robaglia, Christophe; Caranta, Carole

    2015-09-01

    Potyviruses are important plant pathogens that rely on many plant cellular processes for successful infection. TOR (target of rapamycin) signalling is a key eukaryotic energy-signalling pathway controlling many cellular processes such as translation and autophagy. The dependence of potyviruses on active TOR signalling was examined. Arabidopsis lines downregulated for TOR by RNAi were challenged with the potyviruses watermelon mosaic virus (WMV) and turnip mosaic virus (TuMV). WMV accumulation was found to be severely altered while TuMV accumulation was only slightly delayed. In another approach, using AZD-8055, an active site inhibitor of the TOR kinase, WMV infection was found to be strongly affected. Moreover, AZD-8055 application can cure WMV infection. In contrast, TuMV infection was not affected by AZD-8055. This suggests that potyviruses have different cellular requirements for active plant TOR signalling.

  3. Wnt Signaling Is Required for Long-Term Memory Formation

    Directory of Open Access Journals (Sweden)

    Ying Tan

    2013-09-01

    Full Text Available Wnt signaling regulates synaptic plasticity and neurogenesis in the adult nervous system, suggesting a potential role in behavioral processes. Here, we probed the requirement for Wnt signaling during olfactory memory formation in Drosophila using an inducible RNAi approach. Interfering with β-catenin expression in adult mushroom body neurons specifically impaired long-term memory (LTM without altering short-term memory. The impairment was reversible, being rescued by expression of a wild-type β-catenin transgene, and correlated with disruption of a cellular LTM trace. Inhibition of wingless, a Wnt ligand, and arrow, a Wnt coreceptor, also impaired LTM. Wingless expression in wild-type flies was transiently elevated in the brain after LTM conditioning. Thus, inhibiting three key components of the Wnt signaling pathway in adult mushroom bodies impairs LTM, indicating that this pathway mechanistically underlies this specific form of memory.

  4. Required signal-to-interference ratios for shortwave broadcasting

    Science.gov (United States)

    Lane, George

    1997-09-01

    The required signal-to-Interference (RSI) ratio for a specified grade of HF radio service is the hourly median wanted signal power at the input of the receiver needed relative to the sum of the hourly median unwanted signal power and the hourly median radio noise power in the RF bandwidth of the receiver, adjusted so that the hourly median ratio will not fall below the RSI ratio more than a certain percentage of the time due to minute-to-minute fading within the hour. Shortwave listeners are well aware of the deleterious effects of cochannel and adjacent channel interference. This type of interference is especially prevalent in the overcrowded international broadcast bands where it is manifested by cross talk and a beat note produced in the receiver by the carrier of the unwanted signal. Yet little agreement exists as to the magnitude of the amplitude-modulated, double sideband (AM-DSB) interfering signal that can be tolerated by the listener. Numerous protection ratios have been proposed in the literature, as well as by elements of the International Telecommunication Union. These values tend to range from 17 dB [International Frequency Registration Board, 1989] to as high as 50 dB for "good commercial quality," offset in carrier frequency of 500 Hz and 10 dB short-term fade protection [CCIR, 1970]. In this paper, several significant experiments are reviewed for the purpose of normalizing their findings to a common set of parameters. The parameters relate to articulation scoring, type of noise (if used), fading of wanted and unwanted signals, type of interference, listener skill, bandwidth of the receiver, carrier frequency offset, etc. From this compilation of normalized data, RSI values are recommended as they relate to the desired broadcast quality and the signal-to-noise ratio of the wanted signal. The RSI ratios are compatible for use in HF sky wave prediction programs that contain appropriate RF noise and interference combining subroutines. The recommended

  5. An auditory feature detection circuit for sound pattern recognition.

    Science.gov (United States)

    Schöneich, Stefan; Kostarakos, Konstantinos; Hedwig, Berthold

    2015-09-01

    From human language to birdsong and the chirps of insects, acoustic communication is based on amplitude and frequency modulation of sound signals. Whereas frequency processing starts at the level of the hearing organs, temporal features of the sound amplitude such as rhythms or pulse rates require processing by central auditory neurons. Besides several theoretical concepts, brain circuits that detect temporal features of a sound signal are poorly understood. We focused on acoustically communicating field crickets and show how five neurons in the brain of females form an auditory feature detector circuit for the pulse pattern of the male calling song. The processing is based on a coincidence detector mechanism that selectively responds when a direct neural response and an intrinsically delayed response to the sound pulses coincide. This circuit provides the basis for auditory mate recognition in field crickets and reveals a principal mechanism of sensory processing underlying the perception of temporal patterns.

  6. Auditory and Visual Sensations

    CERN Document Server

    Ando, Yoichi

    2010-01-01

    Professor Yoichi Ando, acoustic architectural designer of the Kirishima International Concert Hall in Japan, presents a comprehensive rational-scientific approach to designing performance spaces. His theory is based on systematic psychoacoustical observations of spatial hearing and listener preferences, whose neuronal correlates are observed in the neurophysiology of the human brain. A correlation-based model of neuronal signal processing in the central auditory system is proposed in which temporal sensations (pitch, timbre, loudness, duration) are represented by an internal autocorrelation representation, and spatial sensations (sound location, size, diffuseness related to envelopment) are represented by an internal interaural crosscorrelation function. Together these two internal central auditory representations account for the basic auditory qualities that are relevant for listening to music and speech in indoor performance spaces. Observed psychological and neurophysiological commonalities between auditor...

  7. Auditory Neuropathy

    Science.gov (United States)

    ... field differ in their opinions about the potential benefits of hearing aids, cochlear implants, and other technologies for people with auditory neuropathy. Some professionals report that hearing aids and personal listening devices such as frequency modulation (FM) systems are ...

  8. Research on Auditory Model and Speech Signal Processing Method%听觉模型与语音信号处理方法的研究

    Institute of Scientific and Technical Information of China (English)

    刘婧婕; 张刚; 武淑红

    2012-01-01

    在通信领域中,语音编码是语音信号处理的重要分支.为了适合信道传输,语音必须变换形式,基于承载信息并且保留信号,尽可能地处理.在当今的通信、计算机网络等应用领域中,具备低延迟、低码率两大特性的语音编码算法,发挥着决定性作用.在语音编码中,线性预测分析技术主要应用在感觉加权滤波器、综合滤波器及对数增益滤波器,该技术发挥着关键作用.文中的工作是呈现出一种混合LPC( Auditory- Acoustic - Hybrid- LPC)系数,它结合声学特性与听觉特性,以便提高编码后合成语音的听觉质量,这对编码算法的钻研有积极意义.%In the field of communication, speech coding is an important branch of speech signal processing. It reserves the signal carrying the information,based on the maximum degree of its processing,it transforms into a suitable form of transmission channels. In the today 's society, speech coding algorithms with low bit rate and low delay, plays a key role in the communication, computer networks and many other applications. In the speech coding, feeling weighted filters, synthesis filters, logarithmic gain filters are related to the linear prediction analysis techniques, which plays a central role in the voice processing. The main work of this paper is to propose a combination of acoustic features and auditory features of the mixed LPC coefficients (Auditory-Acoustic-Hybrid-LPC) , making the audio quality of the encoded synthetic voice improved, which has a positive meaning to the research of coding algorithm.

  9. Auditory Neuropathy: Findings of Behavioral, Physiological and Neurophysiological Tests

    Directory of Open Access Journals (Sweden)

    Mohammad Farhadi

    2006-12-01

    Full Text Available Background and Aim: Auditory neuropathy (AN can be diagnosed by abnormal auditory brainstem response (ABR, in the presence of normal cochlear microphonic (CM and otoacoustic emissions (OAEs.The aim of this study was to investigate the ABR and other electrodiagnostic test results of 6 patients suspicious to AN with problems in speech recognition. Materials and Methods: this cross sectional study was conducted on 6 AN patients with different ages evaluated by pure tone audiometry, speech discrimination score (SDS , immittance audiometry. ElectroCochleoGraphy , ABR, middle latency response (MLR, Late latency response (LLR, and OAEs. Results: Behavioral pure tone audiometric tests showed moderate to profound hearing loss. SDS was so poor which is not in accordance with pure tone thresholds. All patients had normal tympanogram but absent acoustic reflexes. CMs and OAEs were within normal limits. There was no contra lateral suppression of OAEs. None of cases had normal ABR or MLR although LLR was recorded in 4. Conclusion: All patients in this study are typical cases of auditory neuropathy. Despite having abnormal input, LLR remains normal that indicates differences in auditory evoked potentials related to required neural synchrony. These findings show that auditory cortex may play a role in regulating presentation of deficient signals along auditory pathways in primary steps.

  10. Seeing the song: left auditory structures may track auditory-visual dynamic alignment.

    Directory of Open Access Journals (Sweden)

    Julia A Mossbridge

    Full Text Available Auditory and visual signals generated by a single source tend to be temporally correlated, such as the synchronous sounds of footsteps and the limb movements of a walker. Continuous tracking and comparison of the dynamics of auditory-visual streams is thus useful for the perceptual binding of information arising from a common source. Although language-related mechanisms have been implicated in the tracking of speech-related auditory-visual signals (e.g., speech sounds and lip movements, it is not well known what sensory mechanisms generally track ongoing auditory-visual synchrony for non-speech signals in a complex auditory-visual environment. To begin to address this question, we used music and visual displays that varied in the dynamics of multiple features (e.g., auditory loudness and pitch; visual luminance, color, size, motion, and organization across multiple time scales. Auditory activity (monitored using auditory steady-state responses, ASSR was selectively reduced in the left hemisphere when the music and dynamic visual displays were temporally misaligned. Importantly, ASSR was not affected when attentional engagement with the music was reduced, or when visual displays presented dynamics clearly dissimilar to the music. These results appear to suggest that left-lateralized auditory mechanisms are sensitive to auditory-visual temporal alignment, but perhaps only when the dynamics of auditory and visual streams are similar. These mechanisms may contribute to correct auditory-visual binding in a busy sensory environment.

  11. Signaled two-way avoidance learning using electrical stimulation of the inferior colliculus as negative reinforcement: effects of visual and auditory cues as warning stimuli

    Directory of Open Access Journals (Sweden)

    A.C. Troncoso

    1998-03-01

    Full Text Available The inferior colliculus is a primary relay for the processing of auditory information in the brainstem. The inferior colliculus is also part of the so-called brain aversion system as animals learn to switch off the electrical stimulation of this structure. The purpose of the present study was to determine whether associative learning occurs between aversion induced by electrical stimulation of the inferior colliculus and visual and auditory warning stimuli. Rats implanted with electrodes into the central nucleus of the inferior colliculus were placed inside an open-field and thresholds for the escape response to electrical stimulation of the inferior colliculus were determined. The rats were then placed inside a shuttle-box and submitted to a two-way avoidance paradigm. Electrical stimulation of the inferior colliculus at the escape threshold (98.12 ± 6.15 (A, peak-to-peak was used as negative reinforcement and light or tone as the warning stimulus. Each session consisted of 50 trials and was divided into two segments of 25 trials in order to determine the learning rate of the animals during the sessions. The rats learned to avoid the inferior colliculus stimulation when light was used as the warning stimulus (13.25 ± 0.60 s and 8.63 ± 0.93 s for latencies and 12.5 ± 2.04 and 19.62 ± 1.65 for frequencies in the first and second halves of the sessions, respectively, P0.05 in both cases. Taken together, the present results suggest that rats learn to avoid the inferior colliculus stimulation when light is used as the warning stimulus. However, this learning process does not occur when the neutral stimulus used is an acoustic one. Electrical stimulation of the inferior colliculus may disturb the signal transmission of the stimulus to be conditioned from the inferior colliculus to higher brain structures such as amygdala

  12. RNA Type III Secretion Signals that require Hfq

    Energy Technology Data Exchange (ETDEWEB)

    Niemann, George; Brown, Roslyn N.; Mushamiri, Ivy T.; Nguyen, Nhu T.; Taiwo, Rukayat; Stufkens, Afke; Smith, Richard D.; Adkins, Joshua N.; McDermott, Jason E.; Heffron, Fred

    2013-05-01

    effector proteins from the bacterium to a host cell; however, the secretion signal is poorly defined. Effector N-termini are thought to contain the signal, but they lack homology, possess no identifiable motif, and adopt intrinsically disordered structures. We identified a panel of RNA secretion signals that facilitated reporter translocation into host cells via a mechanism dependent upon the RNA chaperone Hfq. Each of these signals was localized to an RNA leader sequence preceding the translational start codon. To obtain this panel of RNA signals, we fused untranslated leader sequences from 42 different Salmonella effector proteins to the adenylate cyclase reporter (CyaA'), and tested each of them for translocation into J774 macrophages. RNA sequences derived from five effectors, gtgA, cigR, gogB, sseL, and steD were sufficient for CyaA' injection into host cells. The gtgA RNA also directed translocation of the β-lactamase reporter. To determine the mechanism of signal recognition, we identified proteins that bound specifically to the gtgA RNA. One of the unique proteins identified was Hfq. Translocation of all five UTR fusions was abolished in the Hfq mutant, confirming the importance of Hfq. Our results suggest that Hfq may direct a subset of RNA transcripts to the T3S apparatus for translation and secretion. Signal diversity may explain why the T3S signal has been difficult to define.

  13. Can you hear me now? Musical training shapes functional brain networks for selective auditory attention and hearing speech in noise

    Directory of Open Access Journals (Sweden)

    Dana L Strait

    2011-06-01

    Full Text Available Even in the quietest of rooms, our senses are perpetually inundated by a barrage of sounds, requiring the auditory system to adapt to a variety of listening conditions in order to extract signals of interest (e.g., one speaker’s voice amidst others. Brain networks that promote selective attention are thought to sharpen the neural encoding of a target signal, suppressing competing sounds and enhancing perceptual performance. Here, we ask: does musical training benefit cortical mechanisms that underlie selective attention to speech? To answer this question, we assessed the impact of selective auditory attention on cortical auditory-evoked response variability in musicians and nonmusicians. Outcomes indicate strengthened brain networks for selective auditory attention in musicians in that musicians but not nonmusicians demonstrate decreased prefrontal response variability with auditory attention. Results are interpreted in the context of previous work from our laboratory documenting perceptual and subcortical advantages in musicians for the hearing and neural encoding of speech in background noise. Musicians’ neural proficiency for selectively engaging and sustaining auditory attention to language indicates a potential benefit of music for auditory training. Given the importance of auditory attention for the development of language-related skills, musical training may aid in the prevention, habilitation and remediation of children with a wide range of attention-based language and learning impairments.

  14. 49 CFR 236.205 - Signal control circuits; requirements.

    Science.gov (United States)

    2010-10-01

    ..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic... when any of the following conditions obtain within the block: (a) Occupancy by a train, locomotive,...

  15. Auditory orientation in crickets: Pattern recognition controls reactive steering

    Science.gov (United States)

    Poulet, James F. A.; Hedwig, Berthold

    2005-10-01

    Many groups of insects are specialists in exploiting sensory cues to locate food resources or conspecifics. To achieve orientation, bees and ants analyze the polarization pattern of the sky, male moths orient along the females' odor plume, and cicadas, grasshoppers, and crickets use acoustic signals to locate singing conspecifics. In comparison with olfactory and visual orientation, where learning is involved, auditory processing underlying orientation in insects appears to be more hardwired and genetically determined. In each of these examples, however, orientation requires a recognition process identifying the crucial sensory pattern to interact with a localization process directing the animal's locomotor activity. Here, we characterize this interaction. Using a sensitive trackball system, we show that, during cricket auditory behavior, the recognition process that is tuned toward the species-specific song pattern controls the amplitude of auditory evoked steering responses. Females perform small reactive steering movements toward any sound patterns. Hearing the male's calling song increases the gain of auditory steering within 2-5 s, and the animals even steer toward nonattractive sound patterns inserted into the speciesspecific pattern. This gain control mechanism in the auditory-to-motor pathway allows crickets to pursue species-specific sound patterns temporarily corrupted by environmental factors and may reflect the organization of recognition and localization networks in insects. localization | phonotaxis

  16. Auditory short-term memory in the primate auditory cortex.

    Science.gov (United States)

    Scott, Brian H; Mishkin, Mortimer

    2016-06-01

    Sounds are fleeting, and assembling the sequence of inputs at the ear into a coherent percept requires auditory memory across various time scales. Auditory short-term memory comprises at least two components: an active ׳working memory' bolstered by rehearsal, and a sensory trace that may be passively retained. Working memory relies on representations recalled from long-term memory, and their rehearsal may require phonological mechanisms unique to humans. The sensory component, passive short-term memory (pSTM), is tractable to study in nonhuman primates, whose brain architecture and behavioral repertoire are comparable to our own. This review discusses recent advances in the behavioral and neurophysiological study of auditory memory with a focus on single-unit recordings from macaque monkeys performing delayed-match-to-sample (DMS) tasks. Monkeys appear to employ pSTM to solve these tasks, as evidenced by the impact of interfering stimuli on memory performance. In several regards, pSTM in monkeys resembles pitch memory in humans, and may engage similar neural mechanisms. Neural correlates of DMS performance have been observed throughout the auditory and prefrontal cortex, defining a network of areas supporting auditory STM with parallels to that supporting visual STM. These correlates include persistent neural firing, or a suppression of firing, during the delay period of the memory task, as well as suppression or (less commonly) enhancement of sensory responses when a sound is repeated as a ׳match' stimulus. Auditory STM is supported by a distributed temporo-frontal network in which sensitivity to stimulus history is an intrinsic feature of auditory processing. This article is part of a Special Issue entitled SI: Auditory working memory. PMID:26541581

  17. Auditory short-term memory in the primate auditory cortex.

    Science.gov (United States)

    Scott, Brian H; Mishkin, Mortimer

    2016-06-01

    Sounds are fleeting, and assembling the sequence of inputs at the ear into a coherent percept requires auditory memory across various time scales. Auditory short-term memory comprises at least two components: an active ׳working memory' bolstered by rehearsal, and a sensory trace that may be passively retained. Working memory relies on representations recalled from long-term memory, and their rehearsal may require phonological mechanisms unique to humans. The sensory component, passive short-term memory (pSTM), is tractable to study in nonhuman primates, whose brain architecture and behavioral repertoire are comparable to our own. This review discusses recent advances in the behavioral and neurophysiological study of auditory memory with a focus on single-unit recordings from macaque monkeys performing delayed-match-to-sample (DMS) tasks. Monkeys appear to employ pSTM to solve these tasks, as evidenced by the impact of interfering stimuli on memory performance. In several regards, pSTM in monkeys resembles pitch memory in humans, and may engage similar neural mechanisms. Neural correlates of DMS performance have been observed throughout the auditory and prefrontal cortex, defining a network of areas supporting auditory STM with parallels to that supporting visual STM. These correlates include persistent neural firing, or a suppression of firing, during the delay period of the memory task, as well as suppression or (less commonly) enhancement of sensory responses when a sound is repeated as a ׳match' stimulus. Auditory STM is supported by a distributed temporo-frontal network in which sensitivity to stimulus history is an intrinsic feature of auditory processing. This article is part of a Special Issue entitled SI: Auditory working memory.

  18. A Model of Auditory-Cognitive Processing and Relevance to Clinical Applicability.

    Science.gov (United States)

    Edwards, Brent

    2016-01-01

    Hearing loss and cognitive function interact in both a bottom-up and top-down relationship. Listening effort is tied to these interactions, and models have been developed to explain their relationship. The Ease of Language Understanding model in particular has gained considerable attention in its explanation of the effect of signal distortion on speech understanding. Signal distortion can also affect auditory scene analysis ability, however, resulting in a distorted auditory scene that can affect cognitive function, listening effort, and the allocation of cognitive resources. These effects are explained through an addition to the Ease of Language Understanding model. This model can be generalized to apply to all sounds, not only speech, representing the increased effort required for auditory environmental awareness and other nonspeech auditory tasks. While the authors have measures of speech understanding and cognitive load to quantify these interactions, they are lacking measures of the effect of hearing aid technology on auditory scene analysis ability and how effort and attention varies with the quality of an auditory scene. Additionally, the clinical relevance of hearing aid technology on cognitive function and the application of cognitive measures in hearing aid fittings will be limited until effectiveness is demonstrated in real-world situations. PMID:27355775

  19. Transsynaptic EphB/Ephrin-B signaling regulates growth of presynaptic boutons required for classical conditioning.

    Science.gov (United States)

    Li, Wei; Zheng, Zhaoqing; Keifer, Joyce

    2011-06-01

    Learning-related presynaptic remodeling has been documented in only a few systems, and its molecular mechanisms are largely unknown. Here we describe a role for the bidirectional EphB/ephrin-B signaling system in structural plasticity of presynaptic nerve terminals using an in vitro model of classical conditioning. Conditioning or BDNF application induced significant growth of auditory nerve presynaptic boutons that convey the conditioned stimulus to abducens motor neurons. Interestingly, bouton enlargement occurred only for those synapses apposed to motor neuron dendrites rather than to somata. Phosphorylation of ephrin-B1, but not EphB2, was induced by both conditioning and BDNF application and was inhibited by postsynaptic injections of ephrin-B antibody. Finally, suppression of postsynaptic ephrin-B function inhibited presynaptic bouton enlargement that was rescued by activation of EphB2 by ephrin-B1-Fc. These data provide evidence for ephrin-B-induced EphB2 forward signaling in presynaptic structural plasticity during classical conditioning. They also reveal a functional interaction between BDNF/TrkB and the Eph/ephrin signaling systems in the coordination of presynaptic and postsynaptic modifications during conditioning.

  20. Prefrontal D1 dopamine signaling is required for temporal control.

    Science.gov (United States)

    Narayanan, Nandakumar S; Land, Benjamin B; Solder, John E; Deisseroth, Karl; DiLeone, Ralph J

    2012-12-11

    Temporal control, or how organisms guide movements in time to achieve behavioral goals, depends on dopamine signaling. The medial prefrontal cortex controls many goal-directed behaviors and receives dopaminergic input primarily from the midbrain ventral tegmental area. However, this system has never been linked with temporal control. Here, we test the hypothesis that dopaminergic projections from the ventral tegmental area to the prefrontal cortex influence temporal control. Rodents were trained to perform a fixed-interval timing task with an interval of 20 s. We report several results: first, that decreasing dopaminergic neurotransmission using virally mediated RNA interference of tyrosine hydroxylase impaired temporal control, and second that pharmacological disruption of prefrontal D1 dopamine receptors, but not D2 dopamine receptors, impaired temporal control. We then used optogenetics to specifically and selectively manipulate prefrontal neurons expressing D1 dopamine receptors during fixed-interval timing performance. Selective inhibition of D1-expressing prefrontal neurons impaired fixed-interval timing, whereas stimulation made animals more efficient during task performance. These data provide evidence that ventral tegmental dopaminergic projections to the prefrontal cortex influence temporal control via D1 receptors. The results identify a critical circuit for temporal control of behavior that could serve as a target for the treatment of dopaminergic diseases.

  1. Frequency band-importance functions for auditory and auditory-visual speech recognition

    Science.gov (United States)

    Grant, Ken W.

    2005-04-01

    In many everyday listening environments, speech communication involves the integration of both acoustic and visual speech cues. This is especially true in noisy and reverberant environments where the speech signal is highly degraded, or when the listener has a hearing impairment. Understanding the mechanisms involved in auditory-visual integration is a primary interest of this work. Of particular interest is whether listeners are able to allocate their attention to various frequency regions of the speech signal differently under auditory-visual conditions and auditory-alone conditions. For auditory speech recognition, the most important frequency regions tend to be around 1500-3000 Hz, corresponding roughly to important acoustic cues for place of articulation. The purpose of this study is to determine the most important frequency region under auditory-visual speech conditions. Frequency band-importance functions for auditory and auditory-visual conditions were obtained by having subjects identify speech tokens under conditions where the speech-to-noise ratio of different parts of the speech spectrum is independently and randomly varied on every trial. Point biserial correlations were computed for each separate spectral region and the normalized correlations are interpreted as weights indicating the importance of each region. Relations among frequency-importance functions for auditory and auditory-visual conditions will be discussed.

  2. Sustainable Land Use Requires Attention to Ecological Signals

    Science.gov (United States)

    Halvorson, W.L.; Castellanos, A.E.; Murrieta-Saldivar, J.

    2003-01-01

    This case study details the difficulties of landscape management, highlighting the challenges inherent in managing natural resources when multiple agencies are involved, when the land users have no incentive for conservation, and when government agencies have too few resources for effective management. Pumping of groundwater from the aquifer of La Costa de Hermosillo in the state of Sonora, Mexico, began in 1945 and developed so quickly that by the late 1950s salinity intrusion from the Gulf of California was occurring in the wells. In the 1970s, the irrigatable land in La Costa peaked at 132,516 ha and the extracted volume of water from the aquifer peaked at around 1.14 billion cubic meters annually. By the 1980s, 105 wells of the total of 498 were contaminated with seawater and, therefore, identified for closure. At present La Costa de Hermosillo still represents 15% of the total harvested land, 16% of the total annual production, and 23% of the gross agricultural production of the state of Sonora. However, there are approximately 80,000 ha of abandoned fields due to salt water intension, lack of water and/or lack of credit available to individual farmers. This unstable situation resulted from the interplay of water management policies and practices, and farm-land policies and practices. While government agencies have been able to enforce better water use for agricultural production, there remains a significant area that requires restoration from its degraded state. For this piece of the ecosystem management puzzle, government agencies have thus far been unable to affect a solution.

  3. Central auditory function of deafness genes.

    Science.gov (United States)

    Willaredt, Marc A; Ebbers, Lena; Nothwang, Hans Gerd

    2014-06-01

    The highly variable benefit of hearing devices is a serious challenge in auditory rehabilitation. Various factors contribute to this phenomenon such as the diversity in ear defects, the different extent of auditory nerve hypoplasia, the age of intervention, and cognitive abilities. Recent analyses indicate that, in addition, central auditory functions of deafness genes have to be considered in this context. Since reduced neuronal activity acts as the common denominator in deafness, it is widely assumed that peripheral deafness influences development and function of the central auditory system in a stereotypical manner. However, functional characterization of transgenic mice with mutated deafness genes demonstrated gene-specific abnormalities in the central auditory system as well. A frequent function of deafness genes in the central auditory system is supported by a genome-wide expression study that revealed significant enrichment of these genes in the transcriptome of the auditory brainstem compared to the entire brain. Here, we will summarize current knowledge of the diverse central auditory functions of deafness genes. We furthermore propose the intimately interwoven gene regulatory networks governing development of the otic placode and the hindbrain as a mechanistic explanation for the widespread expression of these genes beyond the cochlea. We conclude that better knowledge of central auditory dysfunction caused by genetic alterations in deafness genes is required. In combination with improved genetic diagnostics becoming currently available through novel sequencing technologies, this information will likely contribute to better outcome prediction of hearing devices.

  4. How Does Auditory Training Work? Joined-Up Thinking and Listening.

    Science.gov (United States)

    Ferguson, Melanie; Henshaw, Helen

    2015-11-01

    Auditory training aims to compensate for degradation in the auditory signal and is offered as an intervention to help alleviate the most common complaint in people with hearing loss, understanding speech in a background noise. Yet there remain many unanswered questions. This article reviews some of the key pieces of evidence that assess the evidence for whether, and how, auditory training benefits adults with hearing loss. The evidence supports that improvements occur on the trained task; however, transfer of that learning to generalized real-world benefit is much less robust. For more than a decade, there has been an increasing awareness of the role that cognition plays in listening. But more recently in the auditory training literature, there has been an increased focus on assessing how cognitive performance relevant for listening may improve with training. We argue that this is specifically the case for measures that index executive processes, such as monitoring, attention switching, and updating of working memory, all of which are required for successful listening and communication in challenging or adverse listening conditions. We propose combined auditory-cognitive training approaches, where training interventions develop cognition embedded within auditory tasks, which are most likely to offer generalized benefits to the real-world listening abilities of people with hearing loss. PMID:27587911

  5. Auditory processing efficiency deficits in children with developmental language impairments

    Science.gov (United States)

    Hartley, Douglas E. H.; Moore, David R.

    2002-12-01

    The ``temporal processing hypothesis'' suggests that individuals with specific language impairments (SLIs) and dyslexia have severe deficits in processing rapidly presented or brief sensory information, both within the auditory and visual domains. This hypothesis has been supported through evidence that language-impaired individuals have excess auditory backward masking. This paper presents an analysis of masking results from several studies in terms of a model of temporal resolution. Results from this modeling suggest that the masking results can be better explained by an ``auditory efficiency'' hypothesis. If impaired or immature listeners have a normal temporal window, but require a higher signal-to-noise level (poor processing efficiency), this hypothesis predicts the observed small deficits in the simultaneous masking task, and the much larger deficits in backward and forward masking tasks amongst those listeners. The difference in performance on these masking tasks is predictable from the compressive nonlinearity of the basilar membrane. The model also correctly predicts that backward masking (i) is more prone to training effects, (ii) has greater inter- and intrasubject variability, and (iii) increases less with masker level than do other masking tasks. These findings provide a new perspective on the mechanisms underlying communication disorders and auditory masking.

  6. An Auditory Model of Improved Adaptive ZCPA

    Directory of Open Access Journals (Sweden)

    Jinping Zhang

    2013-07-01

    Full Text Available An improved ZCAP auditory model with adaptability is proposed in this paper, and the  adaptive method designed for ZCPA model is suitable for other auditory model with inner-hair-cell sub-model. The first step in the implement process of the proposed ZCPA model is to carry out the calculation of inner product between signal and complex Gammatone filters to obtain important frequency components  of signal. And then, according to  the result of the first step, the parameters of the basilar membrane sub-model and frequency box are automatically adjusted, such as the number of the basilar membrane filters, center frequency and bandwith of each basilar membrane filter, position of each frequency box, and so on. Lastly  an auditory model is built, and the final output is auditory spectrum.The results of numerical simulation and experiments have showed that the proposed model could realize accurate frequency selection, and the auditory spectrum is more distinctly than that of conventional ZCPA model. Moreover, the proposed model can completely avoided the influence of the number of filter on the shape of auditory spectrum existing in conventional ZCPA model so that the shape of auditory spectrum is steady, and the data quantity is small.

  7. Pump Linewidth Requirements for Processing Dispersion-Altered DQPSK Signals using FWM

    CERN Document Server

    Dúill, Séan Ó; Barry, Liam P

    2015-01-01

    We report on a potentially deleterious issue regarding the four-wave mixing based processing of dispersion-altered signals. We estimate the baudrate-dependent pump linewidth tolerances by calculating the extra optical signal to noise ratio (OSNR) penalty with respect to the propagation distance. We find that the issue is not important for 10 Gbaud differential quadrature phase shift keying (DQPSK) signals, though for 28 Gbaud (and 56 Gbaud) DQPSK signals we find that the pump linewidth requirements to implement FWM based optical signal processing needs to be in the sub-MHz range in order to avoid excessive OSNR penalties for the case of dispersion-altered signals. These results are pertinent for systems employing FWM, which could be all-optical wavelength converters for packet switching or mid-span spectral inversion techniques.

  8. Poor supplementary motor area activation differentiates auditory verbal hallucination from imagining the hallucination.

    Science.gov (United States)

    Raij, Tuukka T; Riekki, Tapani J J

    2012-01-01

    Neuronal underpinnings of auditory verbal hallucination remain poorly understood. One suggested mechanism is brain activation that is similar to verbal imagery but occurs without the proper activation of the neuronal systems that are required to tag the origins of verbal imagery in one's mind. Such neuronal systems involve the supplementary motor area. The supplementary motor area has been associated with awareness of intention to make a hand movement, but whether this region is related to the sense of ownership of one's verbal thought remains poorly known. We hypothesized that the supplementary motor area is related to the distinction between one's own mental processing (auditory verbal imagery) and similar processing that is attributed to non-self author (auditory verbal hallucination). To test this hypothesis, we asked patients to signal the onset and offset of their auditory verbal hallucinations during functional magnetic resonance imaging. During non-hallucination periods, we asked the same patients to imagine the hallucination they had previously experienced. In addition, healthy control subjects signaled the onset and offset of self-paced imagery of similar voices. Both hallucinations and the imagery of hallucinations were associated with similar activation strengths of the fronto-temporal language-related circuitries, but the supplementary motor area was activated more strongly during the imagery than during hallucination. These findings suggest that auditory verbal hallucination resembles verbal imagery in language processing, but without the involvement of the supplementary motor area, which may subserve the sense of ownership of one's own verbal imagery. PMID:24179739

  9. Poor supplementary motor area activation differentiates auditory verbal hallucination from imagining the hallucination☆

    Science.gov (United States)

    Raij, Tuukka T.; Riekki, Tapani J.J.

    2012-01-01

    Neuronal underpinnings of auditory verbal hallucination remain poorly understood. One suggested mechanism is brain activation that is similar to verbal imagery but occurs without the proper activation of the neuronal systems that are required to tag the origins of verbal imagery in one's mind. Such neuronal systems involve the supplementary motor area. The supplementary motor area has been associated with awareness of intention to make a hand movement, but whether this region is related to the sense of ownership of one's verbal thought remains poorly known. We hypothesized that the supplementary motor area is related to the distinction between one's own mental processing (auditory verbal imagery) and similar processing that is attributed to non-self author (auditory verbal hallucination). To test this hypothesis, we asked patients to signal the onset and offset of their auditory verbal hallucinations during functional magnetic resonance imaging. During non-hallucination periods, we asked the same patients to imagine the hallucination they had previously experienced. In addition, healthy control subjects signaled the onset and offset of self-paced imagery of similar voices. Both hallucinations and the imagery of hallucinations were associated with similar activation strengths of the fronto-temporal language-related circuitries, but the supplementary motor area was activated more strongly during the imagery than during hallucination. These findings suggest that auditory verbal hallucination resembles verbal imagery in language processing, but without the involvement of the supplementary motor area, which may subserve the sense of ownership of one's own verbal imagery. PMID:24179739

  10. Characterization of auditory synaptic inputs to gerbil perirhinal cortex

    Directory of Open Access Journals (Sweden)

    Vibhakar C Kotak

    2015-08-01

    Full Text Available The representation of acoustic cues involves regions downstream from the auditory cortex (ACx. One such area, the perirhinal cortex (PRh, processes sensory signals containing mnemonic information. Therefore, our goal was to assess whether PRh receives auditory inputs from the auditory thalamus (MG and ACx in an auditory thalamocortical brain slice preparation and characterize these afferent-driven synaptic properties. When the MG or ACx was electrically stimulated, synaptic responses were recorded from the PRh neurons. Blockade of GABA-A receptors dramatically increased the amplitude of evoked excitatory potentials. Stimulation of the MG or ACx also evoked calcium transients in most PRh neurons. Separately, when fluoro ruby was injected in ACx in vivo, anterogradely labeled axons and terminals were observed in the PRh. Collectively, these data show that the PRh integrates auditory information from the MG and ACx and that auditory driven inhibition dominates the postsynaptic responses in a non-sensory cortical region downstream from the auditory cortex.

  11. Auditory excitation patterns : the significance of the pulsation threshold method for the measurement of auditory nonlinearity

    NARCIS (Netherlands)

    H. Verschuure (Hans)

    1978-01-01

    textabstractThe auditory system is the toto[ of organs that translates an acoustical signal into the perception of a sound. An acoustic signal is a vibration. It is decribed by physical parameters. The perception of sound is the awareness of a signal being present and the attribution of certain qual

  12. Pre-LTP requires extracellular signal-regulated kinase in the ACC

    Science.gov (United States)

    Yamanaka, Manabu; Tian, Zhen; Darvish-Ghane, Soroush

    2016-01-01

    The extracellular signal-regulated kinase is an important protein kinase for cortical plasticity. Long-term potentiation in the anterior cingulate cortex is believed to play important roles in chronic pain, fear, and anxiety. Previous studies of extracellular signal-regulated kinase are mainly focused on postsynaptic form of long-term potentiation (post-long-term potentiation). Little is known about the relationship between extracellular signal-regulated kinase and presynaptic long-term potentiation (pre-long-term potentiation) in cortical synapses. In this study, we examined whether pre-long-term potentiation in the anterior cingulate cortex requires the activation of presynaptic extracellular signal-regulated kinase. We found that p42/p44 mitogen-activated protein kinase inhibitors, PD98059 and U0126, suppressed the induction of pre-long-term potentiation. By contrast, these inhibitors did not affect the maintenance of pre-long-term potentiation. Using pharmacological inhibitors, we found that pre-long-term potentiation recorded for 1 h did not require transcriptional or translational processes. Our results strongly indicate that the activation of presynaptic extracellular signal-regulated kinase is required for the induction of pre-long-term potentiation, and this involvement may explain the contribution of extracellular signal-regulated kinase to mood disorders. PMID:27178245

  13. Speech Perception Within an Auditory Cognitive Science Framework

    OpenAIRE

    Holt, Lori L.; Lotto, Andrew J.

    2008-01-01

    The complexities of the acoustic speech signal pose many significant challenges for listeners. Although perceiving speech begins with auditory processing, investigation of speech perception has progressed mostly independently of study of the auditory system. Nevertheless, a growing body of evidence demonstrates that cross-fertilization between the two areas of research can be productive. We briefly describe research bridging the study of general auditory processing and speech perception, show...

  14. Specific regions within the embryonic midbrain and cerebellum require different levels of FGF signaling during development

    Science.gov (United States)

    Basson, M. Albert; Echevarria, Diego; Ahn, Christina Petersen; Sudarov, Anamaria; Joyner, Alexandra L.; Mason, Ivor J.; Martinez, Salvador; Martin, Gail R.

    2008-01-01

    SUMMARY Development of the prospective midbrain and cerebellum are coordinated by FGF ligands produced by the isthmic organizer. Previous studies have suggested that the midbrain and cerebellum require different levels of FGF signaling for their development. However, little is known about the extent to which specific regions within these two parts of the brain differ in their requirement for FGF signaling during embryogenesis. In this study, we have explored the effects of inhibiting FGF signaling within the embryonic midbrain (mesencephalon) and cerebellum (rhombomere 1) by misexpressing Sprouty2 (Spry2) specifically in the mouse mesencephalon and rhombomere 1 from an early stage. We show that such Spry2 misexpression moderately reduces FGF signaling, and that this reduction causes the death of cells in the anterior mesencephalon, the region furthest from the source of FGF ligands. Interestingly, the remaining cells in the posterior mesencephalon develop into anterior midbrain, indicating that a low level of FGF signaling is sufficient to promote only anterior midbrain development. Spry2 misexpression also affects development of the vermis, the medial part of the cerebellum that spans the midline. We found that whereas misexpression of Spry2 alone caused loss of the anterior vermis, reducing FGF signaling further, by decreasing Fgf8 gene dosage, resulted in loss of the entire vermis. We provide evidence that cell death is not responsible for this tissue loss. Instead, our data suggest that the vermis fails to develop because reducing FGF signaling perturbs the balance between vermis and roof plate development in rhombomere 1. We suggest a molecular explanation for this phenomenon by providing evidence that FGF signaling functions to inhibit the BMP signaling that promotes roof plate development. PMID:18216176

  15. Auditory model inversion and its application

    Institute of Scientific and Technical Information of China (English)

    ZHAO Heming; WANG Yongqi; CHEN Xueqin

    2005-01-01

    Auditory model has been applied to several aspects of speech signal processing field, and appears to be effective in performance. This paper presents the inverse transform of each stage of one widely used auditory model. First of all it is necessary to invert correlogram and reconstruct phase information by repetitious iterations in order to get auditory-nerve firing rate. The next step is to obtain the negative parts of the signal via the reverse process of the HWR (Half Wave Rectification). Finally the functions of inner hair cell/synapse model and Gammatone filters have to be inverted. Thus the whole auditory model inversion has been achieved. An application of noisy speech enhancement based on auditory model inversion algorithm is proposed. Many experiments show that this method is effective in reducing noise.Especially when SNR of noisy speech is low it is more effective than other methods. Thus this auditory model inversion method given in this paper is applicable to speech enhancement field.

  16. Auditory-visual spatial interaction and modularity

    Science.gov (United States)

    Radeau, M

    1994-02-01

    The results of dealing with the conditions for pairing visual and auditory data coming from spatially separate locations argue for cognitive impenetrability and computational autonomy, the pairing rules being the Gestalt principles of common fate and proximity. Other data provide evidence for pairing with several properties of modular functioning. Arguments for domain specificity are inferred from comparison with audio-visual speech. Suggestion of innate specification can be found in developmental data indicating that the grouping of visual and auditory signals is supported very early in life by the same principles that operate in adults. Support for a specific neural architecture comes from neurophysiological studies of the bimodal (auditory-visual) neurons of the cat superior colliculus. Auditory-visual pairing thus seems to present the four main properties of the Fodorian module.

  17. Auditory filters at low-frequencies

    DEFF Research Database (Denmark)

    Orellana, Carlos Andrés Jurado; Pedersen, Christian Sejer; Møller, Henrik

    2009-01-01

    Prediction and assessment of low-frequency noise problems requires information about the auditory filter characteristics at low-frequencies. Unfortunately, data at low-frequencies is scarce and practically no results have been published for frequencies below 100 Hz. Extrapolation of ERB results......-ear transfer function), the asymmetry of the auditory filter changed from steeper high-frequency slopes at 1000 Hz to steeper low-frequency slopes below 100 Hz. Increasing steepness at low-frequencies of the middle-ear high-pass filter is thought to cause this effect. The dynamic range of the auditory filter...

  18. Requirement for nuclear calcium signaling in Drosophila long-term memory.

    Science.gov (United States)

    Weislogel, Jan-Marek; Bengtson, C Peter; Müller, Michaela K; Hörtzsch, Jan N; Bujard, Martina; Schuster, Christoph M; Bading, Hilmar

    2013-05-07

    Calcium is used throughout evolution as an intracellular signal transducer. In the mammalian central nervous system, calcium mediates the dialogue between the synapse and the nucleus that is required for transcription-dependent persistent neuronal adaptations. A role for nuclear calcium signaling in similar processes in the invertebrate brain has yet to be investigated. Here, we show by in vivo calcium imaging of adult brain neurons of the fruit fly Drosophila melanogaster, that electrical foot shocks used in olfactory avoidance conditioning evoked transient increases in cytosolic and nuclear calcium concentrations in neurons. These calcium signals were detected in Kenyon cells of the flies' mushroom bodies, which are sites of learning and memory related to smell. Acute blockade of nuclear calcium signaling during conditioning selectively and reversibly abolished the formation of long-term olfactory avoidance memory, whereas short-term, middle-term, or anesthesia-resistant olfactory memory remained unaffected. Thus, nuclear calcium signaling is required in flies for the progression of memories from labile to transcription-dependent long-lasting forms. These results identify nuclear calcium as an evolutionarily conserved signal needed in both invertebrate and vertebrate brains for transcription-dependent memory consolidation.

  19. Calcium signaling and the MAPK cascade are required for sperm activation in Caenorhabditis elegans.

    Science.gov (United States)

    Liu, Zhiyu; Wang, Bin; He, Ruijun; Zhao, Yanmei; Miao, Long

    2014-02-01

    In nematode, sperm activation (or spermiogenesis), a process in which the symmetric and non-motile spermatids transform into polarized and crawling spermatozoa, is critical for sperm cells to acquire fertilizing competence. SPE-8 dependent and SPE-8 independent pathways function redundantly during sperm activation in both males and hermaphrodites of Caenorhabditis elegans. However, the downstream signaling for both pathways remains unclear. Here we show that calcium signaling and the MAPK cascade are required for both SPE-8 dependent and SPE-8 independent sperm activation, implying that both pathways share common downstream signaling components during sperm activation. We demonstrate that activation of the MAPK cascade is sufficient to activate spermatids derived from either wild-type or spe-8 group mutant males and that activation of the MAPK cascade bypasses the requirement of calcium signal to induce sperm activation, indicating that the MAPK cascade functions downstream of or parallel with the calcium signaling during sperm activation. Interestingly, the persistent activation of MAPK in activated spermatozoa inhibits Major Sperm Protein (MSP)-based cytoskeleton dynamics. We demonstrate that MAPK plays dual roles in promoting pseudopod extension during sperm activation but also blocking the MSP-based, amoeboid motility of the spermatozoa. Thus, though nematode sperm are crawling cells, morphologically distinct from flagellated sperm, and the molecular machinery for motility of amoeboid and flagellated sperm is different, both types of sperm might utilize conserved signaling pathways to modulate sperm maturation.

  20. Auditory imagery: empirical findings.

    Science.gov (United States)

    Hubbard, Timothy L

    2010-03-01

    The empirical literature on auditory imagery is reviewed. Data on (a) imagery for auditory features (pitch, timbre, loudness), (b) imagery for complex nonverbal auditory stimuli (musical contour, melody, harmony, tempo, notational audiation, environmental sounds), (c) imagery for verbal stimuli (speech, text, in dreams, interior monologue), (d) auditory imagery's relationship to perception and memory (detection, encoding, recall, mnemonic properties, phonological loop), and (e) individual differences in auditory imagery (in vividness, musical ability and experience, synesthesia, musical hallucinosis, schizophrenia, amusia) are considered. It is concluded that auditory imagery (a) preserves many structural and temporal properties of auditory stimuli, (b) can facilitate auditory discrimination but interfere with auditory detection, (c) involves many of the same brain areas as auditory perception, (d) is often but not necessarily influenced by subvocalization, (e) involves semantically interpreted information and expectancies, (f) involves depictive components and descriptive components, (g) can function as a mnemonic but is distinct from rehearsal, and (h) is related to musical ability and experience (although the mechanisms of that relationship are not clear). PMID:20192565

  1. Controlled levels of canonical Wnt signaling are required for neural crest migration.

    Science.gov (United States)

    Maj, Ewa; Künneke, Lutz; Loresch, Elisabeth; Grund, Anita; Melchert, Juliane; Pieler, Tomas; Aspelmeier, Timo; Borchers, Annette

    2016-09-01

    Canonical Wnt signaling plays a dominant role in the development of the neural crest (NC), a highly migratory cell population that generates a vast array of cell types. Canonical Wnt signaling is required for NC induction as well as differentiation, however its role in NC migration remains largely unknown. Analyzing nuclear localization of β-catenin as readout for canonical Wnt activity, we detect nuclear β-catenin in premigratory but not migratory Xenopus NC cells suggesting that canonical Wnt activity has to decrease to basal levels to enable NC migration. To define a possible function of canonical Wnt signaling in Xenopus NC migration, canonical Wnt signaling was modulated at different time points after NC induction. This was accomplished using either chemical modulators affecting β-catenin stability or inducible glucocorticoid fusion constructs of Lef/Tcf transcription factors. In vivo analysis of NC migration by whole mount in situ hybridization demonstrates that ectopic activation of canonical Wnt signaling inhibits cranial NC migration. Further, NC transplantation experiments confirm that this effect is tissue-autonomous. In addition, live-cell imaging in combination with biophysical data analysis of explanted NC cells confirms the in vivo findings and demonstrates that modulation of canonical Wnt signaling affects the ability of NC cells to perform single cell migration. Thus, our data support the hypothesis that canonical Wnt signaling needs to be tightly controlled to enable migration of NC cells. PMID:27341758

  2. Controlled levels of canonical Wnt signaling are required for neural crest migration.

    Science.gov (United States)

    Maj, Ewa; Künneke, Lutz; Loresch, Elisabeth; Grund, Anita; Melchert, Juliane; Pieler, Tomas; Aspelmeier, Timo; Borchers, Annette

    2016-09-01

    Canonical Wnt signaling plays a dominant role in the development of the neural crest (NC), a highly migratory cell population that generates a vast array of cell types. Canonical Wnt signaling is required for NC induction as well as differentiation, however its role in NC migration remains largely unknown. Analyzing nuclear localization of β-catenin as readout for canonical Wnt activity, we detect nuclear β-catenin in premigratory but not migratory Xenopus NC cells suggesting that canonical Wnt activity has to decrease to basal levels to enable NC migration. To define a possible function of canonical Wnt signaling in Xenopus NC migration, canonical Wnt signaling was modulated at different time points after NC induction. This was accomplished using either chemical modulators affecting β-catenin stability or inducible glucocorticoid fusion constructs of Lef/Tcf transcription factors. In vivo analysis of NC migration by whole mount in situ hybridization demonstrates that ectopic activation of canonical Wnt signaling inhibits cranial NC migration. Further, NC transplantation experiments confirm that this effect is tissue-autonomous. In addition, live-cell imaging in combination with biophysical data analysis of explanted NC cells confirms the in vivo findings and demonstrates that modulation of canonical Wnt signaling affects the ability of NC cells to perform single cell migration. Thus, our data support the hypothesis that canonical Wnt signaling needs to be tightly controlled to enable migration of NC cells.

  3. Requirements for Signaling of Pre-Congestion Information in a Diffserv Domain

    NARCIS (Netherlands)

    Karagiannis, G.; Taylor, T.; Chan, K.; Menth, M.; Eardley, P.

    2012-01-01

    Pre-Congestion Notification (PCN) is a means for protecting quality of service for inelastic traffic admitted to a Diffserv domain. The overall PCN architecture is described in RFC 5559. This memo describes the requirements for the signaling applied within the PCN- domain: (1) PCN-feedback-informati

  4. Sprinter: a novel transmembrane protein required for Wg secretion and signaling.

    Science.gov (United States)

    Goodman, Robyn M; Thombre, Shreya; Firtina, Zeynep; Gray, Dione; Betts, Daniella; Roebuck, Jamie; Spana, Eric P; Selva, Erica M

    2006-12-01

    Wingless (Wg) is a secreted ligand that differentially activates gene expression in target tissues. It belongs to the Wnt family of secreted signaling molecules that regulate cell-to-cell interactions during development. Activation of Wg targets is dependent on the ligand concentration in the extracellular milieu; cellular mechanisms that govern the synthesis, delivery and receipt of Wg are elaborate and complex. We have identified sprinter (srt), which encodes a novel, evolutionarily conserved transmembrane protein required for the transmission of the Wg signal. Mutations in srt cause the accumulation of Wg in cells that express it, and retention of the ligand prevents activation of its target genes in signal-receiving cells. In the absence of Srt activity, levels of Wg targets (including Engrailed in embryos lacking maternal and zygotic srt, and Senseless and Achaete in wing discs) are reduced. Activation of Wg targets in the receiving cells does not require srt. Hence, the function of Srt is restricted to events occurring within the Wg-producing cells. We show that srt is not required for any aspect of Hedgehog (Hh) signal transduction, suggesting specificity of srt for the Wg pathway. We propose that srt encodes a protein required for Wg secretion that regulates maturation, membrane targeting or delivery of Wg. Loss of srt function in turn diminishes Wg-pathway activation in receiving cells.

  5. Notch-signalling is required for head regeneration and tentacle patterning in Hydra.

    Science.gov (United States)

    Münder, Sandra; Tischer, Susanne; Grundhuber, Maresa; Büchels, Nathalie; Bruckmeier, Nadine; Eckert, Stefanie; Seefeldt, Carolin A; Prexl, Andrea; Käsbauer, Tina; Böttger, Angelika

    2013-11-01

    Local self-activation and long ranging inhibition provide a mechanism for setting up organising regions as signalling centres for the development of structures in the surrounding tissue. The adult hydra hypostome functions as head organiser. After hydra head removal it is newly formed and complete heads can be regenerated. The molecular components of this organising region involve Wnt-signalling and β-catenin. However, it is not known how correct patterning of hypostome and tentacles are achieved in the hydra head and whether other signals in addition to HyWnt3 are needed for re-establishing the new organiser after head removal. Here we show that Notch-signalling is required for re-establishing the organiser during regeneration and that this is due to its role in restricting tentacle activation. Blocking Notch-signalling leads to the formation of irregular head structures characterised by excess tentacle tissue and aberrant expression of genes that mark the tentacle boundaries. This indicates a role for Notch-signalling in defining the tentacle pattern in the hydra head. Moreover, lateral inhibition by HvNotch and its target HyHes are required for head regeneration and without this the formation of the β-catenin/Wnt dependent head organiser is impaired. Work on prebilaterian model organisms has shown that the Wnt-pathway is important for setting up signalling centres for axial patterning in early multicellular animals. Our data suggest that the integration of Wnt-signalling with Notch-Delta activity was also involved in the evolution of defined body plans in animals.

  6. Deactivation of the Parahippocampal Gyrus Preceding Auditory Hallucinations in Schizophrenia

    NARCIS (Netherlands)

    Diederen, Kelly M. J.; Neggers, Sebastiaan F. W.; Daalman, Kirstin; Blom, Jan Dirk; Goekoop, Rutger; Kahn, Rene S.; Sommer, Iris E. C.

    2010-01-01

    Objective: Activation in a network of language-related regions has been reported during auditory verbal hallucinations. It remains unclear, however, how this activation is triggered. Identifying brain regions that show significant signal changes preceding auditory hallucinations might reveal the ori

  7. Auditory Dysfunction and Its Communicative Impact in the Classroom.

    Science.gov (United States)

    Friedrich, Brad W.

    1982-01-01

    The origins and nature of auditory dysfunction in school age children and the role of the audiologist in the evaluation of the learning disabled child are reviewed. Specific structures and mechanisms responsible for the reception and perception of auditory signals are specified. (Author/SEW)

  8. Effects of an Auditory Lateralization Training in Children Suspected to Central Auditory Processing Disorder

    Science.gov (United States)

    Lotfi, Yones; Moosavi, Abdollah; Bakhshi, Enayatollah; Sadjedi, Hamed

    2016-01-01

    Background and Objectives Central auditory processing disorder [(C)APD] refers to a deficit in auditory stimuli processing in nervous system that is not due to higher-order language or cognitive factors. One of the problems in children with (C)APD is spatial difficulties which have been overlooked despite their significance. Localization is an auditory ability to detect sound sources in space and can help to differentiate between the desired speech from other simultaneous sound sources. Aim of this research was investigating effects of an auditory lateralization training on speech perception in presence of noise/competing signals in children suspected to (C)APD. Subjects and Methods In this analytical interventional study, 60 children suspected to (C)APD were selected based on multiple auditory processing assessment subtests. They were randomly divided into two groups: control (mean age 9.07) and training groups (mean age 9.00). Training program consisted of detection and pointing to sound sources delivered with interaural time differences under headphones for 12 formal sessions (6 weeks). Spatial word recognition score (WRS) and monaural selective auditory attention test (mSAAT) were used to follow the auditory lateralization training effects. Results This study showed that in the training group, mSAAT score and spatial WRS in noise (p value≤0.001) improved significantly after the auditory lateralization training. Conclusions We used auditory lateralization training for 6 weeks and showed that auditory lateralization can improve speech understanding in noise significantly. The generalization of this results needs further researches.

  9. Genetic requirements for signaling from an autoactive plant NB-LRR intracellular innate immune receptor.

    Science.gov (United States)

    Roberts, Melinda; Tang, Saijun; Stallmann, Anna; Dangl, Jeffery L; Bonardi, Vera

    2013-01-01

    Plants react to pathogen attack via recognition of, and response to, pathogen-specific molecules at the cell surface and inside the cell. Pathogen effectors (virulence factors) are monitored by intracellular nucleotide-binding leucine-rich repeat (NB-LRR) sensor proteins in plants and mammals. Here, we study the genetic requirements for defense responses of an autoactive mutant of ADR1-L2, an Arabidopsis coiled-coil (CC)-NB-LRR protein. ADR1-L2 functions upstream of salicylic acid (SA) accumulation in several defense contexts, and it can act in this context as a "helper" to transduce specific microbial activation signals from "sensor" NB-LRRs. This helper activity does not require an intact P-loop. ADR1-L2 and another of two closely related members of this small NB-LRR family are also required for propagation of unregulated runaway cell death (rcd) in an lsd1 mutant. We demonstrate here that, in this particular context, ADR1-L2 function is P-loop dependent. We generated an autoactive missense mutation, ADR1-L2D484V, in a small homology motif termed MHD. Expression of ADR1-L2D848V leads to dwarfed plants that exhibit increased disease resistance and constitutively high SA levels. The morphological phenotype also requires an intact P-loop, suggesting that these ADR1-L2D484V phenotypes reflect canonical activation of this NB-LRR protein. We used ADR1-L2D484V to define genetic requirements for signaling. Signaling from ADR1-L2D484V does not require NADPH oxidase and is negatively regulated by EDS1 and AtMC1. Transcriptional regulation of ADR1-L2D484V is correlated with its phenotypic outputs; these outputs are both SA-dependent and -independent. The genetic requirements for ADR1-L2D484V activity resemble those that regulate an SA-gradient-dependent signal amplification of defense and cell death signaling initially observed in the absence of LSD1. Importantly, ADR1-L2D484V autoactivation signaling is controlled by both EDS1 and SA in separable, but linked pathways

  10. Genetic requirements for signaling from an autoactive plant NB-LRR intracellular innate immune receptor.

    Directory of Open Access Journals (Sweden)

    Melinda Roberts

    Full Text Available Plants react to pathogen attack via recognition of, and response to, pathogen-specific molecules at the cell surface and inside the cell. Pathogen effectors (virulence factors are monitored by intracellular nucleotide-binding leucine-rich repeat (NB-LRR sensor proteins in plants and mammals. Here, we study the genetic requirements for defense responses of an autoactive mutant of ADR1-L2, an Arabidopsis coiled-coil (CC-NB-LRR protein. ADR1-L2 functions upstream of salicylic acid (SA accumulation in several defense contexts, and it can act in this context as a "helper" to transduce specific microbial activation signals from "sensor" NB-LRRs. This helper activity does not require an intact P-loop. ADR1-L2 and another of two closely related members of this small NB-LRR family are also required for propagation of unregulated runaway cell death (rcd in an lsd1 mutant. We demonstrate here that, in this particular context, ADR1-L2 function is P-loop dependent. We generated an autoactive missense mutation, ADR1-L2D484V, in a small homology motif termed MHD. Expression of ADR1-L2D848V leads to dwarfed plants that exhibit increased disease resistance and constitutively high SA levels. The morphological phenotype also requires an intact P-loop, suggesting that these ADR1-L2D484V phenotypes reflect canonical activation of this NB-LRR protein. We used ADR1-L2D484V to define genetic requirements for signaling. Signaling from ADR1-L2D484V does not require NADPH oxidase and is negatively regulated by EDS1 and AtMC1. Transcriptional regulation of ADR1-L2D484V is correlated with its phenotypic outputs; these outputs are both SA-dependent and -independent. The genetic requirements for ADR1-L2D484V activity resemble those that regulate an SA-gradient-dependent signal amplification of defense and cell death signaling initially observed in the absence of LSD1. Importantly, ADR1-L2D484V autoactivation signaling is controlled by both EDS1 and SA in separable, but linked

  11. Zebrafish con/disp1 reveals multiple spatiotemporal requirements for Hedgehog-signaling in craniofacial development

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    Schwend Tyler

    2009-11-01

    Full Text Available Abstract Background The vertebrate head skeleton is derived largely from cranial neural crest cells (CNCC. Genetic studies in zebrafish and mice have established that the Hedgehog (Hh-signaling pathway plays a critical role in craniofacial development, partly due to the pathway's role in CNCC development. Disruption of the Hh-signaling pathway in humans can lead to the spectral disorder of Holoprosencephaly (HPE, which is often characterized by a variety of craniofacial defects including midline facial clefting and cyclopia 12. Previous work has uncovered a role for Hh-signaling in zebrafish dorsal neurocranium patterning and chondrogenesis, however Hh-signaling mutants have not been described with respect to the ventral pharyngeal arch (PA skeleton. Lipid-modified Hh-ligands require the transmembrane-spanning receptor Dispatched 1 (Disp1 for proper secretion from Hh-synthesizing cells to the extracellular field where they act on target cells. Here we study chameleon mutants, lacking a functional disp1(con/disp1. Results con/disp1 mutants display reduced and dysmorphic mandibular and hyoid arch cartilages and lack all ceratobranchial cartilage elements. CNCC specification and migration into the PA primorida occurs normally in con/disp1 mutants, however disp1 is necessary for post-migratory CNCC patterning and differentiation. We show that disp1 is required for post-migratory CNCC to become properly patterned within the first arch, while the gene is dispensable for CNCC condensation and patterning in more posterior arches. Upon residing in well-formed pharyngeal epithelium, neural crest condensations in the posterior PA fail to maintain expression of two transcription factors essential for chondrogenesis, sox9a and dlx2a, yet continue to robustly express other neural crest markers. Histology reveals that posterior arch residing-CNCC differentiate into fibrous-connective tissue, rather than becoming chondrocytes. Treatments with Cyclopamine, to

  12. Across frequency processes involved in auditory detection of coloration

    DEFF Research Database (Denmark)

    Buchholz, Jörg; Kerketsos, P

    2008-01-01

    When an early wall reflection is added to a direct sound, a spectral modulation is introduced to the signal's power spectrum. This spectral modulation typically produces an auditory sensation of coloration or pitch. Throughout this study, auditory spectral-integration effects involved in coloration...... detection are investigated. Coloration detection thresholds were therefore measured as a function of reflection delay and stimulus bandwidth. In order to investigate the involved auditory mechanisms, an auditory model was employed that was conceptually similar to the peripheral weighting model [Yost, JASA...... filterbank was designed to approximate auditory filter-shapes measured by Oxenham and Shera [JARO, 2003, 541-554], derived from forward masking data. The results of the present study demonstrate that a “purely” spectrum-based model approach can successfully describe auditory coloration detection even at high...

  13. Nodal signaling is required for closure of the anterior neural tube in zebrafish

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    Liu Qin

    2007-11-01

    Full Text Available Abstract Background Nodals are secreted signaling proteins with many roles in vertebrate development. Here, we identify a new role for Nodal signaling in regulating closure of the rostral neural tube of zebrafish. Results We find that the neural tube in the presumptive forebrain fails to close in zebrafish Nodal signaling mutants. For instance, the cells that will give rise to the pineal organ fail to move from the lateral edges of the neural plate to the midline of the diencephalon. The open neural tube in Nodal signaling mutants may be due in part to reduced function of N-cadherin, a cell adhesion molecule expressed in the neural tube and required for neural tube closure. N-cadherin expression and localization to the membrane are reduced in fish that lack Nodal signaling. Further, N-cadherin mutants and morphants have a pineal phenotype similar to that of mutants with deficiencies in the Nodal pathway. Overexpression of an activated form of the TGFβ Type I receptor Taram-A (Taram-A* cell autonomously rescues mesendoderm formation in fish with a severe decrease in Nodal signaling. We find that overexpression of Taram-A* also corrects their open neural tube defect. This suggests that, as in mammals, the mesoderm and endoderm have an important role in regulating closure of the anterior neural tube of zebrafish. Conclusion This work helps establish a role for Nodal signals in neurulation, and suggests that defects in Nodal signaling could underlie human neural tube defects such as exencephaly, a fatal condition characterized by an open neural tube in the anterior brain.

  14. Vitamin D Signaling in the Bovine Immune System: A Model for Understanding Human Vitamin D Requirements

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    Corwin D. Nelson

    2012-03-01

    Full Text Available The endocrine physiology of vitamin D in cattle has been rigorously investigated and has yielded information on vitamin D requirements, endocrine function in health and disease, general metabolism, and maintenance of calcium homeostasis in cattle. These results are relevant to human vitamin D endocrinology. The current debate regarding vitamin D requirements is centered on the requirements for proper intracrine and paracrine vitamin D signaling. Studies in adult and young cattle can provide valuable insight for understanding vitamin D requirements as they relate to innate and adaptive immune responses during infectious disease. In cattle, toll-like receptor recognition activates intracrine and paracrine vitamin D signaling mechanism in the immune system that regulates innate and adaptive immune responses in the presence of adequate 25-hydroxyvitamin D. Furthermore, experiments with mastitis in dairy cattle have provided in vivo evidence for the intracrine vitamin D signaling mechanism in macrophages as well as vitamin D mediated suppression of infection. Epidemiological evidence indicates that circulating concentrations above 32 ng/mL of 25-hydroxyvitamin D are necessary for optimal vitamin D signaling in the immune system, but experimental evidence is lacking for that value. Experiments in cattle can provide that evidence as circulating 25-hydroxyvitamin D concentrations can be experimentally manipulated within ranges that are normal for humans and cattle. Additionally, young and adult cattle can be experimentally infected with bacteria and viruses associated with significant diseases in both cattle and humans. Utilizing the bovine model to further delineate the immunomodulatory role of vitamin D will provide potentially valuable insights into the vitamin D requirements of both humans and cattle, especially as they relate to immune response capacity and infectious disease resistance.

  15. Cue-elicited reward-seeking requires extracellular signal-regulated kinase activation in the nucleus accumbens.

    Science.gov (United States)

    Shiflett, Michael W; Martini, Ross P; Mauna, Jocelyn C; Foster, Rebecca L; Peet, Eloise; Thiels, Edda

    2008-02-01

    The motivation to seek out rewards can come under the control of stimuli associated with reward delivery. The ability of cues to motivate reward-seeking behavior depends on the nucleus accumbens (NAcc). The molecular mechanisms in the NAcc that underlie the ability of a cue to motivate reward-seeking are not well understood. We examined whether extracellular signal-regulated kinase (ERK), an important intracellular signaling pathway in learning and memory, has a role in these motivational processes. We first examined p42 ERK (ERK2) activation in the NAcc after rats were trained to associate an auditory stimulus with food delivery and found that, as a consequence of training, presentation of the auditory cue itself was sufficient to increase ERK2 activation in the NAcc. To examine whether inhibition of ERK in the NAcc prevents cue-induced reward-seeking, we infused an inhibitor of ERK, U0126, into the NAcc before assessing rats' instrumental responding in the presence versus absence of the conditioned cue. We found that, whereas vehicle-infused rats showed increased instrumental responding during cue presentation, rats infused with U0126 showed a profound impairment in cue-induced instrumental responding. In contrast, intra-NAcc U0126 infusion had no effect on rats' food-reinforced instrumental responding or their ability to execute conditioned approach behavior. Our results demonstrate learning-related changes in ERK signaling in the NAcc, and that disruption of ERK activation in this structure interferes with the incentive-motivational effects of conditioned stimuli. The molecular mechanisms described here may have implications for cue-elicited drug craving after repeated exposure to drugs of abuse.

  16. In search of an auditory engram

    Science.gov (United States)

    Fritz, Jonathan; Mishkin, Mortimer; Saunders, Richard C.

    2005-01-01

    Monkeys trained preoperatively on a task designed to assess auditory recognition memory were impaired after removal of either the rostral superior temporal gyrus or the medial temporal lobe but were unaffected by lesions of the rhinal cortex. Behavioral analysis indicated that this result occurred because the monkeys did not or could not use long-term auditory recognition, and so depended instead on short-term working memory, which is unaffected by rhinal lesions. The findings suggest that monkeys may be unable to place representations of auditory stimuli into a long-term store and thus question whether the monkey's cerebral memory mechanisms in audition are intrinsically different from those in other sensory modalities. Furthermore, it raises the possibility that language is unique to humans not only because it depends on speech but also because it requires long-term auditory memory. PMID:15967995

  17. Pheromone-induced signal transduction in Saccharomyces cerevisiae requires the sequential function of three protein kinases.

    OpenAIRE

    Z.Zhou; Gartner, A...; Cade, R.; Ammerer, G; Errede, B

    1993-01-01

    Protein phosphorylation plays an important role in pheromone-induced differentiation processes of haploid yeast cells. Among the components necessary for signal transduction are the STE7 and STE11 kinases and either one of the redundant FUS3 and KSS1 kinases. FUS3 and presumably KSS1 are phosphorylated and activated during pheromone induction by a STE7-dependent mechanism. Pheromone also induces the accumulation of STE7 in a hyperphosphorylated form. This modification of STE7 requires the STE...

  18. Neural correlates of auditory temporal predictions during sensorimotor synchronization

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    Nadine ePecenka

    2013-08-01

    Full Text Available Musical ensemble performance requires temporally precise interpersonal action coordination. To play in synchrony, ensemble musicians presumably rely on anticipatory mechanisms that enable them to predict the timing of sounds produced by co-performers. Previous studies have shown that individuals differ in their ability to predict upcoming tempo changes in paced finger-tapping tasks (indexed by cross-correlations between tap timing and pacing events and that the degree of such prediction influences the accuracy of sensorimotor synchronization (SMS and interpersonal coordination in dyadic tapping tasks. The current functional magnetic resonance imaging study investigated the neural correlates of auditory temporal predictions during SMS in a within-subject design. Hemodynamic responses were recorded from 18 musicians while they tapped in synchrony with auditory sequences containing gradual tempo changes under conditions of varying cognitive load (achieved by a simultaneous visual n-back working-memory task comprising three levels of difficulty: observation only, 1-back, and 2-back object comparisons. Prediction ability during SMS decreased with increasing cognitive load. Results of a parametric analysis revealed that the generation of auditory temporal predictions during SMS recruits (1 a distributed network in cortico-cerebellar motor-related brain areas (left dorsal premotor and motor cortex, right lateral cerebellum, SMA proper and bilateral inferior parietal cortex and (2 medial cortical areas (medial prefrontal cortex, posterior cingulate cortex. While the first network is presumably involved in basic sensory prediction, sensorimotor integration, motor timing, and temporal adaptation, activation in the second set of areas may be related to higher-level social-cognitive processes elicited during action coordination with auditory signals that resemble music performed by human agents.

  19. Auditory-motor learning influences auditory memory for music.

    Science.gov (United States)

    Brown, Rachel M; Palmer, Caroline

    2012-05-01

    In two experiments, we investigated how auditory-motor learning influences performers' memory for music. Skilled pianists learned novel melodies in four conditions: auditory only (listening), motor only (performing without sound), strongly coupled auditory-motor (normal performance), and weakly coupled auditory-motor (performing along with auditory recordings). Pianists' recognition of the learned melodies was better following auditory-only or auditory-motor (weakly coupled and strongly coupled) learning than following motor-only learning, and better following strongly coupled auditory-motor learning than following auditory-only learning. Auditory and motor imagery abilities modulated the learning effects: Pianists with high auditory imagery scores had better recognition following motor-only learning, suggesting that auditory imagery compensated for missing auditory feedback at the learning stage. Experiment 2 replicated the findings of Experiment 1 with melodies that contained greater variation in acoustic features. Melodies that were slower and less variable in tempo and intensity were remembered better following weakly coupled auditory-motor learning. These findings suggest that motor learning can aid performers' auditory recognition of music beyond auditory learning alone, and that motor learning is influenced by individual abilities in mental imagery and by variation in acoustic features. PMID:22271265

  20. Amygdala upregulation of NCAM polysialylation induced by auditory fear conditioning is not required for memory formation, but plays a role in fear extinction.

    Science.gov (United States)

    Markram, Kamila; Lopez Fernandez, Miguel Angel; Abrous, Djoher Nora; Sandi, Carmen

    2007-05-01

    There is much interest to understand the mechanisms leading to the establishment, maintenance, and extinction of fear memories. The amygdala has been critically involved in the processing of fear memories and a number of molecular changes have been implicated in this brain region in relation to fear learning. Although neural cell adhesion molecules (NCAMs) have been hypothesized to play a role, information available about their contribution to fear memories is scarce. We investigate here whether polysialylated NCAM (PSA-NCAM) contributes to auditory fear conditioning in the amygdala. First, PSA-NCAM expression was evaluated in different amygdala nuclei after auditory fear conditioning at two different shock intensities. Results showed that PSA-NCAM expression was increased 24 h post-training only in animals subjected to the highest shock intensity (1mA). Second, PSA-NCAM was cleaved in the basolateral amygdaloid complex through micro-infusions of the enzyme endoneuraminidase N, and the consequences of such treatment were investigated on the acquisition, consolidation, remote memory expression, and extinction of conditioned fear memories. Intra-amygdaloid cleavage of PSA-NCAM did not affect acquisition, consolidation or expression of remote fear memories. However, intra-amygdaloid PSA-NCAM cleavage enhanced fear extinction processes. These results suggest that upregulation of PSA-NCAM is a correlate of fear conditioning that is not necessary for the establishment of fear memory in the amygdala, but participates in mechanisms precluding fear extinction. These findings point out PSA-NCAM as a potential target for the treatment of psychopathologies that involve impairment in fear extinction.

  1. Acquisition of heroin conditioned immunosuppression requires IL-1 signaling in the dorsal hippocampus.

    Science.gov (United States)

    Lebonville, Christina L; Jones, Meghan E; Hutson, Lee W; Cooper, Letty B; Fuchs, Rita A; Lysle, Donald T

    2016-08-01

    Opioid users experience increased incidence of infection, which may be partially attributable to both direct opiate-immune interactions and conditioned immune responses. Previous studies have investigated the neural circuitry governing opioid conditioned immune responses, but work remains to elucidate the mechanisms mediating this effect. Our laboratory has previously shown that hippocampal IL-1 signaling, specifically, is required for the expression of heroin conditioned immunosuppression following learning. The current studies were designed to further characterize the role of hippocampal IL-1 in this phenomenon by manipulating IL-1 during learning. Experiment 1 tested whether hippocampal IL-1 is also required for the acquisition of heroin conditioned immunosuppression, while Experiment 2 tested whether hippocampal IL-1 is required for the expression of unconditioned heroin immunosuppression. We found that blocking IL-1 signaling in the dorsal hippocampus with IL-1RA during each conditioning session, but not on interspersed non-conditioning days, significantly attenuated the acquisition of heroin conditioned immunosuppression. Strikingly, we found that the same IL-1RA treatment did not alter unconditioned immunosuppression to a single dose of heroin. Thus, IL-1 signaling is not a critical component of the response to heroin but rather may play a role in the formation of the association between heroin and the context. Collectively, these studies suggest that IL-1 signaling, in addition to being involved in the expression of a heroin conditioned immune response, is also involved in the acquisition of this effect. Importantly, this effect is likely not due to blocking the response to the unconditioned stimulus since IL-1RA did not affect heroin's immunosuppressive effects. PMID:27072068

  2. Elevated CO2-Induced Responses in Stomata Require ABA and ABA Signaling.

    Science.gov (United States)

    Chater, Caspar; Peng, Kai; Movahedi, Mahsa; Dunn, Jessica A; Walker, Heather J; Liang, Yun-Kuan; McLachlan, Deirdre H; Casson, Stuart; Isner, Jean Charles; Wilson, Ian; Neill, Steven J; Hedrich, Rainer; Gray, Julie E; Hetherington, Alistair M

    2015-10-19

    An integral part of global environment change is an increase in the atmospheric concentration of CO2 ([CO2]) [1]. Increased [CO2] reduces leaf stomatal apertures and density of stomata that plays out as reductions in evapotranspiration [2-4]. Surprisingly, given the importance of transpiration to the control of terrestrial water fluxes [5] and plant nutrient acquisition [6], we know comparatively little about the molecular components involved in the intracellular signaling pathways by which [CO2] controls stomatal development and function [7]. Here, we report that elevated [CO2]-induced closure and reductions in stomatal density require the generation of reactive oxygen species (ROS), thereby adding a new common element to these signaling pathways. We also show that the PYR/RCAR family of ABA receptors [8, 9] and ABA itself are required in both responses. Using genetic approaches, we show that ABA in guard cells or their precursors is sufficient to mediate the [CO2]-induced stomatal density response. Taken together, our results suggest that stomatal responses to increased [CO2] operate through the intermediacy of ABA. In the case of [CO2]-induced reductions in stomatal aperture, this occurs by accessing the guard cell ABA signaling pathway. In both [CO2]-mediated responses, our data are consistent with a mechanism in which ABA increases the sensitivity of the system to [CO2] but could also be explained by requirement for a CO2-induced increase in ABA biosynthesis specifically in the guard cell lineage. Furthermore, the dependency of stomatal [CO2] signaling on ABA suggests that the ABA pathway is, in evolutionary terms, likely to be ancestral. PMID:26455301

  3. Psychology of auditory perception.

    Science.gov (United States)

    Lotto, Andrew; Holt, Lori

    2011-09-01

    Audition is often treated as a 'secondary' sensory system behind vision in the study of cognitive science. In this review, we focus on three seemingly simple perceptual tasks to demonstrate the complexity of perceptual-cognitive processing involved in everyday audition. After providing a short overview of the characteristics of sound and their neural encoding, we present a description of the perceptual task of segregating multiple sound events that are mixed together in the signal reaching the ears. Then, we discuss the ability to localize the sound source in the environment. Finally, we provide some data and theory on how listeners categorize complex sounds, such as speech. In particular, we present research on how listeners weigh multiple acoustic cues in making a categorization decision. One conclusion of this review is that it is time for auditory cognitive science to be developed to match what has been done in vision in order for us to better understand how humans communicate with speech and music. WIREs Cogni Sci 2011 2 479-489 DOI: 10.1002/wcs.123 For further resources related to this article, please visit the WIREs website. PMID:26302301

  4. Efficient retina formation requires suppression of both Activin and BMP signaling pathways in pluripotent cells

    Directory of Open Access Journals (Sweden)

    Kimberly A. Wong

    2015-03-01

    Full Text Available Retina formation requires the correct spatiotemporal patterning of key regulatory factors. While it is known that repression of several signaling pathways lead to specification of retinal fates, addition of only Noggin, a known BMP antagonist, can convert pluripotent Xenopus laevis animal cap cells to functional retinal cells. The aim of this study is to determine the intracellular molecular events that occur during this conversion. Surprisingly, blocking BMP signaling alone failed to mimic Noggin treatment. Overexpressing Noggin in pluripotent cells resulted in a concentration-dependent suppression of both Smad1 and Smad2 phosphorylation, which act downstream of BMP and Activin signaling, respectively. This caused a decrease in downstream targets: endothelial marker, xk81, and mesodermal marker, xbra. We treated pluripotent cells with dominant-negative receptors or the chemical inhibitors, dorsomorphin and SB431542, which each target either the BMP or Activin signaling pathway. We determined the effect of these treatments on retina formation using the Animal Cap Transplant (ACT assay; in which treated pluripotent cells were transplanted into the eye field of host embryos. We found that inhibition of Activin signaling, in the presence of BMP signaling inhibition, promotes efficient retinal specification in Xenopus tissue, mimicking the affect of adding Noggin alone. In whole embryos, we found that the eye field marker, rax, expanded when adding both dominant-negative Smad1 and Smad2, as did treating the cells with both dorsomorphin and SB431542. Future studies could translate these findings to a mammalian culture assay, in order to more efficiently produce retinal cells in culture.

  5. Notch signal reception is required in vascular smooth muscle cells for ductus arteriosus closure.

    Science.gov (United States)

    Krebs, Luke T; Norton, Christine R; Gridley, Thomas

    2016-02-01

    The ductus arteriosus is an arterial vessel that shunts blood flow away from the lungs during fetal life, but normally occludes after birth to establish the adult circulation pattern. Failure of the ductus arteriosus to close after birth is termed patent ductus arteriosus, and is one of the most common congenital heart defects. Our previous work demonstrated that vascular smooth muscle cell expression of the Jag1 gene, which encodes a ligand for Notch family receptors, is essential for postnatal closure of the ductus arteriosus in mice. However, it was not known what cell population was responsible for receiving the Jag1-mediated signal. Here we show, using smooth muscle cell-specific deletion of the Rbpj gene, which encodes a transcription factor that mediates all canonical Notch signaling, that Notch signal reception in the vascular smooth muscle cell compartment is required for ductus arteriosus closure. These data indicate that homotypic vascular smooth muscle cell interactions are required for proper contractile smooth muscle cell differentiation and postnatal closure of the ductus arteriosus in mice.

  6. GLABROUS INFLORESCENCE STEMS (GIS) is required for trichome branching through gibberellic acid signaling in Arabidopsis.

    Science.gov (United States)

    An, Lijun; Zhou, Zhongjing; Su, Sha; Yan, An; Gan, Yinbo

    2012-02-01

    Cell differentiation generally corresponds to the cell cycle, typically forming a non-dividing cell with a unique differentiated morphology, and Arabidopsis trichome is an excellent model system to study all aspects of cell differentiation. Although gibberellic acid is reported to be involved in trichome branching in Arabidopsis, the mechanism for such signaling is unclear. Here, we demonstrated that GLABROUS INFLORESCENCE STEMS (GIS) is required for the control of trichome branching through gibberellic acid signaling. The phenotypes of a loss-of-function gis mutant and an overexpressor showed that GIS acted as a repressor to control trichome branching. Our results also show that GIS is not required for cell endoreduplication, and our molecular and genetic study results have shown that GIS functions downstream of the key regulator of trichome branching, STICHEL (STI), to control trichome branching through the endoreduplication-independent pathway. Furthermore, our results also suggest that GIS controls trichome branching in Arabidopsis through two different pathways and acts either upstream or downstream of the negative regulator of gibbellic acid signaling SPINDLY (SPY).

  7. Filamin and phospholipase C-ε are required for calcium signaling in the Caenorhabditis elegans spermatheca.

    Directory of Open Access Journals (Sweden)

    Ismar Kovacevic

    2013-05-01

    Full Text Available The Caenorhabditis elegans spermatheca is a myoepithelial tube that stores sperm and undergoes cycles of stretching and constriction as oocytes enter, are fertilized, and exit into the uterus. FLN-1/filamin, a stretch-sensitive structural and signaling scaffold, and PLC-1/phospholipase C-ε, an enzyme that generates the second messenger IP3, are required for embryos to exit normally after fertilization. Using GCaMP, a genetically encoded calcium indicator, we show that entry of an oocyte into the spermatheca initiates a distinctive series of IP3-dependent calcium oscillations that propagate across the tissue via gap junctions and lead to constriction of the spermatheca. PLC-1 is required for the calcium release mechanism triggered by oocyte entry, and FLN-1 is required for timely initiation of the calcium oscillations. INX-12, a gap junction subunit, coordinates propagation of the calcium transients across the spermatheca. Gain-of-function mutations in ITR-1/IP3R, an IP3-dependent calcium channel, and loss-of-function mutations in LFE-2, a negative regulator of IP3 signaling, increase calcium release and suppress the exit defect in filamin-deficient animals. We further demonstrate that a regulatory cassette consisting of MEL-11/myosin phosphatase and NMY-1/non-muscle myosin is required for coordinated contraction of the spermatheca. In summary, this study answers long-standing questions concerning calcium signaling dynamics in the C. elegans spermatheca and suggests FLN-1 is needed in response to oocyte entry to trigger calcium release and coordinated contraction of the spermathecal tissue.

  8. Hedgehog signaling is required at multiple stages of zebrafish tooth development

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    Stock David W

    2010-11-01

    Full Text Available Abstract Background The accessibility of the developing zebrafish pharyngeal dentition makes it an advantageous system in which to study many aspects of tooth development from early initiation to late morphogenesis. In mammals, hedgehog signaling is known to be essential for multiple stages of odontogenesis; however, potential roles for the pathway during initiation of tooth development or in later morphogenesis are incompletely understood. Results We have identified mRNA expression of the hedgehog ligands shha and the receptors ptc1 and ptc2 during zebrafish pharyngeal tooth development. We looked for, but did not detect, tooth germ expression of the other known zebrafish hedgehog ligands shhb, dhh, ihha, or ihhb, suggesting that as in mammals, only Shh participates in zebrafish tooth development. Supporting this idea, we found that morphological and gene expression evidence of tooth initiation is eliminated in shha mutant embryos, and that morpholino antisense oligonucleotide knockdown of shha, but not shhb, function prevents mature tooth formation. Hedgehog pathway inhibition with the antagonist compound cyclopamine affected tooth formation at each stage in which we applied it: arresting development at early stages and disrupting mature tooth morphology when applied later. These results suggest that hedgehog signaling is required continuously during odontogenesis. In contrast, over-expression of shha had no effect on the developing dentition, possibly because shha is normally extensively expressed in the zebrafish pharyngeal region. Conclusion We have identified previously unknown requirements for hedgehog signaling for early tooth initiation and later morphogenesis. The similarity of our results with data from mouse and other vertebrates suggests that despite gene duplication and changes in the location of where teeth form, the roles of hedgehog signaling in tooth development have been largely conserved during evolution.

  9. Sbds is required for Rac2-mediated monocyte migration and signaling downstream of RANK during osteoclastogenesis.

    Science.gov (United States)

    Leung, Roland; Cuddy, Karl; Wang, Yongqiang; Rommens, Johanna; Glogauer, Michael

    2011-02-10

    Shwachman-Diamond syndrome (SDS) results from mutations in the SBDS gene, characterized by exocrine pancreatic insufficiency and hematologic and skeletal abnormalities. Neutropenia and neutrophil dysfunction are hallmark features of SDS; however, causes for the bone defects are unknown. Dysfunction of bone-resorbing osteoclasts, formed by the fusion of monocytic progenitors derived from the same granulocytic precursors as neutrophils, could be responsible. We report that Sbds is required for in vitro and in vivo osteoclastogenesis (OCG). Sbds-null murine monocytes formed osteoclasts of reduced number and size because of impaired migration and fusion required for OCG. Phenotypically, Sbds-null mice exhibited low-turnover osteoporosis consistent with findings in SDS patients. Western blotting of Rho GTPases that control actin dynamics and migration showed a 5-fold decrease in Rac2, whereas Rac1, Cdc42, and RhoA were unchanged or only mildly reduced. Although migration was rescued on Rac2 supplementation, OCG was not. This was attributed to impaired signaling downstream of receptor activator of nuclear factor-κB (RANK) and reduced expression of the RANK-ligand-dependent fusion receptor DC-STAMP. We conclude that Sbds is required for OCG by regulating monocyte migration via Rac2 and osteoclast differentiation signaling downstream of RANK. Impaired osteoclast formation could disrupt bone homeostasis, resulting in skeletal abnormalities seen in SDS patients. PMID:21084708

  10. Conserved mechanisms of vocalization coding in mammalian and songbird auditory midbrain.

    Science.gov (United States)

    Woolley, Sarah M N; Portfors, Christine V

    2013-11-01

    The ubiquity of social vocalizations among animals provides the opportunity to identify conserved mechanisms of auditory processing that subserve communication. Identifying auditory coding properties that are shared across vocal communicators will provide insight into how human auditory processing leads to speech perception. Here, we compare auditory response properties and neural coding of social vocalizations in auditory midbrain neurons of mammalian and avian vocal communicators. The auditory midbrain is a nexus of auditory processing because it receives and integrates information from multiple parallel pathways and provides the ascending auditory input to the thalamus. The auditory midbrain is also the first region in the ascending auditory system where neurons show complex tuning properties that are correlated with the acoustics of social vocalizations. Single unit studies in mice, bats and zebra finches reveal shared principles of auditory coding including tonotopy, excitatory and inhibitory interactions that shape responses to vocal signals, nonlinear response properties that are important for auditory coding of social vocalizations and modulation tuning. Additionally, single neuron responses in the mouse and songbird midbrain are reliable, selective for specific syllables, and rely on spike timing for neural discrimination of distinct vocalizations. We propose that future research on auditory coding of vocalizations in mouse and songbird midbrain neurons adopt similar experimental and analytical approaches so that conserved principles of vocalization coding may be distinguished from those that are specialized for each species. This article is part of a Special Issue entitled "Communication Sounds and the Brain: New Directions and Perspectives".

  11. Cooperative dynamics in auditory brain response

    CERN Document Server

    Kwapien, J; Liu, L C; Ioannides, A A

    1998-01-01

    Simultaneous estimates of the activity in the left and right auditory cortex of five normal human subjects were extracted from Multichannel Magnetoencephalography recordings. Left, right and binaural stimulation were used, in separate runs, for each subject. The resulting time-series of left and right auditory cortex activity were analysed using the concept of mutual information. The analysis constitutes an objective method to address the nature of inter-hemispheric correlations in response to auditory stimulations. The results provide a clear evidence for the occurrence of such correlations mediated by a direct information transport, with clear laterality effects: as a rule, the contralateral hemisphere leads by 10-20ms, as can be seen in the average signal. The strength of the inter-hemispheric coupling, which cannot be extracted from the average data, is found to be highly variable from subject to subject, but remarkably stable for each subject.

  12. Applied research in auditory data representation

    Science.gov (United States)

    Frysinger, Steve P.

    1990-08-01

    A class of data displays, characterized generally as Auditory Data Representation, is described and motivated. This type of data representation takes advantage of the tremendous pattern recognition capability of the human auditory channel. Audible displays offer an alternative means of conveying quantitative data to the analyst to facilitate information extraction, and are successfully used alone and in conjunction with visual displays. The Auditory Data Representation literature is reviewed, along with elements of the allied fields of investigation, Psychoacoustics and Musical Perception. A methodology for applied research in this field, based upon the well-developed discipline of psychophysics, is elaborated using a recent experiment as a case study. This method permits objective estimation of a data representation technique by comparing it to alternative displays for the pattern recognition task at hand. The psychophysical threshold of signal to noise level, for constant pattern recognition performance, is the measure of display effectiveness.

  13. Auditory Responses of Infants

    Science.gov (United States)

    Watrous, Betty Springer; And Others

    1975-01-01

    Forty infants, 3- to 12-months-old, participated in a study designed to differentiate the auditory response characteristics of normally developing infants in the age ranges 3 - 5 months, 6 - 8 months, and 9 - 12 months. (Author)

  14. Autophagy-associated alpha-arrestin signaling is required for conidiogenous cell development in Magnaporthe oryzae

    Science.gov (United States)

    Dong, Bo; Xu, Xiaojin; Chen, Guoqing; Zhang, Dandan; Tang, Mingzhi; Xu, Fei; Liu, Xiaohong; Wang, Hua; Zhou, Bo

    2016-01-01

    Conidiation patterning is evolutionarily complex and mechanism concerning conidiogenous cell differentiation remains largely unknown. Magnaporthe oryzae conidiates in a sympodial way and uses its conidia to infect host and disseminate blast disease. Arrestins are multifunctional proteins that modulate receptor down-regulation and scaffold components of intracellular trafficking routes. We here report an alpha-arrestin that regulates patterns of conidiation and contributes to pathogenicity in M. oryzae. We show that disruption of ARRDC1 generates mutants which produce conidia in an acropetal array and ARRDC1 significantly affects expression profile of CCA1, a virulence-related transcription factor required for conidiogenous cell differentiation. Although germ tubes normally develop appressoria, penetration peg formation is dramatically impaired and Δarrdc1 mutants are mostly nonpathogenic. Fluorescent analysis indicates that EGFP-ARRDC1 puncta are well colocalized with DsRed2-Atg8, and this distribution profile could not be altered in Δatg9 mutants, suggesting ARRDC1 enters into autophagic flux before autophagosome maturation. We propose that M. oryzae employs ARRDC1 to regulate specific receptors in response to conidiation-related signals for conidiogenous cell differentiation and utilize autophagosomes for desensitization of conidiogenous receptor, which transmits extracellular signal to the downstream elements of transcription factors. Our investigation extends novel significance of autophagy-associated alpha-arrestin signaling to fungal parasites. PMID:27498554

  15. A CRISPR screen defines a signal peptide processing pathway required by flaviviruses.

    Science.gov (United States)

    Zhang, Rong; Miner, Jonathan J; Gorman, Matthew J; Rausch, Keiko; Ramage, Holly; White, James P; Zuiani, Adam; Zhang, Ping; Fernandez, Estefania; Zhang, Qiang; Dowd, Kimberly A; Pierson, Theodore C; Cherry, Sara; Diamond, Michael S

    2016-07-01

    Flaviviruses infect hundreds of millions of people annually, and no antiviral therapy is available. We performed a genome-wide CRISPR/Cas9-based screen to identify host genes that, when edited, resulted in reduced flavivirus infection. Here, we validated nine human genes required for flavivirus infectivity, and these were associated with endoplasmic reticulum functions including translocation, protein degradation, and N-linked glycosylation. In particular, a subset of endoplasmic reticulum-associated signal peptidase complex (SPCS) proteins was necessary for proper cleavage of the flavivirus structural proteins (prM and E) and secretion of viral particles. Loss of SPCS1 expression resulted in markedly reduced yield of all Flaviviridae family members tested (West Nile, Dengue, Zika, yellow fever, Japanese encephalitis, and hepatitis C viruses), but had little impact on alphavirus, bunyavirus, or rhabdovirus infection or the surface expression or secretion of diverse host proteins. We found that SPCS1 dependence could be bypassed by replacing the native prM protein leader sequences with a class I major histocompatibility complex (MHC) antigen leader sequence. Thus, SPCS1, either directly or indirectly via its interactions with unknown host proteins, preferentially promotes the processing of specific protein cargo, and Flaviviridae have a unique dependence on this signal peptide processing pathway. SPCS1 and other signal processing pathway members could represent pharmacological targets for inhibiting infection by the expanding number of flaviviruses of medical concern.

  16. A CRISPR screen defines a signal peptide processing pathway required by flaviviruses.

    Science.gov (United States)

    Zhang, Rong; Miner, Jonathan J; Gorman, Matthew J; Rausch, Keiko; Ramage, Holly; White, James P; Zuiani, Adam; Zhang, Ping; Fernandez, Estefania; Zhang, Qiang; Dowd, Kimberly A; Pierson, Theodore C; Cherry, Sara; Diamond, Michael S

    2016-07-01

    Flaviviruses infect hundreds of millions of people annually, and no antiviral therapy is available. We performed a genome-wide CRISPR/Cas9-based screen to identify host genes that, when edited, resulted in reduced flavivirus infection. Here, we validated nine human genes required for flavivirus infectivity, and these were associated with endoplasmic reticulum functions including translocation, protein degradation, and N-linked glycosylation. In particular, a subset of endoplasmic reticulum-associated signal peptidase complex (SPCS) proteins was necessary for proper cleavage of the flavivirus structural proteins (prM and E) and secretion of viral particles. Loss of SPCS1 expression resulted in markedly reduced yield of all Flaviviridae family members tested (West Nile, Dengue, Zika, yellow fever, Japanese encephalitis, and hepatitis C viruses), but had little impact on alphavirus, bunyavirus, or rhabdovirus infection or the surface expression or secretion of diverse host proteins. We found that SPCS1 dependence could be bypassed by replacing the native prM protein leader sequences with a class I major histocompatibility complex (MHC) antigen leader sequence. Thus, SPCS1, either directly or indirectly via its interactions with unknown host proteins, preferentially promotes the processing of specific protein cargo, and Flaviviridae have a unique dependence on this signal peptide processing pathway. SPCS1 and other signal processing pathway members could represent pharmacological targets for inhibiting infection by the expanding number of flaviviruses of medical concern. PMID:27383988

  17. Lhx9 gene expression during early limb development in mice requires the FGF signalling pathway.

    Science.gov (United States)

    Yang, Yisheng; Wilson, Megan J

    2015-01-01

    Lhx9 is a member of the LIM-homeodomain gene family necessary for the correct development of many organs including gonads, limbs, heart and the nervous system. In the context of limb development, Lhx9 has been implicated as an integrator for Fibroblast growth factor (FGF) and Sonic hedgehog (Shh) signalling required for proximal-distal (PD) and anterior-posterior (AP) development of the limb. Three splice variants of the Lhx9 transcript are expressed during development, two of which are predicted to act in a dominant negative fashion, competing with the DNA binding version of Lhx9 for binding to cofactors via the LIM-domain. We examined the expression pattern for the three alternative splice forms of Lhx9; Lhx9α, Lhx9β and Lhx9c during early limb development. We have found that of the three Lhx9 isoforms, only Lhx9α and Lhx9c (intact homeodomain) are expressed during early limb development, each with their own distinct expression pattern. Additionally we determined that Lhx9 expression overlaps with FGF10 expression in the developing limb bud mesenchyme. Limb bud explant cultures, in the presence of signalling pathway inhibitors, also indicated that Lhx9 mRNA expression in the limb bud was dependent on FGF signalling. PMID:26220830

  18. Automatically detecting auditory P300 in several trials

    Institute of Scientific and Technical Information of China (English)

    莫少锋; 汤井田; 陈洪波

    2015-01-01

    A method was demonstrated based on Infomax independent component analysis (Infomax ICA) for automatically extracting auditory P300 signals within several trials. A signaling equilibrium algorithm was proposed to enhance the effectiveness of the Infomax ICA decomposition. After the mixed signal was decomposed by Infomax ICA, the independent component (IC) used in auditory P300 reconstruction was automatically chosen by using the standard deviation of the fixed temporal pattern. And the result of auditory P300 was reconstructed using the selected ICs. The experimental results show that the auditory P300 can be detected automatically within five trials. The Pearson correlation coefficient between the standard signal and the signal detected using the proposed method is significantly greater than that between the standard signal and the signal detected using the average method within five trials. The wave pattern result obtained using the proposed algorithm is better and more similar to the standard signal than that obtained by the average method for the same number of trials. Therefore, the proposed method can automatically detect the effective auditory P300 within several trials.

  19. [Central auditory prosthesis].

    Science.gov (United States)

    Lenarz, T; Lim, H; Joseph, G; Reuter, G; Lenarz, M

    2009-06-01

    Deaf patients with severe sensory hearing loss can benefit from a cochlear implant (CI), which stimulates the auditory nerve fibers. However, patients who do not have an intact auditory nerve cannot benefit from a CI. The majority of these patients are neurofibromatosis type 2 (NF2) patients who developed neural deafness due to growth or surgical removal of a bilateral acoustic neuroma. The only current solution is the auditory brainstem implant (ABI), which stimulates the surface of the cochlear nucleus in the brainstem. Although the ABI provides improvement in environmental awareness and lip-reading capabilities, only a few NF2 patients have achieved some limited open set speech perception. In the search for alternative procedures our research group in collaboration with Cochlear Ltd. (Australia) developed a human prototype auditory midbrain implant (AMI), which is designed to electrically stimulate the inferior colliculus (IC). The IC has the potential as a new target for an auditory prosthesis as it provides access to neural projections necessary for speech perception as well as a systematic map of spectral information. In this paper the present status of research and development in the field of central auditory prostheses is presented with respect to technology, surgical technique and hearing results as well as the background concepts of ABI and AMI. PMID:19517084

  20. Dehydroepiandrosterone Stimulation of Osteoblastogenesis in Human MSCs Requires IGF-I Signaling.

    Science.gov (United States)

    Liang, Xiaonan; Glowacki, Julie; Hahne, Jochen; Xie, Li; LeBoff, Meryl S; Zhou, Shuanhu

    2016-08-01

    Dehydroepiandrosterone (DHEA) is an adrenal steroid that circulates in high concentrations in humans in its sulfated form, DHEAS. Clinical and epidemiological studies suggested that low DHEAS levels may be associated with low bone mass. Previously, we and others showed that the effects of DHEA on the skeleton may be conferred partly by their ability to inhibit skeletal catabolic agents, for example, bone resorptive cytokine IL-6. In this study, we tested the hypothesis that the anabolic effects of DHEA on osteoblastogenesis require IGF-I signaling pathways. Using both primary cultures and a cell line of human bone marrow-derived mesenchymal stem cells (hMSCs), we show that DHEA and other steroids stimulate osteoblastogenesis as shown by alkaline phosphatase activity and osteoblast gene induction. The stimulation by DHEA on both IGF-I gene expression and osteoblastogenesis in hMSCs requires IGF-I receptor, PI3K, p38 MAPK, or p42/44 MAPK signaling pathways. This study adds information to indicate that DHEA may be useful for treating bone diseases through its inhibition of skeletal catabolic IL-6 and stimulation of anabolic IGF-I-mediated mechanisms. J. Cell. Biochem. 117: 1769-1774, 2016. © 2015 Wiley Periodicals, Inc. PMID:26682953

  1. Sox11 is required to maintain proper levels of Hedgehog signaling during vertebrate ocular morphogenesis.

    Directory of Open Access Journals (Sweden)

    Lakshmi Pillai-Kastoori

    2014-07-01

    Full Text Available Ocular coloboma is a sight-threatening malformation caused by failure of the choroid fissure to close during morphogenesis of the eye, and is frequently associated with additional anomalies, including microphthalmia and cataracts. Although Hedgehog signaling is known to play a critical role in choroid fissure closure, genetic regulation of this pathway remains poorly understood. Here, we show that the transcription factor Sox11 is required to maintain specific levels of Hedgehog signaling during ocular development. Sox11-deficient zebrafish embryos displayed delayed and abnormal lens formation, coloboma, and a specific reduction in rod photoreceptors, all of which could be rescued by treatment with the Hedgehog pathway inhibitor cyclopamine. We further demonstrate that the elevated Hedgehog signaling in Sox11-deficient zebrafish was caused by a large increase in shha transcription; indeed, suppressing Shha expression rescued the ocular phenotypes of sox11 morphants. Conversely, over-expression of sox11 induced cyclopia, a phenotype consistent with reduced levels of Sonic hedgehog. We screened DNA samples from 79 patients with microphthalmia, anophthalmia, or coloboma (MAC and identified two novel heterozygous SOX11 variants in individuals with coloboma. In contrast to wild type human SOX11 mRNA, mRNA containing either variant failed to rescue the lens and coloboma phenotypes of Sox11-deficient zebrafish, and both exhibited significantly reduced transactivation ability in a luciferase reporter assay. Moreover, decreased gene dosage from a segmental deletion encompassing the SOX11 locus resulted in microphthalmia and related ocular phenotypes. Therefore, our study reveals a novel role for Sox11 in controlling Hedgehog signaling, and suggests that SOX11 variants contribute to pediatric eye disorders.

  2. Neural crest induction by paraxial mesoderm in Xenopus embryos requires FGF signals.

    Science.gov (United States)

    Monsoro-Burq, Anne-Hélène; Fletcher, Russell B; Harland, Richard M

    2003-07-01

    At the border of the neural plate, the induction of the neural crest can be achieved by interactions with the epidermis, or with the underlying mesoderm. Wnt signals are required for the inducing activity of the epidermis in chick and amphibian embryos. Here, we analyze the molecular mechanisms of neural crest induction by the mesoderm in Xenopus embryos. Using a recombination assay, we show that prospective paraxial mesoderm induces a panel of neural crest markers (Slug, FoxD3, Zic5 and Sox9), whereas the future axial mesoderm only induces a subset of these genes. This induction is blocked by a dominant negative (dn) form of FGFR1. However, neither dnFGFR4a nor inhibition of Wnt signaling prevents neural crest induction in this system. Among the FGFs, FGF8 is strongly expressed by the paraxial mesoderm. FGF8 is sufficient to induce the neural crest markers FoxD3, Sox9 and Zic5 transiently in the animal cap assay. In vivo, FGF8 injections also expand the Slug expression domain. This suggests that FGF8 can initiate neural crest formation and cooperates with other DLMZ-derived factors to maintain and complete neural crest induction. In contrast to Wnts, eFGF or bFGF, FGF8 elicits neural crest induction in the absence of mesoderm induction and without a requirement for BMP antagonists. In vivo, it is difficult to dissociate the roles of FGF and WNT factors in mesoderm induction and neural patterning. We show that, in most cases, effects on neural crest formation were parallel to altered mesoderm or neural development. However, neural and neural crest patterning can be dissociated experimentally using different dominant-negative manipulations: while Nfz8 blocks both posterior neural plate formation and neural crest formation, dnFGFR4a blocks neural patterning without blocking neural crest formation. These results suggest that different signal transduction mechanisms may be used in neural crest induction, and anteroposterior neural patterning. PMID:12783784

  3. Primary cilia are not required for normal canonical Wnt signaling in the mouse embryo.

    Directory of Open Access Journals (Sweden)

    Polloneal Jymmiel R Ocbina

    Full Text Available Sonic hedgehog (Shh signaling in the mouse requires the microtubule-based organelle, the primary cilium. The primary cilium is assembled and maintained through the process of intraflagellar transport (IFT and the response to Shh is blocked in mouse mutants that lack proteins required for IFT. Although the phenotypes of mouse IFT mutants do not overlap with phenotypes of known Wnt pathway mutants, recent studies report data suggesting that the primary cilium modulates responses to Wnt signals.We therefore carried out a systematic analysis of canonical Wnt signaling in mutant embryos and cells that lack primary cilia because of loss of the anterograde IFT kinesin-II motor (Kif3a or IFT complex B proteins (Ift172 or Ift88. We also analyzed mutant embryos with abnormal primary cilia due to defects in retrograde IFT (Dync2h1. The mouse IFT mutants express the canonical Wnt target Axin2 and activate a transgenic canonical Wnt reporter, BAT-gal, in the normal spatial pattern and to the same quantitative level as wild type littermates. Similarly, mouse embryonic fibroblasts (MEFs derived from IFT mutants respond normally to added Wnt3a. The switch from canonical to non-canonical Wnt also appears normal in IFT mutant MEFs, as both wild-type and mutant cells do not activate the canonical Wnt reporter in the presence of both Wnt3a and Wnt5a.We conclude that loss of primary cilia or defects in retrograde IFT do not affect the response of the midgestation embryo or embryo-derived fibroblasts to Wnt ligands.

  4. Auditory-model-based Feature Extraction Method for Mechanical Faults Diagnosis

    Institute of Scientific and Technical Information of China (English)

    LI Yungong; ZHANG Jinping; DAI Li; ZHANG Zhanyi; LIU Jie

    2010-01-01

    It is well known that the human auditory system possesses remarkable capabilities to analyze and identify signals. Therefore, it would be significant to build an auditory model based on the mechanism of human auditory systems, which may improve the effects of mechanical signal analysis and enrich the methods of mechanical faults features extraction. However the existing methods are all based on explicit senses of mathematics or physics, and have some shortages on distinguishing different faults, stability, and suppressing the disturbance noise, etc. For the purpose of improving the performances of the work of feature extraction, an auditory model, early auditory(EA) model, is introduced for the first time. This auditory model transforms time domain signal into auditory spectrum via bandpass filtering, nonlinear compressing, and lateral inhibiting by simulating the principle of the human auditory system. The EA model is developed with the Gammatone filterbank as the basilar membrane. According to the characteristics of vibration signals, a method is proposed for determining the parameter of inner hair cells model of EA model. The performance of EA model is evaluated through experiments on four rotor faults, including misalignment, rotor-to-stator rubbing, oil film whirl, and pedestal looseness. The results show that the auditory spectrum, output of EA model, can effectively distinguish different faults with satisfactory stability and has the ability to suppress the disturbance noise. Then, it is feasible to apply auditory model, as a new method, to the feature extraction for mechanical faults diagnosis with effect.

  5. Identification of genes required for nonhost resistance to Xanthomonas oryzae pv. oryzae reveals novel signaling components.

    Directory of Open Access Journals (Sweden)

    Wen Li

    Full Text Available BACKGROUND: Nonhost resistance is a generalized, durable, broad-spectrum resistance exhibited by plant species to a wide variety of microbial pathogens. Although nonhost resistance is an attractive breeding strategy, the molecular basis of this form of resistance remains unclear for many plant-microbe pathosystems, including interactions with the bacterial pathogen of rice, Xanthomonas oryzae pv. oryzae (Xoo. METHODS AND FINDINGS: Virus-induced gene silencing (VIGS and an assay to detect the hypersensitive response (HR were used to screen for genes required for nonhost resistance to Xoo in N. benthamiana. When infiltrated with Xoo strain YN-1, N. benthamiana plants exhibited a strong necrosis within 24 h and produced a large amount of H(2O(2 in the infiltrated area. Expression of HR- and defense-related genes was induced, whereas bacterial numbers dramatically decreased during necrosis. VIGS of 45 ACE (Avr/Cf-elicited genes revealed identified seven genes required for nonhost resistance to Xoo in N. benthamiana. The seven genes encoded a calreticulin protein (ACE35, an ERF transcriptional factor (ACE43, a novel Solanaceous protein (ACE80, a hydrolase (ACE117, a peroxidase (ACE175 and two proteins with unknown function (ACE95 and ACE112. The results indicate that oxidative burst and calcium-dependent signaling pathways play an important role in nonhost resistance to Xoo. VIGS analysis further revealed that ACE35, ACE80, ACE95 and ACE175, but not the other three ACE genes, interfered with the Cf-4/Avr4-dependent HR. CONCLUSIONS/SIGNIFICANCE: N. benthamiana plants inoculated with Xoo respond by rapidly eliciting an HR and nonhost resistance. The oxidative burst and other signaling pathways are pivotal in Xoo-N. benthamiana nonhost resistance, and genes involved in this response partially overlap with those involved in Cf/Avr4-dependent HR. The seven genes required for N. benthamiana-mediated resistance to Xoo provide a basis for further dissecting

  6. Shaping the aging brain: Role of auditory input patterns in the emergence of auditory cortical impairments

    Directory of Open Access Journals (Sweden)

    Brishna Soraya Kamal

    2013-09-01

    Full Text Available Age-related impairments in the primary auditory cortex (A1 include poor tuning selectivity, neural desynchronization and degraded responses to low-probability sounds. These changes have been largely attributed to reduced inhibition in the aged brain, and are thought to contribute to substantial hearing impairment in both humans and animals. Since many of these changes can be partially reversed with auditory training, it has been speculated that they might not be purely degenerative, but might rather represent negative plastic adjustments to noisy or distorted auditory signals reaching the brain. To test this hypothesis, we examined the impact of exposing young adult rats to 8 weeks of low-grade broadband noise on several aspects of A1 function and structure. We then characterized the same A1 elements in aging rats for comparison. We found that the impact of noise exposure on A1 tuning selectivity, temporal processing of auditory signal and responses to oddball tones was almost indistinguishable from the effect of natural aging. Moreover, noise exposure resulted in a reduction in the population of parvalbumin inhibitory interneurons and cortical myelin as previously documented in the aged group. Most of these changes reversed after returning the rats to a quiet environment. These results support the hypothesis that age-related changes in A1 have a strong activity-dependent component and indicate that the presence or absence of clear auditory input patterns might be a key factor in sustaining adult A1 function.

  7. Spatial auditory processing in pinnipeds

    Science.gov (United States)

    Holt, Marla M.

    Given the biological importance of sound for a variety of activities, pinnipeds must be able to obtain spatial information about their surroundings thorough acoustic input in the absence of other sensory cues. The three chapters of this dissertation address spatial auditory processing capabilities of pinnipeds in air given that these amphibious animals use acoustic signals for reproduction and survival on land. Two chapters are comparative lab-based studies that utilized psychophysical approaches conducted in an acoustic chamber. Chapter 1 addressed the frequency-dependent sound localization abilities at azimuth of three pinniped species (the harbor seal, Phoca vitulina, the California sea lion, Zalophus californianus, and the northern elephant seal, Mirounga angustirostris). While performances of the sea lion and harbor seal were consistent with the duplex theory of sound localization, the elephant seal, a low-frequency hearing specialist, showed a decreased ability to localize the highest frequencies tested. In Chapter 2 spatial release from masking (SRM), which occurs when a signal and masker are spatially separated resulting in improvement in signal detectability relative to conditions in which they are co-located, was determined in a harbor seal and sea lion. Absolute and masked thresholds were measured at three frequencies and azimuths to determine the detection advantages afforded by this type of spatial auditory processing. Results showed that hearing sensitivity was enhanced by up to 19 and 12 dB in the harbor seal and sea lion, respectively, when the signal and masker were spatially separated. Chapter 3 was a field-based study that quantified both sender and receiver variables of the directional properties of male northern elephant seal calls produce within communication system that serves to delineate dominance status. This included measuring call directivity patterns, observing male-male vocally-mediated interactions, and an acoustic playback study

  8. ERK1/ERK2 MAPK signaling is required to increase myelin thickness independent of oligodendrocyte differentiation and initiation of myelination

    OpenAIRE

    Ishii, A.; Fyffe-Maricich, S.L.; Furusho, M.; Miller, R. H.; Bansal, R.

    2012-01-01

    Wrapping of the myelin sheath around axons by oligodendrocytes is critical for the rapid conduction of electrical signals, required for the normal functioning of the central nervous system (CNS). Myelination is a multistep process where oligodendrocytes progress through a well-coordinated differentiation program regulated by multiple extracellular growth and differentiation signals. The intracellular-transduction of the extracellular signals that regulate myelination is poorly understood. Her...

  9. Biological impact of music and software-based auditory training

    Science.gov (United States)

    Kraus, Nina

    2012-01-01

    Auditory-based communication skills are developed at a young age and are maintained throughout our lives. However, some individuals – both young and old – encounter difficulties in achieving or maintaining communication proficiency. Biological signals arising from hearing sounds relate to real-life communication skills such as listening to speech in noisy environments and reading, pointing to an intersection between hearing and cognition. Musical experience, amplification, and software-based training can improve these biological signals. These findings of biological plasticity, in a variety of subject populations, relate to attention and auditory memory, and represent an integrated auditory system influenced by both sensation and cognition. Learning outcomes The reader will (1) understand that the auditory system is malleable to experience and training, (2) learn the ingredients necessary for auditory learning to successfully be applied to communication, (3) learn that the auditory brainstem response to complex sounds (cABR) is a window into the integrated auditory system, and (4) see examples of how cABR can be used to track the outcome of experience and training. PMID:22789822

  10. Functional requirements for inhibitory signal transmission by the immunomodulatory receptor CD300a

    Directory of Open Access Journals (Sweden)

    DeBell Karen E

    2012-04-01

    Full Text Available Abstract Background Activation signals can be negatively regulated by cell surface receptors bearing immunoreceptor tyrosine-based inhibitory motifs (ITIMs. CD300a, an ITIM bearing type I transmembrane protein, is expressed on many hematopoietic cells, including subsets of lymphocytes. Results We have taken two approaches to further define the mechanism by which CD300a acts as an inhibitor of immune cell receptor signaling. First, we have expressed in Jurkat T cells a chimeric receptor consisting of the extracellular domains of killer-cell immunoglobulin-like receptor (KIR2DL2 fused to the transmembrane and cytoplasmic segments of CD300a (KIR-CD300a to explore surrogate ligand-stimulated inhibition of superantigen stimulated T cell receptor (TCR mediated cell signaling. We found that intact CD300a ITIMs were essential for inhibition and that the tyrosine phosphorylation of these ITIMs required the src tyrosine kinase Lck. Tyrosine phosphorylation of the CD300a ITIMs created docking sites for both src homology 2 domain containing protein tyrosine phosphatase (SHP-1 and SHP-2. Suppression of SHP-1 and SHP-2 expression in KIR-CD300a Jurkat T cells with siRNA and the use of DT40 chicken B cell lines expressing CD300a and deficient in several phosphatases revealed that SHP-1, but not SHP-2 or the src homology 2 domain containing inositol 5’ phosphatase SHIP, was utilized by CD300a for its inhibitory activity. Conclusion These studies provide new insights into the function of CD300a in tuning T and B cell responses.

  11. Does murine spermatogenesis require WNT signalling? A lesson from Gpr177 conditional knockout mouse models.

    Science.gov (United States)

    Chen, Su-Ren; Tang, J-X; Cheng, J-M; Hao, X-X; Wang, Y-Q; Wang, X-X; Liu, Y-X

    2016-01-01

    Wingless-related MMTV integration site (WNT) proteins and several other components of the WNT signalling pathway are expressed in the murine testes. However, mice mutant for WNT signalling effector β-catenin using different Cre drivers have phenotypes that are inconsistent with each other. The complexity and overlapping expression of WNT signalling cascades have prevented researchers from dissecting their function in spermatogenesis. Depletion of the Gpr177 gene (the mouse orthologue of Drosophila Wntless), which is required for the secretion of various WNTs, makes it possible to genetically dissect the overall effect of WNTs in testis development. In this study, the Gpr177 gene was conditionally depleted in germ cells (Gpr177(flox/flox), Mvh-Cre; Gpr177(flox/flox), Stra8-Cre) and Sertoli cells (Gpr177(flox/flox), Amh-Cre). No obvious defects in fertility and spermatogenesis were observed in these three Gpr177 conditional knockout (cKO) mice at 8 weeks. However, late-onset testicular atrophy and fertility decline in two germ cell-specific Gpr177 deletion mice were noted at 8 months. In contrast, we did not observe any abnormalities of spermatogenesis and fertility, even in 8-month-old Gpr177(flox/flox), Amh-Cre mice. Elevation of reactive oxygen species (ROS) was detected in Gpr177 cKO germ cells and Sertoli cells and exhibited an age-dependent manner. However, significant increase in the activity of Caspase 3 was only observed in germ cells from 8-month-old germ cell-specific Gpr177 knockout mice. In conclusion, GPR177 in Sertoli cells had no apparent influence on spermatogenesis, whereas loss of GPR177 in germ cells disrupted spermatogenesis in an age-dependent manner via elevating ROS levels and triggering germ cell apoptosis. PMID:27362799

  12. Lysophosphatidic Acid Signaling through the Lysophosphatidic Acid-1 Receptor Is Required for Alveolarization.

    Science.gov (United States)

    Funke, Manuela; Knudsen, Lars; Lagares, David; Ebener, Simone; Probst, Clemens K; Fontaine, Benjamin A; Franklin, Alicia; Kellner, Manuela; Kühnel, Mark; Matthieu, Stephanie; Grothausmann, Roman; Chun, Jerold; Roberts, Jesse D; Ochs, Matthias; Tager, Andrew M

    2016-07-01

    Lysophosphatidic acid (LPA) signaling through one of its receptors, LPA1, contributes to both the development and the pathological remodeling after injury of many organs. Because we found previously that LPA-LPA1 signaling contributes to pulmonary fibrosis, here we investigated whether this pathway is also involved in lung development. Quantitative assessment of lung architecture of LPA1-deficient knock-out (KO) and wild-type (WT) mice at 3, 12, and 24 weeks of age using design-based stereology suggested the presence of an alveolarization defect in LPA1 KO mice at 3 weeks, which persisted as alveolar numbers increased in WT mice into adulthood. Across the ages examined, the lungs of LPA1 KO mice exhibited decreased alveolar numbers, septal tissue volumes, and surface areas, and increased volumes of the distal airspaces. Elastic fibers, critical to the development of alveolar septa, appeared less organized and condensed and more discontinuous in KO alveoli starting at P4. Tropoelastin messenger RNA expression was decreased in KO lungs, whereas expression of matrix metalloproteinases degrading elastic fibers was either decreased or unchanged. These results are consistent with the abnormal lung phenotype of LPA1 KO mice, being attributable to reduced alveolar septal formation during development, rather than to increased septal destruction as occurs in the emphysema of chronic obstructive pulmonary disease. Peripheral septal fibroblasts and myofibroblasts, which direct septation in late alveolarization, demonstrated reduced production of tropoelastin and matrix metalloproteinases, and diminished LPA-induced migration, when isolated from LPA1 KO mice. Taken together, our data suggest that LPA-LPA1 signaling is critically required for septation during alveolarization. PMID:27082727

  13. β1 integrin-mediated signals are required for platelet granule secretion and hemostasis in mouse.

    Science.gov (United States)

    Petzold, Tobias; Ruppert, Raphael; Pandey, Dharmendra; Barocke, Verena; Meyer, Hannelore; Lorenz, Michael; Zhang, Lin; Siess, Wolfgang; Massberg, Steffen; Moser, Markus

    2013-10-10

    Integrins are critical for platelet adhesion and aggregation during arterial thrombosis and hemostasis. Although the platelet-specific αIIbβ3 integrin is known to be crucial for these processes, the in vivo role of β1 integrins is a matter of debate. Here we demonstrate that mice expressing reduced levels of β1 integrins or an activation-deficient β1 integrin show strongly reduced platelet adhesion to collagen in vitro and in a carotis ligation model in vivo. Interestingly, hypomorphic mice expressing only 3% of β1 integrins on platelets show normal bleeding times despite reduced platelet adhesion. The residual 3% of β1 integrins are able to trigger intracellular signals driving Rac-1-dependent granule release required for platelet aggregation and hemostasis. Our findings support a model, in which platelet β1 integrins serve as an important signaling receptor rather than an adhesion receptor in vivo and therefore promote β1 integrins as a promising and so far clinically unemployed antithrombotic target.

  14. Different requirements for GFRα2-signaling in three populations of cutaneous sensory neurons.

    Directory of Open Access Journals (Sweden)

    Jussi Kupari

    Full Text Available Many primary sensory neurons in mouse dorsal root ganglia (DRG express one or several GFRα's, the ligand-binding receptors of the GDNF family, and their common signaling receptor Ret. GFRα2, the principal receptor for neurturin, is expressed in most of the small nonpeptidergic DRG neurons, but also in some large DRG neurons that start to express Ret earlier. Previously, GFRα2 has been shown to be crucial for the soma size of small nonpeptidergic nociceptors and for their target innervation of glabrous epidermis. However, little is known about this receptor in other Ret-expressing DRG neuron populations. Here we have investigated two populations of Ret-positive low-threshold mechanoreceptors that innervate different types of hair follicles on mouse back skin: the small C-LTMRs and the large Aβ-LTMRs. Using GFRα2-KO mice and immunohistochemistry we found that, similar to the nonpeptidergic nociceptors, GFRα2 controls the cell size but not the survival of both C-LTMRs and Aβ-LTMRs. In contrast to the nonpeptidergic neurons, GFRα2 is not required for the target innervation of C-LTMRs and Aβ-LTMRs in the back skin. These results suggest that different factors drive target innervation in these three populations of neurons. In addition, the observation that the large Ret-positive DRG neurons lack GFRα2 immunoreactivity in mature animals suggests that these neurons switch their GFRα signaling pathways during postnatal development.

  15. Reciprocal requirements for Eda/Edar/NF-κB and Wnt/β-catenin signaling pathways in hair follicle induction

    Science.gov (United States)

    Zhang, Yuhang; Tomann, Philip; Andl, Thomas; Gallant, Natalie M.; Huelsken, Joerg; Jerchow, Boris; Birchmeier, Walter; Paus, Ralf; Piccolo, Stefano; Mikkola, Marja L.; Morrisey, Edward E.; Overbeek, Paul A.; Scheidereit, Claus; Millar, Sarah E.; Schmidt-Ullrich, Ruth

    2009-01-01

    SUMMARY Wnt/β-catenin and NF-κB signaling mechanisms provide central controls in development and disease, but how these pathways intersect is unclear. Using hair follicle induction as a model system, we show that patterning of dermal Wnt/β-catenin signaling requires epithelial β-catenin activity. We find that Wnt/β-catenin signaling is absolutely required for NF-κB activation, and that Edar is a direct Wnt target gene. Wnt/β-catenin signaling is initially activated independently of Eda/Edar/NF-κB activity in primary hair follicle primordia. However, Eda/Edar/NF-κB signaling is required to refine the pattern of Wnt/β-catenin activity, and to maintain this activity at later stages of placode development. We show that maintenance of localized expression of Wnt10b and Wnt10a requires NF-κB signaling, providing a molecular explanation for the latter observation, and identify Wnt10b as a direct NF-κB target. These data reveal a complex interplay and inter-dependence of Wnt/β-catenin and Eda/Edar/NF-κB signaling pathways in initiation and maintenance of primary hair follicle placodes. PMID:19619491

  16. Ror2 signaling is required for local upregulation of GFD6 and activation of BMP signaling at the neural plate border.

    Science.gov (United States)

    Schille, Carolin; Bayerlová, Michaela; Bleckmann, Annalen; Schambony, Alexandra

    2016-09-01

    The receptor tyrosine kinase Ror2 is a major Wnt receptor that activates β-catenin-independent signaling and plays a conserved role in the regulation of convergent extension movements and planar cell polarity in vertebrates. Mutations in the ROR2 gene cause recessive Robinow syndrome in humans, a short-limbed dwarfism associated with craniofacial malformations. Here, we show that Ror2 is required for local upregulation of gdf6 at the neural plate border in Xenopus embryos. Ror2 morphant embryos fail to upregulate neural plate border genes and show defects in the induction of neural crest cell fate. These embryos lack the spatially restricted activation of BMP signaling at the neural plate border at early neurula stages, which is required for neural crest induction. Ror2-dependent planar cell polarity signaling is required in the dorsolateral marginal zone during gastrulation indirectly to upregulate the BMP ligand Gdf6 at the neural plate border and Gdf6 is sufficient to rescue neural plate border specification in Ror2 morphant embryos. Thereby, Ror2 links Wnt/planar cell polarity signaling to BMP signaling in neural plate border specification and neural crest induction. PMID:27578181

  17. Maternal Mga is required for Wnt signaling and organizer formation in the early Xenopus embryo.

    Science.gov (United States)

    Gu, Fei; Shi, Huijuan; Gao, Li; Zhang, Haiyan; Tao, Qinghua

    2012-11-01

    Maternal Wnt11 is both necessary and sufficient for the formation of Spemann organizer in Xenopus embryo. Xnr3 and Siamois have been identified as the direct target genes of maternal Wnt11/β-catenin during organizer induction. The depletion of maternal XTcf3 resulted in the ectopic expression of Xnr3 and Siamois, suggesting the activity of β-catenin/XTcf3 is strictly regulated in the early Xenopus embryos. Here, we show that Xenopus mga (Xmga) is a maternal gene required for dorsal axis formation. Overexpression experiments indicate that mouse Mga potentiates the activity of β-catenin in the induction of organizer-specific genes. Depletion of maternal Xmga results in the dramatic decrease of the expression of organizer genes and ventralization phenotype, indicating that Xmga is required for β-catenin function and organizer formation. Depletion of XTcf3 cannot rescue organizer gene expression and axis formation in Xmga-depleted embryos, suggesting Xmga is downstream of XTcf3 during organizer induction. We conclude that maternal Xmga is critical for the function of β-catenin during organizer formation and dorsal development of Xenopus embryo. To our knowledge, this is a report for the first time to implicate Mga in regulating Wnt signaling. PMID:23070227

  18. Maternal Mga is required for Wnt signaling and organizer formation in the early Xenopus embryo

    Institute of Scientific and Technical Information of China (English)

    Fei Gu; Huijuan Shi; Li Gao; Haiyan Zhang; Qinghua Tao

    2012-01-01

    Maternal Wnt11 is both necessary and sufficient for the formation of Spemann organizer in Xenopus embryo.Xnr3 and Siamois have been identified as the direct target genes of maternal Wnt11/β-catenin during organizer induction.The depletion of maternal XTcf3 resulted in the ectopic expression of Xnr3 and Siamois,suggesting the activity of β-catenin/XTcf3 is strictly regulated in the early Xenopus embryos.Here,we show that Xenopus mga (Xmga) is a maternal gene required for dorsal axis formation.Overexpression experiments indicate that mouse Mga potentiates the activity of β-catenin in the induction of organizer-specific genes.Depletion of maternal Xmga results in the dramatic decrease of the expression of organizer genes and ventralization phenotype,indicating that Xmga is required for β-catenin function and organizer formation.Depletion of XTcf3 cannot rescue organizer gene expression and axis formation in Xmga-depleted embryos,suggesting Xmga is downstream of XTcf3 during organizer induction.We conclude that maternal Xmga is critical for the function of β-catenin during organizer formation and dorsal development of Xenopus embryo.To our knowledge,this is a report for the first time to implicate Mga in regulating Wnt signaling.

  19. Transcription-dependent nuclear localization of DAZAP1 requires an N-terminal signal

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yi-Tzu; Wen, Wan-Ching [Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan (China); Yen, Pauline H., E-mail: pyen@ibms.sinica.edu.tw [Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan (China)

    2012-11-23

    Highlights: Black-Right-Pointing-Pointer DAZAP1 shuttles between the nucleus and the cytoplasm. Black-Right-Pointing-Pointer DAZAP1 accumulates in the cytoplasm when the nuclear transcription is inhibited. Black-Right-Pointing-Pointer DAZAP1's transcription-dependent nuclear localization requires N-terminal N42. Black-Right-Pointing-Pointer SLIRP binds to N42 and may be involved in the process. -- Abstract: Deleted in Azoospermia Associated Protein 1 (DAZAP1) is a ubiquitous hnRNP protein required for normal development and spermatogenesis. It resides predominantly in the nucleus and moves between the nucleus and the cytoplasm via a ZNS shuttling signal at its C-terminus. DAZAP1 accumulates in the cytoplasm when RNA polymerase II activity is inhibited by actinomycin D. Here we report the mapping of a 42-amino acid segment (N42) at the N-terminus of DAZAP1 that is both necessary and sufficient for its transcription-dependent nuclear localization. In addition, using a yeast two-hybrid system, we have identified SLIRP as a N42-binding protein which may regulate DAZAP1 subcellular localization.

  20. Wnt/β-catenin signaling is required for development of the exocrine pancreas

    Directory of Open Access Journals (Sweden)

    Sklenka Angela

    2007-01-01

    conclude that β-catenin expression is required for development of the exocrine pancreas, but is not required for development of the endocrine compartment. In contrast, β-catenin/Wnt signaling appears to be critical for proliferation of PTF1+ nascent acinar cells and may also function, in part, to maintain an undifferentiated state in exocrine/acinar cell precursors. Finally, β-catenin may be required to maintain positional identity of the pancreatic endoderm along the anterior-posterior axis. This data is consistent with the findings of frequent β-catenin mutations in carcinomas of acinar cell lineage seen in humans.

  1. Central auditory neurons have composite receptive fields.

    Science.gov (United States)

    Kozlov, Andrei S; Gentner, Timothy Q

    2016-02-01

    High-level neurons processing complex, behaviorally relevant signals are sensitive to conjunctions of features. Characterizing the receptive fields of such neurons is difficult with standard statistical tools, however, and the principles governing their organization remain poorly understood. Here, we demonstrate multiple distinct receptive-field features in individual high-level auditory neurons in a songbird, European starling, in response to natural vocal signals (songs). We then show that receptive fields with similar characteristics can be reproduced by an unsupervised neural network trained to represent starling songs with a single learning rule that enforces sparseness and divisive normalization. We conclude that central auditory neurons have composite receptive fields that can arise through a combination of sparseness and normalization in neural circuits. Our results, along with descriptions of random, discontinuous receptive fields in the central olfactory neurons in mammals and insects, suggest general principles of neural computation across sensory systems and animal classes. PMID:26787894

  2. Use of the Kalman filter in signal processing to reduce beam requirements for alpha-particle diagnostics

    International Nuclear Information System (INIS)

    Several techniques proposed for diagnosing the velocity distribution of fast alpha-particles in a burning plasma require the injection of a beam of fast neutral atoms as probes. The author discusses how improving signal detection techniques is a high leverage factor in reducing the cost of the diagnostic beam. Optimal estimation theory provides a computational algorithm, the Kalman filter, that can optimally estimate the amplitude of a signal with arbitrary (but known) time dependence in the presence of noise. In one example presented, based on a square-wave signal and assumed noise levels, the Kalman filter achieves an enhancement of signal detection efficiency of about a factor of 10 (as compared with the straightforward observation of the signal superimposed on noise) with an observation time of 100 signal periods

  3. Impact of Educational Level on Performance on Auditory Processing Tests.

    Science.gov (United States)

    Murphy, Cristina F B; Rabelo, Camila M; Silagi, Marcela L; Mansur, Letícia L; Schochat, Eliane

    2016-01-01

    Research has demonstrated that a higher level of education is associated with better performance on cognitive tests among middle-aged and elderly people. However, the effects of education on auditory processing skills have not yet been evaluated. Previous demonstrations of sensory-cognitive interactions in the aging process indicate the potential importance of this topic. Therefore, the primary purpose of this study was to investigate the performance of middle-aged and elderly people with different levels of formal education on auditory processing tests. A total of 177 adults with no evidence of cognitive, psychological or neurological conditions took part in the research. The participants completed a series of auditory assessments, including dichotic digit, frequency pattern and speech-in-noise tests. A working memory test was also performed to investigate the extent to which auditory processing and cognitive performance were associated. The results demonstrated positive but weak correlations between years of schooling and performance on all of the tests applied. The factor "years of schooling" was also one of the best predictors of frequency pattern and speech-in-noise test performance. Additionally, performance on the working memory, frequency pattern and dichotic digit tests was also correlated, suggesting that the influence of educational level on auditory processing performance might be associated with the cognitive demand of the auditory processing tests rather than auditory sensory aspects itself. Longitudinal research is required to investigate the causal relationship between educational level and auditory processing skills.

  4. Impact of Educational Level on Performance on Auditory Processing Tests.

    Science.gov (United States)

    Murphy, Cristina F B; Rabelo, Camila M; Silagi, Marcela L; Mansur, Letícia L; Schochat, Eliane

    2016-01-01

    Research has demonstrated that a higher level of education is associated with better performance on cognitive tests among middle-aged and elderly people. However, the effects of education on auditory processing skills have not yet been evaluated. Previous demonstrations of sensory-cognitive interactions in the aging process indicate the potential importance of this topic. Therefore, the primary purpose of this study was to investigate the performance of middle-aged and elderly people with different levels of formal education on auditory processing tests. A total of 177 adults with no evidence of cognitive, psychological or neurological conditions took part in the research. The participants completed a series of auditory assessments, including dichotic digit, frequency pattern and speech-in-noise tests. A working memory test was also performed to investigate the extent to which auditory processing and cognitive performance were associated. The results demonstrated positive but weak correlations between years of schooling and performance on all of the tests applied. The factor "years of schooling" was also one of the best predictors of frequency pattern and speech-in-noise test performance. Additionally, performance on the working memory, frequency pattern and dichotic digit tests was also correlated, suggesting that the influence of educational level on auditory processing performance might be associated with the cognitive demand of the auditory processing tests rather than auditory sensory aspects itself. Longitudinal research is required to investigate the causal relationship between educational level and auditory processing skills. PMID:27013958

  5. Auditory spatial perception dynamically realigns with changing eye position.

    Science.gov (United States)

    Razavi, Babak; O'Neill, William E; Paige, Gary D

    2007-09-19

    Audition and vision both form spatial maps of the environment in the brain, and their congruency requires alignment and calibration. Because audition is referenced to the head and vision is referenced to movable eyes, the brain must accurately account for eye position to maintain alignment between the two modalities as well as perceptual space constancy. Changes in eye position are known to variably, but inconsistently, shift sound localization, suggesting subtle shortcomings in the accuracy or use of eye position signals. We systematically and directly quantified sound localization across a broad spatial range and over time after changes in eye position. A sustained fixation task addressed the spatial (steady-state) attributes of eye position-dependent effects on sound localization. Subjects continuously fixated visual reference spots straight ahead (center), to the left (20 degrees), or to the right (20 degrees) of the midline in separate sessions while localizing auditory targets using a laser pointer guided by peripheral vision. An alternating fixation task focused on the temporal (dynamic) aspects of auditory spatial shifts after changes in eye position. Localization proceeded as in sustained fixation, except that eye position alternated between the three fixation references over multiple epochs, each lasting minutes. Auditory space shifted by approximately 40% toward the new eye position and dynamically over several minutes. We propose that this spatial shift reflects an adaptation mechanism for aligning the "straight-ahead" of perceived sensory-motor maps, particularly during early childhood when normal ocular alignment is achieved, but also resolving challenges to normal spatial perception throughout life. PMID:17881531

  6. Interface Design Implications for Recalling the Spatial Configuration of Virtual Auditory Environments

    Science.gov (United States)

    McMullen, Kyla A.

    Although the concept of virtual spatial audio has existed for almost twenty-five years, only in the past fifteen years has modern computing technology enabled the real-time processing needed to deliver high-precision spatial audio. Furthermore, the concept of virtually walking through an auditory environment did not exist. The applications of such an interface have numerous potential uses. Spatial audio has the potential to be used in various manners ranging from enhancing sounds delivered in virtual gaming worlds to conveying spatial locations in real-time emergency response systems. To incorporate this technology in real-world systems, various concerns should be addressed. First, to widely incorporate spatial audio into real-world systems, head-related transfer functions (HRTFs) must be inexpensively created for each user. The present study further investigated an HRTF subjective selection procedure previously developed within our research group. Users discriminated auditory cues to subjectively select their preferred HRTF from a publicly available database. Next, the issue of training to find virtual sources was addressed. Listeners participated in a localization training experiment using their selected HRTFs. The training procedure was created from the characterization of successful search strategies in prior auditory search experiments. Search accuracy significantly improved after listeners performed the training procedure. Next, in the investigation of auditory spatial memory, listeners completed three search and recall tasks with differing recall methods. Recall accuracy significantly decreased in tasks that required the storage of sound source configurations in memory. To assess the impacts of practical scenarios, the present work assessed the performance effects of: signal uncertainty, visual augmentation, and different attenuation modeling. Fortunately, source uncertainty did not affect listeners' ability to recall or identify sound sources. The present

  7. A corollary discharge maintains auditory sensitivity during sound production.

    Science.gov (United States)

    Poulet, James F A; Hedwig, Berthold

    2002-08-22

    Speaking and singing present the auditory system of the caller with two fundamental problems: discriminating between self-generated and external auditory signals and preventing desensitization. In humans and many other vertebrates, auditory neurons in the brain are inhibited during vocalization but little is known about the nature of the inhibition. Here we show, using intracellular recordings of auditory neurons in the singing cricket, that presynaptic inhibition of auditory afferents and postsynaptic inhibition of an identified auditory interneuron occur in phase with the song pattern. Presynaptic and postsynaptic inhibition persist in a fictively singing, isolated cricket central nervous system and are therefore the result of a corollary discharge from the singing motor network. Mimicking inhibition in the interneuron by injecting hyperpolarizing current suppresses its spiking response to a 100-dB sound pressure level (SPL) acoustic stimulus and maintains its response to subsequent, quieter stimuli. Inhibition by the corollary discharge reduces the neural response to self-generated sound and protects the cricket's auditory pathway from self-induced desensitization.

  8. The neglected neglect: auditory neglect.

    Science.gov (United States)

    Gokhale, Sankalp; Lahoti, Sourabh; Caplan, Louis R

    2013-08-01

    Whereas visual and somatosensory forms of neglect are commonly recognized by clinicians, auditory neglect is often not assessed and therefore neglected. The auditory cortical processing system can be functionally classified into 2 distinct pathways. These 2 distinct functional pathways deal with recognition of sound ("what" pathway) and the directional attributes of the sound ("where" pathway). Lesions of higher auditory pathways produce distinct clinical features. Clinical bedside evaluation of auditory neglect is often difficult because of coexisting neurological deficits and the binaural nature of auditory inputs. In addition, auditory neglect and auditory extinction may show varying degrees of overlap, which makes the assessment even harder. Shielding one ear from the other as well as separating the ear from space is therefore critical for accurate assessment of auditory neglect. This can be achieved by use of specialized auditory tests (dichotic tasks and sound localization tests) for accurate interpretation of deficits. Herein, we have reviewed auditory neglect with an emphasis on the functional anatomy, clinical evaluation, and basic principles of specialized auditory tests.

  9. Integration and segregation in auditory scene analysis

    Science.gov (United States)

    Sussman, Elyse S.

    2005-03-01

    Assessment of the neural correlates of auditory scene analysis, using an index of sound change detection that does not require the listener to attend to the sounds [a component of event-related brain potentials called the mismatch negativity (MMN)], has previously demonstrated that segregation processes can occur without attention focused on the sounds and that within-stream contextual factors influence how sound elements are integrated and represented in auditory memory. The current study investigated the relationship between the segregation and integration processes when they were called upon to function together. The pattern of MMN results showed that the integration of sound elements within a sound stream occurred after the segregation of sounds into independent streams and, further, that the individual streams were subject to contextual effects. These results are consistent with a view of auditory processing that suggests that the auditory scene is rapidly organized into distinct streams and the integration of sequential elements to perceptual units takes place on the already formed streams. This would allow for the flexibility required to identify changing within-stream sound patterns, needed to appreciate music or comprehend speech..

  10. Learned stressor resistance requires extracellular signal-regulated kinase in the prefrontal cortex

    Directory of Open Access Journals (Sweden)

    John Paul Christianson

    2014-10-01

    Full Text Available Behaviorally controllable stressors confer protection from the neurochemical and behavioral consequences of future uncontrollable stressors, a phenomenon termed behavioral immunization. Recent data implicate neuroplasticity within the ventromedial prefrontal cortex (mPFC as critical to behavioral immunization. Adult, male Sprague-Dawley rats were exposed to a series of controllable tailshocks and one week later to uncontrollable tailshocks, followed 24h later by social exploration and shuttlebox escape tests. To test the involvement of N-methyl-D-aspartate receptors (NMDAR and the extracellular signal-regulated kinase (ERK cascade in behavioral immunization, either D-AP5 or the MEK inhibitor U0126 was injected to the prelimbic (PL or infralimbic (IL mPFC prior to controllable stress exposure. Phosphorylated ERK and P70S6K, regulators of transcription and translation, were quantified by Western blot or immunohistochemistry after controllable or uncontrollable tailshocks. Prior controllable stress prevented the social exploration and shuttlebox performance deficits caused by the later uncontrollable stressor, and this effect was blocked by injections of D-AP5 into mPFC. A significant increase in phosphorylated ERK1 and ERK2, but not P70S6K, occurred within the PL and IL in rats exposed to controllable stress, but not to uncontrollable stress. However, U0126 only prevented behavioral immunization when injected to the PL. We provide evidence that NMDAR and ERK dependent plasticity within the PL region is required for behavioral immunization, a learned form of stressor resistance.

  11. α2δ-3 Is Required for Rapid Transsynaptic Homeostatic Signaling.

    Science.gov (United States)

    Wang, Tingting; Jones, Ryan T; Whippen, Jenna M; Davis, Graeme W

    2016-09-13

    The homeostatic modulation of neurotransmitter release, termed presynaptic homeostatic potentiation (PHP), is a fundamental type of neuromodulation, conserved from Drosophila to humans, that stabilizes information transfer at synaptic connections throughout the nervous system. Here, we demonstrate that α2δ-3, an auxiliary subunit of the presynaptic calcium channel, is required for PHP. The α2δ gene family has been linked to chronic pain, epilepsy, autism, and the action of two psychiatric drugs: gabapentin and pregabalin. We demonstrate that loss of α2δ-3 blocks both the rapid induction and sustained expression of PHP due to a failure to potentiate presynaptic calcium influx and the RIM-dependent readily releasable vesicle pool. These deficits are independent of α2δ-3-mediated regulation of baseline calcium influx and presynaptic action potential waveform. α2δ proteins reside at the extracellular face of presynaptic release sites throughout the nervous system, a site ideal for mediating rapid, transsynaptic homeostatic signaling in health and disease. PMID:27626659

  12. Online contributions of auditory feedback to neural activity in avian song control circuitry

    OpenAIRE

    Sakata, Jon T.; Michael S. Brainard

    2008-01-01

    Birdsong, like human speech, relies critically on auditory feedback to provide information about the quality of vocalizations. Although the importance of auditory feedback to vocal learning is well established, whether and how feedback signals influence vocal premotor circuitry has remained obscure. Previous studies in singing birds have not detected changes to vocal premotor activity following perturbations of auditory feedback, leading to the hypothesis that contributions of feedback to voc...

  13. Visual-auditory integration for visual search: a behavioral study in barn owls

    OpenAIRE

    Yael eHazan; Inna eYarin; Yonatan eKra; Hermann eWagner; Yoram eGutfreund

    2015-01-01

    Barn owls are nocturnal predators that rely on both vision and hearing for survival. The optic tectum of barn owls, a midbrain structure involved in selective attention, has been used as a model for studying visual- auditory integration at the neuronal level. However, behavioral data on visual- auditory integration in barn owls are lacking. The goal of this study was to examine if the integration of visual and auditory signals contributes to the process of guiding attention towards salient st...

  14. PSYCHOACOUSTICS: a comprehensive MATLAB toolbox for auditory testing.

    Science.gov (United States)

    Soranzo, Alessandro; Grassi, Massimo

    2014-01-01

    PSYCHOACOUSTICS is a new MATLAB toolbox which implements three classic adaptive procedures for auditory threshold estimation. The first includes those of the Staircase family (method of limits, simple up-down and transformed up-down); the second is the Parameter Estimation by Sequential Testing (PEST); and the third is the Maximum Likelihood Procedure (MLP). The toolbox comes with more than twenty built-in experiments each provided with the recommended (default) parameters. However, if desired, these parameters can be modified through an intuitive and user friendly graphical interface and stored for future use (no programming skills are required). Finally, PSYCHOACOUSTICS is very flexible as it comes with several signal generators and can be easily extended for any experiment.

  15. Intercellular calcium signaling occurs between human osteoblasts and osteoclasts and requires activation of osteoclast P2X7 receptors

    DEFF Research Database (Denmark)

    Jørgensen, Niklas R; Henriksen, Zanne; Sørensen, Ole;

    2002-01-01

    Signaling between osteoblasts and osteoclasts is important in bone homeostasis. We previously showed that human osteoblasts propagate intercellular calcium signals via two mechanisms: autocrine activation of P2Y receptors, and gap junctional communication. In the current work we identified...... mechanically induced intercellular calcium signaling between osteoblasts and osteoclasts and among osteoclasts. Intercellular calcium responses in osteoclasts required P2 receptor activation but not gap junctional communication. Pharmacological studies and reverse transcriptase-PCR amplification demonstrated...... that human osteoclasts expressed functional P2Y1 receptors, but, unexpectedly, desensitization of P2Y1 did not block calcium signaling to osteoclasts. We also found that osteoclasts expressed functional P2X7 receptors and showed that pharmacological inhibition of these receptors blocked calcium signaling...

  16. Prospects for replacement of auditory neurons by stem cells.

    Science.gov (United States)

    Shi, Fuxin; Edge, Albert S B

    2013-03-01

    Sensorineural hearing loss is caused by degeneration of hair cells or auditory neurons. Spiral ganglion cells, the primary afferent neurons of the auditory system, are patterned during development and send out projections to hair cells and to the brainstem under the control of largely unknown guidance molecules. The neurons do not regenerate after loss and even damage to their projections tends to be permanent. The genesis of spiral ganglion neurons and their synapses forms a basis for regenerative approaches. In this review we critically present the current experimental findings on auditory neuron replacement. We discuss the latest advances with a focus on (a) exogenous stem cell transplantation into the cochlea for neural replacement, (b) expression of local guidance signals in the cochlea after loss of auditory neurons, (c) the possibility of neural replacement from an endogenous cell source, and (d) functional changes from cell engraftment. PMID:23370457

  17. Measuring Auditory Selective Attention using Frequency Tagging

    Directory of Open Access Journals (Sweden)

    Hari M Bharadwaj

    2014-02-01

    Full Text Available Frequency tagging of sensory inputs (presenting stimuli that fluctuate periodically at rates to which the cortex can phase lock has been used to study attentional modulation of neural responses to inputs in different sensory modalities. For visual inputs, the visual steady-state response (VSSR at the frequency modulating an attended object is enhanced, while the VSSR to a distracting object is suppressed. In contrast, the effect of attention on the auditory steady-state response (ASSR is inconsistent across studies. However, most auditory studies analyzed results at the sensor level or used only a small number of equivalent current dipoles to fit cortical responses. In addition, most studies of auditory spatial attention used dichotic stimuli (independent signals at the ears rather than more natural, binaural stimuli. Here, we asked whether these methodological choices help explain discrepant results. Listeners attended to one of two competing speech streams, one simulated from the left and one from the right, that were modulated at different frequencies. Using distributed source modeling of magnetoencephalography results, we estimate how spatially directed attention modulates the ASSR in neural regions across the whole brain. Attention enhances the ASSR power at the frequency of the attended stream in the contralateral auditory cortex. The attended-stream modulation frequency also drives phase-locked responses in the left (but not right precentral sulcus (lPCS, a region implicated in control of eye gaze and visual spatial attention. Importantly, this region shows no phase locking to the distracting stream suggesting that the lPCS in engaged in an attention-specific manner. Modeling results that take account of the geometry and phases of the cortical sources phase locked to the two streams (including hemispheric asymmetry of lPCS activity help partly explain why past ASSR studies of auditory spatial attention yield seemingly contradictory

  18. Auditory pitch imagery and its relationship to musical synchronization.

    Science.gov (United States)

    Pecenka, Nadine; Keller, Peter E

    2009-07-01

    Musical ensemble performance requires precise coordination of action. To play in synchrony, ensemble musicians presumably anticipate the sounds that will be produced by their co-performers. These predictions may be based on auditory images in working memory. This study examined the contribution of auditory imagery abilities to sensorimotor synchronization (SMS) in 20 musicians. The acuity of single-tone pitch images was measured by an adjustment method and by adaptive threshold estimation. Different types of finger tapping tasks were administered to assess SMS. Auditory imagery and SMS abilities were found to be positively correlated with one another and with musical experience. PMID:19673794

  19. Robust speech features representation based on computational auditory model

    Institute of Scientific and Technical Information of China (English)

    LU Xugang; JIA Chuan; DANG Jianwu

    2004-01-01

    A speech signal processing and features extracting method based on computational auditory model is proposed. The computational model is based on psychological, physiological knowledge and digital signal processing methods. In each stage of a hearing perception system, there is a corresponding computational model to simulate its function. Based on this model, speech features are extracted. In each stage, the features in different kinds of level are extracted. A further processing for primary auditory spectrum based on lateral inhibition is proposed to extract much more robust speech features. All these features can be regarded as the internal representations of speech stimulation in hearing system. The robust speech recognition experiments are conducted to test the robustness of the features. Results show that the representations based on the proposed computational auditory model are robust representations for speech signals.

  20. Psychophysical and Neural Correlates of Auditory Attraction and Aversion

    Science.gov (United States)

    Patten, Kristopher Jakob

    This study explores the psychophysical and neural processes associated with the perception of sounds as either pleasant or aversive. The underlying psychophysical theory is based on auditory scene analysis, the process through which listeners parse auditory signals into individual acoustic sources. The first experiment tests and confirms that a self-rated pleasantness continuum reliably exists for 20 various stimuli (r = .48). In addition, the pleasantness continuum correlated with the physical acoustic characteristics of consonance/dissonance (r = .78), which can facilitate auditory parsing processes. The second experiment uses an fMRI block design to test blood oxygen level dependent (BOLD) changes elicited by a subset of 5 exemplar stimuli chosen from Experiment 1 that are evenly distributed over the pleasantness continuum. Specifically, it tests and confirms that the pleasantness continuum produces systematic changes in brain activity for unpleasant acoustic stimuli beyond what occurs with pleasant auditory stimuli. Results revealed that the combination of two positively and two negatively valenced experimental sounds compared to one neutral baseline control elicited BOLD increases in the primary auditory cortex, specifically the bilateral superior temporal gyrus, and left dorsomedial prefrontal cortex; the latter being consistent with a frontal decision-making process common in identification tasks. The negatively-valenced stimuli yielded additional BOLD increases in the left insula, which typically indicates processing of visceral emotions. The positively-valenced stimuli did not yield any significant BOLD activation, consistent with consonant, harmonic stimuli being the prototypical acoustic pattern of auditory objects that is optimal for auditory scene analysis. Both the psychophysical findings of Experiment 1 and the neural processing findings of Experiment 2 support that consonance is an important dimension of sound that is processed in a manner that aids

  1. Auditory pathways: anatomy and physiology.

    Science.gov (United States)

    Pickles, James O

    2015-01-01

    This chapter outlines the anatomy and physiology of the auditory pathways. After a brief analysis of the external, middle ears, and cochlea, the responses of auditory nerve fibers are described. The central nervous system is analyzed in more detail. A scheme is provided to help understand the complex and multiple auditory pathways running through the brainstem. The multiple pathways are based on the need to preserve accurate timing while extracting complex spectral patterns in the auditory input. The auditory nerve fibers branch to give two pathways, a ventral sound-localizing stream, and a dorsal mainly pattern recognition stream, which innervate the different divisions of the cochlear nucleus. The outputs of the two streams, with their two types of analysis, are progressively combined in the inferior colliculus and onwards, to produce the representation of what can be called the "auditory objects" in the external world. The progressive extraction of critical features in the auditory stimulus in the different levels of the central auditory system, from cochlear nucleus to auditory cortex, is described. In addition, the auditory centrifugal system, running from cortex in multiple stages to the organ of Corti of the cochlea, is described.

  2. Mitogen-activated protein kinases with distinct requirements for Ste5 scaffolding influence signaling specificity in Saccharomyces cerevisiae.

    Science.gov (United States)

    Flatauer, Laura J; Zadeh, Sheena F; Bardwell, Lee

    2005-03-01

    Scaffold proteins are believed to enhance specificity in cell signaling when different pathways share common components. The prototype scaffold Ste5 binds to multiple components of the Saccharomyces cerevisiae mating pheromone response pathway, thereby conducting the mating signal to the Fus3 mitogen-activated protein kinase (MAPK). Some of the kinases that Ste5 binds to, however, are also shared with other pathways. Thus, it has been presumed that Ste5 prevents its bound kinases from transgressing into other pathways and protects them from intrusions from those pathways. Here we found that Fus3MAPK required Ste5 scaffolding to receive legitimate signals from the mating pathway as well as misdirected signals leaking from other pathways. Furthermore, increasing the cellular concentration of active Ste5 enhanced the channeling of inappropriate stimuli to Fus3. This aberrant signal crossover resulted in the erroneous induction of cell cycle arrest and mating. In contrast to Fus3, the Kss1 MAPK did not require Ste5 scaffolding to receive either authentic or leaking signals. Furthermore, the Ste11 kinase, once activated via Ste5, was able to signal to Kss1 independently of Ste5 scaffolding. These results argue that Ste5 does not act as a barrier that actively prevents signal crossover to Fus3 and that Ste5 may not effectively sequester its activated kinases away from other pathways. Rather, we suggest that specificity in this network is promoted by the selective activation of Ste5 and the distinct requirements of the MAPKs for Ste5 scaffolding. PMID:15713635

  3. Attention to sound improves auditory reliability in audio-tactile spatial optimal integration

    Directory of Open Access Journals (Sweden)

    Tiziana eVercillo

    2015-05-01

    Full Text Available The role of attention on multisensory processing is still poorly understood. In particular, it is unclear whether directing attention toward a sensory cue dynamically reweights cue reliability during integration of multiple sensory signals. In this study, we investigated the impact of attention in combining audio-tactile signals in an optimal fashion. We used the Maximum Likelihood Estimation (MLE model to predict audio-tactile spatial localization on the body surface. We developed a new audio-tactile device composed by several small units, each one consisting of a speaker and a tactile vibrator independently controllable by external software. We tested subjects in an attentional and a non-attentional condition. In the attention experiment participants performed a dual task paradigm: they were required to evaluate the duration of a sound while performing an audio-tactile spatial task. Three unisensory or multisensory stimuli (conflictual or not conflictual sounds and vibrations arranged along the horizontal axis were presented sequentially. In the primary task subjects had to evaluate the position of the second stimulus (the probe with respect to the others (in a space bisection task. In the secondary task they had to report occasionally changes in duration of the second auditory stimulus. In the non-attentional task participants had only to perform the primary task (space bisection. Our results showed enhanced auditory precision (and auditory weights in the auditory attentional condition with respect to the control non-attentional condition. Interestingly in both conditions the multisensory results are well predicted by the MLE model. The results of this study support the idea that modality-specific attention modulates multisensory integration.

  4. Rice Rab11 is required for JA-mediated defense signaling

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Min Ji [Department of Molecular Biotechnology, Dong-A University, Busan 604-714 (Korea, Republic of); BK21 Center for Silver-Bio Industrialization, Dong-A University, Busan 604-714 (Korea, Republic of); Lee, Yun mi [Department of Molecular Biotechnology, Dong-A University, Busan 604-714 (Korea, Republic of); Son, Young Sim [Division of Applied Life Sciences (BK21), Graduate School of Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Im, Chak Han [Eco-Friendliness Research Department, Gyeongsangnam-do Agricultural Research and Extension Services, Jinju 660-360 (Korea, Republic of); Yi, Young Byung [Department of Molecular Biotechnology, Dong-A University, Busan 604-714 (Korea, Republic of); Rim, Yeong Gil [Systems and Synthetic Agrobiotech Center, Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Bahk, Jeong Dong, E-mail: jdbahk@gnu.ac.kr [Division of Applied Life Sciences (BK21), Graduate School of Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Heo, Jae Bok, E-mail: jbheo72@dau.ac.kr [Department of Molecular Biotechnology, Dong-A University, Busan 604-714 (Korea, Republic of); BK21 Center for Silver-Bio Industrialization, Dong-A University, Busan 604-714 (Korea, Republic of)

    2013-05-17

    Highlights: •OsRab11 interacts with OsOPR8. •OsOPR8 is localized in the cytosol and peroxisome. •OsRab11 enhances the NADPH consumption by OsOPR8. •Transgenic Arabidopsis overexpressing OsRab11 represents a pathogen-resistant phenotype. -- Abstract: Rab proteins play an essential role in regulating vesicular transport in eukaryotic cells. Previously, we characterized OsRab11, which in concert with OsGAP1 and OsGDI3 regulates vesicular trafficking from the trans-Golgi network (TGN) to the plasma membrane or vacuole. To further elucidate the physiological function of OsRab11 in plants, we performed yeast two-hybrid screens using OsRab11 as bait. OsOPR8 was isolated and shown to interact with OsRab11. A co-immunoprecipitation assay confirmed this interaction. The green fluorescent protein-OsOPR8 fusion product was targeted to the cytoplasm and peroxisomes of protoplasts from Arabidopsis thaliana. OsOPR8 exhibited NADPH-dependent reduction activity when 2-cyclohexen-1-one (CyHE) and 12-oxo-phytodienoic acid (OPDA) were supplied as possible substrates. Interestingly, NADPH oxidation by OsOPR8 was increased when wild-type OsRab11 or the constitutively active form of OsRab11 (Q78L) were included in the reaction mix, but not when the dominant negative form of OsRab11 (S28N) was included. OsRab11 was expressed broadly in plants and both OsRab11 and OsOPR8 were induced by jasmonic acid (JA) and elicitor treatments. Overexpressed OsRab11 transgenic plants showed resistance to pathogens through induced expression of JA-responsive genes. In conclusion, OsRab11 may be required for JA-mediated defense signaling by activating the reducing activity of OsOPR8.

  5. Visual–auditory spatial processing in auditory cortical neurons

    OpenAIRE

    Bizley, Jennifer K.; King, Andrew J

    2008-01-01

    Neurons responsive to visual stimulation have now been described in the auditory cortex of various species, but their functions are largely unknown. Here we investigate the auditory and visual spatial sensitivity of neurons recorded in 5 different primary and non-primary auditory cortical areas of the ferret. We quantified the spatial tuning of neurons by measuring the responses to stimuli presented across a range of azimuthal positions and calculating the mutual information (MI) between the ...

  6. Development of Receiver Stimulator for Auditory Prosthesis

    Directory of Open Access Journals (Sweden)

    K. Raja Kumar

    2010-05-01

    Full Text Available The Auditory Prosthesis (AP is an electronic device that can provide hearing sensations to people who are profoundly deaf by stimulating the auditory nerve via an array of electrodes with an electric current allowing them to understand the speech. The AP system consists of two hardware functional units such as Body Worn Speech Processor (BWSP and Receiver Stimulator. The prototype model of Receiver Stimulator for Auditory Prosthesis (RSAP consists of Speech Data Decoder, DAC, ADC, constant current generator, electrode selection logic, switch matrix and simulated electrode resistance array. The laboratory model of speech processor is designed to implement the Continuous Interleaved Sampling (CIS speech processing algorithm which generates the information required for electrode stimulation based on the speech / audio data. Speech Data Decoder receives the encoded speech data via an inductive RF transcutaneous link from speech processor. Twelve channels of auditory Prosthesis with selectable eight electrodes for stimulation of simulated electrode resistance array are used for testing. The RSAP is validated by using the test data generated by the laboratory prototype of speech processor. The experimental results are obtained from specific speech/sound tests using a high-speed data acquisition system and found satisfactory.

  7. Auditory confrontation naming in Alzheimer's disease.

    Science.gov (United States)

    Brandt, Jason; Bakker, Arnold; Maroof, David Aaron

    2010-11-01

    Naming is a fundamental aspect of language and is virtually always assessed with visual confrontation tests. Tests of the ability to name objects by their characteristic sounds would be particularly useful in the assessment of visually impaired patients, and may be particularly sensitive in Alzheimer's disease (AD). We developed an auditory naming task, requiring the identification of the source of environmental sounds (i.e., animal calls, musical instruments, vehicles) and multiple-choice recognition of those not identified. In two separate studies mild-to-moderate AD patients performed more poorly than cognitively normal elderly on the auditory naming task. This task was also more difficult than two versions of a comparable visual naming task, and correlated more highly with Mini-Mental State Exam score. Internal consistency reliability was acceptable, although ROC analysis revealed auditory naming to be slightly less successful than visual confrontation naming in discriminating AD patients from normal participants. Nonetheless, our auditory naming task may prove useful in research and clinical practice, especially with visually impaired patients. PMID:20981630

  8. Resizing Auditory Communities

    DEFF Research Database (Denmark)

    Kreutzfeldt, Jacob

    2012-01-01

    Heard through the ears of the Canadian composer and music teacher R. Murray Schafer the ideal auditory community had the shape of a village. Schafer’s work with the World Soundscape Project in the 70s represent an attempt to interpret contemporary environments through musical and auditory...... of sound as an active component in shaping urban environments. As urban conditions spreads globally, new scales, shapes and forms of communities appear and call for new distinctions and models in the study and representation of sonic environments. Particularly so, since urban environments are increasingly...... presents some terminologies for mapping urban environments through its sonic configuration. Such probing into the practices of acoustic territorialisation may direct attention to some of the conflicting and disharmonious interests defining public inclusive domains. The paper investigates the concept...

  9. A role for nitric oxide-driven retrograde signaling in the consolidation of a fear memory

    Directory of Open Access Journals (Sweden)

    Kathie A Overeem

    2010-02-01

    Full Text Available In both invertebrate and vertebrate models of synaptic plasticity, signaling via the putative “retrograde messenger” nitric oxide (NO has been hypothesized to serve as a critical link between functional and structural alterations at pre- and postsynaptic sites. However, while in vitro models of synaptic plasticity have consistently implicated NO signaling in linking postsynaptic induction mechanisms with accompanying presynaptic changes, a convincing role of such “retrograde signaling” in mammalian memory formation has remained elusive. Using auditory Pavlovian fear conditioning, we show that synaptic plasticity and NO signaling in the lateral nucleus of the amygdala (LA regulate the expression of the ERK-driven immediate early gene early growth response gene I (EGR-1 in regions of the auditory thalamus that are presynaptic to the LA. Further, antisense knockdown of EGR-1 in the auditory thalamus impairs both fear memory consolidation and the training-induced elevation of two presynaptically localized proteins in the LA. These findings indicate that synaptic plasticity and NO signaling in the LA during auditory fear conditioning promote alterations in ERK-driven gene expression in auditory thalamic neurons that are required for both fear memory consolidation as well as presynaptic correlates of fear memory formation in the LA, and provide general support for a role of NO as a “retrograde signal” in mammalian memory formation.

  10. Communication and control by listening: towards optimal design of a two-class auditory streaming brain-computer interface

    Directory of Open Access Journals (Sweden)

    N. Jeremy Hill

    2012-12-01

    Full Text Available Most brain-computer interface (BCI systems require users to modulate brain signals in response to visual stimuli. Thus, they may not be useful to people with limited vision, such as those with severe paralysis. One important approach for overcoming this issue is auditory streaming, an approach whereby a BCI system is driven by shifts of attention between two dichotically presented auditory stimulus streams. Motivated by the long-term goal of translating such a system into a reliable, simple yes-no interface for clinical usage, we aim to answer two main questions. First, we asked which of two previously-published variants provides superior performance: a fixed-phase (FP design in which the streams have equal period and opposite phase, or a drifting-phase (DP design where the periods are unequal. We found FP to be superior to DP (p = 0.002: average performance levels were 80% and 72% correct, respectively. We were also able to show, in a pilot with one subject, that auditory streaming can support continuous control and neurofeedback applications: by shifting attention between ongoing left and right auditory streams, the subject was able to control the position of a paddle in a computer game. Second, we examined whether the system is dependent on eye movements, since it is known that eye movements and auditory attention may influence each other, and any dependence on the ability to move one’s eyes would be a barrier to translation to paralyzed users. We discovered that, despite instructions, some subjects did make eye movements that were indicative of the direction of attention. However, there was no correlation, across subjects, between the reliability of the eye movement signal and the reliability of the BCI system, indicating that our system was configured to work independently of eye movement. Together, these findings are an encouraging step forward toward BCIs that provide practical communication and control options for the most severely

  11. Anatomy and Physiology of the Auditory Tracts

    Directory of Open Access Journals (Sweden)

    Mohammad hosein Hekmat Ara

    1999-03-01

    Full Text Available Hearing is one of the excel sense of human being. Sound waves travel through the medium of air and enter the ear canal and then hit the tympanic membrane. Middle ear transfer almost 60-80% of this mechanical energy to the inner ear by means of “impedance matching”. Then, the sound energy changes to traveling wave and is transferred based on its specific frequency and stimulates organ of corti. Receptors in this organ and their synapses transform mechanical waves to the neural waves and transfer them to the brain. The central nervous system tract of conducting the auditory signals in the auditory cortex will be explained here briefly.

  12. Neural responses in songbird forebrain reflect learning rates, acquired salience, and stimulus novelty after auditory discrimination training.

    Science.gov (United States)

    Bell, Brittany A; Phan, Mimi L; Vicario, David S

    2015-03-01

    How do social interactions form and modulate the neural representations of specific complex signals? This question can be addressed in the songbird auditory system. Like humans, songbirds learn to vocalize by imitating tutors heard during development. These learned vocalizations are important in reproductive and social interactions and in individual recognition. As a model for the social reinforcement of particular songs, male zebra finches were trained to peck for a food reward in response to one song stimulus (GO) and to withhold responding for another (NoGO). After performance reached criterion, single and multiunit neural responses to both trained and novel stimuli were obtained from multiple electrodes inserted bilaterally into two songbird auditory processing areas [caudomedial mesopallium (CMM) and caudomedial nidopallium (NCM)] of awake, restrained birds. Neurons in these areas undergo stimulus-specific adaptation to repeated song stimuli, and responses to familiar stimuli adapt more slowly than to novel stimuli. The results show that auditory responses differed in NCM and CMM for trained (GO and NoGO) stimuli vs. novel song stimuli. When subjects were grouped by the number of training days required to reach criterion, fast learners showed larger neural responses and faster stimulus-specific adaptation to all stimuli than slow learners in both areas. Furthermore, responses in NCM of fast learners were more strongly left-lateralized than in slow learners. Thus auditory responses in these sensory areas not only encode stimulus familiarity, but also reflect behavioral reinforcement in our paradigm, and can potentially be modulated by social interactions.

  13. A loudspeaker-based room auralization system for auditory perception research

    DEFF Research Database (Denmark)

    Buchholz, Jörg; Favrot, Sylvain Emmanuel

    2009-01-01

    . This system provides a flexible research platform for conducting auditory experiments with normal-hearing, hearing-impaired, and aided hearing-impaired listeners in a fully controlled and realistic environment. This includes measures of basic auditory function (e.g., signal detection, distance perception...

  14. Design of a New Audio Watermarking System Based on Human Auditory System

    Energy Technology Data Exchange (ETDEWEB)

    Shin, D.H. [Maqtech Co., Ltd., (Korea); Shin, S.W.; Kim, J.W.; Choi, J.U. [Markany Co., Ltd., (Korea); Kim, D.Y. [Bucheon College, Bucheon (Korea); Kim, S.H. [The University of Seoul, Seoul (Korea)

    2002-07-01

    In this paper, we propose a robust digital copyright-protection technique based on the concept of human auditory system. First, we propose a watermarking technique that accepts the various attacks such as, time scaling, pitch shift, add noise and a lot of lossy compression such as MP3, AAC, WMA. Second, we implement audio PD(portable device) for copyright protection using proposed method. The proposed watermarking technique is developed using digital filtering technique. Being designed according to critical band of HAS(human auditory system), the digital filters embed watermark without nearly affecting audio quality. Before processing of digital filtering, wavelet transform decomposes the input audio signal into several signals that are composed of specific frequencies. Then, we embed watermark in the decomposed signal (0kHz-11kHz) by designed band-stop digital filter. Watermarking detection algorithm is implemented on audio PD(portable device). Proposed watermarking technology embeds 2bits information per 15 seconds. If PD detects watermark '11', which means illegal song, PD displays 'Illegal Song' message on LCD, skips the song and plays the next song. The implemented detection algorithm in PD requires 19 MHz computational power, 7.9kBytes ROM and 10kBytes RAM. The suggested technique satisfies SDMI(secure digital music initiative) requirements of platform3 based on ARM9E core. (author). 9 refs., 8 figs.

  15. The catalytic activity of the CD45 membrane-proximal phosphatase domain is required for TCR signaling and regulation

    DEFF Research Database (Denmark)

    Desai, D M; Sap, J; Silvennoinen, O;

    1994-01-01

    Cell surface expression of CD45, a receptor-like protein tyrosine phosphatase (PTPase), is required for T cell antigen receptor (TCR)-mediated signal transduction. Like the majority of transmembrane PTPases, CD45 contains two cytoplasmic phosphatase domains, whose relative in vivo function is not...

  16. Interaction with both ZNRF3 and LGR4 is required for the signalling activity of R-spondin

    OpenAIRE

    Xie, Yang; Zamponi, Raffaella; Charlat, Olga; Ramones, Melissa; Swalley, Susanne; Jiang, Xiaomo; Rivera, Daniel; Tschantz, William; Lu, Bo; Quinn, Lisa; Dimitri, Chris; Parker, Jefferson; Jeffery, Doug; Wilcox, Sheri K; Watrobka, Mike

    2013-01-01

    This study shows that both ZNRF3- and LGR4-binding motifs of R-spondin are required for its Wnt-promoting activity. These results support a dual receptor model of R-spondin signalling, where LGR4 serves as the engagement receptor while ZNRF3 functions as the effector receptor.

  17. beta-Catenin signaling is required for TGF-beta(1)-induced extracellular matrix production by airway smooth muscle cells

    NARCIS (Netherlands)

    Baarsma, Hoeke A.; Menzen, Mark H.; Halayko, Andrew J.; Meurs, Herman; Kerstjens, Huib A. M.; Gosens, Reinoud

    2011-01-01

    Baarsma HA, Menzen MH, Halayko AJ, Meurs H, Kerstjens HA, Gosens R. beta-Catenin signaling is required for TGF-beta(1)-induced extracellular matrix production by airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 301: L956-L965, 2011. First published September 9, 2011; doi: 10.1152/ajplu

  18. Extraembryonic signals under the control of MGA, Max, and Smad4 are required for dorsoventral patterning.

    Science.gov (United States)

    Sun, Yuhua; Tseng, Wei-Chia; Fan, Xiang; Ball, Rebecca; Dougan, Scott T

    2014-02-10

    In vertebrates, extraembryonic tissues can act as signaling centers that impose a reproducible pattern of cell types upon the embryo. Here, we show that the zebrafish yolk syncytial layer (YSL) secretes a ventralizing signal during gastrulation. This activity is mediated by Bmp2b/Swirl (Swr) expressed under the control of Max's giant associated protein (MGA) and its binding partners, Max and Smad4. MGA coimmunoprecipitates with both Max and Smad4 in embryo extracts, and the three proteins form a complex in vitro. Furthermore, all three proteins bind to a DNA fragment upstream of the bmp2b transcription start site. Targeted depletion of MGA, its binding partners, or Bmp2b/Swr from the YSL reduces BMP signaling throughout the embryo, resulting in a mildly dorsalized phenotype. We conclude that MGA, Max, and Smad4 act in the extraembryonic YSL to initiate a positive feedback loop of Bmp signaling within the embryo. PMID:24525188

  19. Intrahepatic Bile Duct Regeneration in Mice Does Not Require Hnf6 or Notch Signaling through Rbpj

    OpenAIRE

    Walter, Teagan J.; Vanderpool, Charles; Cast, Ashley E.; Huppert, Stacey S.

    2014-01-01

    The potential for intrahepatic bile duct (IHBD) regeneration in patients with bile duct insufficiency diseases is poorly understood. Notch signaling and Hnf6 have each been shown to be important for the morphogenesis of IHBDs in mice. One congenital pediatric liver disease characterized by reduced numbers of IHBDs, Alagille syndrome, is associated with mutations in Notch signaling components. Therefore, we investigated whether liver cell plasticity could contribute to IHBD regeneration in mic...

  20. The Acute Effects of Leptin Require PI3K Signaling in the Hypothalamic Ventral Premammillary Nucleus

    OpenAIRE

    Williams, Kevin W; Sohn, Jong-Woo; Donato, Jose; Lee, Charlotte E.; Zhao, Jean J.; Elmquist, Joel K.; Elias, Carol F.

    2011-01-01

    Evidence suggests that the role played by the adipocyte-derived hormone leptin in female reproductive physiologyis mediated in part by neurons located within the ventral premammillary nucleus (PMV). Leptin activates PMV neurons; however, the intracellular signaling pathway and channel(s) involved remain undefined. Notably, leptin's excitatory and inhibitory effects within hypothalamic and brainstem nuclei share the intracellular signaling cascade phosphoinositide 3 kinase (PI3K). Therefore, w...

  1. Scribble participates in Hippo signaling and is required for normal zebrafish pronephros development

    OpenAIRE

    Skouloudaki, Kassiani; Puetz, Michael; Simons, Matias; Courbard, Jean-Remy; Boehlke, Christopher; Hartleben, Björn; Engel, Christina; Moeller, Marcus J.; Englert, Christoph; Bollig, Frank; Schäfer, Tobias; Ramachandran, Haribaskar; Mlodzik, Marek; Huber, Tobias B.; Kuehn, E. Wolfgang

    2009-01-01

    Spatial organization of cells and their appendages is controlled by the planar cell polarity pathway, a signaling cascade initiated by the protocadherin Fat in Drosophila. Vertebrates express 4 Fat molecules, Fat1–4. We found that depletion of Fat1 caused cyst formation in the zebrafish pronephros. Knockdown of the PDZ domain containing the adaptor protein Scribble intensified the cyst-promoting phenotype of Fat1 depletion, suggesting that Fat1 and Scribble act in overlapping signaling cascad...

  2. Pediatric central auditory processing disorder showing elevated threshold on pure tone audiogram.

    Science.gov (United States)

    Maeda, Yukihide; Nakagawa, Atsuko; Nagayasu, Rie; Sugaya, Akiko; Omichi, Ryotaro; Kariya, Shin; Fukushima, Kunihiro; Nishizaki, Kazunori

    2016-10-01

    Central auditory processing disorder (CAPD) is a condition in which dysfunction in the central auditory system causes difficulty in listening to conversations, particularly under noisy conditions, despite normal peripheral auditory function. Central auditory testing is generally performed in patients with normal hearing on the pure tone audiogram (PTA). This report shows that diagnosis of CAPD is possible even in the presence of an elevated threshold on the PTA, provided that the normal function of the peripheral auditory pathway was verified by distortion product otoacoustic emission (DPOAE), auditory brainstem response (ABR), and auditory steady state response (ASSR). Three pediatric cases (9- and 10-year-old girls and an 8-year-old boy) of CAPD with elevated thresholds on PTAs are presented. The chief complaint was difficulty in listening to conversations. PTA showed elevated thresholds, but the responses and thresholds for DPOAE, ABR, and ASSR were normal, showing that peripheral auditory function was normal. Significant findings of central auditory testing such as dichotic speech tests, time compression of speech signals, and binaural interaction tests confirmed the diagnosis of CAPD. These threshold shifts in PTA may provide a new concept of a clinical symptom due to central auditory dysfunction in CAPD. PMID:26922127

  3. Requirement of cAMP signaling for Schwann cell differentiation restricts the onset of myelination.

    Science.gov (United States)

    Bacallao, Ketty; Monje, Paula V

    2015-01-01

    Isolated Schwann cells (SCs) respond to cAMP elevation by adopting a differentiated post-mitotic state that exhibits high levels of Krox-20, a transcriptional enhancer of myelination, and mature SC markers such as the myelin lipid galactocerebroside (O1). To address how cAMP controls myelination, we performed a series of cell culture experiments which compared the differentiating responses of isolated and axon-related SCs to cAMP analogs and ascorbate, a known inducer of axon ensheathment, basal lamina formation and myelination. In axon-related SCs, cAMP induced the expression of Krox-20 and O1 without a concomitant increase in the expression of myelin basic protein (MBP) and without promoting axon ensheathment, collagen synthesis or basal lamina assembly. When cAMP was provided together with ascorbate, a dramatic enhancement of MBP expression occurred, indicating that cAMP primes SCs to form myelin only under conditions supportive of basal lamina formation. Experiments using a combination of cell permeable cAMP analogs and type-selective adenylyl cyclase (AC) agonists and antagonists revealed that selective transmembrane AC (tmAC) activation with forskolin was not sufficient for full SC differentiation and that the attainment of an O1 positive state also relied on the activity of the soluble AC (sAC), a bicarbonate sensor that is insensitive to forskolin and GPCR activation. Pharmacological and immunological evidence indicated that SCs expressed sAC and that sAC activity was required for morphological differentiation and the expression of myelin markers such as O1 and protein zero. To conclude, our data indicates that cAMP did not directly drive myelination but rather the transition into an O1 positive state, which is perhaps the most critical cAMP-dependent rate limiting step for the onset of myelination. The temporally restricted role of cAMP in inducing differentiation independently of basal lamina formation provides a clear example of the uncoupling of signals

  4. Requirement of cAMP signaling for Schwann cell differentiation restricts the onset of myelination.

    Directory of Open Access Journals (Sweden)

    Ketty Bacallao

    Full Text Available Isolated Schwann cells (SCs respond to cAMP elevation by adopting a differentiated post-mitotic state that exhibits high levels of Krox-20, a transcriptional enhancer of myelination, and mature SC markers such as the myelin lipid galactocerebroside (O1. To address how cAMP controls myelination, we performed a series of cell culture experiments which compared the differentiating responses of isolated and axon-related SCs to cAMP analogs and ascorbate, a known inducer of axon ensheathment, basal lamina formation and myelination. In axon-related SCs, cAMP induced the expression of Krox-20 and O1 without a concomitant increase in the expression of myelin basic protein (MBP and without promoting axon ensheathment, collagen synthesis or basal lamina assembly. When cAMP was provided together with ascorbate, a dramatic enhancement of MBP expression occurred, indicating that cAMP primes SCs to form myelin only under conditions supportive of basal lamina formation. Experiments using a combination of cell permeable cAMP analogs and type-selective adenylyl cyclase (AC agonists and antagonists revealed that selective transmembrane AC (tmAC activation with forskolin was not sufficient for full SC differentiation and that the attainment of an O1 positive state also relied on the activity of the soluble AC (sAC, a bicarbonate sensor that is insensitive to forskolin and GPCR activation. Pharmacological and immunological evidence indicated that SCs expressed sAC and that sAC activity was required for morphological differentiation and the expression of myelin markers such as O1 and protein zero. To conclude, our data indicates that cAMP did not directly drive myelination but rather the transition into an O1 positive state, which is perhaps the most critical cAMP-dependent rate limiting step for the onset of myelination. The temporally restricted role of cAMP in inducing differentiation independently of basal lamina formation provides a clear example of the

  5. ROS-Induced JNK and p38 Signaling Is Required for Unpaired Cytokine Activation during Drosophila Regeneration.

    Directory of Open Access Journals (Sweden)

    Paula Santabárbara-Ruiz

    2015-10-01

    Full Text Available Upon apoptotic stimuli, epithelial cells compensate the gaps left by dead cells by activating proliferation. This has led to the proposal that dying cells signal to surrounding living cells to maintain homeostasis. Although the nature of these signals is not clear, reactive oxygen species (ROS could act as a signaling mechanism as they can trigger pro-inflammatory responses to protect epithelia from environmental insults. Whether ROS emerge from dead cells and what is the genetic response triggered by ROS is pivotal to understand regeneration of Drosophila imaginal discs. We genetically induced cell death in wing imaginal discs, monitored the production of ROS and analyzed the signals required for repair. We found that cell death generates a burst of ROS that propagate to the nearby surviving cells. Propagated ROS activate p38 and induce tolerable levels of JNK. The activation of JNK and p38 results in the expression of the cytokines Unpaired (Upd, which triggers the JAK/STAT signaling pathway required for regeneration. Our findings demonstrate that this ROS/JNK/p38/Upd stress responsive module restores tissue homeostasis. This module is not only activated after cell death induction but also after physical damage and reveals one of the earliest responses for imaginal disc regeneration.

  6. ROS-Induced JNK and p38 Signaling Is Required for Unpaired Cytokine Activation during Drosophila Regeneration.

    Science.gov (United States)

    Santabárbara-Ruiz, Paula; López-Santillán, Mireya; Martínez-Rodríguez, Irene; Binagui-Casas, Anahí; Pérez, Lídia; Milán, Marco; Corominas, Montserrat; Serras, Florenci

    2015-10-01

    Upon apoptotic stimuli, epithelial cells compensate the gaps left by dead cells by activating proliferation. This has led to the proposal that dying cells signal to surrounding living cells to maintain homeostasis. Although the nature of these signals is not clear, reactive oxygen species (ROS) could act as a signaling mechanism as they can trigger pro-inflammatory responses to protect epithelia from environmental insults. Whether ROS emerge from dead cells and what is the genetic response triggered by ROS is pivotal to understand regeneration of Drosophila imaginal discs. We genetically induced cell death in wing imaginal discs, monitored the production of ROS and analyzed the signals required for repair. We found that cell death generates a burst of ROS that propagate to the nearby surviving cells. Propagated ROS activate p38 and induce tolerable levels of JNK. The activation of JNK and p38 results in the expression of the cytokines Unpaired (Upd), which triggers the JAK/STAT signaling pathway required for regeneration. Our findings demonstrate that this ROS/JNK/p38/Upd stress responsive module restores tissue homeostasis. This module is not only activated after cell death induction but also after physical damage and reveals one of the earliest responses for imaginal disc regeneration.

  7. A novel 9-class auditory ERP paradigm driving a predictive text entry system

    Directory of Open Access Journals (Sweden)

    Johannes eHöhne

    2011-08-01

    Full Text Available Brain-Computer Interfaces (BCIs based on Event Related Potentials (ERPs strive for offering communication pathways which are independent of muscle activity. While most visual ERP-based BCI paradigms require good control of the user's gaze direction, auditory BCI paradigms overcome this restriction. The present work proposes a novel approach using Auditory Evoked Potentials (AEP for the example of a multiclass text spelling application. To control the ERP speller, BCI users focus their attention to two-dimensional auditory stimuli that vary in both, pitch (high/medium/low and direction (left/middle/right and that are presented via headphones. The resulting nine different control signals are exploited to drive a predictive text entry system. It enables the user to spell a letter by a single 9-class decision plus two additional decisions to confirm a spelled word.This paradigm - called PASS2D - was investigated in an online study with twelve healthy participants. Users spelled with more than 0.8 characters per minute on average (3.4 bits per minute which makes PASS2D a competitive method. It could enrich the toolbox of existing ERP paradigms for BCI end users like late-stage ALS patients.

  8. Using an auditory sensory substitution device to augment vision: evidence from eye movements.

    Science.gov (United States)

    Wright, Thomas D; Margolis, Aaron; Ward, Jamie

    2015-03-01

    Sensory substitution devices convert information normally associated with one sense into another sense (e.g. converting vision into sound). This is often done to compensate for an impaired sense. The present research uses a multimodal approach in which both natural vision and sound-from-vision ('soundscapes') are simultaneously presented. Although there is a systematic correspondence between what is seen and what is heard, we introduce a local discrepancy between the signals (the presence of a target object that is heard but not seen) that the participant is required to locate. In addition to behavioural responses, the participants' gaze is monitored with eye-tracking. Although the target object is only presented in the auditory channel, behavioural performance is enhanced when visual information relating to the non-target background is presented. In this instance, vision may be used to generate predictions about the soundscape that enhances the ability to detect the hidden auditory object. The eye-tracking data reveal that participants look for longer in the quadrant containing the auditory target even when they subsequently judge it to be located elsewhere. As such, eye movements generated by soundscapes reveal the knowledge of the target location that does not necessarily correspond to the actual judgment made. The results provide a proof of principle that multimodal sensory substitution may be of benefit to visually impaired people with some residual vision and, in normally sighted participants, for guiding search within complex scenes. PMID:25511162

  9. Left hemispheric dominance during auditory processing in a noisy environment

    Directory of Open Access Journals (Sweden)

    Ross Bernhard

    2007-11-01

    Full Text Available Abstract Background In daily life, we are exposed to different sound inputs simultaneously. During neural encoding in the auditory pathway, neural activities elicited by these different sounds interact with each other. In the present study, we investigated neural interactions elicited by masker and amplitude-modulated test stimulus in primary and non-primary human auditory cortex during ipsi-lateral and contra-lateral masking by means of magnetoencephalography (MEG. Results We observed significant decrements of auditory evoked responses and a significant inter-hemispheric difference for the N1m response during both ipsi- and contra-lateral masking. Conclusion The decrements of auditory evoked neural activities during simultaneous masking can be explained by neural interactions evoked by masker and test stimulus in peripheral and central auditory systems. The inter-hemispheric differences of N1m decrements during ipsi- and contra-lateral masking reflect a basic hemispheric specialization contributing to the processing of complex auditory stimuli such as speech signals in noisy environments.

  10. Auditory and non-auditory effects of noise on health

    NARCIS (Netherlands)

    Basner, M.; Babisch, W.; Davis, A.; Brink, M.; Clark, C.; Janssen, S.A.; Stansfeld, S.

    2013-01-01

    Noise is pervasive in everyday life and can cause both auditory and non-auditory health eff ects. Noise-induced hearing loss remains highly prevalent in occupational settings, and is increasingly caused by social noise exposure (eg, through personal music players). Our understanding of molecular mec

  11. Stimulator with arbitrary waveform for auditory evoked potentials

    Energy Technology Data Exchange (ETDEWEB)

    Martins, H R; Romao, M; Placido, D; Provenzano, F; Tierra-Criollo, C J [Universidade Federal de Minas Gerais (UFMG), Departamento de Engenharia Eletrica (DEE), Nucleo de Estudos e Pesquisa em Engenharia Biomedica NEPEB, Av. Ant. Carlos, 6627, sala 2206, Pampulha, Belo Horizonte, MG, 31.270-901 (Brazil)

    2007-11-15

    The technological improvement helps many medical areas. The audiometric exams involving the auditory evoked potentials can make better diagnoses of auditory disorders. This paper proposes the development of a stimulator based on Digital Signal Processor. This stimulator is the first step of an auditory evoked potential system based on the ADSP-BF533 EZ KIT LITE (Analog Devices Company - USA). The stimulator can generate arbitrary waveform like Sine Waves, Modulated Amplitude, Pulses, Bursts and Pips. The waveforms are generated through a graphical interface programmed in C++ in which the user can define the parameters of the waveform. Furthermore, the user can set the exam parameters as number of stimuli, time with stimulation (Time ON) and time without stimulus (Time OFF). In future works will be implemented another parts of the system that includes the acquirement of electroencephalogram and signal processing to estimate and analyze the evoked potential.

  12. The Effects of Auditory Contrast Tuning upon Speech Intelligibility

    Science.gov (United States)

    Killian, Nathan J.; Watkins, Paul V.; Davidson, Lisa S.; Barbour, Dennis L.

    2016-01-01

    We have previously identified neurons tuned to spectral contrast of wideband sounds in auditory cortex of awake marmoset monkeys. Because additive noise alters the spectral contrast of speech, contrast-tuned neurons, if present in human auditory cortex, may aid in extracting speech from noise. Given that this cortical function may be underdeveloped in individuals with sensorineural hearing loss, incorporating biologically-inspired algorithms into external signal processing devices could provide speech enhancement benefits to cochlear implantees. In this study we first constructed a computational signal processing algorithm to mimic auditory cortex contrast tuning. We then manipulated the shape of contrast channels and evaluated the intelligibility of reconstructed noisy speech using a metric to predict cochlear implant user perception. Candidate speech enhancement strategies were then tested in cochlear implantees with a hearing-in-noise test. Accentuation of intermediate contrast values or all contrast values improved computed intelligibility. Cochlear implant subjects showed significant improvement in noisy speech intelligibility with a contrast shaping procedure.

  13. Lens regeneration from the cornea requires suppression of Wnt/β-catenin signaling.

    Science.gov (United States)

    Hamilton, Paul W; Sun, Yu; Henry, Jonathan J

    2016-04-01

    The frog, Xenopus laevis, possesses a high capacity to regenerate various larval tissues, including the lens, which is capable of complete regeneration from the cornea epithelium. However, the molecular signaling mechanisms of cornea-lens regeneration are not fully understood. Previous work has implicated the involvement of the Wnt signaling pathway, but molecular studies have been very limited. Iris-derived lens regeneration in the newt (Wolffian lens regeneration) has shown a necessity for active Wnt signaling in order to regenerate a new lens. Here we provide evidence that the Wnt signaling pathway plays a different role in the context of cornea-lens regeneration in Xenopus. We examined the expression of frizzled receptors and wnt ligands in the frog cornea epithelium. Numerous frizzled receptors (fzd1, fzd2, fzd3, fzd4, fzd6, fzd7, fzd8, and fzd10) and wnt ligands (wnt2b.a, wnt3a, wnt4, wnt5a, wnt5b, wnt6, wnt7b, wnt10a, wnt11, and wnt11b) are expressed in the cornea epithelium, demonstrating that this tissue is transcribing many of the ligands and receptors of the Wnt signaling pathway. When compared to flank epithelium, which is lens regeneration incompetent, only wnt11 and wnt11b are different (present only in the cornea epithelium), identifying them as potential regulators of cornea-lens regeneration. To detect changes in canonical Wnt/β-catenin signaling occurring within the cornea epithelium, axin2 expression was measured over the course of regeneration. axin2 is a well-established reporter of active Wnt/β-catenin signaling, and its expression shows a significant decrease at 24 h post-lentectomy. This decrease recovers to normal endogenous levels by 48 h. To test whether this signaling decrease was necessary for lens regeneration to occur, regenerating eyes were treated with either 6-bromoindirubin-3'-oxime (BIO) or 1-azakenpaullone - both activators of Wnt signaling - resulting in a significant reduction in the percentage of cases with successful

  14. Requirements of transcription factor Smad-dependent and -independent TGF-β signaling to control discrete T-cell functions

    OpenAIRE

    Gu, Ai-di; Wang, Yunqi; Lin, Lin; Zhang, Song S.; Wan, Yisong Y.

    2012-01-01

    TGF-β modulates immune response by suppressing non-regulatory T (Treg) function and promoting Treg function. The question of whether TGF-β achieves distinct effects on non-Treg and Treg cells through discrete signaling pathways remains outstanding. In this study, we investigated the requirements of Smad-dependent and -independent TGF-β signaling for T-cell function. Smad2 and Smad3 double deficiency in T cells led to lethal inflammatory disorder in mice. Non-Treg cells were spontaneously acti...

  15. The plastic ear and perceptual relearning in auditory spatial perception.

    Science.gov (United States)

    Carlile, Simon

    2014-01-01

    The auditory system of adult listeners has been shown to accommodate to altered spectral cues to sound location which presumably provides the basis for recalibration to changes in the shape of the ear over a life time. Here we review the role of auditory and non-auditory inputs to the perception of sound location and consider a range of recent experiments looking at the role of non-auditory inputs in the process of accommodation to these altered spectral cues. A number of studies have used small ear molds to modify the spectral cues that result in significant degradation in localization performance. Following chronic exposure (10-60 days) performance recovers to some extent and recent work has demonstrated that this occurs for both audio-visual and audio-only regions of space. This begs the questions as to the teacher signal for this remarkable functional plasticity in the adult nervous system. Following a brief review of influence of the motor state in auditory localization, we consider the potential role of auditory-motor learning in the perceptual recalibration of the spectral cues. Several recent studies have considered how multi-modal and sensory-motor feedback might influence accommodation to altered spectral cues produced by ear molds or through virtual auditory space stimulation using non-individualized spectral cues. The work with ear molds demonstrates that a relatively short period of training involving audio-motor feedback (5-10 days) significantly improved both the rate and extent of accommodation to altered spectral cues. This has significant implications not only for the mechanisms by which this complex sensory information is encoded to provide spatial cues but also for adaptive training to altered auditory inputs. The review concludes by considering the implications for rehabilitative training with hearing aids and cochlear prosthesis. PMID:25147497

  16. The plastic ear and perceptual relearning in auditory spatial perception.

    Science.gov (United States)

    Carlile, Simon

    2014-01-01

    The auditory system of adult listeners has been shown to accommodate to altered spectral cues to sound location which presumably provides the basis for recalibration to changes in the shape of the ear over a life time. Here we review the role of auditory and non-auditory inputs to the perception of sound location and consider a range of recent experiments looking at the role of non-auditory inputs in the process of accommodation to these altered spectral cues. A number of studies have used small ear molds to modify the spectral cues that result in significant degradation in localization performance. Following chronic exposure (10-60 days) performance recovers to some extent and recent work has demonstrated that this occurs for both audio-visual and audio-only regions of space. This begs the questions as to the teacher signal for this remarkable functional plasticity in the adult nervous system. Following a brief review of influence of the motor state in auditory localization, we consider the potential role of auditory-motor learning in the perceptual recalibration of the spectral cues. Several recent studies have considered how multi-modal and sensory-motor feedback might influence accommodation to altered spectral cues produced by ear molds or through virtual auditory space stimulation using non-individualized spectral cues. The work with ear molds demonstrates that a relatively short period of training involving audio-motor feedback (5-10 days) significantly improved both the rate and extent of accommodation to altered spectral cues. This has significant implications not only for the mechanisms by which this complex sensory information is encoded to provide spatial cues but also for adaptive training to altered auditory inputs. The review concludes by considering the implications for rehabilitative training with hearing aids and cochlear prosthesis.

  17. The plastic ear and perceptual relearning in auditory spatial perception.

    Directory of Open Access Journals (Sweden)

    Simon eCarlile

    2014-08-01

    Full Text Available The auditory system of adult listeners has been shown to accommodate to altered spectral cues to sound location which presumably provides the basis for recalibration to changes in the shape of the ear over a life time. Here we review the role of auditory and non-auditory inputs to the perception of sound location and consider a range of recent experiments looking at the role of non-auditory inputs in the process of accommodation to these altered spectral cues. A number of studies have used small ear moulds to modify the spectral cues that result in significant degradation in localization performance. Following chronic exposure (10-60 days performance recovers to some extent and recent work has demonstrated that this occurs for both audio-visual and audio-only regions of space. This begs the questions as to the teacher signal for this remarkable functional plasticity in the adult nervous system. Following a brief review of influence of the motor state in auditory localisation, we consider the potential role of auditory-motor learning in the perceptual recalibration of the spectral cues. Several recent studies have considered how multi-modal and sensory-motor feedback might influence accommodation to altered spectral cues produced by ear moulds or through virtual auditory space stimulation using non-individualised spectral cues. The work with ear moulds demonstrates that a relatively short period of training involving sensory-motor feedback (5 – 10 days significantly improved both the rate and extent of accommodation to altered spectral cues. This has significant implications not only for the mechanisms by which this complex sensory information is encoded to provide a spatial code but also for adaptive training to altered auditory inputs. The review concludes by considering the implications for rehabilitative training with hearing aids and cochlear prosthesis.

  18. Retinoic Acid Stimulates Regeneration of Mammalian Auditory Hair Cells

    Science.gov (United States)

    Lefebvre, Philippe P.; Malgrange, Brigitte; Staecker, Hinrich; Moonen, Gustave; van de Water, Thomas R.

    1993-04-01

    Sensorineural hearing loss resulting from the loss of auditory hair cells is thought to be irreversible in mammals. This study provides evidence that retinoic acid can stimulate the regeneration in vitro of mammalian auditory hair cells in ototoxic-poisoned organ of Corti explants in the rat. In contrast, treatment with retinoic acid does not stimulate the formation of extra hair cells in control cultures of Corti's organ. Retinoic acid-stimulated hair cell regeneration can be blocked by cytosine arabinoside, which suggests that a period of mitosis is required for the regeneration of auditory hair cells in this system. These results provide hope for a recovery of hearing function in mammals after auditory hair cell damage.

  19. BMP signaling requires retromer-dependent recycling of the type I receptor

    OpenAIRE

    Gleason, Ryan J; Akintobi, Adenrele M.; Barth D Grant; Padgett, Richard W.

    2014-01-01

    The mechanisms that mediate bone morphogenetic protein (BMP) receptor recycling, and the importance of such recycling for signaling in vivo, have remained poorly understood. We find that the retromer complex functions as a linchpin in the recycling of the BMP type I receptor SMA-6 (small-6). In the absence of retromer-dependent recycling, retromer mutants result in the missorting of SMA-6 to lysosomes and a loss of BMP-mediated signaling. Surprisingly, we find that the BMP type II receptor, D...

  20. PV plasticity sustained through D1/5 dopamine signaling required for long-term memory consolidation.

    Science.gov (United States)

    Karunakaran, Smitha; Chowdhury, Ananya; Donato, Flavio; Quairiaux, Charles; Michel, Christoph M; Caroni, Pico

    2016-03-01

    Long-term consolidation of memories depends on processes occurring many hours after acquisition. Whether this involves plasticity that is specifically required for long-term consolidation remains unclear. We found that learning-induced plasticity of local parvalbumin (PV) basket cells was specifically required for long-term, but not short/intermediate-term, memory consolidation in mice. PV plasticity, which involves changes in PV and GAD67 expression and connectivity onto PV neurons, was regulated by cAMP signaling in PV neurons. Following induction, PV plasticity depended on local D1/5 dopamine receptor signaling at 0-5 h to regulate its magnitude, and at 12-14 h for its continuance, ensuring memory consolidation. D1/5 dopamine receptor activation selectively induced DARPP-32 and ERK phosphorylation in PV neurons. At 12-14 h, PV plasticity was required for enhanced sharp-wave ripple densities and c-Fos expression in pyramidal neurons. Our results reveal general network mechanisms of long-term memory consolidation that requires plasticity of PV basket cells induced after acquisition and sustained subsequently through D1/5 receptor signaling.

  1. APC mutant zebrafish uncover a changing temporal requirement for wnt signaling in liver development.

    NARCIS (Netherlands)

    Goessling, W.; North, T.E.; Lord, A.M.; Ceol, C.; Lee, S.; Weidinger, G.; Bourque, C.; Strijbosch, R.; Haramis, A.P.; Puder, M.; Clevers, H.; Moon, R.T.; Zon, L.I.

    2008-01-01

    Developmental signaling pathways hold the keys to unlocking the promise of adult tissue regeneration, and to inhibiting carcinogenesis. Patients with mutations in the Adenomatous Polyposis Coli (APC) gene are at increased risk of developing hepatoblastoma, an embryonal form of liver cancer, suggesti

  2. Partial Epilepsy with Auditory Features

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2004-07-01

    Full Text Available The clinical characteristics of 53 sporadic (S cases of idiopathic partial epilepsy with auditory features (IPEAF were analyzed and compared to previously reported familial (F cases of autosomal dominant partial epilepsy with auditory features (ADPEAF in a study at the University of Bologna, Italy.

  3. Phosphorylation of Sox9 is required for neural crest delamination and is regulated downstream of BMP and canonical Wnt signaling.

    Science.gov (United States)

    Liu, Jessica A J; Wu, Ming-Hoi; Yan, Carol H; Chau, Bolton K H; So, Henry; Ng, Alvis; Chan, Alan; Cheah, Kathryn S E; Briscoe, James; Cheung, Martin

    2013-02-19

    Coordination of neural crest cell (NCC) induction and delamination is orchestrated by several transcription factors. Among these, Sry-related HMG box-9 (Sox9) and Snail2 have been implicated in both the induction of NCC identity and, together with phoshorylation, NCC delamination. How phosphorylation effects this function has not been clear. Here we show, in the developing chick neural tube, that phosphorylation of Sox9 on S64 and S181 facilitates its SUMOylation, and the phosphorylated forms of Sox9 are essential for trunk neural crest delamination. Both phosphorylation and to a lesser extent SUMOylation, of Sox9 are required to cooperate with Snail2 to promote delamination. Moreover, bone morphogenetic protein and canonical Wnt signaling induce phosphorylation of Sox9, thereby connecting extracellular signals with the delamination of NCCs. Together the data suggest a model in which extracellular signals initiate phosphorylation of Sox9 and its cooperation with Snail2 to induce NCC delamination. PMID:23382206

  4. Recording of electrically evoked auditory brainstem responses (E-ABR) with an integrated stimulus generator in Matlab.

    Science.gov (United States)

    Bahmer, Andreas; Peter, Otto; Baumann, Uwe

    2008-08-30

    Electrical auditory brainstem responses (E-ABRs) of subjects with cochlear implants are used for monitoring the physiologic responses of early signal processing of the auditory system. Additionally, E-ABR measurements allow the diagnosis of retro-cochlear diseases. Therefore, E-ABR should be available in every cochlear implant center as a diagnostic tool. In this paper, we introduce a low-cost setup designed to perform an E-ABR as well as a conventional ABR for research purposes. The distributable form was developed with Matlab and the Matlab Compiler (The Mathworks Inc.). For the ABR, only a PC with a soundcard, conventional system headphones, and an EEG pre-amplifier are necessary; for E-ABR, in addition, an interface to the cochlea implant is required. For our purposes, we implemented an interface for the Combi 40+/Pulsar implant (MED-EL, Innsbruck).

  5. The Perception of Auditory Motion.

    Science.gov (United States)

    Carlile, Simon; Leung, Johahn

    2016-01-01

    The growing availability of efficient and relatively inexpensive virtual auditory display technology has provided new research platforms to explore the perception of auditory motion. At the same time, deployment of these technologies in command and control as well as in entertainment roles is generating an increasing need to better understand the complex processes underlying auditory motion perception. This is a particularly challenging processing feat because it involves the rapid deconvolution of the relative change in the locations of sound sources produced by rotational and translations of the head in space (self-motion) to enable the perception of actual source motion. The fact that we perceive our auditory world to be stable despite almost continual movement of the head demonstrates the efficiency and effectiveness of this process. This review examines the acoustical basis of auditory motion perception and a wide range of psychophysical, electrophysiological, and cortical imaging studies that have probed the limits and possible mechanisms underlying this perception. PMID:27094029

  6. Response recovery in the locust auditory pathway.

    Science.gov (United States)

    Wirtssohn, Sarah; Ronacher, Bernhard

    2016-01-01

    Temporal resolution and the time courses of recovery from acute adaptation of neurons in the auditory pathway of the grasshopper Locusta migratoria were investigated with a response recovery paradigm. We stimulated with a series of single click and click pair stimuli while performing intracellular recordings from neurons at three processing stages: receptors and first and second order interneurons. The response to the second click was expressed relative to the single click response. This allowed the uncovering of the basic temporal resolution in these neurons. The effect of adaptation increased with processing layer. While neurons in the auditory periphery displayed a steady response recovery after a short initial adaptation, many interneurons showed nonlinear effects: most prominent a long-lasting suppression of the response to the second click in a pair, as well as a gain in response if a click was preceded by a click a few milliseconds before. Our results reveal a distributed temporal filtering of input at an early auditory processing stage. This set of specified filters is very likely homologous across grasshopper species and thus forms the neurophysiological basis for extracting relevant information from a variety of different temporal signals. Interestingly, in terms of spike timing precision neurons at all three processing layers recovered very fast, within 20 ms. Spike waveform analysis of several neuron types did not sufficiently explain the response recovery profiles implemented in these neurons, indicating that temporal resolution in neurons located at several processing layers of the auditory pathway is not necessarily limited by the spike duration and refractory period.

  7. Midbrain auditory selectivity to natural sounds.

    Science.gov (United States)

    Wohlgemuth, Melville J; Moss, Cynthia F

    2016-03-01

    This study investigated auditory stimulus selectivity in the midbrain superior colliculus (SC) of the echolocating bat, an animal that relies on hearing to guide its orienting behaviors. Multichannel, single-unit recordings were taken across laminae of the midbrain SC of the awake, passively listening big brown bat, Eptesicus fuscus. Species-specific frequency-modulated (FM) echolocation sound sequences with dynamic spectrotemporal features served as acoustic stimuli along with artificial sound sequences matched in bandwidth, amplitude, and duration but differing in spectrotemporal structure. Neurons in dorsal sensory regions of the bat SC responded selectively to elements within the FM sound sequences, whereas neurons in ventral sensorimotor regions showed broad response profiles to natural and artificial stimuli. Moreover, a generalized linear model (GLM) constructed on responses in the dorsal SC to artificial linear FM stimuli failed to predict responses to natural sounds and vice versa, but the GLM produced accurate response predictions in ventral SC neurons. This result suggests that auditory selectivity in the dorsal extent of the bat SC arises through nonlinear mechanisms, which extract species-specific sensory information. Importantly, auditory selectivity appeared only in responses to stimuli containing the natural statistics of acoustic signals used by the bat for spatial orientation-sonar vocalizations-offering support for the hypothesis that sensory selectivity enables rapid species-specific orienting behaviors. The results of this study are the first, to our knowledge, to show auditory spectrotemporal selectivity to natural stimuli in SC neurons and serve to inform a more general understanding of mechanisms guiding sensory selectivity for natural, goal-directed orienting behaviors.

  8. Peripheral Auditory Mechanisms

    CERN Document Server

    Hall, J; Hubbard, A; Neely, S; Tubis, A

    1986-01-01

    How weIl can we model experimental observations of the peripheral auditory system'? What theoretical predictions can we make that might be tested'? It was with these questions in mind that we organized the 1985 Mechanics of Hearing Workshop, to bring together auditory researchers to compare models with experimental observations. Tbe workshop forum was inspired by the very successful 1983 Mechanics of Hearing Workshop in Delft [1]. Boston University was chosen as the site of our meeting because of the Boston area's role as a center for hearing research in this country. We made a special effort at this meeting to attract students from around the world, because without students this field will not progress. Financial support for the workshop was provided in part by grant BNS- 8412878 from the National Science Foundation. Modeling is a traditional strategy in science and plays an important role in the scientific method. Models are the bridge between theory and experiment. Tbey test the assumptions made in experim...

  9. Protease activated receptor signaling is required for African trypanosome traversal of human brain microvascular endothelial cells.

    Directory of Open Access Journals (Sweden)

    Dennis J Grab

    Full Text Available BACKGROUND: Using human brain microvascular endothelial cells (HBMECs as an in vitro model for how African trypanosomes cross the human blood-brain barrier (BBB we recently reported that the parasites cross the BBB by generating calcium activation signals in HBMECs through the activity of parasite cysteine proteases, particularly cathepsin L (brucipain. In the current study, we examined the possible role of a class of protease stimulated HBMEC G protein coupled receptors (GPCRs known as protease activated receptors (PARs that might be implicated in calcium signaling by African trypanosomes. METHODOLOGY/PRINCIPAL FINDINGS: Using RNA interference (RNAi we found that in vitro PAR-2 gene (F2RL1 expression in HBMEC monolayers could be reduced by over 95%. We also found that the ability of Trypanosoma brucei rhodesiense to cross F2RL1-silenced HBMEC monolayers was reduced (39%-49% and that HBMECs silenced for F2RL1 maintained control levels of barrier function in the presence of the parasite. Consistent with the role of PAR-2, we found that HBMEC barrier function was also maintained after blockade of Galpha(q with Pasteurella multocida toxin (PMT. PAR-2 signaling has been shown in other systems to have neuroinflammatory and neuroprotective roles and our data implicate a role for proteases (i.e. brucipain and PAR-2 in African trypanosome/HBMEC interactions. Using gene-profiling methods to interrogate candidate HBMEC pathways specifically triggered by brucipain, several pathways that potentially link some pathophysiologic processes associated with CNS HAT were identified. CONCLUSIONS/SIGNIFICANCE: Together, the data support a role, in part, for GPCRs as molecular targets for parasite proteases that lead to the activation of Galpha(q-mediated calcium signaling. The consequence of these events is predicted to be increased permeability of the BBB to parasite transmigration and the initiation of neuroinflammation, events precursory to CNS disease.

  10. Requirement of JIP scaffold proteins for NMDA-mediated signal transduction

    OpenAIRE

    Kennedy, Norman J.; Martin, Gilles; Ehrhardt, Anka G.; Cavanagh-Kyros, Julie; Kuan, Chia-Yi; Rakic, Pasko; Richard A Flavell; Treistman, Steven N.; Davis, Roger J

    2007-01-01

    JIP scaffold proteins are implicated in the regulation of protein kinase signal transduction pathways. To test the physiological role of these scaffold proteins, we examined the phenotype of compound mutant mice that lack expression of JIP proteins. These mice were found to exhibit severe defects in N-methyl-D-aspartic acid (NMDA) receptor function, including decreased NMDA-evoked current amplitude, cytoplasmic Ca++, and gene expression. The decreased NMDA receptor activity in JIP-deficient n...

  11. Antidepressant effects of sleep deprivation require astrocyte-dependent adenosine mediated signaling

    OpenAIRE

    Hines, D J; Schmitt, L I; Hines, R. M.; Moss, S J; Haydon, P. G.

    2013-01-01

    Major depressive disorder is a debilitating condition with a lifetime risk of ten percent. Most treatments take several weeks to achieve clinical efficacy, limiting the ability to bring instant relief needed in psychiatric emergencies. One intervention that rapidly alleviates depressive symptoms is sleep deprivation; however, its mechanism of action is unknown. Astrocytes regulate responses to sleep deprivation, raising the possibility that glial signaling mediates antidepressive-like actions...

  12. Hedgehog signaling is required at multiple stages of zebrafish tooth development

    OpenAIRE

    Stock David W; Yoo James J; Jackman William R

    2010-01-01

    Abstract Background The accessibility of the developing zebrafish pharyngeal dentition makes it an advantageous system in which to study many aspects of tooth development from early initiation to late morphogenesis. In mammals, hedgehog signaling is known to be essential for multiple stages of odontogenesis; however, potential roles for the pathway during initiation of tooth development or in later morphogenesis are incompletely understood. Results We have identified mRNA expression of the he...

  13. Integration of hormonal signaling networks and mobile microRNAs is required for vascular patterning in Arabidopsis roots

    KAUST Repository

    Muraro, D.

    2013-12-31

    As multicellular organisms grow, positional information is continually needed to regulate the pattern in which cells are arranged. In the Arabidopsis root, most cell types are organized in a radially symmetric pattern; however, a symmetry-breaking event generates bisymmetric auxin and cytokinin signaling domains in the stele. Bidirectional cross-talk between the stele and the surrounding tissues involving a mobile transcription factor, SHORT ROOT (SHR), and mobile microRNA species also determines vascular pattern, but it is currently unclear how these signals integrate. We use a multicellular model to determine a minimal set of components necessary for maintaining a stable vascular pattern. Simulations perturbing the signaling network show that, in addition to the mutually inhibitory interaction between auxin and cytokinin, signaling through SHR, microRNA165/6, and PHABULOSA is required to maintain a stable bisymmetric pattern. We have verified this prediction by observing loss of bisymmetry in shr mutants. The model reveals the importance of several features of the network, namely the mutual degradation of microRNA165/6 and PHABULOSA and the existence of an additional negative regulator of cytokinin signaling. These components form a plausible mechanism capable of patterning vascular tissues in the absence of positional inputs provided by the transport of hormones from the shoot.

  14. MRTF-SRF signaling is required for seeding of HSC/Ps in bone marrow during development.

    Science.gov (United States)

    Costello, Patrick; Sargent, Mathew; Maurice, Diane; Esnault, Cyril; Foster, Katie; Anjos-Afonso, Fernando; Treisman, Richard

    2015-02-19

    Chemokine signaling is important for the seeding of different sites by hematopoietic stem cells (HSCs) during development. Serum response factor (SRF) controls multiple genes governing adhesion and migration, mainly by recruiting members of the myocardin-related transcription factor (MRTF) family of G-actin-regulated cofactors. We used vav-iCre to inactivate MRTF-SRF signaling early during hematopoietic development. In both Srf- and Mrtf-deleted animals, hematopoiesis in fetal liver and spleen is intact but does not become established in fetal bone marrow. Srf-null HSC progenitor cells (HSC/Ps) fail to effectively engraft in transplantation experiments, exhibiting normal proximal signaling responses to SDF-1, but reduced adhesiveness, F-actin assembly, and reduced motility. Srf-null HSC/Ps fail to polarize in response to SDF-1 and cannot migrate through restrictive membrane pores to SDF-1 or Scf in vitro. Mrtf-null HSC/Ps were also defective in chemotactic responses to SDF-1. Srf-null HSC/Ps exhibit substantial deficits in cytoskeletal gene expression. MRTF-SRF signaling is thus critical for expression of genes required for the response to chemokine signaling during hematopoietic development. PMID:25573994

  15. PDK1 is required for the hormonal signaling pathway leading to meiotic resumption in starfish oocytes.

    Science.gov (United States)

    Hiraoka, Daisaku; Hori-Oshima, Sawako; Fukuhara, Takeshi; Tachibana, Kazunori; Okumura, Eiichi; Kishimoto, Takeo

    2004-12-15

    Meiotic resumption is generally under the control of an extracellular maturation-inducing hormone. It is equivalent to the G2-M phase transition in somatic cell mitosis and is regulated by cyclin B-Cdc2 kinase. However, the complete signaling pathway from the hormone to cyclin B-Cdc2 is yet unclear in any organism. A model system to analyze meiotic resumption is the starfish oocyte, in which Akt/protein kinase B (PKB) plays a key mediator in hormonal signaling that leads to cyclin B-Cdc2 activation. Here we show in starfish oocytes that when PDK1 activity is inhibited by a neutralizing antibody, maturation-inducing hormone fails to induce cyclin B-Cdc2 activation at the meiotic G2-M phase transition, even though PDK2 activity becomes detectable. These observations assign a novel role to PDK1 for a hormonal signaling intermediate toward meiotic resumption. They further support that PDK2 is a molecule distinct from PDK1 and Akt, and that PDK2 activity is not sufficient for the full activation of Akt in the absence of PDK1 activity. PMID:15581868

  16. Human neural stem cell-induced endothelial morphogenesis requires autocrine/paracrine and juxtacrine signaling

    Science.gov (United States)

    Chou, Chung-Hsing; Modo, Michel

    2016-01-01

    Transplanted neural stem cells (NSC) interact with the host brain microenvironment. A neovascularization is commonly observed in the vicinity of the cell deposit, which is correlated with behavioral improvements. To elucidate the signaling mechanisms between human NSCs and endothelial cells (ECs), these were cocultured in an in vitro model in which NSC-induced endothelial morphogenesis produced a neurovascular environment. Soluble (autocrine/paracrine) and contact–mediated (juxtacrine) signaling molecules were evaluated for two conditionally immortalized fetal NSC lines derived from the cortical anlage (CTXOE03) and ganglionic eminence (STROC05), as well as an adult EC line (D3) derived from the cerebral microvasculature of a hippocampal biopsy. STROC05 were 4 times as efficient to induce endothelial morphogenesis compared to CTXOE03. The cascade of reciprocal interactions between NSCs and ECs in this process was determined by quantifying soluble factors, receptor mapping, and immunocytochemistry for extracellular matrix molecules. The mechanistic significance of these was further evaluated by pharmacological blockade. The sequential cell-specific regulation of autocrine/paracrine and juxtacrine signaling accounted for the differential efficiency of NSCs to induce endothelial morphogenesis. These in vitro studies shed new light on the reciprocal interactions between NSCs and ECs, which are pivotal for our mechanistic understanding of the efficacy of NSC transplantation. PMID:27374240

  17. Virus-induced gene silencing reveals signal transduction components required for the Pvr9-mediated hypersensitive response in Nicotiana benthamiana.

    Science.gov (United States)

    Tran, Phu-Tri; Choi, Hoseong; Choi, Doil; Kim, Kook-Hyung

    2016-08-01

    Resistance to pathogens mediated by plant resistance (R) proteins requires different signaling transduction components and pathways. Our previous studies revealed that a potyvirus resistance gene in pepper, Pvr9, confers a hypersensitive response (HR) to pepper mottle virus in Nicotiana benthamiana. Our results show that the Pvr9-mediated HR against pepper mottle virus infection requires HSP90, SGT1, NDR1, but not EDS1. These results suggest that the Pvr9-mediated HR is possibly related to the SA pathway but not the ET, JA, ROS or NO pathways.

  18. Frequency-specific modulation of population-level frequency tuning in human auditory cortex

    Directory of Open Access Journals (Sweden)

    Roberts Larry E

    2009-01-01

    Full Text Available Abstract Background Under natural circumstances, attention plays an important role in extracting relevant auditory signals from simultaneously present, irrelevant noises. Excitatory and inhibitory neural activity, enhanced by attentional processes, seems to sharpen frequency tuning, contributing to improved auditory performance especially in noisy environments. In the present study, we investigated auditory magnetic fields in humans that were evoked by pure tones embedded in band-eliminated noises during two different stimulus sequencing conditions (constant vs. random under auditory focused attention by means of magnetoencephalography (MEG. Results In total, we used identical auditory stimuli between conditions, but presented them in a different order, thereby manipulating the neural processing and the auditory performance of the listeners. Constant stimulus sequencing blocks were characterized by the simultaneous presentation of pure tones of identical frequency with band-eliminated noises, whereas random sequencing blocks were characterized by the simultaneous presentation of pure tones of random frequencies and band-eliminated noises. We demonstrated that auditory evoked neural responses were larger in the constant sequencing compared to the random sequencing condition, particularly when the simultaneously presented noises contained narrow stop-bands. Conclusion The present study confirmed that population-level frequency tuning in human auditory cortex can be sharpened in a frequency-specific manner. This frequency-specific sharpening may contribute to improved auditory performance during detection and processing of relevant sound inputs characterized by specific frequency distributions in noisy environments.

  19. AUDITORY REACTION TIME IN BASKETBALL PLAYERS AND HEALTHY CONTROLS

    Directory of Open Access Journals (Sweden)

    Ghuntla Tejas P.

    2013-08-01

    Full Text Available Reaction is purposeful voluntary response to different stimuli as visual or auditory stimuli. Auditory reaction time is time required to response to auditory stimuli. Quickness of response is very important in games like basketball. This study was conducted to compare auditory reaction time of basketball players and healthy controls. The auditory reaction time was measured by the reaction time instrument in healthy controls and basketball players. Simple reaction time and choice reaction time measured. During the reaction time testing, auditory stimuli were given for three times and minimum reaction time was taken as the final reaction time for that sensory modality of that subject. The results were statistically analyzed and were recorded as mean + standard deviation and student’s unpaired t-test was applied to check the level of significance. The study shows that basketball players have shorter reaction time than healthy controls. As reaction time gives the information how fast a person gives a response to sensory stimuli, it is a good indicator of performance in reactive sports like basketball. Sportsman should be trained to improve their reaction time to improve their performance.

  20. A unique cellular scaling rule in the avian auditory system.

    Science.gov (United States)

    Corfield, Jeremy R; Long, Brendan; Krilow, Justin M; Wylie, Douglas R; Iwaniuk, Andrew N

    2016-06-01

    Although it is clear that neural structures scale with body size, the mechanisms of this relationship are not well understood. Several recent studies have shown that the relationship between neuron numbers and brain (or brain region) size are not only different across mammalian orders, but also across auditory and visual regions within the same brains. Among birds, similar cellular scaling rules have not been examined in any detail. Here, we examine the scaling of auditory structures in birds and show that the scaling rules that have been established in the mammalian auditory pathway do not necessarily apply to birds. In galliforms, neuronal densities decrease with increasing brain size, suggesting that auditory brainstem structures increase in size faster than neurons are added; smaller brains have relatively more neurons than larger brains. The cellular scaling rules that apply to auditory brainstem structures in galliforms are, therefore, different to that found in primate auditory pathway. It is likely that the factors driving this difference are associated with the anatomical specializations required for sound perception in birds, although there is a decoupling of neuron numbers in brain structures and hair cell numbers in the basilar papilla. This study provides significant insight into the allometric scaling of neural structures in birds and improves our understanding of the rules that govern neural scaling across vertebrates. PMID:26002617

  1. An anatomical and functional topography of human auditory cortical areas

    Directory of Open Access Journals (Sweden)

    Michelle eMoerel

    2014-07-01

    Full Text Available While advances in magnetic resonance imaging (MRI throughout the last decades have enabled the detailed anatomical and functional inspection of the human brain non-invasively, to date there is no consensus regarding the precise subdivision and topography of the areas forming the human auditory cortex. Here, we propose a topography of the human auditory areas based on insights on the anatomical and functional properties of human auditory areas as revealed by studies of cyto- and myelo-architecture and fMRI investigations at ultra-high magnetic field (7 Tesla. Importantly, we illustrate that - whereas a group-based approach to analyze functional (tonotopic maps is appropriate to highlight the main tonotopic axis - the examination of tonotopic maps at single subject level is required to detail the topography of primary and non-primary areas that may be more variable across subjects. Furthermore, we show that considering multiple maps indicative of anatomical (i.e. myelination as well as of functional properties (e.g. broadness of frequency tuning is helpful in identifying auditory cortical areas in individual human brains. We propose and discuss a topography of areas that is consistent with old and recent anatomical post mortem characterizations of the human auditory cortex and that may serve as a working model for neuroscience studies of auditory functions.

  2. The Wnt Signaling Antagonist Kremen1 is Required for Development of Thymic Architecture

    Directory of Open Access Journals (Sweden)

    Masako Osada

    2006-01-01

    Full Text Available Wnt signaling has been reported to regulate thymocyte proliferation and selection at several stages during T cell ontogeny, as well as the expression of FoxN1 in thymic epithelial cells (TECs. Kremen1 (Krm1 is a negative regulator of the canonical Wnt signaling pathway, and functions together with the secreted Wnt inhibitor Dickkopf (Dkk by competing for the lipoprotein receptor-related protein (LRP-6 co-receptor for Wnts. Here krm1 knockout mice were used to examine krm1 expression in the thymus and its function in thymocyte and TEC development. krm1 expression was detected in both cortical and medullary TEC subsets, as well as in immature thymocyte subsets, beginning at the CD25+CD44+ (DN2 stage and continuing until the CD4+CD8+(DP stage. Neonatal mice show elevated expression of krm1 in all TEC subsets. krm1− / − mice exhibit a severe defect in thymic cortical architecture, including large epithelial free regions. Much of the epithelial component remains at an immature Keratin 5+ (K5 Keratin 8+(K8 stage, with a loss of defined cortical and medullary regions. A TOPFlash assay revealed a 2-fold increase in canonical Wnt signaling in TEC lines derived from krm1− / − mice, when compared with krm1+ / + derived TEC lines. Fluorescence activated cell sorting (FACS analysis of dissociated thymus revealed a reduced frequency of both cortical (BP1+EpCAM+ and medullary (UEA-1+ EpCAMhi epithelial subsets, within the krm1− / − thymus. Surprisingly, no change in thymus size, total thymocyte number or the frequency of thymocyte subsets was detected in krm1− / − mice. However, our data suggest that a loss of Krm1 leads to a severe defect in thymic architecture. Taken together, this study revealed a new role for Krm1 in proper development of thymic epithelium.

  3. Signaling through urokinase and urokinase receptor in lung cancer cells requires interactions with beta1 integrins.

    Science.gov (United States)

    Tang, Chi-Hui; Hill, Marla L; Brumwell, Alexis N; Chapman, Harold A; Wei, Ying

    2008-11-15

    The urokinase receptor (uPAR) is upregulated upon tumor cell invasion and correlates with poor lung cancer survival. Although a cis-interaction with integrins has been ascribed to uPAR, whether this interaction alone is critical to urokinase (uPA)- and uPAR-dependent signaling and tumor promotion is unclear. Here we report the functional consequences of point mutations of uPAR (H249A-D262A) that eliminate beta1 integrin interactions but maintain uPA binding, vitronectin attachment and association with alphaV integrins, caveolin and epidermal growth factor receptor. Disruption of uPAR interactions with beta1 integrins recapitulated previously reported findings with beta1-integrin-derived peptides that attenuated matrix-dependent ERK activation, MMP expression and in vitro migration by human lung adenocarcinoma cell lines. The uPAR mutant cells acquired enhanced capacity to adhere to vitronectin via uPAR-alphaVbeta5-integrin, rather than through the uPAR-alpha3beta1-integrin complex and they were unable to initiate uPA signaling to activate ERK, Akt or Stat1. In an orthotopic lung cancer model, uPAR mutant cells exhibited reduced tumor size compared with cells expressing wild-type uPAR. Taken together, the results indicate that uPAR-beta1-integrin interactions are essential to signals induced by integrin matrix ligands or uPA that support lung cancer cell invasion in vitro and progression in vivo. PMID:18940913

  4. CCN2 is required for the TGF-β induced activation of Smad1-Erk1/2 signaling network.

    Directory of Open Access Journals (Sweden)

    Sashidhar S Nakerakanti

    Full Text Available Connective tissue growth factor (CCN2 is a multifunctional matricellular protein, which is frequently overexpressed during organ fibrosis. CCN2 is a mediator of the pro-fibrotic effects of TGF-β in cultured cells, but the specific function of CCN2 in the fibrotic process has not been elucidated. In this study we characterized the CCN2-dependent signaling pathways that are required for the TGF-β induced fibrogenic response. By depleting endogenous CCN2 we show that CCN2 is indispensable for the TGF-β-induced phosphorylation of Smad1 and Erk1/2, but it is unnecessary for the activation of Smad3. TGF-β stimulation triggered formation of the CCN2/β(3 integrin protein complexes and activation of Src signaling. Furthermore, we demonstrated that signaling through the α(vβ(3 integrin receptor and Src was required for the TGF-β induced Smad1 phosphorylation. Recombinant CCN2 activated Src and Erk1/2 signaling, and induced phosphorylation of Fli1, but was unable to stimulate Smad1 or Smad3 phosphorylation. Additional experiments were performed to investigate the role of CCN2 in collagen production. Consistent with the previous studies, blockade of CCN2 abrogated TGF-β-induced collagen mRNA and protein levels. Recombinant CCN2 potently stimulated collagen mRNA levels and upregulated activity of the COL1A2 promoter, however CCN2 was a weak inducer of collagen protein levels. CCN2 stimulation of collagen was dose-dependent with the lower doses (<50 ng/ml having a stimulatory effect and higher doses having an inhibitory effect on collagen gene expression. In conclusion, our study defines a novel CCN2/α(vβ(3 integrin/Src/Smad1 axis that contributes to the pro-fibrotic TGF-β signaling and suggests that blockade of this pathway may be beneficial for the treatment of fibrosis.

  5. Effects of Presentation Rate and Attention on Auditory Discrimination: A Comparison of Long-Latency Auditory Evoked Potentials in School-Aged Children and Adults.

    Science.gov (United States)

    Choudhury, Naseem A; Parascando, Jessica A; Benasich, April A

    2015-01-01

    Decoding human speech requires both perception and integration of brief, successive auditory stimuli that enter the central nervous system as well as the allocation of attention to language-relevant signals. This study assesses the role of attention on processing rapid transient stimuli in adults and children. Cortical responses (EEG/ERPs), specifically mismatch negativity (MMN) responses, to paired tones (standard 100-100 Hz; deviant 100-300 Hz) separated by a 300, 70 or 10 ms silent gap (ISI) were recorded under Ignore and Attend conditions in 21 adults and 23 children (6-11 years old). In adults, an attention-related enhancement was found for all rate conditions and laterality effects (L>R) were observed. In children, 2 auditory discrimination-related peaks were identified from the difference wave (deviant-standard): an early peak (eMMN) at about 100-300 ms indexing sensory processing, and a later peak (LDN), at about 400-600 ms, thought to reflect reorientation to the deviant stimuli or "second-look" processing. Results revealed differing patterns of activation and attention modulation for the eMMN in children as compared to the MMN in adults: The eMMN had a more frontal topography as compared to adults and attention played a significantly greater role in childrens' rate processing. The pattern of findings for the LDN was consistent with hypothesized mechanisms related to further processing of complex stimuli. The differences between eMMN and LDN observed here support the premise that separate cognitive processes and mechanisms underlie these ERP peaks. These findings are the first to show that the eMMN and LDN differ under different temporal and attentional conditions, and that a more complete understanding of children's responses to rapid successive auditory stimulation requires an examination of both peaks. PMID:26368126

  6. Effects of Presentation Rate and Attention on Auditory Discrimination: A Comparison of Long-Latency Auditory Evoked Potentials in School-Aged Children and Adults.

    Directory of Open Access Journals (Sweden)

    Naseem A Choudhury

    Full Text Available Decoding human speech requires both perception and integration of brief, successive auditory stimuli that enter the central nervous system as well as the allocation of attention to language-relevant signals. This study assesses the role of attention on processing rapid transient stimuli in adults and children. Cortical responses (EEG/ERPs, specifically mismatch negativity (MMN responses, to paired tones (standard 100-100 Hz; deviant 100-300 Hz separated by a 300, 70 or 10 ms silent gap (ISI were recorded under Ignore and Attend conditions in 21 adults and 23 children (6-11 years old. In adults, an attention-related enhancement was found for all rate conditions and laterality effects (L>R were observed. In children, 2 auditory discrimination-related peaks were identified from the difference wave (deviant-standard: an early peak (eMMN at about 100-300 ms indexing sensory processing, and a later peak (LDN, at about 400-600 ms, thought to reflect reorientation to the deviant stimuli or "second-look" processing. Results revealed differing patterns of activation and attention modulation for the eMMN in children as compared to the MMN in adults: The eMMN had a more frontal topography as compared to adults and attention played a significantly greater role in childrens' rate processing. The pattern of findings for the LDN was consistent with hypothesized mechanisms related to further processing of complex stimuli. The differences between eMMN and LDN observed here support the premise that separate cognitive processes and mechanisms underlie these ERP peaks. These findings are the first to show that the eMMN and LDN differ under different temporal and attentional conditions, and that a more complete understanding of children's responses to rapid successive auditory stimulation requires an examination of both peaks.

  7. A songbird forebrain area potentially involved in auditory discrimination and memory formation

    Indian Academy of Sciences (India)

    Raphael Pinaud; Thomas A Terleph

    2008-03-01

    Songbirds rely on auditory processing of natural communication signals for a number of social behaviors, including mate selection, individual recognition and the rare behavior of vocal learning – the ability to learn vocalizations through imitation of an adult model, rather than by instinct. Like mammals, songbirds possess a set of interconnected ascending and descending auditory brain pathways that process acoustic information and that are presumably involved in the perceptual processing of vocal communication signals. Most auditory areas studied to date are located in the caudomedial forebrain of the songbird and include the thalamo-recipient field L (subfields L1, L2 and L3), the caudomedial and caudolateral mesopallium (CMM and CLM, respectively) and the caudomedial nidopallium (NCM). This review focuses on NCM, an auditory area previously proposed to be analogous to parts of the primary auditory cortex in mammals. Stimulation of songbirds with auditory stimuli drives vigorous electrophysiological responses and the expression of several activity-regulated genes in NCM. Interestingly, NCM neurons are tuned to species-specific songs and undergo some forms of experience-dependent plasticity in-vivo. These activity-dependent changes may underlie long-term modifications in the functional performance of NCM and constitute a potential neural substrate for auditory discrimination. We end this review by discussing evidence that suggests that NCM may be a site of auditory memory formation and/or storage.

  8. Effects of multitasking on operator performance using computational and auditory tasks.

    Science.gov (United States)

    Fasanya, Bankole K

    2016-09-01

    This study investigated the effects of multiple cognitive tasks on human performance. Twenty-four students at North Carolina A&T State University participated in the study. The primary task was auditory signal change perception and the secondary task was a computational task. Results showed that participants' performance in a single task was statistically significantly different from their performance in combined tasks: (a) algebra problems (algebra problem primary and auditory perception secondary); (b) auditory perception tasks (auditory perception primary and algebra problems secondary); and (c) mean false-alarm score in auditory perception (auditory detection primary and algebra problems secondary). Using signal detection theory (SDT), participants' performance measured in terms of sensitivity was calculated as -0.54 for combined tasks (algebra problems the primary task) and -0.53 auditory perceptions the primary task. During auditory perception tasks alone, SDT was found to be 2.51. Performance was 83% in a single task compared to 17% when combined tasks. PMID:26886505

  9. Hedgehog signaling is required for cranial neural crest morphogenesis and chondrogenesis at the midline in the zebrafish skull.

    Science.gov (United States)

    Wada, Naoyuki; Javidan, Yashar; Nelson, Sarah; Carney, Thomas J; Kelsh, Robert N; Schilling, Thomas F

    2005-09-01

    Neural crest cells that form the vertebrate head skeleton migrate and interact with surrounding tissues to shape the skull, and defects in these processes underlie many human craniofacial syndromes. Signals at the midline play a crucial role in the development of the anterior neurocranium, which forms the ventral braincase and palate, and here we explore the role of Hedgehog (Hh) signaling in this process. Using sox10:egfp transgenics to follow neural crest cell movements in the living embryo, and vital dye labeling to generate a fate map, we show that distinct populations of neural crest form the two main cartilage elements of the larval anterior neurocranium: the paired trabeculae and the midline ethmoid. By analyzing zebrafish mutants that disrupt sonic hedgehog (shh) expression, we demonstrate that shh is required to specify the movements of progenitors of these elements at the midline, and to induce them to form cartilage. Treatments with cyclopamine, to block Hh signaling at different stages, suggest that although requirements in morphogenesis occur during neural crest migration beneath the brain, requirements in chondrogenesis occur later, as cells form separate trabecular and ethmoid condensations. Cell transplantations indicate that these also reflect different sources of Shh, one from the ventral neural tube that controls trabecular morphogenesis and one from the oral ectoderm that promotes chondrogenesis. Our results suggest a novel role for Shh in the movements of neural crest cells at the midline, as well as in their differentiation into cartilage, and help to explain why both skeletal fusions and palatal clefting are associated with the loss of Hh signaling in holoprosencephalic humans.

  10. A loudspeaker-based room auralization system for auditory research

    DEFF Research Database (Denmark)

    Favrot, Sylvain Emmanuel

    systematically study the signal processing of realistic sounds by normal-hearing and hearing-impaired listeners, a flexible, reproducible and fully controllable auditory environment is needed. A loudspeaker-based room auralization (LoRA) system was developed in this thesis to provide virtual auditory...... investigated the perception of distance in VAEs generated by the LoRA system. These results showed that the distance of far field sources are similarly perceived in these VAEs as in real environments. For close sources (<1 m), a comprehensive study about the near field compensated HOA method was presented and...

  11. Xbp1-Independent Ire1 Signaling Is Required for Photoreceptor Differentiation and Rhabdomere Morphogenesis in Drosophila

    Directory of Open Access Journals (Sweden)

    Dina S. Coelho

    2013-11-01

    Full Text Available The unfolded protein response (UPR is composed by homeostatic signaling pathways that are activated by excessive protein misfolding in the endoplasmic reticulum. Ire1 signaling is an important mediator of the UPR, leading to the activation of the transcription factor Xbp1. Here, we show that Drosophila Ire1 mutant photoreceptors have defects in the delivery of rhodopsin-1 to the rhabdomere and in the secretion of Spacemaker/Eyes Shut into the interrhabdomeral space. However, these defects are not observed in Xbp1 mutant photoreceptors. Ire1 mutant retinas have higher mRNA levels for targets of regulated Ire1-dependent decay (RIDD, including for the fatty acid transport protein (fatp. Importantly, the downregulation of fatp by RNAi rescues the rhodopsin-1 delivery defects observed in Ire1 mutant photoreceptors. Our results show that the role of Ire1 during photoreceptor differentiation is independent of Xbp1 function and demonstrate the physiological relevance of the RIDD mechanism in this specific paradigm.

  12. Rectification is required to extract oscillatory envelope modulation from surface electromyographic signals.

    Science.gov (United States)

    Dakin, Christopher J; Dalton, Brian H; Luu, Billy L; Blouin, Jean-Sébastien

    2014-10-01

    Rectification of surface electromyographic (EMG) recordings prior to their correlation with other signals is a widely used form of preprocessing. Recently this practice has come into question, elevating the subject of EMG rectification to a topic of much debate. Proponents for rectifying suggest it accentuates the EMG spike timing information, whereas opponents indicate it is unnecessary and its nonlinear distortion of data is potentially destructive. Here we examine the necessity of rectification on the extraction of muscle responses, but for the first time using a known oscillatory input to the muscle in the form of electrical vestibular stimulation. Participants were exposed to sinusoidal vestibular stimuli while surface and intramuscular EMG were recorded from the left medial gastrocnemius. We compared the unrectified and rectified surface EMG to single motor units to determine which method best identified stimulus-EMG coherence and phase at the single-motor unit level. Surface EMG modulation at the stimulus frequency was obvious in the unrectified surface EMG. However, this modulation was not identified by the fast Fourier transform, and therefore stimulus coherence with the unrectified EMG signal failed to capture this covariance. Both the rectified surface EMG and single motor units displayed significant coherence over the entire stimulus bandwidth (1-20 Hz). Furthermore, the stimulus-phase relationship for the rectified EMG and motor units shared a moderate correlation (r = 0.56). These data indicate that rectification of surface EMG is a necessary step to extract EMG envelope modulation due to motor unit entrainment to a known stimulus.

  13. Astrocytic Ca2+ signals are required for the functional integrity of tripartite synapses

    Directory of Open Access Journals (Sweden)

    Tanaka Mika

    2013-01-01

    Full Text Available Abstract Background Neuronal activity alters calcium ion (Ca2+ dynamics in astrocytes, but the physiologic relevance of these changes is controversial. To examine this issue further, we generated an inducible transgenic mouse model in which the expression of an inositol 1,4,5-trisphosphate absorbent, “IP3 sponge”, attenuates astrocytic Ca2+ signaling. Results Attenuated Ca2+ activity correlated with reduced astrocytic coverage of asymmetric synapses in the hippocampal CA1 region in these animals. The decreased astrocytic ‘protection’ of the synapses facilitated glutamate ‘spillover’, which was reflected by prolonged glutamate transporter currents in stratum radiatum astrocytes and enhanced N-methyl-D-aspartate receptor currents in CA1 pyramidal neurons in response to burst stimulation. These mice also exhibited behavioral impairments in spatial reference memory and remote contextual fear memory, in which hippocampal circuits are involved. Conclusions Our findings suggest that IP3-mediated astrocytic Ca2+ signaling correlates with the formation of functional tripartite synapses in the hippocampus.

  14. cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission.

    Directory of Open Access Journals (Sweden)

    Ghania Ramdani

    2015-05-01

    Full Text Available Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites.

  15. Auditory processing models

    DEFF Research Database (Denmark)

    Dau, Torsten

    2008-01-01

    The Handbook of Signal Processing in Acoustics will compile the techniques and applications of signal processing as they are used in the many varied areas of Acoustics. The Handbook will emphasize the interdisciplinary nature of signal processing in acoustics. Each Section of the Handbook will pr...

  16. Sounds, signals and space maps

    OpenAIRE

    Carr, Catherine

    2002-01-01

    The auditory system transforms information from one frame of reference into another to create a map of space in the brain. The source of a visual signal that guides this transformation in barn owls has now been found.

  17. Distinct requirements for TrkB and TrkC signaling in target innervation by sensory neurons

    Science.gov (United States)

    Postigo, Antonio; Calella, Anna Maria; Fritzsch, Bernd; Knipper, Marlies; Katz, David; Eilers, Andreas; Schimmang, Thomas; Lewin, Gary R.; Klein, Rudiger; Minichiello, Liliana

    2002-01-01

    Signaling by brain-derived neurotrophic factor (BDNF) via the TrkB receptor, or by neurotrophin-3 (NT3) through the TrkC receptor support distinct populations of sensory neurons. The intracellular signaling pathways activated by Trk (tyrosine kinase) receptors, which in vivo promote neuronal survival and target innervation, are not well understood. Using mice with TrkB or TrkC receptors lacking the docking site for Shc adaptors (trkB(shc/shc) and trkC(shc/shc) mice), we show that TrkB and TrkC promote survival of sensory neurons mainly through Shc site-independent pathways, suggesting that these receptors use similar pathways to prevent apoptosis. In contrast, the regulation of target innervation appears different: in trkB(shc/shc) mice neurons lose target innervation, whereas in trkC(shc/shc) mice the surviving TrkC-dependent neurons maintain target innervation and function. Biochemical analysis indicates that phosphorylation at the Shc site positively regulates autophosphorylation of TrkB, but not of TrkC. Our findings show that although TrkB and TrkC signals mediating survival are largely similar, TrkB and TrkC signals required for maintenance of target innervation in vivo are regulated by distinct mechanisms.

  18. Tactile feedback improves auditory spatial localization

    OpenAIRE

    Gori, Monica; Vercillo, Tiziana; Sandini, Giulio; Burr, David

    2014-01-01

    Our recent studies suggest that congenitally blind adults have severely impaired thresholds in an auditory spatial bisection task, pointing to the importance of vision in constructing complex auditory spatial maps (Gori et al., 2014). To explore strategies that may improve the auditory spatial sense in visually impaired people, we investigated the impact of tactile feedback on spatial auditory localization in 48 blindfolded sighted subjects. We measured auditory spatial bisection thresholds b...

  19. Tactile feedback improves auditory spatial localization

    OpenAIRE

    Monica eGori; Tiziana eVercillo; Giulio eSandini; David eBurr

    2014-01-01

    Our recent studies suggest that congenitally blind adults have severely impaired thresholds in an auditory spatial-bisection task, pointing to the importance of vision in constructing complex auditory spatial maps (Gori et al., 2014). To explore strategies that may improve the auditory spatial sense in visually impaired people, we investigated the impact of tactile feedback on spatial auditory localization in 48 blindfolded sighted subjects. We measured auditory spatial bisection thresholds b...

  20. Auditory Sketches: Very Sparse Representations of Sounds Are Still Recognizable.

    Directory of Open Access Journals (Sweden)

    Vincent Isnard

    Full Text Available Sounds in our environment like voices, animal calls or musical instruments are easily recognized by human listeners. Understanding the key features underlying this robust sound recognition is an important question in auditory science. Here, we studied the recognition by human listeners of new classes of sounds: acoustic and auditory sketches, sounds that are severely impoverished but still recognizable. Starting from a time-frequency representation, a sketch is obtained by keeping only sparse elements of the original signal, here, by means of a simple peak-picking algorithm. Two time-frequency representations were compared: a biologically grounded one, the auditory spectrogram, which simulates peripheral auditory filtering, and a simple acoustic spectrogram, based on a Fourier transform. Three degrees of sparsity were also investigated. Listeners were asked to recognize the category to which a sketch sound belongs: singing voices, bird calls, musical instruments, and vehicle engine noises. Results showed that, with the exception of voice sounds, very sparse representations of sounds (10 features, or energy peaks, per second could be recognized above chance. No clear differences could be observed between the acoustic and the auditory sketches. For the voice sounds, however, a completely different pattern of results emerged, with at-chance or even below-chance recognition performances, suggesting that the important features of the voice, whatever they are, were removed by the sketch process. Overall, these perceptual results were well correlated with a model of auditory distances, based on spectro-temporal excitation patterns (STEPs. This study confirms the potential of these new classes of sounds, acoustic and auditory sketches, to study sound recognition.

  1. Auditory Sketches: Very Sparse Representations of Sounds Are Still Recognizable.

    Science.gov (United States)

    Isnard, Vincent; Taffou, Marine; Viaud-Delmon, Isabelle; Suied, Clara

    2016-01-01

    Sounds in our environment like voices, animal calls or musical instruments are easily recognized by human listeners. Understanding the key features underlying this robust sound recognition is an important question in auditory science. Here, we studied the recognition by human listeners of new classes of sounds: acoustic and auditory sketches, sounds that are severely impoverished but still recognizable. Starting from a time-frequency representation, a sketch is obtained by keeping only sparse elements of the original signal, here, by means of a simple peak-picking algorithm. Two time-frequency representations were compared: a biologically grounded one, the auditory spectrogram, which simulates peripheral auditory filtering, and a simple acoustic spectrogram, based on a Fourier transform. Three degrees of sparsity were also investigated. Listeners were asked to recognize the category to which a sketch sound belongs: singing voices, bird calls, musical instruments, and vehicle engine noises. Results showed that, with the exception of voice sounds, very sparse representations of sounds (10 features, or energy peaks, per second) could be recognized above chance. No clear differences could be observed between the acoustic and the auditory sketches. For the voice sounds, however, a completely different pattern of results emerged, with at-chance or even below-chance recognition performances, suggesting that the important features of the voice, whatever they are, were removed by the sketch process. Overall, these perceptual results were well correlated with a model of auditory distances, based on spectro-temporal excitation patterns (STEPs). This study confirms the potential of these new classes of sounds, acoustic and auditory sketches, to study sound recognition.

  2. Compression of auditory space during forward self-motion.

    Directory of Open Access Journals (Sweden)

    Wataru Teramoto

    shifts in the auditory receptive field locations driven by afferent signals from vestibular system.

  3. Prkci is required for a non-autonomous signal that coordinates cell polarity during cavitation.

    Science.gov (United States)

    Mah, In Kyoung; Soloff, Rachel; Izuhara, Audrey K; Lakeland, Daniel L; Wang, Charles; Mariani, Francesca V

    2016-08-01

    Polarized epithelia define boundaries, spaces, and cavities within organisms. Cavitation, a process by which multicellular hollow balls or tubes are produced, is typically associated with the formation of organized epithelia. In order for these epithelial layers to form, cells must ultimately establish a distinct apical-basal polarity. Atypical PKCs have been proposed to be required for apical-basal polarity in diverse species. Here we show that while cells null for the Prkci isozyme exhibit some polarity characteristics, they fail to properly segregate apical-basal proteins, form a coordinated ectodermal epithelium, or participate in normal cavitation. A failure to cavitate could be due to an overgrowth of interior cells or to an inability of interior cells to die. Null cells however, do not have a marked change in proliferation rate and are still capable of undergoing cell death, suggesting that alterations in these processes are not the predominant cause of the failed cavitation. Overexpression of BMP4 or EZRIN can partially rescue the phenotype possibly by promoting cell death, polarity, and differentiation. However, neither is sufficient to provide the required cues to generate a polarized epithelium and fully rescue cavitation. Interestingly, when wildtype and Prkci(-/-) ES cells are mixed together, a polarized ectodermal epithelium forms and cavitation is rescued, likely due to the ability of wildtype cells to produce non-autonomous polarity cues. We conclude that Prkci is not required for cells to respond to these cues, though it is required to produce them. Together these findings indicate that environmental cues can facilitate the formation of polarized epithelia and that cavitation requires the proper coordination of multiple basic cellular processes including proliferation, differentiation, cell death, and apical-basal polarization. PMID:27312576

  4. Perlecan is required for FGF-2 signaling in the neural stem cell niche

    Directory of Open Access Journals (Sweden)

    Aurelien Kerever

    2014-03-01

    Full Text Available In the adult subventricular zone (neurogenic niche, neural stem cells double-positive for two markers of subsets of neural stem cells in the adult central nervous system, glial fibrillary acidic protein and CD133, lie in proximity to fractones and to blood vessel basement membranes, which contain the heparan sulfate proteoglycan perlecan. Here, we demonstrate that perlecan deficiency reduces the number of both GFAP/CD133-positive neural stem cells in the subventricular zone and new neurons integrating into the olfactory bulb. We also show that FGF-2 treatment induces the expression of cyclin D2 through the activation of the Akt and Erk1/2 pathways and promotes neurosphere formation in vitro. However, in the absence of perlecan, FGF-2 fails to promote neurosphere formation. These results suggest that perlecan is a component of the neurogenic niche that regulates FGF-2 signaling and acts by promoting neural stem cell self-renewal and neurogenesis.

  5. TWEAK/Fn14 signaling is required for liver regeneration after partial hepatectomy in mice.

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    Gamze Karaca

    Full Text Available BACKGROUND & AIMS: Pro-inflammatory cytokines are important for liver regeneration after partial hepatectomy (PH. Expression of Fibroblast growth factor-inducible 14 (Fn14, the receptor for TNF-like weak inducer of apoptosis (TWEAK, is induced rapidly after PH and remains elevated throughout the period of peak hepatocyte replication. The role of Fn14 in post-PH liver regeneration is uncertain because Fn14 is expressed by liver progenitors and TWEAK-Fn14 interactions stimulate progenitor growth, but replication of mature hepatocytes is thought to drive liver regeneration after PH. METHODS: To clarify the role of TWEAK-Fn14 after PH, we compared post-PH regenerative responses in wild type (WT mice, Fn14 knockout (KO mice, TWEAK KO mice, and WT mice treated with anti-TWEAK antibodies. RESULTS: In WT mice, rare Fn14(+ cells localized with other progenitor markers in peri-portal areas before PH. PH rapidly increased proliferation of Fn14(+ cells; hepatocytic cells that expressed Fn14 and other progenitor markers, such as Lgr5, progressively accumulated from 12-8 h post-PH and then declined to baseline by 96 h. When TWEAK/Fn14 signaling was disrupted, progenitor accumulation, induction of pro-regenerative cytokines, hepatocyte and cholangiocyte proliferation, and over-all survival were inhibited, while post-PH liver damage and bilirubin levels were increased. TWEAK stimulated proliferation and increased Lgr5 expression in cultured liver progenitors, but had no effect on either parameter in cultured primary hepatocytes. CONCLUSIONS: TWEAK-FN14 signaling is necessary for the healthy adult liver to regenerate normally after acute partial hepatectomy.

  6. Gap junction signalling mediated through connexin-43 is required for chick limb development.

    Science.gov (United States)

    Makarenkova, H; Patel, K

    1999-03-15

    During chick limb development the gap junction protein Connexin-43 (Cx43) is expressed in discrete spatially restricted domains in the apical ectodermal ridge (AER) and mesenchyme of the zone of polarising activity. Antisense oligonucleotides (ODNs) were used to investigate the role of Connexin-43 (Cx43) in the development of the chick limb bud. We have used unmodified ODNs in Pluronic F-127 gel, which is liquid at low temperature but sets at room temperature and so remains situated at the point of application. As a mild surfactant, the gel increases antisense ODN penetration and supplies ODNs to the embryo continually for 12-18 h. We have shown a strong decrease in Cx43 protein expression after application of specific antisense oligonucleotides but the abundance of a closely related protein, Connexin-32 (Cx32), was not affected. Application of antisense Cx43 ODNs at stages 8-15 HH before limb outgrowth resulted in dramatic limb phenotypes. About 40% of treated embryos exhibited defects such as truncation of the limb bud, fragmentation into two or more domains, or complete splitting of the limb bud into two or three branches. Molecular analysis of antisense treated embryos failed to detect Shh or Bmp-2 in anterior structures and suggested that extra lobes seen in nicked and split limbs were not a result of establishment of new signalling centres as found after the application of FGF to the flank. However, examination of markers for the AER showed a number of abnormalities. In severely truncated specimens we were unable to detect the expression of either Fgf-4 or Fgf-8. In both nicked and split limbs the expression of these genes was discontinuous. Down-regulation of Cx43 after the antisense application could be comparable to AER removal and results in distal truncation of the limb bud. Taken together these data suggest the existence of a feedback loop between the FGFs and signalling mediated by Cx43.

  7. Auditory Neuropathy - A Case of Auditory Neuropathy after Hyperbilirubinemia

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    Maliheh Mazaher Yazdi

    2007-12-01

    Full Text Available Background and Aim: Auditory neuropathy is an hearing disorder in which peripheral hearing is normal, but the eighth nerve and brainstem are abnormal. By clinical definition, patient with this disorder have normal OAE, but exhibit an absent or severely abnormal ABR. Auditory neuropathy was first reported in the late 1970s as different methods could identify discrepancy between absent ABR and present hearing threshold. Speech understanding difficulties are worse than can be predicted from other tests of hearing function. Auditory neuropathy may also affect vestibular function. Case Report: This article presents electrophysiological and behavioral data from a case of auditory neuropathy in a child with normal hearing after bilirubinemia in a 5 years follow-up. Audiological findings demonstrate remarkable changes after multidisciplinary rehabilitation. Conclusion: auditory neuropathy may involve damage to the inner hair cells-specialized sensory cells in the inner ear that transmit information about sound through the nervous system to the brain. Other causes may include faulty connections between the inner hair cells and the nerve leading from the inner ear to the brain or damage to the nerve itself. People with auditory neuropathy have OAEs response but absent ABR and hearing loss threshold that can be permanent, get worse or get better.

  8. Recovery characteristics of the electrically stimulated auditory nerve in deafened guinea pigs : Relation to neuronal status

    NARCIS (Netherlands)

    Ramekers, Dyan; Versnel, Huib; Strahl, Stefan B.; Klis, Sjaak F L; Grolman, Wilko

    2015-01-01

    Successful cochlear implant performance requires adequate responsiveness of the auditory nerve to prolonged pulsatile electrical stimulation. Degeneration of the auditory nerve as a result of severe hair cell loss could considerably compromise this ability. The main objective of this study was to ch

  9. Intact spectral but abnormal temporal processing of auditory stimuli in autism.

    NARCIS (Netherlands)

    Groen, W.B.; Orsouw, L. van; Huurne, N.; Swinkels, S.H.N.; Gaag, R.J. van der; Buitelaar, J.K.; Zwiers, M.P.

    2009-01-01

    The perceptual pattern in autism has been related to either a specific localized processing deficit or a pathway-independent, complexity-specific anomaly. We examined auditory perception in autism using an auditory disembedding task that required spectral and temporal integration. 23 children with h

  10. Calcineurin/Nfat signaling is required for perinatal lung maturation and function

    OpenAIRE

    Davé, Vrushank; Childs, Tawanna; Xu, Yan; Ikegami, Machiko; Besnard, Valérie; Maeda, Yutaka; Wert, Susan E.; Neilson, Joel R.; Crabtree, Gerald R.; Whitsett, Jeffrey A.

    2006-01-01

    Pulmonary surfactant proteins and lipids are required for lung function after birth. Lung immaturity and resultant surfactant deficiency cause respiratory distress syndrome, a common disorder contributing to morbidity and mortality in preterm infants. Surfactant synthesis increases prior to birth in association with formation of the alveoli that mediate efficient gas exchange. To identify mechanisms controlling perinatal lung maturation, the Calcineurin b1 (Cnb1) gene was deleted in the respi...

  11. Auditory Processing Disorder in Children

    Science.gov (United States)

    ... free publications Find organizations Related Topics Auditory Neuropathy Autism Spectrum Disorder: Communication Problems in Children Dysphagia Quick ... NIH… Turning Discovery Into Health ® National Institute on Deafness and Other Communication Disorders 31 Center Drive, MSC ...

  12. Auditory Processing Disorder (For Parents)

    Science.gov (United States)

    ... and school. A positive, realistic attitude and healthy self-esteem in a child with APD can work wonders. And kids with APD can go on to ... Parents MORE ON THIS TOPIC Auditory Processing Disorder Special ...

  13. Neuromagnetic evidence for early auditory restoration of fundamental pitch.

    Directory of Open Access Journals (Sweden)

    Philip J Monahan

    Full Text Available BACKGROUND: Understanding the time course of how listeners reconstruct a missing fundamental component in an auditory stimulus remains elusive. We report MEG evidence that the missing fundamental component of a complex auditory stimulus is recovered in auditory cortex within 100 ms post stimulus onset. METHODOLOGY: Two outside tones of four-tone complex stimuli were held constant (1200 Hz and 2400 Hz, while two inside tones were systematically modulated (between 1300 Hz and 2300 Hz, such that the restored fundamental (also knows as "virtual pitch" changed from 100 Hz to 600 Hz. Constructing the auditory stimuli in this manner controls for a number of spectral properties known to modulate the neuromagnetic signal. The tone complex stimuli only diverged on the value of the missing fundamental component. PRINCIPAL FINDINGS: We compared the M100 latencies of these tone complexes to the M100 latencies elicited by their respective pure tone (spectral pitch counterparts. The M100 latencies for the tone complexes matched their pure sinusoid counterparts, while also replicating the M100 temporal latency response curve found in previous studies. CONCLUSIONS: Our findings suggest that listeners are reconstructing the inferred pitch by roughly 100 ms after stimulus onset and are consistent with previous electrophysiological research suggesting that the inferential pitch is perceived in early auditory cortex.

  14. The role of auditory feedback in sustaining vocal vibratoa)

    Science.gov (United States)

    Leydon, Ciara; Bauer, Jay J.; Larson, Charles R.

    2006-01-01

    Vocal vibrato and tremor are characterized by oscillations in voice fundamental frequency (F0). These oscillations may be sustained by a control loop within the auditory system. One component of the control loop is the pitch-shift reflex (PSR). The PSR is a closed loop negative feedback reflex that is triggered in response to discrepancies between intended and perceived pitch with a latency of ~ 100 ms. Consecutive compensatory reflexive responses lead to oscillations in pitch every ~200 ms, resulting in ~5-Hz modulation of F0. Pitch-shift reflexes were elicited experimentally in six subjects while they sustained /u/ vowels at a comfortable pitch and loudness. Auditory feedback was sinusoidally modulated at discrete integer frequencies (1 to 10 Hz) with ±25 cents amplitude. Modulated auditory feedback induced oscillations in voice F0 output of all subjects at rates consistent with vocal vibrato and tremor. Transfer functions revealed peak gains at 4 to 7 Hz in all subjects, with an average peak gain at 5 Hz. These gains occurred in the modulation frequency region where the voice output and auditory feedback signals were in phase. A control loop in the auditory system may sustain vocal vibrato and tremorlike oscillations in voice F0. PMID:14514211

  15. The role of auditory feedback in sustaining vocal vibrato

    Science.gov (United States)

    Leydon, Ciara; Bauer, Jay J.; Larson, Charles R.

    2003-09-01

    Vocal vibrato and tremor are characterized by oscillations in voice fundamental frequency (F0). These oscillations may be sustained by a control loop within the auditory system. One component of the control loop is the pitch-shift reflex (PSR). The PSR is a closed loop negative feedback reflex that is triggered in response to discrepancies between intended and perceived pitch with a latency of ~100 ms. Consecutive compensatory reflexive responses lead to oscillations in pitch every ~200 ms, resulting in ~5-Hz modulation of F0. Pitch-shift reflexes were elicited experimentally in six subjects while they sustained /you/ vowels at a comfortable pitch and loudness. Auditory feedback was sinusoidally modulated at discrete integer frequencies (1 to 10 Hz) with +/-25 cents amplitude. Modulated auditory feedback induced oscillations in voice F0 output of all subjects at rates consistent with vocal vibrato and tremor. Transfer functions revealed peak gains at 4 to 7 Hz in all subjects, with an average peak gain at 5 Hz. These gains occurred in the modulation frequency region where the voice output and auditory feedback signals were in phase. A control loop in the auditory system may sustain vocal vibrato and tremorlike oscillations in voice F0.

  16. ST2 negatively regulates TLR2 signaling, but is not required for bacterial lipoprotein-induced tolerance.

    LENUS (Irish Health Repository)

    Liu, Jinghua

    2010-05-15

    Activation of TLR signaling is critical for host innate immunity against bacterial infection. Previous studies reported that the ST2 receptor, a member of the Toll\\/IL-1 receptor superfamily, functions as a negative regulator of TLR4 signaling and maintains LPS tolerance. However, it is undetermined whether ST2 negatively regulates TLR2 signaling and furthermore, whether a TLR2 agonist, bacterial lipoprotein (BLP)-induced tolerance is dependent on ST2. In this study, we show that BLP stimulation-induced production of proinflammatory cytokines and immunocomplex formation of TLR2-MyD88 and MyD88-IL-1R-associated kinase (IRAK) were significantly enhanced in ST2-deficient macrophages compared with those in wild-type controls. Furthermore, overexpression of ST2 dose-dependently attenuated BLP-induced NF-kappaB activation, suggesting a negative regulatory role of ST2 in TLR2 signaling. A moderate but significantly attenuated production of TNF-alpha and IL-6 on a second BLP stimulation was observed in BLP-pretreated, ST2-deficient macrophages, which is associated with substantially reduced IRAK-1 protein expression and downregulated TLR2-MyD88 and MyD88-IRAK immunocomplex formation. ST2-deficient mice, when pretreated with a nonlethal dose of BLP, benefitted from an improved survival against a subsequent lethal BLP challenge, indicating BLP tolerance develops in the absence of the ST2 receptor. Taken together, our results demonstrate that ST2 acts as a negative regulator of TLR2 signaling, but is not required for BLP-induced tolerance.

  17. Vitamin D receptor signaling is required for heart development in zebrafish embryo.

    Science.gov (United States)

    Kwon, Hye-Joo

    2016-02-12

    Vitamin D has been found to be associated with cardiovascular diseases. However, the role of vitamin D in heart development during embryonic period is largely unknown. Vitamin D induces its genomic effects through its nuclear receptor, the vitamin D receptor (VDR). The present study investigated the role of VDR on heart development by antisense-mediated knockdown approaches in zebrafish model system. In zebrafish embryos, two distinct VDR genes (vdra and vdrb) have been identified. Knockdown of vdra has little effect on heart development, whereas disrupting vdrb gene causes various cardiac phenotypes, characterized by pericardial edema, slower heart rate and laterality defects. Depletion of both vdra and vdrb (vdra/b) produce additive, but not synergistic effects. To determine whether atrioventricular (AV) cardiomyocytes are properly organized in these embryos, the expression of bmp4, which marks the developing AV boundary at 48 h post-fertilization, was examined. Notably, vdra/b-deficient embryos display ectopic expression of bmp4 towards the ventricle or throughout atrial and ventricular chambers. Taken together, these results suggest that VDR signaling plays an essential role in heart development. PMID:26797277

  18. Polycystin Signaling Is Required for Directed Endothelial Cell Migration and Lymphatic Development

    Directory of Open Access Journals (Sweden)

    Patricia Outeda

    2014-05-01

    Full Text Available Autosomal dominant polycystic kidney disease is a common form of inherited kidney disease that is caused by mutations in two genes, PKD1 (polycystin-1 and PKD2 (polycystin-2. Mice with germline deletion of either gene die in midgestation with a vascular phenotype that includes profound edema. Although an endothelial cell defect has been suspected, the basis of this phenotype remains poorly understood. Here, we demonstrate that edema in Pkd1- and Pkd2-null mice is likely to be caused by defects in lymphatic development. Pkd1 and Pkd2 mutant embryos exhibit reduced lymphatic vessel density and vascular branching along with aberrant migration of early lymphatic endothelial cell precursors. We used cell-based assays to confirm that PKD1- and PKD2-depleted endothelial cells have an intrinsic defect in directional migration that is associated with a failure to establish front-rear polarity. Our studies reveal a role for polycystin signaling in lymphatic development.

  19. Neuronal target identification requires AHA-1-mediated fine-tuning of Wnt signaling in C. elegans.

    Directory of Open Access Journals (Sweden)

    Jingyan Zhang

    2013-06-01

    Full Text Available Electrical synaptic transmission through gap junctions is a vital mode of intercellular communication in the nervous system. The mechanism by which reciprocal target cells find each other during the formation of gap junctions, however, is poorly understood. Here we show that gap junctions are formed between BDU interneurons and PLM mechanoreceptors in C. elegans and the connectivity of BDU with PLM is influenced by Wnt signaling. We further identified two PAS-bHLH family transcription factors, AHA-1 and AHR-1, which function cell-autonomously within BDU and PLM to facilitate the target identification process. aha-1 and ahr-1 act genetically upstream of cam-1. CAM-1, a membrane-bound receptor tyrosine kinase, is present on both BDU and PLM cells and likely serves as a Wnt antagonist. By binding to a cis-regulatory element in the cam-1 promoter, AHA-1 enhances cam-1 transcription. Our study reveals a Wnt-dependent fine-tuning mechanism that is crucial for mutual target cell identification during the formation of gap junction connections.

  20. Dissecting and circumventing the requirement for RAM in CSL-dependent Notch signaling.

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    Scott E Johnson

    Full Text Available The Notch signaling pathway is an intercellular communication network vital to metazoan development. Notch activation leads to the nuclear localization of the intracellular portion (NICD of the Notch receptor. Once in the nucleus, NICD binds the transcription factor CSL through a bivalent interaction involving the high-affinity RAM region and the lower affinity ANK domain, converting CSL from a transcriptionally-repressed to an active state. This interaction is believed to directly displace co-repressor proteins from CSL and recruit co-activator proteins. Here we investigate the consequences of this bivalent organization in converting CSL from the repressed to active form. One proposed function of RAM is to promote the weak ANK:CSL interaction; thus, fusion of CSL-ANK should bypass this function of RAM. We find that a CSL-ANK fusion protein is transcriptionally active in reporter assays, but that the addition of RAM in trans further increases transcriptional activity, suggesting another role of RAM in activation. A single F235L point substitution, which disrupts co-repressor binding to CSL, renders the CSL-ANK fusion fully active and refractory to further stimulation by RAM in trans. These results suggest that in the context of a mammalian CSL-ANK fusion protein, the main role of RAM is to displace co-repressor proteins from CSL.

  1. Smad3 signaling is required for satellite cell function and myogenic differentiation of myoblasts

    Institute of Scientific and Technical Information of China (English)

    Xiaojia Ge; Ravi Kambadur; Craig McFarlane; Anuradha Vajjala; Sudarsanareddy Lokireddy; Zhi Hui Ng; Chek Kun Tan; Nguan Soon Tan; Walter Wahli; Mridula Sharma

    2011-01-01

    TGF-β and myostatin are the two most important regulators of muscle growth.Both growth factors have been shown to signal through a Smad3-dependent pathway.However to date,the role of Smad3 in muscle growth and differentiation is not investigated.Here,we demonstrate that Smad3-null mice have decreased muscle mass and pronounced skeletal muscle atrophy.Consistent with this,we also find increased protein ubiquitination and elevated levels of the ubiquitin E3 ligase MuRF1 in muscle tissue isolated from Smad3-null mice.Loss of Smad3 also led to defective satellite cell (SC) functionality.Smad3-null SCs showed reduced propensity for self-renewal,which may lead to a progressive loss of SC number.Indeed,decreased SC number was observed in skeletal muscle from Smad3- null mice showing signs of severe muscle wasting.Further in vitro analysis of primary myoblast cultures identified that Smad3-nuil myoblasts exhibit impaired proliferation,differentiation and fusion,resulting in the formation of atrophied myotubes.A search for the molecular mechanism revealed that loss of Smad3 results in increased myostatin expression in Smad3-null muscle and myoblasts.Given that myostatin is a negative regulator,we hypothesize that increased myostatin levels are responsible for the atrophic phenotype in Smad3-null mice.Consistent with this theory,inactivation of myostatin in Smad3-null mice rescues the muscle atrophy phenotype.

  2. Xanthogranuloma of the External Auditory Canal Mimicking a Benign Tumor: A Case Report

    Directory of Open Access Journals (Sweden)

    Keisuke Yoshihama

    2012-01-01

    Full Text Available Exostosis, osteoma, and adenoma are the most commonly encountered benign lesions in the external auditory canal. Herein, we report a case of the mass arising from the external auditory canal in a 24-year-old Japanese man. CT revealed the soft tissue mass without bony erosion, and MRI revealed that the mass showed a homogenous, iso signal intensity on a both T1- and T2-weighted image, suggesting that the mass is a benign tumor such as adenoma. Pathological examination showed that the specimen demonstrated xanthogranuloma in the external auditory canal. Although xanthogranuloma of the external auditory canal is extremely rare, otolaryngologists should recognize this condition during the inspection of the external auditory canal.

  3. Musical experience, auditory perception and reading-related skills in children.

    Directory of Open Access Journals (Sweden)

    Karen Banai

    Full Text Available BACKGROUND: The relationships between auditory processing and reading-related skills remain poorly understood despite intensive research. Here we focus on the potential role of musical experience as a confounding factor. Specifically we ask whether the pattern of correlations between auditory and reading related skills differ between children with different amounts of musical experience. METHODOLOGY/PRINCIPAL FINDINGS: Third grade children with various degrees of musical experience were tested on a battery of auditory processing and reading related tasks. Very poor auditory thresholds and poor memory skills were abundant only among children with no musical education. In this population, indices of auditory processing (frequency and interval discrimination thresholds were significantly correlated with and accounted for up to 13% of the variance in reading related skills. Among children with more than one year of musical training, auditory processing indices were better, yet reading related skills were not correlated with them. A potential interpretation for the reduction in the correlations might be that auditory and reading-related skills improve at different rates as a function of musical training. CONCLUSIONS/SIGNIFICANCE: Participants' previous musical training, which is typically ignored in studies assessing the relations between auditory and reading related skills, should be considered. Very poor auditory and memory skills are rare among children with even a short period of musical training, suggesting musical training could have an impact on both. The lack of correlation in the musically trained population suggests that a short period of musical training does not enhance reading related skills of individuals with within-normal auditory processing skills. Further studies are required to determine whether the associations between musical training, auditory processing and memory are indeed causal or whether children with poor auditory and

  4. On Optimality in Auditory Information Processing

    CERN Document Server

    Karlsson, M

    2000-01-01

    We study limits for the detection and estimation of weak sinusoidal signals in the primary part of the mammalian auditory system using a stochastic Fitzhugh-Nagumo (FHN) model and an action-reaction model for synaptic plasticity. Our overall model covers the chain from a hair cell to a point just after the synaptic connection with a cell in the cochlear nucleus. The information processing performance of the system is evaluated using so called phi-divergences from statistics which quantify a dissimilarity between probability measures and are intimately related to a number of fundamental limits in statistics and information theory (IT). We show that there exists a set of parameters that can optimize several important phi-divergences simultaneously and that this set corresponds to a constant quiescent firing rate (QFR) of the spiral ganglion neuron. The optimal value of the QFR is frequency dependent but is essentially independent of the amplitude of the signal (for small amplitudes). Consequently, optimal proce...

  5. FAAH inhibitor OL-135 disrupts contextual, but not auditory, fear conditioning in rats.

    Science.gov (United States)

    Burman, Michael A; Szolusha, Kerribeth; Bind, Rebecca; Kerney, Kristen; Boger, Dale L; Bilsky, Edward J

    2016-07-15

    Anxiety disorders are among the most prevalent psychological disorders, have significant negative impacts on quality of life and the healthcare system, and yet effective treatments remain elusive. Manipulating the endocannabinoid system has demonstrated potential for treating anxiety, although the side effects of direct manipulations of cannabinoid receptors keeps them from widespread clinical use. Disrupting the degradation enzyme fatty acid amide hydrolase (FAAH) enhances endogenous signaling and may produce similar efficacy without the side effects. The current experiments examine the effects of low (5.6mg/kg) or moderate (10.0mg/kg) doses of OL-135, a FAAH inhibitor, on the acquisition and consolidation of classical fear conditioning, a common model of trauma-induced anxiety. The acquisition of contextual, but not auditory, fear conditioning was disrupted by both doses of OL-135. Shock reactivity was not affected. Due to the additional neural circuitry required for contextual, but not auditory, fear conditioning, these data suggest that endocannabinoid signaling outside the amygdala may be critical for a subset of fearful memories.

  6. FAAH inhibitor OL-135 disrupts contextual, but not auditory, fear conditioning in rats.

    Science.gov (United States)

    Burman, Michael A; Szolusha, Kerribeth; Bind, Rebecca; Kerney, Kristen; Boger, Dale L; Bilsky, Edward J

    2016-07-15

    Anxiety disorders are among the most prevalent psychological disorders, have significant negative impacts on quality of life and the healthcare system, and yet effective treatments remain elusive. Manipulating the endocannabinoid system has demonstrated potential for treating anxiety, although the side effects of direct manipulations of cannabinoid receptors keeps them from widespread clinical use. Disrupting the degradation enzyme fatty acid amide hydrolase (FAAH) enhances endogenous signaling and may produce similar efficacy without the side effects. The current experiments examine the effects of low (5.6mg/kg) or moderate (10.0mg/kg) doses of OL-135, a FAAH inhibitor, on the acquisition and consolidation of classical fear conditioning, a common model of trauma-induced anxiety. The acquisition of contextual, but not auditory, fear conditioning was disrupted by both doses of OL-135. Shock reactivity was not affected. Due to the additional neural circuitry required for contextual, but not auditory, fear conditioning, these data suggest that endocannabinoid signaling outside the amygdala may be critical for a subset of fearful memories. PMID:27083303

  7. SDCCAG8 Interacts with RAB Effector Proteins RABEP2 and ERC1 and Is Required for Hedgehog Signaling.

    Directory of Open Access Journals (Sweden)

    Rannar Airik

    Full Text Available Recessive mutations in the SDCCAG8 gene cause a nephronophthisis-related ciliopathy with Bardet-Biedl syndrome-like features in humans. Our previous characterization of the orthologous Sdccag8gt/gt mouse model recapitulated the retinal-renal disease phenotypes and identified impaired DNA damage response signaling as an underlying disease mechanism in the kidney. However, several other phenotypic and mechanistic features of Sdccag8gt/gt mice remained unexplored. Here we show that Sdccag8gt/gt mice exhibit developmental and structural abnormalities of the skeleton and limbs, suggesting impaired Hedgehog (Hh signaling. Indeed, cell culture studies demonstrate the requirement of SDCCAG8 for ciliogenesis and Hh signaling. Using an affinity proteomics approach, we demonstrate that SDCCAG8 interacts with proteins of the centriolar satellites (OFD1, AZI1, of the endosomal sorting complex (RABEP2, ERC1, and with non-muscle myosin motor proteins (MYH9, MYH10, MYH14 at the centrosome. Furthermore, we show that RABEP2 localization at the centrosome is regulated by SDCCAG8. siRNA mediated RABEP2 knockdown in hTERT-RPE1 cells leads to defective ciliogenesis, indicating a critical role for RABEP2 in this process. Together, this study identifies several centrosome-associated proteins as novel SDCCAG8 interaction partners, and provides new insights into the function of SDCCAG8 at this structure.

  8. S1P-Yap1 signaling regulates endoderm formation required for cardiac precursor cell migration in zebrafish.

    Science.gov (United States)

    Fukui, Hajime; Terai, Kenta; Nakajima, Hiroyuki; Chiba, Ayano; Fukuhara, Shigetomo; Mochizuki, Naoki

    2014-10-13

    To form the primary heart tube in zebrafish, bilateral cardiac precursor cells (CPCs) migrate toward the midline beneath the endoderm. Mutants lacking endoderm and fish with defective sphingosine 1-phosphate (S1P) signaling exhibit cardia bifida. Endoderm defects lead to the lack of foothold for the CPCs, whereas the cause of cardia bifida in S1P signaling mutants remains unclear. Here we show that S1P signaling regulates CPC migration through Yes-associated protein 1 (Yap1)-dependent endoderm survival. Cardia bifida seen in spns2 (S1P transporter) morphants and s1pr2 (S1P receptor-2) morphants could be rescued by endodermal expression of nuclear localized form of yap1. yap1 morphants had decreased expression of the Yap1/Tead target connective tissue growth factor a (Ctgfa) and consequently increased endodermal cell apoptosis. Consistently, ctgfa morphants showed defects of the endodermal sheet and cardia bifida. Collectively, we show that S1pr2/Yap1-regulated ctgfa expression is essential for the proper endoderm formation required for CPC migration.

  9. Subcortical neural coding mechanisms for auditory temporal processing.

    Science.gov (United States)

    Frisina, R D

    2001-08-01

    Biologically relevant sounds such as speech, animal vocalizations and music have distinguishing temporal features that are utilized for effective auditory perception. Common temporal features include sound envelope fluctuations, often modeled in the laboratory by amplitude modulation (AM), and starts and stops in ongoing sounds, which are frequently approximated by hearing researchers as gaps between two sounds or are investigated in forward masking experiments. The auditory system has evolved many neural processing mechanisms for encoding important temporal features of sound. Due to rapid progress made in the field of auditory neuroscience in the past three decades, it is not possible to review all progress in this field in a single article. The goal of the present report is to focus on single-unit mechanisms in the mammalian brainstem auditory system for encoding AM and gaps as illustrative examples of how the system encodes key temporal features of sound. This report, following a systems analysis approach, starts with findings in the auditory nerve and proceeds centrally through the cochlear nucleus, superior olivary complex and inferior colliculus. Some general principles can be seen when reviewing this entire field. For example, as one ascends the central auditory system, a neural encoding shift occurs. An emphasis on synchronous responses for temporal coding exists in the auditory periphery, and more reliance on rate coding occurs as one moves centrally. In addition, for AM, modulation transfer functions become more bandpass as the sound level of the signal is raised, but become more lowpass in shape as background noise is added. In many cases, AM coding can actually increase in the presence of background noise. For gap processing or forward masking, coding for gaps changes from a decrease in spike firing rate for neurons of the peripheral auditory system that have sustained response patterns, to an increase in firing rate for more central neurons with

  10. Differentiation of the lateral compartment of the cochlea requires a temporally restricted FGF20 signal.

    Directory of Open Access Journals (Sweden)

    Sung-Ho Huh

    2012-01-01

    Full Text Available A large proportion of age-related hearing loss is caused by loss or damage to outer hair cells in the organ of Corti. The organ of Corti is the mechanosensory transducing apparatus in the inner ear and is composed of inner hair cells, outer hair cells, and highly specialized supporting cells. The mechanisms that regulate differentiation of inner and outer hair cells are not known. Here we report that fibroblast growth factor 20 (FGF20 is required for differentiation of cells in the lateral cochlear compartment (outer hair and supporting cells within the organ of Corti during a specific developmental time. In the absence of FGF20, mice are deaf and lateral compartment cells remain undifferentiated, postmitotic, and unresponsive to Notch-dependent lateral inhibition. These studies identify developmentally distinct medial (inner hair and supporting cells and lateral compartments in the developing organ of Corti. The viability and hearing loss in Fgf20 knockout mice suggest that FGF20 may also be a deafness-associated gene in humans.

  11. Slit2 signaling through Robo1 and Robo2 is required for retinal neovascularization.

    Science.gov (United States)

    Rama, Nicolas; Dubrac, Alexandre; Mathivet, Thomas; Ní Chárthaigh, Róisín-Ana; Genet, Gael; Cristofaro, Brunella; Pibouin-Fragner, Laurence; Ma, Le; Eichmann, Anne; Chédotal, Alain

    2015-05-01

    Ocular neovascular diseases are a leading cause of blindness. Vascular endothelial growth factor (VEGF) blockade improves vision, but not all individuals respond to anti-VEGF treatment, making additional means to prevent neovascularization necessary. Slit-family proteins (Slits) are ligands of Roundabout (Robo) receptors that repel developing axons in the nervous system. Robo1 expression is altered in ocular neovascular diseases, and previous in vitro studies have reported both pro- and anti-angiogenic effects of Slits. However, genetic evidence supporting a role for Slits in ocular neovascularization is lacking. Here we generated conditional knockout mice deficient in various Slit and Robo proteins and found that Slit2 potently and selectively promoted angiogenesis via Robo1 and Robo2 in mouse postnatal retina and in a model of ocular neovascular disease. Mechanistically, Slit2 acting through Robo1 and Robo2 promoted the migration of endothelial cells. These receptors are required for both Slit2- and VEGF-induced Rac1 activation and lamellipodia formation. Thus, Slit2 blockade could potentially be used therapeutically to inhibit angiogenesis in individuals with ocular neovascular disease.

  12. A nuclear export signal within the structural Gag protein is required for prototype foamy virus replication

    Directory of Open Access Journals (Sweden)

    Coiffic Audrey

    2011-01-01

    Full Text Available Abstract Background The Gag polyproteins play distinct roles during the replication cycle of retroviruses, hijacking many cellular machineries to fulfill them. In the case of the prototype foamy virus (PFV, Gag structural proteins undergo transient nuclear trafficking after their synthesis, returning back to the cytoplasm for capsid assembly and virus egress. The functional role of this nuclear stage as well as the molecular mechanism(s responsible for Gag nuclear export are not understood. Results We have identified a leptomycin B (LMB-sensitive nuclear export sequence (NES within the N-terminus of PFV Gag that is absolutely required for the completion of late stages of virus replication. Point mutations of conserved residues within this motif lead to nuclear redistribution of Gag, preventing subsequent virus egress. We have shown that a NES-defective PFV Gag acts as a dominant negative mutant by sequestrating its wild-type counterpart in the nucleus. Trans-complementation experiments with the heterologous NES of HIV-1 Rev allow the cytoplasmic redistribution of FV Gag, but fail to restore infectivity. Conclusions PFV Gag-Gag interactions are finely tuned in the cytoplasm to regulate their functions, capsid assembly, and virus release. In the nucleus, we have shown Gag-Gag interactions which could be involved in the nuclear export of Gag and viral RNA. We propose that nuclear export of unspliced and partially spliced PFV RNAs relies on two complementary mechanisms, which take place successively during the replication cycle.

  13. Acute high fat diet consumption activates the mesolimbic circuit and requires orexin signaling in a mouse model.

    Directory of Open Access Journals (Sweden)

    Spring Valdivia

    Full Text Available Overconsumption of palatable energy-dense foods has negative health implications and it is associated with obesity and several eating disorders. Currently, little is known about the neuronal circuitries activated by the acute ingestion of a rewarding stimulus. Here, we used a combination of immunohistochemistry, pharmacology and neuronal tracing analyses to examine the role of the mesolimbic system in general, and the orexin neurons in particular, in a simple experimental test in which naïve mice are allowed to spontaneously eat a pellet of a high fat diet (HFD for 2 h. We found that acute HFD activates c-Fos expression in several reward-related brain areas, including the ventral tegmental area (VTA, nucleus accumbens, central amygdala and lateral hypothalamic area. We also found that: i- HFD-mediated orosensory stimulation was required for the mesolimbic pathway activation, ii- acute HFD differentially activates dopamine neurons of the paranigral, parabrachial pigmented and interfascicular sub-regions of the VTA, and iii- orexin neurons of the lateral hypothalamic area are responsive to acute HFD. Moreover, orexin signaling blockade, with the orexin 1 receptor antagonist SB-334867, reduces acute HFD consumption and c-Fos induction in the VTA but not in the other mesolimbic nuclei under study. Finally, we found that most orexin neurons responsive to acute HFD innervate the VTA. Our results show that acute HFD consumption recruits the mesolimbic system and that the full manifestation of this eating behavior requires the activation of orexin signaling.

  14. Activation of auditory white matter tracts as revealed by functional magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Tae, Woo Suk [Kangwon National University, Neuroscience Research Institute, School of Medicine, Chuncheon (Korea, Republic of); Yakunina, Natalia; Nam, Eui-Cheol [Kangwon National University, Neuroscience Research Institute, School of Medicine, Chuncheon (Korea, Republic of); Kangwon National University, Department of Otolaryngology, School of Medicine, Chuncheon, Kangwon-do (Korea, Republic of); Kim, Tae Su [Kangwon National University Hospital, Department of Otolaryngology, Chuncheon (Korea, Republic of); Kim, Sam Soo [Kangwon National University, Neuroscience Research Institute, School of Medicine, Chuncheon (Korea, Republic of); Kangwon National University, Department of Radiology, School of Medicine, Chuncheon (Korea, Republic of)

    2014-07-15

    The ability of functional magnetic resonance imaging (fMRI) to detect activation in brain white matter (WM) is controversial. In particular, studies on the functional activation of WM tracts in the central auditory system are scarce. We utilized fMRI to assess and characterize the entire auditory WM pathway under robust experimental conditions involving the acquisition of a large number of functional volumes, the application of broadband auditory stimuli of high intensity, and the use of sparse temporal sampling to avoid scanner noise effects and increase signal-to-noise ratio. Nineteen healthy volunteers were subjected to broadband white noise in a block paradigm; each run had four sound-on/off alternations and was repeated nine times for each subject. Sparse sampling (TR = 8 s) was used. In addition to traditional gray matter (GM) auditory center activation, WM activation was detected in the isthmus and midbody of the corpus callosum (CC), tapetum, auditory radiation, lateral lemniscus, and decussation of the superior cerebellar peduncles. At the individual level, 13 of 19 subjects (68 %) had CC activation. Callosal WM exhibited a temporal delay of approximately 8 s in response to the stimulation compared with GM. These findings suggest that direct evaluation of the entire functional network of the central auditory system may be possible using fMRI, which may aid in understanding the neurophysiological basis of the central auditory system and in developing treatment strategies for various central auditory disorders. (orig.)

  15. Stat2 binding to the interferon-alpha receptor 2 subunit is not required for interferon-alpha signaling.

    Science.gov (United States)

    Nguyen, Vinh-Phúc; Saleh, Abu Z M; Arch, Allison E; Yan, Hai; Piazza, Flavia; Kim, John; Krolewski, John J

    2002-03-22

    The interferon-alpha (IFNalpha) receptor consists of two subunits, the IFNalpha receptor 1 (IFNaR1) and 2 (IFNaR2) chains. Following ligand binding, IFNaR1 is phosphorylated on tyrosine 466, and this site recruits Stat2 via its SH2 domain. In contrast, IFNaR2 binds Stat2 constitutively. In this study we have characterized the Stat2-IFNaR2 interaction and examined its role in IFNalpha signaling. Stat2 binds the major IFNaR2 protein but not a variant containing a shorter cytoplasmic domain. The interaction does not require a STAT SH2 domain. Both tyrosine-phosphorylated and non-phosphorylated Stat2 bind IFNaR2 in vitro; however, relatively little phosphorylated Stat2 associates with IFNaR2 in vivo. In vitro binding assays defined IFNaR2 residues 418-444 as the minimal interaction domain and site-specific mutation of conserved acidic residues within this domain disrupted in vitro and in vivo binding. An IFNaR2 construct carrying these mutations was either (i) overexpressed in 293T cells or (ii) used to complement IFNaR2-deficient U5A cells. Unexpectedly, the activity of an IFNalpha-dependent reporter gene was not reduced but, instead, was enhanced up to 2-fold. This suggests that this particular IFNaR2-Stat2 interaction is not required for IFNalpha signaling, but might act to negatively inhibit signaling. Finally, a doubly truncated recombinant fragment of Stat2, spanning residues 136-702, associated with IFNaR2 in vitro, indicating that the interaction with IFNaR2 is direct and occurs in a central region of Stat2 marked by a hydrophobic core.

  16. Effects of Background Music on Objective and Subjective Performance Measures in an Auditory BCI

    Science.gov (United States)

    Zhou, Sijie; Allison, Brendan Z.; Kübler, Andrea; Cichocki, Andrzej; Wang, Xingyu; Jin, Jing

    2016-01-01

    Several studies have explored brain computer interface (BCI) systems based on auditory stimuli, which could help patients with visual impairments. Usability and user satisfaction are important considerations in any BCI. Although background music can influence emotion and performance in other task environments, and many users may wish to listen to music while using a BCI, auditory, and other BCIs are typically studied without background music. Some work has explored the possibility of using polyphonic music in auditory BCI systems. However, this approach requires users with good musical skills, and has not been explored in online experiments. Our hypothesis was that an auditory BCI with background music would be preferred by subjects over a similar BCI without background music, without any difference in BCI performance. We introduce a simple paradigm (which does not require musical skill) using percussion instrument sound stimuli and background music, and evaluated it in both offline and online experiments. The result showed that subjects preferred the auditory BCI with background music. Different performance measures did not reveal any significant performance effect when comparing background music vs. no background. Since the addition of background music does not impair BCI performance but is preferred by users, auditory (and perhaps other) BCIs should consider including it. Our study also indicates that auditory BCIs can be effective even if the auditory channel is simultaneously otherwise engaged. PMID:27790111

  17. Auditory Short-Term Memory Activation during Score Reading

    OpenAIRE

    Simoens, Veerle L; Mari Tervaniemi

    2013-01-01

    Performing music on the basis of reading a score requires reading ahead of what is being played in order to anticipate the necessary actions to produce the notes. Score reading thus not only involves the decoding of a visual score and the comparison to the auditory feedback, but also short-term storage of the musical information due to the delay of the auditory feedback during reading ahead. This study investigates the mechanisms of encoding of musical information in short-term memory during ...

  18. Association between language development and auditory processing disorders

    Directory of Open Access Journals (Sweden)

    Caroline Nunes Rocha-Muniz

    2014-06-01

    Full Text Available INTRODUCTION: It is crucial to understand the complex processing of acoustic stimuli along the auditory pathway ;comprehension of this complex processing can facilitate our understanding of the processes that underlie normal and altered human communication. AIM: To investigate the performance and lateralization effects on auditory processing assessment in children with specific language impairment (SLI, relating these findings to those obtained in children with auditory processing disorder (APD and typical development (TD. MATERIAL AND METHODS: Prospective study. Seventy-five children, aged 6-12 years, were separated in three groups: 25 children with SLI, 25 children with APD, and 25 children with TD. All went through the following tests: speech-in-noise test, Dichotic Digit test and Pitch Pattern Sequencing test. RESULTS: The effects of lateralization were observed only in the SLI group, with the left ear presenting much lower scores than those presented to the right ear. The inter-group analysis has shown that in all tests children from APD and SLI groups had significantly poorer performance compared to TD group. Moreover, SLI group presented worse results than APD group. CONCLUSION: This study has shown, in children with SLI, an inefficient processing of essential sound components and an effect of lateralization. These findings may indicate that neural processes (required for auditory processing are different between auditory processing and speech disorders.

  19. Options for Auditory Training for Adults with Hearing Loss.

    Science.gov (United States)

    Olson, Anne D

    2015-11-01

    Hearing aid devices alone do not adequately compensate for sensory losses despite significant technological advances in digital technology. Overall use rates of amplification among adults with hearing loss remain low, and overall satisfaction and performance in noise can be improved. Although improved technology may partially address some listening problems, auditory training may be another alternative to improve speech recognition in noise and satisfaction with devices. The literature underlying auditory plasticity following placement of sensory devices suggests that additional auditory training may be needed for reorganization of the brain to occur. Furthermore, training may be required to acquire optimal performance from devices. Several auditory training programs that are readily accessible for adults with hearing loss, hearing aids, or cochlear implants are described. Programs that can be accessed via Web-based formats and smartphone technology are reviewed. A summary table is provided for easy access to programs with descriptions of features that allow hearing health care providers to assist clients in selecting the most appropriate auditory training program to fit their needs. PMID:27587915

  20. Neural Correlates of an Auditory Afterimage in Primary Auditory Cortex

    OpenAIRE

    Noreña, A. J.; Eggermont, J. J.

    2003-01-01

    The Zwicker tone (ZT) is defined as an auditory negative afterimage, perceived after the presentation of an appropriate inducer. Typically, a notched noise (NN) with a notch width of 1/2 octave induces a ZT with a pitch falling in the frequency range of the notch. The aim of the present study was to find potential neural correlates of the ZT in the primary auditory cortex of ketamine-anesthetized cats. Responses of multiunits were recorded simultaneously with two 8-electrode arrays during 1 s...

  1. Sensory Responses during Sleep in Primate Primary and Secondary Auditory Cortex

    OpenAIRE

    Issa, Elias B.; Wang, Xiaoqin

    2008-01-01

    Most sensory stimuli do not reach conscious perception during sleep. It has been thought that the thalamus prevents the relay of sensory information to cortex during sleep, but the consequences for cortical responses to sensory signals in this physiological state remain unclear. We recorded from two auditory cortical areas downstream of the thalamus in naturally sleeping marmoset monkeys. Single neurons in primary auditory cortex either increased or decreased their responses during sleep comp...

  2. Long-latency auditory evoked potentials with verbal and nonverbal stimuli,

    OpenAIRE

    Sheila Jacques Oppitz; Dayane Domeneghini Didoné; Débora Durigon da Silva; Marjana Gois; Jordana Folgearini; Geise Corrêa Ferreira; Michele Vargas Garcia

    2015-01-01

    ABSTRACT INTRODUCTION: Long-latency auditory evoked potentials represent the cortical activity related to attention, memory, and auditory discrimination skills. Acoustic signal processing occurs differently between verbal and nonverbal stimuli, influencing the latency and amplitude patterns. OBJECTIVE: To describe the latencies of the cortical potentials P1, N1, P2, N2, and P3, as well as P3 amplitude, with different speech stimuli and tone bursts, and to classify them in the presence and...

  3. Auditory Speech Perception Tests in Relation to the Coding Strategy in Cochlear Implant

    OpenAIRE

    Bazon, Aline Cristine; Mantello, Erika Barioni; Gonçales, Alina Sanches; Isaac, Myriam de Lima; Hyppolito, Miguel Angelo; Reis, Ana Cláudia Mirândola Barbosa

    2015-01-01

    Introduction  The objective of the evaluation of auditory perception of cochlear implant users is to determine how the acoustic signal is processed, leading to the recognition and understanding of sound. Objective  To investigate the differences in the process of auditory speech perception in individuals with postlingual hearing loss wearing a cochlear implant, using two different speech coding strategies, and to analyze speech perception and handicap perception in relation to the strategy us...

  4. Deriving cochlear delays in humans using otoacoustic emissions and auditory evoked potentials

    DEFF Research Database (Denmark)

    Pigasse, Gilles

    . These methods include: otoacoustic emissions (OAEs), auditory brainstem responses (ABRs) and auditory steady-state responses (ASSRs). A comparison between the three methods was made across and within subjects, in order to highlight the impact of inter-subject variability on the cochlear delay estimates...... results are also given for an experiment using stimuli designed to compensate for OAE delays. These were designed to try and reproduce the success of similar stimuli now used routinely to improve ABR signal-to-noise ratio....

  5. Requirement of TLR4 signaling for the induction of a Th1 immune response elicited by oligomannose-coated liposomes.

    Science.gov (United States)

    Matsuoka, Yuko; Takagi, Hideaki; Yamatani, Minami; Kuroda, Yasuhiro; Sato, Katsuaki; Kojima, Naoya

    2016-10-01

    We have previously demonstrated that administration of oligomannose-coated liposomes (OMLs), in which an antigen is encased, induce antigen-specific Th1 immune responses and CTLs. In the present study, we showed that TLR4 signaling is required for the induction of specific immune responses following OML administration. In C3H/HeJ mice, which express a dysfunctional TLR4, the antigen-specific Th1 immune response could not be elicited following intraperitoneal administration of OVA-encased OMLs (OML/OVA). However, OML uptake by peritoneal cells, the subsequent production of IL-12 and the upregulation of co-stimulatory molecules and MHC class II on the cells in response to OML uptake occurred in C3H/HeJ mice to the same extent as in wild type C3H/HeN mice. In addition, peritoneal phagocytic cells from TLR4(-/-) mice that ingest OML/OVA can activate CD4(+) T cells from OT-II mice. On the other hand, the number of OML-ingesting peritoneal cells that migrated into mesenteric lymph nodes in C3H/HeJ mice was significantly less than that in C3H/HeN mice. Therefore, the chemotactic capability of OML-ingesting peritoneal phagocytes to the draining lymph nodes rather than the activation and maturation of the cells in response to OML uptake is impaired by lack of TLR4 signaling, and disorder of the Th1 immune response elicited by OMLs in mice, which lack TLR4 signaling, is due to the impairment of cell migration following OML uptake. PMID:27485186

  6. An Elk transcription factor is required for Runx-dependent survival signaling in the sea urchin embryo.

    Science.gov (United States)

    Rizzo, Francesca; Coffman, James A; Arnone, Maria Ina

    2016-08-01

    Elk proteins are Ets family transcription factors that regulate cell proliferation, survival, and differentiation in response to ERK (extracellular-signal regulated kinase)-mediated phosphorylation. Here we report the embryonic expression and function of Sp-Elk, the single Elk gene of the sea urchin Strongylocentrotus purpuratus. Sp-Elk is zygotically expressed throughout the embryo beginning at late cleavage stage, with peak expression occurring at blastula stage. Morpholino antisense-mediated knockdown of Sp-Elk causes blastula-stage developmental arrest and embryo disintegration due to apoptosis, a phenotype that is rescued by wild-type Elk mRNA. Development is also rescued by Elk mRNA encoding a serine to aspartic acid substitution (S402D) that mimics ERK-mediated phosphorylation of a conserved site that enhances DNA binding, but not by Elk mRNA encoding an alanine substitution at the same site (S402A). This demonstrates both that the apoptotic phenotype of the morphants is specifically caused by Elk depletion, and that phosphorylation of serine 402 of Sp-Elk is critical for its anti-apoptotic function. Knockdown of Sp-Elk results in under-expression of several regulatory genes involved in cell fate specification, cell cycle control, and survival signaling, including the transcriptional regulator Sp-Runt-1 and its target Sp-PKC1, both of which were shown previously to be required for cell survival during embryogenesis. Both Sp-Runt-1 and Sp-PKC1 have sequences upstream of their transcription start sites that specifically bind Sp-Elk. These results indicate that Sp-Elk is the signal-dependent activator of a feed-forward gene regulatory circuit, consisting also of Sp-Runt-1 and Sp-PKC1, which actively suppresses apoptosis in the early embryo. PMID:27235147

  7. Auditory Hallucinations in Acute Stroke

    Directory of Open Access Journals (Sweden)

    Yair Lampl

    2005-01-01

    Full Text Available Auditory hallucinations are uncommon phenomena which can be directly caused by acute stroke, mostly described after lesions of the brain stem, very rarely reported after cortical strokes. The purpose of this study is to determine the frequency of this phenomenon. In a cross sectional study, 641 stroke patients were followed in the period between 1996–2000. Each patient underwent comprehensive investigation and follow-up. Four patients were found to have post cortical stroke auditory hallucinations. All of them occurred after an ischemic lesion of the right temporal lobe. After no more than four months, all patients were symptom-free and without therapy. The fact the auditory hallucinations may be of cortical origin must be taken into consideration in the treatment of stroke patients. The phenomenon may be completely reversible after a couple of months.

  8. Adaptation in the auditory system: an overview

    OpenAIRE

    David ePérez-González; Malmierca, Manuel S.

    2014-01-01

    The early stages of the auditory system need to preserve the timing information of sounds in order to extract the basic features of acoustic stimuli. At the same time, different processes of neuronal adaptation occur at several levels to further process the auditory information. For instance, auditory nerve fiber responses already experience adaptation of their firing rates, a type of response that can be found in many other auditory nuclei and may be useful for emphasizing the onset of the s...

  9. Mutational analysis of the vacuolar sorting signal of procarboxypeptidase Y in yeast shows a low requirement for sequence conservation

    DEFF Research Database (Denmark)

    van Voorst, F; Kielland-Brandt, Morten; Winther, Jakob R.

    1996-01-01

    be exchanged with the other hydrophobic amino acid residues, isoleucine, valine, and phenylalanine. Tolerance toward various substitutions for Arg25 is fairly high, while substitution of Pro26 for uncharged amino acid residues also resulted in only weak missorting. In addition to the low requirement......The core of the vacuolar targeting signal of yeast carboxypeptidase Y (CPY) is recognized by the receptor Vps10p and consists of four contiguous amino acid residues, Gln24-Arg-Pro-Leu27, near the amino terminus of the propeptide (Valls, L.A., Winther, J. R., and Stevens, T. H. (1990) J. Cell Biol...... site-directed mutagenesis. The efficiency of vacuolar sorting by the mutants was determined by immunoprecipitation of CPY from pulse-labeled cells. It was found that amino acid residues Gln24 and Leu27 were the most important ones. While it appears that Gln24 is essential for proper function, Leu27 can...

  10. Auditory complaints in scuba divers: an overview.

    Science.gov (United States)

    Evens, Rachel A; Bardsley, Barry; C Manchaiah, Vinaya K

    2012-03-01

    Pre-1970s, diving was seen as a predominantly male working occupation. Since then it has become a popular hobby, with increasing access to SCUBA diving while on holiday. For a leisure activity, diving puts the auditory system at the risk of a wide variety of complaints. However, there is still insufficient consensus on the frequency of these conditions, which ultimately would require more attention from hearing-healthcare professionals. A literature search of epidemiology studies of eight auditory complaints was conducted, using both individual and large-scale diving studies, with some reference to large-scale non-diving populations . A higher incidence was found for middle ear barotrauma, eustachian tube dysfunction, and alternobaric vertigo with a high correlation among females. Comparing these findings with a non-diving population found no statistically significant difference for hearing loss or tinnitus. Increased awareness of health professionals is required, training, and implementation of the Frenzel technique would help resolve the ambiguities of the Valsalva technique underwater. PMID:23448900

  11. Minimal effects of visual memory training on auditory performance of adult cochlear implant users

    Directory of Open Access Journals (Sweden)

    Sandra I. Oba, MS

    2013-02-01

    Full Text Available Auditory training has been shown to significantly improve cochlear implant (CI users’ speech and music perception. However, it is unclear whether posttraining gains in performance were due to improved auditory perception or to generally improved attention, memory, and/or cognitive processing. In this study, speech and music perception, as well as auditory and visual memory, were assessed in 10 CI users before, during, and after training with a nonauditory task. A visual digit span (VDS task was used for training, in which subjects recalled sequences of digits presented visually. After the VDS training, VDS performance significantly improved. However, there were no significant improvements for most auditory outcome measures (auditory digit span, phoneme recognition, sentence recognition in noise, digit recognition in noise, except for small (but significant improvements in vocal emotion recognition and melodic contour identification. Posttraining gains were much smaller with the nonauditory VDS training than observed in previous auditory training studies with CI users. The results suggest that posttraining gains observed in previous studies were not solely attributable to improved attention or memory and were more likely due to improved auditory perception. The results also suggest that CI users may require targeted auditory training to improve speech and music perception.

  12. Grasping the sound: Auditory pitch influences size processing in motor planning.

    Science.gov (United States)

    Rinaldi, Luca; Lega, Carlotta; Cattaneo, Zaira; Girelli, Luisa; Bernardi, Nicolò Francesco

    2016-01-01

    Growing evidence shows that individuals consistently match auditory pitch with visual size. For instance, high-pitched sounds are perceptually associated with smaller visual stimuli, whereas low-pitched sounds with larger ones. The present study explores whether this crossmodal correspondence, reported so far for perceptual processing, also modulates motor planning. To address this issue, we carried out a series of kinematic experiments to verify whether actions implying size processing are affected by auditory pitch. Experiment 1 showed that grasping movements toward small/large objects were initiated faster in response to high/low pitches, respectively, thus extending previous findings in the literature to more complex motor behavior. Importantly, auditory pitch influenced the relative scaling of the hand preshaping, with high pitches associated with smaller grip aperture compared with low pitches. Notably, no effect of auditory pitch was found in case of pointing movements (no grasp implied, Experiment 2), as well as when auditory pitch was irrelevant to the programming of the grip aperture, that is, in case of grasping an object of uniform size (Experiment 3). Finally, auditory pitch influenced also symbolic manual gestures expressing "small" and "large" concepts (Experiment 4). In sum, our results are novel in revealing the impact of auditory pitch on motor planning when size processing is required, and shed light on the role of auditory information in driving actions. (PsycINFO Database Record PMID:26280267

  13. The impact of educational level on performance on auditory processing tests

    Directory of Open Access Journals (Sweden)

    Cristina F.B. Murphy

    2016-03-01

    Full Text Available Research has demonstrated that a higher level of education is associated with better performance on cognitive tests among middle-aged and elderly people. However, the effects of education on auditory processing skills have not yet been evaluated. Previous demonstrations of sensory-cognitive interactions in the aging process indicate the potential importance of this topic. Therefore, the primary purpose of this study was to investigate the performance of middle-aged and elderly people with different levels of formal education on auditory processing tests. A total of 177 adults with no evidence of cognitive, psychological or neurological conditions took part in the research. The participants completed a series of auditory assessments, including dichotic digit, frequency pattern and speech-in-noise tests. A working memory test was also performed to investigate the extent to which auditory processing and cognitive performance were associated. The results demonstrated positive but weak correlations between years of schooling and performance on all of the tests applied. The factor years of schooling was also one of the best predictors of frequency pattern and speech-in-noise test performance. Additionally, performance on the working memory, frequency pattern and dichotic digit tests was also correlated, suggesting that the influence of educational level on auditory processing performance might be associated with the cognitive demand of the auditory processing tests rather than auditory sensory aspects itself. Longitudinal research is required to investigate the causal relationship between educational level and auditory processing skills.

  14. Seeing sounds and hearing colors: an event-related potential study of auditory-visual synesthesia.

    Science.gov (United States)

    Goller, Aviva I; Otten, Leun J; Ward, Jamie

    2009-10-01

    In auditory-visual synesthesia, sounds automatically elicit conscious and reliable visual experiences. It is presently unknown whether this reflects early or late processes in the brain. It is also unknown whether adult audiovisual synesthesia resembles auditory-induced visual illusions that can sometimes occur in the general population or whether it resembles the electrophysiological deflection over occipital sites that has been noted in infancy and has been likened to synesthesia. Electrical brain activity was recorded from adult synesthetes and control participants who were played brief tones and required to monitor for an infrequent auditory target. The synesthetes were instructed to attend either to the auditory or to the visual (i.e., synesthetic) dimension of the tone, whereas the controls attended to the auditory dimension alone. There were clear differences between synesthetes and controls that emerged early (100 msec after tone onset). These differences tended to lie in deflections of the auditory-evoked potential (e.g., the auditory N1, P2, and N2) rather than the presence of an additional posterior deflection. The differences occurred irrespective of what the synesthetes attended to (although attention had a late effect). The results suggest that differences between synesthetes and others occur early in time, and that synesthesia is qualitatively different from similar effects found in infants and certain auditory-induced visual illusions in adults. In addition, we report two novel cases of synesthesia in which colors elicit sounds, and vice versa. PMID:18823243

  15. Biological impact of music and software-based auditory training

    OpenAIRE

    Kraus, Nina

    2012-01-01

    Auditory-based communication skills are developed at a young age and are maintained throughout our lives. However, some individuals – both young and old – encounter difficulties in achieving or maintaining communication proficiency. Biological signals arising from hearing sounds relate to real-life communication skills such as listening to speech in noisy environments and reading, pointing to an intersection between hearing and cognition. Musical experience, amplification, and software-based ...

  16. Auditory Evoked Potential Response and Hearing Loss: A Review

    OpenAIRE

    Paulraj, M. P; Subramaniam, Kamalraj; Yaccob, Sazali Bin; Adom, Abdul H. Bin; Hema, C.R.

    2015-01-01

    Hypoacusis is the most prevalent sensory disability in the world and consequently, it can lead to impede speech in human beings. One best approach to tackle this issue is to conduct early and effective hearing screening test using Electroencephalogram (EEG). EEG based hearing threshold level determination is most suitable for persons who lack verbal communication and behavioral response to sound stimulation. Auditory evoked potential (AEP) is a type of EEG signal emanated from the brain scalp...

  17. Linking topography to tonotopy in the mouse auditory thalamocortical circuit

    DEFF Research Database (Denmark)

    Hackett, Troy A; Rinaldi Barkat, Tania; O'Brien, Barbara M J;

    2011-01-01

    order of subthreshold VSD maps was reduced in layer IV and even further degraded in layer II/III. Therefore, the precision of AI topography varies according to the source and layer of the mapping signal. Our findings further bridge the gap between in vivo and in vitro approaches for the detailed...... cellular study of auditory thalamocortical circuit organization and plasticity in the genetically tractable mouse model....

  18. Functional MRI Evaluation of Multiple Neural Networks Underlying Auditory Verbal Hallucinations in Schizophrenia Spectrum Disorders.

    Science.gov (United States)

    Thoma, Robert J; Chaze, Charlotte; Lewine, Jeffrey David; Calhoun, Vince D; Clark, Vincent P; Bustillo, Juan; Houck, Jon; Ford, Judith; Bigelow, Rose; Wilhelmi, Corbin; Stephen, Julia M; Turner, Jessica A

    2016-01-01

    Functional MRI studies have identified a distributed set of brain activations to be associated with auditory verbal hallucinations (AVH). However, very little is known about how activated brain regions may be linked together into AVH-generating networks. Fifteen volunteers with schizophrenia or schizoaffective disorder pressed buttons to indicate onset and offset of AVH during fMRI scanning. When a general linear model was used to compare blood oxygenation level dependence signals during periods in which subjects indicated that they were versus were not experiencing AVH ("AVH-on" versus "AVH-off"), it revealed AVH-related activity in bilateral inferior frontal and superior temporal regions; the right middle temporal gyrus; and the left insula, supramarginal gyrus, inferior parietal lobule, and extranuclear white matter. In an effort to identify AVH-related networks, the raw data were also processed using independent component analyses (ICAs). Four ICA components were spatially consistent with an a priori network framework based upon published meta-analyses of imaging correlates of AVH. Of these four components, only a network involving bilateral auditory cortices and posterior receptive language areas was significantly and positively correlated to the pattern of AVH-on versus AVH-off. The ICA also identified two additional networks (occipital-temporal and medial prefrontal), not fully matching the meta-analysis framework, but nevertheless containing nodes reported as active in some studies of AVH. Both networks showed significant AVH-related profiles, but both were most active during AVH-off periods. Overall, the data suggest that AVH generation requires specific and selective activation of auditory cortical and posterior language regions, perhaps coupled to a release of indirect influence by occipital and medial frontal structures. PMID:27065889

  19. SGT1 interacts with the Prf resistance protein and is required for Prf accumulation and Prf-mediated defense signaling.

    Science.gov (United States)

    Kud, Joanna; Zhao, Zhulu; Du, Xinran; Liu, Yule; Zhao, Yun; Xiao, Fangming

    2013-02-15

    The highly conserved eukaryotic co-chaperone SGT1 (suppressor of the G2 allele of skp1) is an important signaling component of plant defense responses and positively regulates disease resistance conferred by many resistance (R) proteins. In this study, we investigated the contribution of SGT1 in the Prf-mediated defense responses in both Nicotiana benthamiana and tomato (Solanum lycopersicum). SGT1 was demonstrated to interact with Prf in plant cells by co-immunoprecipitation. The requirement of SGT1 in the accumulation of Prf or autoactive Prf(D1416V) was determined by the degradation of these proteins in N. benthamiana, in which SGT1 was repressed by virus-induced gene silencing (VIGS). Pseudomonas pathogen assay on the SGT1-silenced tomato plants implicates SGT1 is required for the Prf-mediated full resistance to Pseudomonas syringae pv. tomato (Pst). These results suggest that, in both N. benthamiana and tomato, SGT1 contributes to the Prf-mediated defense responses by stabilizing Prf protein via its co-chaperone activity.

  20. Activation of L-type calcium channels is required for gap junction-mediated intercellular calcium signaling in osteoblastic cells

    Science.gov (United States)

    Jorgensen, Niklas Rye; Teilmann, Stefan Cuoni; Henriksen, Zanne; Civitelli, Roberto; Sorensen, Ole Helmer; Steinberg, Thomas H.

    2003-01-01

    The propagation of mechanically induced intercellular calcium waves (ICW) among osteoblastic cells occurs both by activation of P2Y (purinergic) receptors by extracellular nucleotides, resulting in "fast" ICW, and by gap junctional communication in cells that express connexin43 (Cx43), resulting in "slow" ICW. Human osteoblastic cells transmit intercellular calcium signals by both of these mechanisms. In the current studies we have examined the mechanism of slow gap junction-dependent ICW in osteoblastic cells. In ROS rat osteoblastic cells, gap junction-dependent ICW were inhibited by removal of extracellular calcium, plasma membrane depolarization by high extracellular potassium, and the L-type voltage-operated calcium channel inhibitor, nifedipine. In contrast, all these treatments enhanced the spread of P2 receptor-mediated ICW in UMR rat osteoblastic cells. Using UMR cells transfected to express Cx43 (UMR/Cx43) we confirmed that nifedipine sensitivity of ICW required Cx43 expression. In human osteoblastic cells, gap junction-dependent ICW also required activation of L-type calcium channels and influx of extracellular calcium.

  1. Mitophagy is primarily due to alternative autophagy and requires the MAPK1 and MAPK14 signaling pathways.

    Science.gov (United States)

    Hirota, Yuko; Yamashita, Shun-ichi; Kurihara, Yusuke; Jin, Xiulian; Aihara, Masamune; Saigusa, Tetsu; Kang, Dongchon; Kanki, Tomotake

    2015-01-01

    In cultured cells, not many mitochondria are degraded by mitophagy induced by physiological cellular stress. We observed mitophagy in HeLa cells using a method that relies on the pH-sensitive fluorescent protein Keima. With this approach, we found that mitophagy was barely induced by carbonyl cyanide m-chlorophenyl hydrazone treatment, which is widely used as an inducer of PARK2/Parkin-related mitophagy, whereas a small but modest amount of mitochondria were degraded by mitophagy under conditions of starvation or hypoxia. Mitophagy induced by starvation or hypoxia was marginally suppressed by knockdown of ATG7 and ATG12, or MAP1LC3B, which are essential for conventional macroautophagy. In addition, mitophagy was efficiently induced in Atg5 knockout mouse embryonic fibroblasts. However, knockdown of RAB9A and RAB9B, which are essential for alternative autophagy, but not conventional macroautophagy, severely suppressed mitophagy. Finally, we found that the MAPKs MAPK1/ERK2 and MAPK14/p38 were required for mitophagy. Based on these findings, we conclude that mitophagy in mammalian cells predominantly occurs through an alternative autophagy pathway, requiring the MAPK1 and MAPK14 signaling pathways.

  2. You can't stop the music: reduced auditory alpha power and coupling between auditory and memory regions facilitate the illusory perception of music during noise.

    Science.gov (United States)

    Müller, Nadia; Keil, Julian; Obleser, Jonas; Schulz, Hannah; Grunwald, Thomas; Bernays, René-Ludwig; Huppertz, Hans-Jürgen; Weisz, Nathan

    2013-10-01

    Our brain has the capacity of providing an experience of hearing even in the absence of auditory stimulation. This can be seen as illusory conscious perception. While increasing evidence postulates that conscious perception requires specific brain states that systematically relate to specific patterns of oscillatory activity, the relationship between auditory illusions and oscillatory activity remains mostly unexplained. To investigate this we recorded brain activity with magnetoencephalography and collected intracranial data from epilepsy patients while participants listened to familiar as well as unknown music that was partly replaced by sections of pink noise. We hypothesized that participants have a stronger experience of hearing music throughout noise when the noise sections are embedded in familiar compared to unfamiliar music. This was supported by the behavioral results showing that participants rated the perception of music during noise as stronger when noise was presented in a familiar context. Time-frequency data show that the illusory perception of music is associated with a decrease in auditory alpha power pointing to increased auditory cortex excitability. Furthermore, the right auditory cortex is concurrently synchronized with the medial temporal lobe, putatively mediating memory aspects associated with the music illusion. We thus assume that neuronal activity in the highly excitable auditory cortex is shaped through extensive communication between the auditory cortex and the medial temporal lobe, thereby generating the illusion of hearing music during noise. PMID:23664946

  3. You can't stop the music: reduced auditory alpha power and coupling between auditory and memory regions facilitate the illusory perception of music during noise.

    Science.gov (United States)

    Müller, Nadia; Keil, Julian; Obleser, Jonas; Schulz, Hannah; Grunwald, Thomas; Bernays, René-Ludwig; Huppertz, Hans-Jürgen; Weisz, Nathan

    2013-10-01

    Our brain has the capacity of providing an experience of hearing even in the absence of auditory stimulation. This can be seen as illusory conscious perception. While increasing evidence postulates that conscious perception requires specific brain states that systematically relate to specific patterns of oscillatory activity, the relationship between auditory illusions and oscillatory activity remains mostly unexplained. To investigate this we recorded brain activity with magnetoencephalography and collected intracranial data from epilepsy patients while participants listened to familiar as well as unknown music that was partly replaced by sections of pink noise. We hypothesized that participants have a stronger experience of hearing music throughout noise when the noise sections are embedded in familiar compared to unfamiliar music. This was supported by the behavioral results showing that participants rated the perception of music during noise as stronger when noise was presented in a familiar context. Time-frequency data show that the illusory perception of music is associated with a decrease in auditory alpha power pointing to increased auditory cortex excitability. Furthermore, the right auditory cortex is concurrently synchronized with the medial temporal lobe, putatively mediating memory aspects associated with the music illusion. We thus assume that neuronal activity in the highly excitable auditory cortex is shaped through extensive communication between the auditory cortex and the medial temporal lobe, thereby generating the illusion of hearing music during noise.

  4. Auditory hedonic phenotypes in dementia: A behavioural and neuroanatomical analysis.

    Science.gov (United States)

    Fletcher, Phillip D; Downey, Laura E; Golden, Hannah L; Clark, Camilla N; Slattery, Catherine F; Paterson, Ross W; Schott, Jonathan M; Rohrer, Jonathan D; Rossor, Martin N; Warren, Jason D

    2015-06-01

    Patients with dementia may exhibit abnormally altered liking for environmental sounds and music but such altered auditory hedonic responses have not been studied systematically. Here we addressed this issue in a cohort of 73 patients representing major canonical dementia syndromes (behavioural variant frontotemporal dementia (bvFTD), semantic dementia (SD), progressive nonfluent aphasia (PNFA) amnestic Alzheimer's disease (AD)) using a semi-structured caregiver behavioural questionnaire and voxel-based morphometry (VBM) of patients' brain MR images. Behavioural responses signalling abnormal aversion to environmental sounds, aversion to music or heightened pleasure in music ('musicophilia') occurred in around half of the cohort but showed clear syndromic and genetic segregation, occurring in most patients with bvFTD but infrequently in PNFA and more commonly in association with MAPT than C9orf72 mutations. Aversion to sounds was the exclusive auditory phenotype in AD whereas more complex phenotypes including musicophilia were common in bvFTD and SD. Auditory hedonic alterations correlated with grey matter loss in a common, distributed, right-lateralised network including antero-mesial temporal lobe, insula, anterior cingulate and nucleus accumbens. Our findings suggest that abnormalities of auditory hedonic processing are a significant issue in common dementias. Sounds may constitute a novel probe of brain mechanisms for emotional salience coding that are targeted by neurodegenerative disease. PMID:25929717

  5. Auditory Scene Analysis and sonified visual images. Does consonance negatively impact on object formation when using complex sonified stimuli?

    Directory of Open Access Journals (Sweden)

    David J Brown

    2015-10-01

    Full Text Available A critical task for the brain is the sensory representation and identification of perceptual objects in the world. When the visual sense is impaired, hearing and touch must take primary roles and in recent times compensatory techniques have been developed that employ the tactile or auditory system as a substitute for the visual system. Visual-to-auditory sonifications provide a complex, feature-based auditory representation that must be decoded and integrated into an object-based representation by the listener. However, we don’t yet know what role the auditory system plays in the object integration stage and whether the principles of auditory scene analysis apply. Here we used coarse sonified images in a two-tone discrimination task to test whether auditory feature-based representations of visual objects would be confounded when their features conflicted with the principles of auditory consonance. We found that listeners (N = 36 performed worse in an object recognition task when the auditory feature-based representation was harmonically consonant. We also found that this conflict was not negated with the provision of congruent audio-visual information. The findings suggest that early auditory processes of harmonic grouping dominate the object formation process and that the complexity of the signal, and additional sensory information have limited effect on this.

  6. Neuronal activity in primate prefrontal cortex related to goal-directed behavior during auditory working memory tasks.

    Science.gov (United States)

    Huang, Ying; Brosch, Michael

    2016-06-01

    Prefrontal cortex (PFC) has been documented to play critical roles in goal-directed behaviors, like representing goal-relevant events and working memory (WM). However, neurophysiological evidence for such roles of PFC has been obtained mainly with visual tasks but rarely with auditory tasks. In the present study, we tested roles of PFC in auditory goal-directed behaviors by recording local field potentials in the auditory region of left ventrolateral PFC while a monkey performed auditory WM tasks. The tasks consisted of multiple events and required the monkey to change its mental states to achieve the reward. The events were auditory and visual stimuli, as well as specific actions. Mental states were engaging in the tasks and holding task-relevant information in auditory WM. We found that, although based on recordings from one hemisphere in one monkey only, PFC represented multiple events that were important for achieving reward, including auditory and visual stimuli like turning on and off an LED, as well as bar touch. The responses to auditory events depended on the tasks and on the context of the tasks. This provides support for the idea that neuronal representations in PFC are flexible and can be related to the behavioral meaning of stimuli. We also found that engaging in the tasks and holding information in auditory WM were associated with persistent changes of slow potentials, both of which are essential for auditory goal-directed behaviors. Our study, on a single hemisphere in a single monkey, reveals roles of PFC in auditory goal-directed behaviors similar to those in visual goal-directed behaviors, suggesting that functions of PFC in goal-directed behaviors are probably common across the auditory and visual modality. This article is part of a Special Issue entitled SI: Auditory working memory. PMID:26874071

  7. Fibroblast growth factor 10-fibroblast growth factor receptor 2b mediated signaling is not required for adult glandular stomach homeostasis.

    Directory of Open Access Journals (Sweden)

    Allison L Speer

    Full Text Available The signaling pathways that are essential for gastric organogenesis have been studied in some detail; however, those that regulate the maintenance of the gastric epithelium during adult homeostasis remain unclear. In this study, we investigated the role of Fibroblast growth factor 10 (FGF10 and its main receptor, Fibroblast growth factor receptor 2b (FGFR2b, in adult glandular stomach homeostasis. We first showed that mouse adult glandular stomach expressed Fgf10, its receptors, Fgfr1b and Fgfr2b, and most of the other FGFR2b ligands (Fgf1, Fgf7, Fgf22 except for Fgf3 and Fgf20. Fgf10 expression was mesenchymal whereas FGFR1 and FGFR2 expression were mostly epithelial. Studying double transgenic mice that allow inducible overexpression of Fgf10 in adult mice, we showed that Fgf10 overexpression in normal adult glandular stomach increased epithelial proliferation, drove mucous neck cell differentiation, and reduced parietal and chief cell differentiation. Although a similar phenotype can be associated with the development of metaplasia, we found that Fgf10 overexpression for a short duration does not cause metaplasia. Finally, investigating double transgenic mice that allow the expression of a soluble form of Fgfr2b, FGF10's main receptor, which acts as a dominant negative, we found no significant changes in gastric epithelial proliferation or differentiation in the mutants. Our work provides evidence, for the first time, that the FGF10-FGFR2b signaling pathway is not required for epithelial proliferation and differentiation during adult glandular stomach homeostasis.

  8. Achilles' ear? Inferior human short-term and recognition memory in the auditory modality.

    Directory of Open Access Journals (Sweden)

    James Bigelow

    Full Text Available Studies of the memory capabilities of nonhuman primates have consistently revealed a relative weakness for auditory compared to visual or tactile stimuli: extensive training is required to learn auditory memory tasks, and subjects are only capable of retaining acoustic information for a brief period of time. Whether a parallel deficit exists in human auditory memory remains an outstanding question. In the current study, a short-term memory paradigm was used to test human subjects' retention of simple auditory, visual, and tactile stimuli that were carefully equated in terms of discriminability, stimulus exposure time, and temporal dynamics. Mean accuracy did not differ significantly among sensory modalities at very short retention intervals (1-4 s. However, at longer retention intervals (8-32 s, accuracy for auditory stimuli fell substantially below that observed for visual and tactile stimuli. In the interest of extending the ecological validity of these findings, a second experiment tested recognition memory for complex, naturalistic stimuli that would likely be encountered in everyday life. Subjects were able to identify all stimuli when retention was not required, however, recognition accuracy following a delay period was again inferior for auditory compared to visual and tactile stimuli. Thus, the outcomes of both experiments provide a human parallel to the pattern of results observed in nonhuman primates. The results are interpreted in light of neuropsychological data from nonhuman primates, which suggest a difference in the degree to which auditory, visual, and tactile memory are mediated by the perirhinal and entorhinal cortices.

  9. Theory of Auditory Thresholds in Primates

    Science.gov (United States)

    Harrison, Michael J.

    2001-03-01

    The influence of thermal pressure fluctuations at the tympanic membrane has been previously investigated as a possible determinant of the threshold of hearing in humans (L.J. Sivian and S.D. White, J. Acoust. Soc. Am. IV, 4;288(1933).). More recent work has focussed more precisely on the relation between statistical mechanics and sensory signal processing by biological means in creatures' brains (W. Bialek, in ``Physics of Biological Systems: from molecules to species'', H. Flyvberg et al, (Eds), p. 252; Springer 1997.). Clinical data on the frequency dependence of hearing thresholds in humans and other primates (W.C. Stebbins, ``The Acoustic Sense of Animals'', Harvard 1983.) has long been available. I have derived an expression for the frequency dependence of hearing thresholds in primates, including humans, by first calculating the frequency dependence of thermal pressure fluctuations at eardrums from damped normal modes excited in model ear canals of given simple geometry. I then show that most of the features of the clinical data are directly related to the frequency dependence of the ratio of thermal noise pressure arising from without to that arising from within the masking bandwidth which signals must dominate in order to be sensed. The higher intensity of threshold signals in primates smaller than humans, which is clinically observed over much but not all of the human auditory spectrum is shown to arise from their smaller meatus dimensions. note

  10. The synthetic cationic lipid diC14 activates a sector of the Arabidopsis defence network requiring endogenous signalling components.

    Science.gov (United States)

    Cambiagno, Damián Alejandro; Lonez, Caroline; Ruysschaert, Jean-Marie; Alvarez, María Elena

    2015-12-01

    Natural and synthetic elicitors have contributed significantly to the study of plant immunity. Pathogen-derived proteins and carbohydrates that bind to immune receptors, allow the fine dissection of certain defence pathways. Lipids of a different nature that act as defence elicitors, have also been studied, but their specific effects have been less well characterized, and their receptors have not been identified. In animal cells, nanoliposomes of the synthetic cationic lipid 3-tetradecylamino-tert-butyl-N-tetradecylpropionamidine (diC14) activate the TLR4-dependent immune cascade. Here, we have investigated whether this lipid induces Arabidopsis defence responses. At the local level, diC14 activated early and late defence gene markers (FRK1, WRKY29, ICS1 and PR1), acting in a dose-dependent manner. This lipid induced the salicylic acid (SA)-dependent, but not jasmonic acid (JA)-dependent, pathway and protected plants against Pseudomonas syringae pv. tomato (Pst), but not Botrytis cinerea. diC14 was not toxic to plant or pathogen, and potentiated pathogen-induced callose deposition. At the systemic level, diC14 induced PR1 expression and conferred resistance against Pst. diC14-induced defence responses required the signalling protein EDS1, but not NDR1. Curiously, the lipid-induced defence gene expression was lower in the fls2/efr/cerk1 triple mutant, but still unchanged in the single mutants. The amidine headgroup and chain length were important for its activity. Given the robustness of the responses triggered by diC14, its specific action on a defence pathway and the requirement for well-known defence components, this synthetic lipid is emerging as a useful tool to investigate the initial events involved in plant innate immunity.

  11. Psychoacoustic and cognitive aspects of auditory roughness: definitions, models, and applications

    Science.gov (United States)

    Vassilakis, Pantelis N.; Kendall, Roger A.

    2010-02-01

    The term "auditory roughness" was first introduced in the 19th century to describe the buzzing, rattling auditory sensation accompanying narrow harmonic intervals (i.e. two tones with frequency difference in the range of ~15-150Hz, presented simultaneously). A broader definition and an overview of the psychoacoustic correlates of the auditory roughness sensation, also referred to as sensory dissonance, is followed by an examination of efforts to quantify it over the past one hundred and fifty years and leads to the introduction of a new roughness calculation model and an application that automates spectral and roughness analysis of sound signals. Implementation of spectral and roughness analysis is briefly discussed in the context of two pilot perceptual experiments, designed to assess the relationship among cultural background, music performance practice, and aesthetic attitudes towards the auditory roughness sensation.

  12. Cortical contributions to the auditory frequency-following response revealed by MEG.

    Science.gov (United States)

    Coffey, Emily B J; Herholz, Sibylle C; Chepesiuk, Alexander M P; Baillet, Sylvain; Zatorre, Robert J

    2016-01-01

    The auditory frequency-following response (FFR) to complex periodic sounds is used to study the subcortical auditory system, and has been proposed as a biomarker for disorders that feature abnormal sound processing. Despite its value in fundamental and clinical research, the neural origins of the FFR are unclear. Using magnetoencephalography, we observe a strong, right-asymmetric contribution to the FFR from the human auditory cortex at the fundamental frequency of the stimulus, in addition to signal from cochlear nucleus, inferior colliculus and medial geniculate. This finding is highly relevant for our understanding of plasticity and pathology in the auditory system, as well as higher-level cognition such as speech and music processing. It suggests that previous interpretations of the FFR may need re-examination using methods that allow for source separation. PMID:27009409

  13. Oryza sativa Chloroplast Signal Recognition Particle 43 (OscpSRP43 Is Required for Chloroplast Development and Photosynthesis.

    Directory of Open Access Journals (Sweden)

    Xiang-guang Lv

    Full Text Available A rice chlorophyll-deficient mutant w67 was isolated from an ethyl methane sulfonate (EMS-induced IR64 (Oryza sativa L. ssp. indica mutant bank. The mutant exhibited a distinct yellow-green leaf phenotype in the whole plant growth duration with significantly reduced levels of chlorophyll and carotenoid, impaired chloroplast development and lowered capacity of photosynthesis compared with the wild-type IR64. Expression of a number of genes associated with chlorophyll metabolism, chloroplast biogenesis and photosynthesis was significantly altered in the mutant. Genetic analysis indicated that the yellow-green phenotype was controlled by a single recessive nuclear gene located on the short arm of chromosome 3. Using map-based strategy, the mutation was isolated and predicted to encode a chloroplast signal recognition particle 43 KD protein (cpSRP43 with 388 amino acid residuals. A single base substitution from A to T at position 160 resulted in a premature stop codon. OscpSRP43 was constitutively expressed in various organs with the highest level in the leaf. Functional complementation could rescue the mutant phenotype and subcellular localization showed that the cpSRP43:GFP fusion protein was targeted to the chloroplast. The data suggested that Oryza sativa cpSRP43 (OscpSRP43 was required for the normal development of chloroplasts and photosynthesis in rice.

  14. Induction of interleukin-8 by Naegleria fowleri lysates requires activation of extracellular signal-regulated kinase in human astroglial cells.

    Science.gov (United States)

    Kim, Jong-Hyun; Sohn, Hae-Jin; Lee, Sang-Hee; Kwon, Daeho; Shin, Ho-Joon

    2012-08-01

    Naegleria fowleri is a pathogenic free-living amoeba which causes primary amoebic meningoencephalitis in humans and experimental animals. To investigate the mechanisms of such inflammatory diseases, potential chemokine gene activation in human astroglial cells was investigated following treatment with N. fowleri lysates. We demonstrated that N. fowleri are potent inducers for the expression of interleukin-8 (IL-8) genes in human astroglial cells which was preceded by activation of extracellular signal-regulated kinase (ERK). In addition, N. fowleri lysates induces the DNA binding activity of activator protein-1 (AP-1), an important transcription factor for IL-8 induction. The specific mitogen-activated protein kinase kinase/ERK inhibitor, U0126, blocks N. fowleri-mediated AP-1 activation and subsequent IL-8 induction. N. fowleri-induced IL-8 expression requires activation of ERK in human astroglial cells. These findings indicate that treatment of N. fowleri on human astroglial cells leads to the activation of AP-1 and subsequent expression of IL-8 which are dependent on ERK activation. These results may help understand the N. fowleri-mediated upregulation of chemokine and cytokine expression in the astroglial cells.

  15. Gbx2 is required for the morphogenesis of the mouse inner ear: a downstream candidate of hindbrain signaling.

    Science.gov (United States)

    Lin, Zhengshi; Cantos, Raquel; Patente, Maria; Wu, Doris K

    2005-05-01

    Gbx2 is a homeobox-containing transcription factor that is related to unplugged in Drosophila. In mice, Gbx2 and Otx2 negatively regulate each other to establish the mid-hindbrain boundary in the neural tube. Here, we show that Gbx2 is required for the development of the mouse inner ear. Absence of the endolymphatic duct and swelling of the membranous labyrinth are common features in Gbx2-/- inner ears. More severe mutant phenotypes include absence of the anterior and posterior semicircular canals, and a malformed saccule and cochlear duct. However, formation of the lateral semicircular canal and its ampulla is usually unaffected. These inner ear phenotypes are remarkably similar to those reported in kreisler mice, which have inner ear defects attributed to defects in the hindbrain. Based on gene expression analyses, we propose that activation of Gbx2 expression within the inner ear is an important pathway whereby signals from the hindbrain regulate inner ear development. In addition, our results suggest that Gbx2 normally promotes dorsal fates such as the endolymphatic duct and semicircular canals by positively regulating genes such as Wnt2b and Dlx5. However, Gbx2 promotes ventral fates such as the saccule and cochlear duct, possibly by restricting Otx2 expression.

  16. Melanocortin-4 receptor signaling is not required for short-term weight loss after sleeve gastrectomy in pediatric patients.

    Science.gov (United States)

    Jelin, E B; Daggag, H; Speer, A L; Hameed, N; Lessan, N; Barakat, M; Nadler, E P

    2016-03-01

    Homozygous or compound heterozygous melanocortin-4 receptor (MC4R) mutations are rare with fewer than 10 patients described in current literature. Here we report the short- and long-term outcomes for four children ages 4.5-14 who are homozygous for loss-of-function mutations in the MC4R and underwent laparoscopic sleeve gastrectomy. All four patients experienced significant weight loss and improvement in, or resolution of, their comorbidities in the short term. One patient, however, has had significant weight regain in the long term. We conclude that MC4R signaling is not required for short-term weight loss after laparoscopic sleeve gastrectomy in children. Behavior modification may be more important for long-term weight maintenance, but patients with homozygous MC4R deficiency should not be excluded from consideration for sleeve gastrectomy. However, as at least one copy of functional MC4R is necessary and sufficient to induce long-term postoperative weight loss benefits, patients with complete loss of MC4R functionality might be less likely to exhibit the same benefits resulting from bariatric surgery. PMID:26538186

  17. Oryza sativa Chloroplast Signal Recognition Particle 43 (OscpSRP43) Is Required for Chloroplast Development and Photosynthesis.

    Science.gov (United States)

    Lv, Xiang-guang; Shi, Yong-feng; Xu, Xia; Wei, Yan-lin; Wang, Hui-mei; Zhang, Xiao-bo; Wu, Jian-li

    2015-01-01

    A rice chlorophyll-deficient mutant w67 was isolated from an ethyl methane sulfonate (EMS)-induced IR64 (Oryza sativa L. ssp. indica) mutant bank. The mutant exhibited a distinct yellow-green leaf phenotype in the whole plant growth duration with significantly reduced levels of chlorophyll and carotenoid, impaired chloroplast development and lowered capacity of photosynthesis compared with the wild-type IR64. Expression of a number of genes associated with chlorophyll metabolism, chloroplast biogenesis and photosynthesis was significantly altered in the mutant. Genetic analysis indicated that the yellow-green phenotype was controlled by a single recessive nuclear gene located on the short arm of chromosome 3. Using map-based strategy, the mutation was isolated and predicted to encode a chloroplast signal recognition particle 43 KD protein (cpSRP43) with 388 amino acid residuals. A single base substitution from A to T at position 160 resulted in a premature stop codon. OscpSRP43 was constitutively expressed in various organs with the highest level in the leaf. Functional complementation could rescue the mutant phenotype and subcellular localization showed that the cpSRP43:GFP fusion protein was targeted to the chloroplast. The data suggested that Oryza sativa cpSRP43 (OscpSRP43) was required for the normal development of chloroplasts and photosynthesis in rice.

  18. Adapting the Theory of Visual Attention (TVA) to model auditory attention

    DEFF Research Database (Denmark)

    Roberts, Katherine L.; Andersen, Tobias; Kyllingsbæk, Søren;

    2014-01-01

    Mathematical and computational models have provided useful insights into normal and impaired visual attention, but less progress has been made in modelling auditory attention. We are developing a Theory of Auditory Attention (TAA), based on an influential visual model, the Theory of Visual...... the auditory data, producing good estimates of the rate at which information is encoded (C), the minimum exposure duration required for processing to begin (t0), and the relative attentional weight to targets versus distractors (α). Future work will address the issue of target-distractor confusion, and extend...

  19. Modelling the emergence and dynamics of perceptual organisation in auditory streaming.

    Science.gov (United States)

    Mill, Robert W; Bőhm, Tamás M; Bendixen, Alexandra; Winkler, István; Denham, Susan L

    2013-01-01

    Many sound sources can only be recognised from the pattern of sounds they emit, and not from the individual sound events that make up their emission sequences. Auditory scene analysis addresses the difficult task of interpreting the sound world in terms of an unknown number of discrete sound sources (causes) with possibly overlapping signals, and therefore of associating each event with the appropriate source. There are potentially many different ways in which incoming events can be assigned to different causes, which means that the auditory system has to choose between them. This problem has been studied for many years using the auditory streaming paradigm, and recently it has become apparent that instead of making one fixed perceptual decision, given sufficient time, auditory perception switches back and forth between the alternatives-a phenomenon known as perceptual bi- or multi-stability. We propose a new model of auditory scene analysis at the core of which is a process that seeks to discover predictable patterns in the ongoing sound sequence. Representations of predictable fragments are created on the fly, and are maintained, strengthened or weakened on the basis of their predictive success, and conflict with other representations. Auditory perceptual organisation emerges spontaneously from the nature of the competition between these representations. We present detailed comparisons between the model simulations and data from an auditory streaming experiment, and show that the model accounts for many important findings, including: the emergence of, and switching between, alternative organisations; the influence of stimulus parameters on perceptual dominance, switching rate and perceptual phase durations; and the build-up of auditory streaming. The principal contribution of the model is to show that a two-stage process of pattern discovery and competition between incompatible patterns can account for both the contents (perceptual organisations) and the dynamics

  20. Modelling the emergence and dynamics of perceptual organisation in auditory streaming.

    Directory of Open Access Journals (Sweden)

    Robert W Mill

    Full Text Available Many sound sources can only be recognised from the pattern of sounds they emit, and not from the individual sound events that make up their emission sequences. Auditory scene analysis addresses the difficult task of interpreting the sound world in terms of an unknown number of discrete sound sources (causes with possibly overlapping signals, and therefore of associating each event with the appropriate source. There are potentially many different ways in which incoming events can be assigned to different causes, which means that the auditory system has to choose between them. This problem has been studied for many years using the auditory streaming paradigm, and recently it has become apparent that instead of making one fixed perceptual decision, given sufficient time, auditory perception switches back and forth between the alternatives-a phenomenon known as perceptual bi- or multi-stability. We propose a new model of auditory scene analysis at the core of which is a process that seeks to discover predictable patterns in the ongoing sound sequence. Representations of predictable fragments are created on the fly, and are maintained, strengthened or weakened on the basis of their predictive success, and conflict with other representations. Auditory perceptual organisation emerges spontaneously from the nature of the competition between these representations. We present detailed comparisons between the model simulations and data from an auditory streaming experiment, and show that the model accounts for many important findings, including: the emergence of, and switching between, alternative organisations; the influence of stimulus parameters on perceptual dominance, switching rate and perceptual phase durations; and the build-up of auditory streaming. The principal contribution of the model is to show that a two-stage process of pattern discovery and competition between incompatible patterns can account for both the contents (perceptual

  1. Conceptual priming for realistic auditory scenes and for auditory words.

    Science.gov (United States)

    Frey, Aline; Aramaki, Mitsuko; Besson, Mireille

    2014-02-01

    Two experiments were conducted using both behavioral and Event-Related brain Potentials methods to examine conceptual priming effects for realistic auditory scenes and for auditory words. Prime and target sounds were presented in four stimulus combinations: Sound-Sound, Word-Sound, Sound-Word and Word-Word. Within each combination, targets were conceptually related to the prime, unrelated or ambiguous. In Experiment 1, participants were asked to judge whether the primes and targets fit together (explicit task) and in Experiment 2 they had to decide whether the target was typical or ambiguous (implicit task). In both experiments and in the four stimulus combinations, reaction times and/or error rates were longer/higher and the N400 component was larger to ambiguous targets than to conceptually related targets, thereby pointing to a common conceptual system for processing auditory scenes and linguistic stimuli in both explicit and implicit tasks. However, fine-grained analyses also revealed some differences between experiments and conditions in scalp topography and duration of the priming effects possibly reflecting differences in the integration of perceptual and cognitive attributes of linguistic and nonlinguistic sounds. These results have clear implications for the building-up of virtual environments that need to convey meaning without words. PMID:24378910

  2. Changes in auditory perceptions and cortex resulting from hearing recovery after extended congenital unilateral hearing loss

    Directory of Open Access Journals (Sweden)

    Jill B Firszt

    2013-12-01

    Full Text Available Monaural hearing induces auditory system reorganization. Imbalanced input also degrades time-intensity cues for sound localization and signal segregation for listening in noise. While there have been studies of bilateral auditory deprivation and later hearing restoration (e.g. cochlear implants, less is known about unilateral auditory deprivation and subsequent hearing improvement. We investigated effects of long-term congenital unilateral hearing loss on localization, speech understanding, and cortical organization following hearing recovery. Hearing in the congenitally affected ear of a 41 year old female improved significantly after stapedotomy and reconstruction. Pre-operative hearing threshold levels showed unilateral, mixed, moderately-severe to profound hearing loss. The contralateral ear had hearing threshold levels within normal limits. Testing was completed prior to, and three and nine months after surgery. Measurements were of sound localization with intensity-roved stimuli and speech recognition in various noise conditions. We also evoked magnetic resonance signals with monaural stimulation to the unaffected ear. Activation magnitudes were determined in core, belt, and parabelt auditory cortex regions via an interrupted single event design. Hearing improvement following 40 years of congenital unilateral hearing loss resulted in substantially improved sound localization and speech recognition in noise. Auditory cortex also reorganized. Contralateral auditory cortex responses were increased after hearing recovery and the extent of activated cortex was bilateral, including a greater portion of the posterior superior temporal plane. Thus, prolonged predominant monaural stimulation did not prevent auditory system changes consequent to restored binaural hearing. Results support future research of unilateral auditory deprivation effects and plasticity, with consideration for length of deprivation, age at hearing correction, degree and type

  3. The effects of auditory contrast tuning upon speech intelligibility

    Directory of Open Access Journals (Sweden)

    Nathaniel J Killian

    2016-08-01

    Full Text Available We have previously identified neurons tuned to spectral contrast of wideband sounds in auditory cortex of awake marmoset monkeys. Because additive noise alters the spectral contrast of speech, contrast-tuned neurons, if present in human auditory cortex, may aid in extracting speech from noise. Given that this cortical function may be underdeveloped in individuals with sensorineural hearing loss, incorporating biologically-inspired algorithms into external signal processing devices could provide speech enhancement benefits to cochlear implantees. In this study we first constructed a computational signal processing algorithm to mimic auditory cortex contrast tuning. We then manipulated the shape of contrast channels and evaluated the intelligibility of reconstructed noisy speech using a metric to predict cochlear implant user perception. Candidate speech enhancement strategies were then tested in cochlear implantees with a hearing-in-noise test. Accentuation of intermediate contrast values or all contrast values improved computed intelligibility. Cochlear implant subjects showed significant improvement in noisy speech intelligibility with a contrast shaping procedure.

  4. The Effects of Auditory Contrast Tuning upon Speech Intelligibility.

    Science.gov (United States)

    Killian, Nathan J; Watkins, Paul V; Davidson, Lisa S; Barbour, Dennis L

    2016-01-01

    We have previously identified neurons tuned to spectral contrast of wideband sounds in auditory cortex of awake marmoset monkeys. Because additive noise alters the spectral contrast of speech, contrast-tuned neurons, if present in human auditory cortex, may aid in extracting speech from noise. Given that this cortical function may be underdeveloped in individuals with sensorineural hearing loss, incorporating biologically-inspired algorithms into external signal processing devices could provide speech enhancement benefits to cochlear implantees. In this study we first constructed a computational signal processing algorithm to mimic auditory cortex contrast tuning. We then manipulated the shape of contrast channels and evaluated the intelligibility of reconstructed noisy speech using a metric to predict cochlear implant user perception. Candidate speech enhancement strategies were then tested in cochlear implantees with a hearing-in-noise test. Accentuation of intermediate contrast values or all contrast values improved computed intelligibility. Cochlear implant subjects showed significant improvement in noisy speech intelligibility with a contrast shaping procedure. PMID:27555826

  5. Towards an auditory account of speech rhythm: application of a model of the auditory 'primal sketch' to two multi-language corpora.

    Science.gov (United States)

    Lee, Christopher S; Todd, Neil P McAngus

    2004-10-01

    The world's languages display important differences in their rhythmic organization; most particularly, different languages seem to privilege different phonological units (mora, syllable, or stress foot) as their basic rhythmic unit. There is now considerable evidence that such differences have important consequences for crucial aspects of language acquisition and processing. Several questions remain, however, as to what exactly characterizes the rhythmic differences, how they are manifested at an auditory/acoustic level and how listeners, whether adult native speakers or young infants, process rhythmic information. In this paper it is proposed that the crucial determinant of rhythmic organization is the variability in the auditory prominence of phonetic events. In order to test this auditory prominence hypothesis, an auditory model is run on two multi-language data-sets, the first consisting of matched pairs of English and French sentences, and the second consisting of French, Italian, English and Dutch sentences. The model is based on a theory of the auditory primal sketch, and generates a primitive representation of an acoustic signal (the rhythmogram) which yields a crude segmentation of the speech signal and assigns prominence values to the obtained sequence of events. Its performance is compared with that of several recently proposed phonetic measures of vocalic and consonantal variability.

  6. Neural Representation of Concurrent Vowels in Macaque Primary Auditory Cortex.

    Science.gov (United States)

    Fishman, Yonatan I; Micheyl, Christophe; Steinschneider, Mitchell

    2016-01-01

    Successful speech perception in real-world environments requires that the auditory system segregate competing voices that overlap in frequency and time into separate streams. Vowels are major constituents of speech and are comprised of frequencies (harmonics) that are integer multiples of a common fundamental frequency (F0). The pitch and identity of a vowel are determined by its F0 and spectral envelope (formant structure), respectively. When two spectrally overlapping vowels differing in F0 are presented concurrently, they can be readily perceived as two separate "auditory objects" with pitches at their respective F0s. A difference in pitch between two simultaneous vowels provides a powerful cue for their segregation, which in turn, facilitates their individual identification. The neural mechanisms underlying the segregation of concurrent vowels based on pitch differences are poorly understood. Here, we examine neural population responses in macaque primary auditory cortex (A1) to single and double concurrent vowels (/a/ and /i/) that differ in F0 such that they are heard as two separate auditory objects with distinct pitches. We find that neural population responses in A1 can resolve, via a rate-place code, lower harmonics of both single and double concurrent vowels. Furthermore, we show that the formant structures, and hence the identities, of single vowels can be reliably recovered from the neural representation of double concurrent vowels. We conclude that A1 contains sufficient spectral information to enable concurrent vowel segregation and identification by downstream cortical areas.

  7. Implications of blast exposure for central auditory function: A review

    Directory of Open Access Journals (Sweden)

    Frederick J. Gallun, PhD

    2012-10-01

    Full Text Available Auditory system functions, from peripheral sensitivity to central processing capacities, are all at risk from a blast event. Accurate encoding of auditory patterns in time, frequency, and space are required for a clear understanding of speech and accurate localization of sound sources in environments with background noise, multiple sound sources, and/or reverberation. Further work is needed to refine the battery of clinical tests sensitive to the sorts of central auditory dysfunction observed in individuals with blast exposure. Treatment options include low-gain hearing aids, remote-microphone technology, and auditory-training regimens, but clinical evidence does not yet exist for recommending one or more of these options. As this population ages, the natural aging process and other potential brain injuries (such as stroke and blunt trauma may combine with blast-related brain changes to produce a population for which the current clinical diagnostic and treatment tools may prove inadequate. It is important to maintain an updated understanding of the scope of the issues present in this population and to continue to identify those solutions that can provide measurable improvements in the lives of Veterans who have been exposed to high-intensity blasts during the course of their military service.

  8. Making and monitoring errors based on altered auditory feedback

    Directory of Open Access Journals (Sweden)

    Peter ePfordresher

    2014-08-01

    Full Text Available Previous research has demonstrated that altered auditory feedback (AAF disrupts music performance and causes disruptions in both action planning and the perception of feedback events. It has been proposed that this disruption occurs because of interference within a shared representation for perception and action (Pfordresher, 2006. Studies reported here address this claim from the standpoint of error monitoring. In Experiment 1 participants performed short melodies on a keyboard while hearing no auditory feedback, normal auditory feedback, or alterations to feedback pitch on some subset of events. Participants overestimated error frequency when AAF was present but not for normal feedback. Experiment 2 introduced a concurrent load task to determine whether error monitoring requires executive resources. Although the concurrent task enhanced the effect of AAF, it did not alter participants’ tendency to overestimate errors when AAF was present. A third correlational study addressed whether effects of AAF are reduced for a subset of the population who may lack the kind of perception/action associations that lead to AAF disruption: poor-pitch singers. Effects of manipulations similar to those presented in Experiments 1 and 2 were reduced for these individuals. We propose that these results are consistent with the notion that AAF interference is based on associations between perception and action within a forward internal model of auditory-motor relationships.

  9. Psychophysiological responses to auditory change.

    Science.gov (United States)

    Chuen, Lorraine; Sears, David; McAdams, Stephen

    2016-06-01

    A comprehensive characterization of autonomic and somatic responding within the auditory domain is currently lacking. We studied whether simple types of auditory change that occur frequently during music listening could elicit measurable changes in heart rate, skin conductance, respiration rate, and facial motor activity. Participants heard a rhythmically isochronous sequence consisting of a repeated standard tone, followed by a repeated target tone that changed in pitch, timbre, duration, intensity, or tempo, or that deviated momentarily from rhythmic isochrony. Changes in all parameters produced increases in heart rate. Skin conductance response magnitude was affected by changes in timbre, intensity, and tempo. Respiratory rate was sensitive to deviations from isochrony. Our findings suggest that music researchers interpreting physiological responses as emotional indices should consider acoustic factors that may influence physiology in the absence of induced emotions. PMID:26927928

  10. Reality of auditory verbal hallucinations

    Science.gov (United States)

    Valkonen-Korhonen, Minna; Holi, Matti; Therman, Sebastian; Lehtonen, Johannes; Hari, Riitta

    2009-01-01

    Distortion of the sense of reality, actualized in delusions and hallucinations, is the key feature of psychosis but the underlying neuronal correlates remain largely unknown. We studied 11 highly functioning subjects with schizophrenia or schizoaffective disorder while they rated the reality of auditory verbal hallucinations (AVH) during functional magnetic resonance imaging (fMRI). The subjective reality of AVH correlated strongly and specifically with the hallucination-related activation strength of the inferior frontal gyri (IFG), including the Broca's language region. Furthermore, how real the hallucination that subjects experienced was depended on the hallucination-related coupling between the IFG, the ventral striatum, the auditory cortex, the right posterior temporal lobe, and the cingulate cortex. Our findings suggest that the subjective reality of AVH is related to motor mechanisms of speech comprehension, with contributions from sensory and salience-detection-related brain regions as well as circuitries related to self-monitoring and the experience of agency. PMID:19620178

  11. Three distinct domains of SSI-1/SOCS-1/JAB protein are required for its suppression of interleukin 6 signaling

    OpenAIRE

    Narazaki, Masashi; Fujimoto, Minoru; Matsumoto, Tomoshige; Morita, Yoshiaki; SAITO, HIROSHI; Kajita, Tadahiro; Yoshizaki, Kazuyuki; Naka, Tetsuji; Kishimoto, Tadamitsu

    1998-01-01

    Cytokine-inducible protein SSI-1 [signal transducers and activators of transcription (STAT)-induced STAT inhibitor 1, also referred to as SOCS-1 (suppressor of cytokine signaling 1) or JAB (Janus kinase-binding protein)] negatively regulates cytokine receptor signaling by inhibition of JAK kinases. The SSI family of proteins includes eight members that are structurally characterized by an SH2 domain and a C-terminal conserved region that we have called the SC-motif. In this study, we investig...

  12. Characterization of a Dchs1 mutant mouse reveals requirements for Dchs1-Fat4 signaling during mammalian development

    OpenAIRE

    Mao, Yaopan; Mulvaney, Joanna; Zakaria, Sana; Yu, Tian; Morgan, Katherine Malanga; Allen, Steve; Basson, M. Albert; Francis-West, Philippa; Irvine, Kenneth D.

    2011-01-01

    The Drosophila Dachsous and Fat proteins function as ligand and receptor, respectively, for an intercellular signaling pathway that regulates Hippo signaling and planar cell polarity. Although gene-targeted mutations in two mammalian Fat genes have been described, whether mammals have a Fat signaling pathway equivalent to that in Drosophila, and what its biological functions might be, have remained unclear. Here, we describe a gene-targeted mutation in a murine Dachsous homolog, Dchs1. Analys...

  13. Auditory distraction and serial memory

    OpenAIRE

    Jones, D M; Hughes, Rob; Macken, W.J.

    2010-01-01

    One mental activity that is very vulnerable to auditory distraction is serial recall. This review of the contemporary findings relating to serial recall charts the key determinants of distraction. It is evident that there is one form of distraction that is a joint product of the cognitive characteristics of the task and of the obligatory cognitive processing of the sound. For sequences of sound, distraction appears to be an ineluctable product of similarity-of-process, specifically, the seria...

  14. Reality of auditory verbal hallucinations

    OpenAIRE

    Raij TT; Valkonen-Korhonen M; Holi M; Therman S; Lehtonen J; Hari R

    2009-01-01

    Distortion of the sense of reality, actualized in delusions and hallucinations, is the key feature of psychosis but the underlying neuronal correlates remain largely unknown. We studied 11 highly functioning subjects with schizophrenia or schizoaffective disorder while they rated the reality of auditory verbal hallucinations (AVH) during functional magnetic resonance imaging (fMRI). The subjective reality of AVH correlated strongly and specifically with the hallucination-related activation st...

  15. Acquisition, Analyses and Interpretation of fMRI Data: A Study on the Effective Connectivity in Human Primary Auditory Cortices

    International Nuclear Information System (INIS)

    A study on the effective connectivity characteristics in auditory cortices was conducted on five healthy Malay male subjects with the age of 20 to 40 years old using functional magnetic resonance imaging (fMRI), statistical parametric mapping (SPM5) and dynamic causal modelling (DCM). A silent imaging paradigm was used to reduce the scanner sound artefacts on functional images. The subjects were instructed to pay attention to the white noise stimulus binaurally given at intensity level of 70 dB higher than the hearing level for normal people. Functional specialisation was studied using Matlab-based SPM5 software by means of fixed effects (FFX), random effects (RFX) and conjunction analyses. Individual analyses on all subjects indicate asymmetrical bilateral activation between the left and right auditory cortices in Brodmann areas (BA)22, 41 and 42 involving the primary and secondary auditory cortices. The three auditory areas in the right and left auditory cortices are selected for the determination of the effective connectivity by constructing 9 network models. The effective connectivity is determined on four out of five subjects with the exception of one subject who has the BA22 coordinates located too far from BA22 coordinates obtained from group analysis. DCM results showed the existence of effective connectivity between the three selected auditory areas in both auditory cortices. In the right auditory cortex, BA42 is identified as input centre with unidirectional parallel effective connectivities of BA42→BA41and BA42→BA22. However, for the left auditory cortex, the input is BA41 with unidirectional parallel effective connectivities of BA41→BA42 and BA41→BA22. The connectivity between the activated auditory areas suggests the existence of signal pathway in the auditory cortices even when the subject is listening to noise. (author)

  16. Auditory cortical processing: Binaural interaction in healthy and ROBO1-deficient subjects

    OpenAIRE

    LamminmÀki, Satu

    2012-01-01

    Two functioning ears provide clear advantages over monaural listening. During natural binaural listening, robust brain-level interaction occurs between the slightly different inputs from the left and the right ear. Binaural interaction requires convergence of inputs from the two ears somewhere in the auditory system, and it therefore relies on midline crossing of auditory pathways, a fundamental property of the mammalian central nervous system. Binaural interaction plays a significant ro...

  17. A Novel 9-Class Auditory ERP Paradigm Driving a Predictive Text Entry System

    OpenAIRE

    Johannes eHöhne; Martijn eSchreuder; Benjamin eBlankertz; Michael eTangermann

    2011-01-01

    Brain–computer interfaces (BCIs) based on event related potentials (ERPs) strive for offering communication pathways which are independent of muscle activity. While most visual ERP-based BCI paradigms require good control of the user's gaze direction, auditory BCI paradigms overcome this restriction. The present work proposes a novel approach using auditory evoked potentials for the example of a multiclass text spelling application. To control the ERP speller, BCI users focus their attention ...

  18. Auditory sequence analysis and phonological skill.

    Science.gov (United States)

    Grube, Manon; Kumar, Sukhbinder; Cooper, Freya E; Turton, Stuart; Griffiths, Timothy D

    2012-11-01

    This work tests the relationship between auditory and phonological skill in a non-selected cohort of 238 school students (age 11) with the specific hypothesis that sound-sequence analysis would be more relevant to phonological skill than the analysis of basic, single sounds. Auditory processing was assessed across the domains of pitch, time and timbre; a combination of six standard tests of literacy and language ability was used to assess phonological skill. A significant correlation between general auditory and phonological skill was demonstrated, plus a significant, specific correlation between measures of phonological skill and the auditory analysis of short sequences in pitch and time. The data support a limited but significant link between auditory and phonological ability with a specific role for sound-sequence analysis, and provide a possible new focus for auditory training strategies to aid language development in early adolescence. PMID:22951739

  19. Neuron class-specific requirements for Fragile X Mental Retardation Protein in critical period development of calcium signaling in learning and memory circuitry.

    Science.gov (United States)

    Doll, Caleb A; Broadie, Kendal

    2016-05-01

    Neural circuit optimization occurs through sensory activity-dependent mechanisms that refine synaptic connectivity and information processing during early-use developmental critical periods. Fragile X Mental Retardation Protein (FMRP), the gene product lost in Fragile X syndrome (FXS), acts as an activity sensor during critical period development, both as an RNA-binding translation regulator and channel-binding excitability regulator. Here, we employ a Drosophila FXS disease model to assay calcium signaling dynamics with a targeted transgenic GCaMP reporter during critical period development of the mushroom body (MB) learning/memory circuit. We find FMRP regulates depolarization-induced calcium signaling in a neuron-specific manner within this circuit, suppressing activity-dependent calcium transients in excitatory cholinergic MB input projection neurons and enhancing calcium signals in inhibitory GABAergic MB output neurons. Both changes are restricted to the developmental critical period and rectified at maturity. Importantly, conditional genetic (dfmr1) rescue of null mutants during the critical period corrects calcium signaling defects in both neuron classes, indicating a temporally restricted FMRP requirement. Likewise, conditional dfmr1 knockdown (RNAi) during the critical period replicates constitutive null mutant defects in both neuron classes, confirming cell-autonomous requirements for FMRP in developmental regulation of calcium signaling dynamics. Optogenetic stimulation during the critical period enhances depolarization-induced calcium signaling in both neuron classes, but this developmental change is eliminated in dfmr1 null mutants, indicating the activity-dependent regulation requires FMRP. These results show FMRP shapes neuron class-specific calcium signaling in excitatory vs. inhibitory neurons in developing learning/memory circuitry, and that FMRP mediates activity-dependent regulation of calcium signaling specifically during the early

  20. Neuron class-specific requirements for Fragile X Mental Retardation Protein in critical period development of calcium signaling in learning and memory circuitry.

    Science.gov (United States)

    Doll, Caleb A; Broadie, Kendal

    2016-05-01

    Neural circuit optimization occurs through sensory activity-dependent mechanisms that refine synaptic connectivity and information processing during early-use developmental critical periods. Fragile X Mental Retardation Protein (FMRP), the gene product lost in Fragile X syndrome (FXS), acts as an activity sensor during critical period development, both as an RNA-binding translation regulator and channel-binding excitability regulator. Here, we employ a Drosophila FXS disease model to assay calcium signaling dynamics with a targeted transgenic GCaMP reporter during critical period development of the mushroom body (MB) learning/memory circuit. We find FMRP regulates depolarization-induced calcium signaling in a neuron-specific manner within this circuit, suppressing activity-dependent calcium transients in excitatory cholinergic MB input projection neurons and enhancing calcium signals in inhibitory GABAergic MB output neurons. Both changes are restricted to the developmental critical period and rectified at maturity. Importantly, conditional genetic (dfmr1) rescue of null mutants during the critical period corrects calcium signaling defects in both neuron classes, indicating a temporally restricted FMRP requirement. Likewise, conditional dfmr1 knockdown (RNAi) during the critical period replicates constitutive null mutant defects in both neuron classes, confirming cell-autonomous requirements for FMRP in developmental regulation of calcium signaling dynamics. Optogenetic stimulation during the critical period enhances depolarization-induced calcium signaling in both neuron classes, but this developmental change is eliminated in dfmr1 null mutants, indicating the activity-dependent regulation requires FMRP. These results show FMRP shapes neuron class-specific calcium signaling in excitatory vs. inhibitory neurons in developing learning/memory circuitry, and that FMRP mediates activity-dependent regulation of calcium signaling specifically during the early

  1. RCN1-regulated phosphatase activity and EIN2 modulate hypocotyl gravitropism by a mechanism that does not require ethylene signaling.

    Science.gov (United States)

    Muday, Gloria K; Brady, Shari R; Argueso, Cristiana; Deruère, Jean; Kieber, Joseph J; DeLong, Alison

    2006-08-01

    The roots curl in naphthylphthalamic acid1 (rcn1) mutant of Arabidopsis (Arabidopsis thaliana) has altered auxin transport, gravitropism, and ethylene response, providing an opportunity to analyze the interplay between ethylene and auxin in control of seedling growth. Roots of rcn1 seedlings were previously shown to have altered auxin transport, growth, and gravitropism, while rcn1 hypocotyl elongation exhibited enhanced ethylene response. We have characterized auxin transport and gravitropism phenotypes of rcn1 hypocotyls and have explored the roles of auxin and ethylene in controlling these phenotypes. As in roots, auxin transport is increased in etiolated rcn1 hypocotyls. Hypocotyl gravity response is accelerated, although overall elongation is reduced, in etiolated rcn1 hypocotyls. Etiolated, but not light grown, rcn1 seedlings also overproduce ethylene, and mutations conferring ethylene insensitivity restore normal hypocotyl elongation to rcn1. Auxin transport is unaffected by treatment with the ethylene precursor 1-aminocyclopropane carboxylic acid in etiolated hypocotyls of wild-type and rcn1 seedlings. Surprisingly, the ethylene insensitive2-1 (ein2-1) and ein2-5 mutations dramatically reduce gravitropic bending in hypocotyls. However, the ethylene resistant1-3 (etr1-3) mutation does not significantly affect hypocotyl gravity response. Furthermore, neither the etr1 nor the ein2 mutation abrogates the accelerated gravitropism observed in rcn1 hypocotyls, indicating that both wild-type gravity response and enhanced gravity response in rcn1 do not require an intact ethylene-signaling pathway. We therefore conclude that the RCN1 protein affects overall hypocotyl elongation via negative regulation of ethylene synthesis in etiolated seedlings, and that RCN1 and EIN2 modulate hypocotyl gravitropism and ethylene responses through independent pathways.

  2. Speech distortion measure based on auditory properties

    Institute of Scientific and Technical Information of China (English)

    CHEN Guo; HU Xiulin; ZHANG Yunyu; ZHU Yaoting

    2000-01-01

    The Perceptual Spectrum Distortion (PSD), based on auditory properties of human being, is presented to measure speech distortion. The PSD measure calculates the speech distortion distance by simulating the auditory properties of human being and converting short-time speech power spectrum to auditory perceptual spectrum. Preliminary simulative experiments in comparison with the Itakura measure have been done. The results show that the PSD measure is a perferable speech distortion measure and more consistent with subjective assessment of speech quality.

  3. Auditory stimulation and cardiac autonomic regulation

    OpenAIRE

    Vitor E Valenti; Guida, Heraldo L.; Frizzo, Ana C F; Cardoso, Ana C. V.; Vanderlei, Luiz Carlos M; Luiz Carlos de Abreu

    2012-01-01

    Previous studies have already demonstrated that auditory stimulation with music influences the cardiovascular system. In this study, we described the relationship between musical auditory stimulation and heart rate variability. Searches were performed with the Medline, SciELO, Lilacs and Cochrane databases using the following keywords: "auditory stimulation", "autonomic nervous system", "music" and "heart rate variability". The selected studies indicated that there is a strong correlation bet...

  4. Mechanisms of Auditory Verbal Hallucination in Schizophrenia

    OpenAIRE

    Raymond eCho; Wayne eWu

    2013-01-01

    Recent work on the mechanisms underlying auditory verbal hallucination (AVH) has been heavily informed by self-monitoring accounts that postulate defects in an internal monitoring mechanism as the basis of AVH. A more neglected alternative is an account focusing on defects in auditory processing, namely a spontaneous activation account of auditory activity underlying AVH. Science is often aided by putting theories in competition. Accordingly, a discussion that systematically contrasts the two...

  5. Lef1 is required for the transition of Wnt signaling from mesenchymal to epithelial cells in the mouse embryonic mammary gland.

    Science.gov (United States)

    Boras-Granic, Kata; Chang, Hong; Grosschedl, Rudolf; Hamel, Paul A

    2006-07-01

    Inductive reciprocal signaling between mesenchymal and adjacent epithelia gives rise to skin appendages such as hair follicles and mammary glands. Lef1-mediated canonical Wnt signaling is required for morphogenesis of these skin appendages during embryogenesis. In order to define the role of canonical Wnt signaling during early embryonic mammary gland development, we determined the temporal and spatial changes in Wnt signaling during embryogenesis in wild-type and Lef1-deficient embryos harboring a Tcf/Lef1-betagal reporter (TOPGAL) transgene. In contrast to previous studies using TOPGAL mice from a distinct founder, we observe that Wnt signaling acts initially on mesenchymal cells associated with the sequential appearance of mammary placodes. As placode development progresses between 12.5 and 15.5 dpc, Wnt signaling progressively accumulates in the mammary epithelial compartment. By 18.5 dpc, betagal activity is confined to mesenchymal and epithelial cells near the nipple region. In Lef1-deficient embryos, the transition of Wnt signaling from mesenchyme to the mammary epithelia is blocked for placodes #1, 4 and 5 despite the expression of Tcf1 in epithelial cells. These placodes ultimately disappear by 15.5 dpc, while placodes 2 and 3 typically did not form in the absence of Lef1. Progressive loss of placodes 1, 4, and 5 is accompanied by increased apoptosis in mesenchymal cells adjacent to the mammary epithelial placodes. While factors important for embryonic mammary gland development, such as FGF7, are expressed normally in Lef1-deficient animals, one mediator of the Hedgehog (Hh)-signaling pathway is aberrantly expressed. Specifically, Shh, Ihh, and Gli2 are expressed in mammary epithelial cells at levels in Lef1-deficient animals similar to wild-type littermates. However, the signal for Ptc-1 is strongly reduced in mesenchymal cells surrounding the mammary placode in Lef1 mutants relative to wild-type embryos. The loss of Ptc-1, both a receptor for and

  6. Auditory Training and Its Effects upon the Auditory Discrimination and Reading Readiness of Kindergarten Children.

    Science.gov (United States)

    Cullen, Minga Mustard

    The purpose of this investigation was to evaluate the effects of a systematic auditory training program on the auditory discrimination ability and reading readiness of 55 white, middle/upper middle class kindergarten students. Following pretesting with the "Wepman Auditory Discrimination Test,""The Clymer-Barrett Prereading Battery," and the…

  7. Effects of Methylphenidate (Ritalin) on Auditory Performance in Children with Attention and Auditory Processing Disorders.

    Science.gov (United States)

    Tillery, Kim L.; Katz, Jack; Keller, Warren D.

    2000-01-01

    A double-blind, placebo-controlled study examined effects of methylphenidate (Ritalin) on auditory processing in 32 children with both attention deficit hyperactivity disorder and central auditory processing (CAP) disorder. Analyses revealed that Ritalin did not have a significant effect on any of the central auditory processing measures, although…

  8. Auditory Confrontation Naming in Alzheimer’s Disease

    OpenAIRE

    Brandt, Jason; Bakker, Arnold; Maroof, David Aaron

    2010-01-01

    Naming is a fundamental aspect of language and is virtually always assessed with visual confrontation tests. Tests of the ability to name objects by their characteristic sounds would be particularly useful in the assessment of visually impaired patients, and may be particularly sensitive in Alzheimer’s disease (AD). We developed an Auditory Naming Task, requiring the identification of the source of environmental sounds (i.e., animal calls, musical instruments, vehicles) and multiple-choice re...

  9. Crossmodal interactions during non-linguistic auditory processing in cochlear-implanted deaf patients.

    Science.gov (United States)

    Barone, Pascal; Chambaudie, Laure; Strelnikov, Kuzma; Fraysse, Bernard; Marx, Mathieu; Belin, Pascal; Deguine, Olivier

    2016-10-01

    Due to signal distortion, speech comprehension in cochlear-implanted (CI) patients relies strongly on visual information, a compensatory strategy supported by important cortical crossmodal reorganisations. Though crossmodal interactions are evident for speech processing, it is unclear whether a visual influence is observed in CI patients during non-linguistic visual-auditory processing, such as face-voice interactions, which are important in social communication. We analyse and compare visual-auditory interactions in CI patients and normal-hearing subjects (NHS) at equivalent auditory performance levels. Proficient CI patients and NHS performed a voice-gender categorisation in the visual-auditory modality from a morphing-generated voice continuum between male and female speakers, while ignoring the presentation of a male or female visual face. Our data show that during the face-voice interaction, CI deaf patients are strongly influenced by visual information when performing an auditory gender categorisation task, in spite of maximum recovery of auditory speech. No such effect is observed in NHS, even in situations of CI simulation. Our hypothesis is that the functional crossmodal reorganisation that occurs in deafness could influence nonverbal processing, such as face-voice interaction; this is important for patient internal supramodal representation. PMID:27622640

  10. Electrophysiological correlates of predictive coding of auditory location in the perception of natural audiovisual events

    Directory of Open Access Journals (Sweden)

    Jeroen eStekelenburg

    2012-05-01

    Full Text Available In many natural audiovisual events (e.g., a clap of the two hands, the visual signal precedes the sound and thus allows observers to predict when, where, and which sound will occur. Previous studies have already reported that there are distinct neural correlates of temporal (when versus phonetic/semantic (which content on audiovisual integration. Here we examined the effect of visual prediction of auditory location (where in audiovisual biological motion stimuli by varying the spatial congruency between the auditory and visual part of the audiovisual stimulus. Visual stimuli were presented centrally, whereas auditory stimuli were presented either centrally or at 90° azimuth. Typical subadditive amplitude reductions (AV – V < A were found for the auditory N1 and P2 for spatially congruent and incongruent conditions. The new finding is that the N1 suppression was larger for spatially congruent stimuli. A very early audiovisual interaction was also found at 30-50 ms in the spatially congruent condition, while no effect of congruency was found on the suppression of the P2. This indicates that visual prediction of auditory location can be coded very early in auditory processing.

  11. Stimulation of the human auditory nerve with optical radiation

    Science.gov (United States)

    Fishman, Andrew; Winkler, Piotr; Mierzwinski, Jozef; Beuth, Wojciech; Izzo Matic, Agnella; Siedlecki, Zygmunt; Teudt, Ingo; Maier, Hannes; Richter, Claus-Peter

    2009-02-01

    A novel, spatially selective method to stimulate cranial nerves has been proposed: contact free stimulation with optical radiation. The radiation source is an infrared pulsed laser. The Case Report is the first report ever that shows that optical stimulation of the auditory nerve is possible in the human. The ethical approach to conduct any measurements or tests in humans requires efficacy and safety studies in animals, which have been conducted in gerbils. This report represents the first step in a translational research project to initiate a paradigm shift in neural interfaces. A patient was selected who required surgical removal of a large meningioma angiomatum WHO I by a planned transcochlear approach. Prior to cochlear ablation by drilling and subsequent tumor resection, the cochlear nerve was stimulated with a pulsed infrared laser at low radiation energies. Stimulation with optical radiation evoked compound action potentials from the human auditory nerve. Stimulation of the auditory nerve with infrared laser pulses is possible in the human inner ear. The finding is an important step for translating results from animal experiments to human and furthers the development of a novel interface that uses optical radiation to stimulate neurons. Additional measurements are required to optimize the stimulation parameters.

  12. Caution and Warning Alarm Design and Evaluation for NASA CEV Auditory Displays: SHFE Information Presentation Directed Research Project (DRPP) report 12.07

    Science.gov (United States)

    Begault, Durand R.; Godfroy, Martine; Sandor, Aniko; Holden, Kritina

    2008-01-01

    The design of caution-warning signals for NASA s Crew Exploration Vehicle (CEV) and other future spacecraft will be based on both best practices based on current research and evaluation of current alarms. A design approach is presented based upon cross-disciplinary examination of psychoacoustic research, human factors experience, aerospace practices, and acoustical engineering requirements. A listening test with thirteen participants was performed involving ranking and grading of current and newly developed caution-warning stimuli under three conditions: (1) alarm levels adjusted for compliance with ISO 7731, "Danger signals for work places - Auditory Danger Signals", (2) alarm levels adjusted to an overall 15 dBA s/n ratio and (3) simulated codec low-pass filtering. Questionnaire data yielded useful insights regarding cognitive associations with the sounds.

  13. Focal Adhesion Kinase Is Required for Intestinal Regeneration and Tumorigenesis Downstream of Wnt/c-Myc Signaling

    OpenAIRE

    Ashton, Gabrielle H.; Morton, Jennifer P; Myant, Kevin; Phesse, Toby J.; Ridgway, Rachel A.; Marsh, Victoria; Wilkins, Julie A.; Athineos, Dimitris; Muncan, Vanesa; Kemp, Richard; Neufeld, Kristi; Clevers, Hans; Brunton, Valerie; Winton, Douglas J.; Wang, Xiaoyan

    2010-01-01

    The intestinal epithelium has a remarkable capacity to regenerate after injury and DNA damage. Here, we show that the integrin effector protein Focal Adhesion Kinase (FAK) is dispensable for normal intestinal homeostasis and DNA damage signaling, but is essential for intestinal regeneration following DNA damage. Given Wnt/c-Myc signaling is activated following intestinal regeneration, we investigated the functional importance of FAK following deletion of the Apc tumor suppressor protein withi...

  14. Nodal signaling is required for mesodermal and ventral but not for dorsal fates in the indirect developing hemichordate, Ptychodera flava

    OpenAIRE

    Eric Röttinger; DuBuc, Timothy Q.; Aldine R. Amiel; Martindale, Mark Q.

    2015-01-01

    ABSTRACT Nodal signaling plays crucial roles in vertebrate developmental processes such as endoderm and mesoderm formation, and axial patterning events along the anteroposterior, dorsoventral and left-right axes. In echinoderms, Nodal plays an essential role in the establishment of the dorsoventral axis and left-right asymmetry, but not in endoderm or mesoderm induction. In protostomes, Nodal signaling appears to be involved only in establishing left-right asymmetry. Hence, it is hypothesized...

  15. Def6 Is Required for Convergent Extension Movements during Zebrafish Gastrulation Downstream of Wnt5b Signaling

    OpenAIRE

    Goudevenou, Katerina; Martin, Paul; Yeh, Yu-Jung; Jones, Peter; Sablitzky, Fred

    2011-01-01

    During gastrulation, convergent extension (CE) cell movements are regulated through the non-canonical Wnt signaling pathway. Wnt signaling results in downstream activation of Rho GTPases that in turn regulate actin cytoskeleton rearrangements essential for co-ordinated CE cell movement. Rho GTPases are bi-molecular switches that are inactive in their GDP-bound stage but can be activated to bind GTP through guanine nucleotide exchange factors (GEFs). Here we show that def6, a novel GEF, regula...

  16. Shh signaling from the nucleus pulposus is required for the postnatal growth and differentiation of the mouse intervertebral disc.

    Directory of Open Access Journals (Sweden)

    Chitra Lekha Dahia

    Full Text Available Intervertebral discs (IVD are essential components of the vertebral column. They maintain separation, and provide shock absorbing buffers, between adjacent vertebrae, while also allowing movements between them. Each IVD consists of a central semi-liquid nucleus pulposus (NP surrounded by a multi-layered fibrocartilagenous annulus fibrosus (AF. Although the IVDs grow and differentiate after birth along with the vertebral column, little is known about the mechanism of this. Understanding the signals that control normal IVD growth and differentiation would also provide potential therapies for degenerative disc disease, which is the major cause of lower back pain and affects a large proportion of the population. In this work, we show that during postnatal growth of the mouse, Sonic hedgehog (Shh signaling from the NP cells controls many aspects of growth and differentiation of both the NP cells themselves and of the surrounding AF, and that it acts, at least partly, by regulating other signaling pathways in the NP and AF. Recent studies have shown that the NP cells arise from the embryonic notochord, which acts as a major signaling center in the embryo. This work shows that this notochord-derived tissue continues to carry out a major signaling function in the postnatal body and that the IVDs are signaling centers, in addition to their already known functions in the mechanics of vertebral column function.

  17. Daple is a novel non-receptor GEF required for trimeric G protein activation in Wnt signaling.

    Science.gov (United States)

    Aznar, Nicolas; Midde, Krishna K; Dunkel, Ying; Lopez-Sanchez, Inmaculada; Pavlova, Yelena; Marivin, Arthur; Barbazán, Jorge; Murray, Fiona; Nitsche, Ulrich; Janssen, Klaus-Peter; Willert, Karl; Goel, Ajay; Abal, Miguel; Garcia-Marcos, Mikel; Ghosh, Pradipta

    2015-01-01

    Wnt signaling is essential for tissue homeostasis and its dysregulation causes cancer. Wnt ligands trigger signaling by activating Frizzled receptors (FZDRs), which belong to the G-protein coupled receptor superfamily. However, the mechanisms of G protein activation in Wnt signaling remain controversial. In this study, we demonstrate that FZDRs activate G proteins and trigger non-canonical Wnt signaling via the Dishevelled-binding protein, Daple. Daple contains a Gα-binding and activating (GBA) motif, which activates Gαi proteins and an adjacent domain that directly binds FZDRs, thereby linking Wnt stimulation to G protein activation. This triggers non-canonical Wnt responses, that is, suppresses the β-catenin/TCF/LEF pathway and tumorigenesis, but enhances PI3K-Akt and Rac1 signals and tumor cell invasiveness. In colorectal cancers, Daple is suppressed during adenoma-to-carcinoma transformation and expressed later in metastasized tumor cells. Thus, Daple activates Gαi and enhances non-canonical Wnt signaling by FZDRs, and its dysregulation can impact both tumor initiation and progression to metastasis. PMID:26126266

  18. Auditory hallucinations suppressed by etizolam in a patient with schizophrenia.

    Science.gov (United States)

    Benazzi, F; Mazzoli, M; Rossi, E

    1993-10-01

    A patient presented with a 15 year history of schizophrenia with auditory hallucinations. Though unresponsive to prolonged trials of neuroleptics, the auditory hallucinations disappeared with etizolam. PMID:7902201

  19. Auditory Association Cortex Lesions Impair Auditory Short-Term Memory in Monkeys

    Science.gov (United States)

    Colombo, Michael; D'Amato, Michael R.; Rodman, Hillary R.; Gross, Charles G.

    1990-01-01

    Monkeys that were trained to perform auditory and visual short-term memory tasks (delayed matching-to-sample) received lesions of the auditory association cortex in the superior temporal gyrus. Although visual memory was completely unaffected by the lesions, auditory memory was severely impaired. Despite this impairment, all monkeys could discriminate sounds closer in frequency than those used in the auditory memory task. This result suggests that the superior temporal cortex plays a role in auditory processing and retention similar to the role the inferior temporal cortex plays in visual processing and retention.

  20. Diverse Roles of Axonemal Dyneins in Drosophila Auditory Neuron Function and Mechanical Amplification in Hearing.

    Science.gov (United States)

    Karak, Somdatta; Jacobs, Julie S; Kittelmann, Maike; Spalthoff, Christian; Katana, Radoslaw; Sivan-Loukianova, Elena; Schon, Michael A; Kernan, Maurice J; Eberl, Daniel F; Göpfert, Martin C

    2015-11-26

    Much like vertebrate hair cells, the chordotonal sensory neurons that mediate hearing in Drosophila are motile and amplify the mechanical input of the ear. Because the neurons bear mechanosensory primary cilia whose microtubule axonemes display dynein arms, we hypothesized that their motility is powered by dyneins. Here, we describe two axonemal dynein proteins that are required for Drosophila auditory neuron function, localize to their primary cilia, and differently contribute to mechanical amplification in hearing. Promoter fusions revealed that the two axonemal dynein genes Dmdnah3 (=CG17150) and Dmdnai2 (=CG6053) are expressed in chordotonal neurons, including the auditory ones in the fly's ear. Null alleles of both dyneins equally abolished electrical auditory neuron responses, yet whereas mutations in Dmdnah3 facilitated mechanical amplification, amplification was abolished by mutations in Dmdnai2. Epistasis analysis revealed that Dmdnah3 acts downstream of Nan-Iav channels in controlling the amplificatory gain. Dmdnai2, in addition to being required for amplification, was essential for outer dynein arms in auditory neuron cilia. This establishes diverse roles of axonemal dyneins in Drosophila auditory neuron function and links auditory neuron motility to primary cilia and axonemal dyneins. Mutant defects in sperm competition suggest that both dyneins also function in sperm motility.

  1. Different auditory feedback control for echolocation and communication in horseshoe bats.

    Directory of Open Access Journals (Sweden)

    Ying Liu

    Full Text Available Auditory feedback from the animal's own voice is essential during bat echolocation: to optimize signal detection, bats continuously adjust various call parameters in response to changing echo signals. Auditory feedback seems also necessary for controlling many bat communication calls, although it remains unclear how auditory feedback control differs in echolocation and communication. We tackled this question by analyzing echolocation and communication in greater horseshoe bats, whose echolocation pulses are dominated by a constant frequency component that matches the frequency range they hear best. To maintain echoes within this "auditory fovea", horseshoe bats constantly adjust their echolocation call frequency depending on the frequency of the returning echo signal. This Doppler-shift compensation (DSC behavior represents one of the most precise forms of sensory-motor feedback known. We examined the variability of echolocation pulses emitted at rest (resting frequencies, RFs and one type of communication signal which resembles an echolocation pulse but is much shorter (short constant frequency communication calls, SCFs and produced only during social interactions. We found that while RFs varied from day to day, corroborating earlier studies in other constant frequency bats, SCF-frequencies remained unchanged. In addition, RFs overlapped for some bats whereas SCF-frequencies were always distinctly different. This indicates that auditory feedback during echolocation changed with varying RFs but remained constant or may have been absent during emission of SCF calls for communication. This fundamentally different feedback mechanism for echolocation and communication may have enabled these bats to use SCF calls for individual recognition whereas they adjusted RF calls to accommodate the daily shifts of their auditory fovea.

  2. Nodal signaling is required for mesodermal and ventral but not for dorsal fates in the indirect developing hemichordate, Ptychodera flava

    Directory of Open Access Journals (Sweden)

    Eric Röttinger

    2015-07-01

    Full Text Available Nodal signaling plays crucial roles in vertebrate developmental processes such as endoderm and mesoderm formation, and axial patterning events along the anteroposterior, dorsoventral and left-right axes. In echinoderms, Nodal plays an essential role in the establishment of the dorsoventral axis and left-right asymmetry, but not in endoderm or mesoderm induction. In protostomes, Nodal signaling appears to be involved only in establishing left-right asymmetry. Hence, it is hypothesized that Nodal signaling has been co-opted to pattern the dorsoventral axis of deuterostomes and for endoderm, mesoderm formation as well as anteroposterior patterning in chordates. Hemichordata, together with echinoderms, represent the sister taxon to chordates. In this study, we analyze the role of Nodal signaling in the indirect developing hemichordate Ptychodera flava. In particular, we show that during gastrulation nodal transcripts are detected in a ring of cells at the vegetal pole that gives rise to endomesoderm and in the ventral ectoderm at later stages of development. Inhibition of Nodal function disrupts dorsoventral fates and also blocks formation of the larval mesoderm. Interestingly, molecular analysis reveals that only mesodermal, apical and ventral gene expression is affected while the dorsal side appears to be patterned correctly. Taken together, this study suggests that the co-option of Nodal signaling in mesoderm formation and potentially in anteroposterior patterning has occurred prior to the emergence of chordates and that Nodal signaling on the ventral side is uncoupled from BMP signaling on the dorsal side, representing a major difference from the molecular mechanisms of dorsoventral patterning events in echinoderms.

  3. Narrow, duplicated internal auditory canal

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, T. [Servico de Neurorradiologia, Hospital Garcia de Orta, Avenida Torrado da Silva, 2801-951, Almada (Portugal); Shayestehfar, B. [Department of Radiology, UCLA Oliveview School of Medicine, Los Angeles, California (United States); Lufkin, R. [Department of Radiology, UCLA School of Medicine, Los Angeles, California (United States)

    2003-05-01

    A narrow internal auditory canal (IAC) constitutes a relative contraindication to cochlear implantation because it is associated with aplasia or hypoplasia of the vestibulocochlear nerve or its cochlear branch. We report an unusual case of a narrow, duplicated IAC, divided by a bony septum into a superior relatively large portion and an inferior stenotic portion, in which we could identify only the facial nerve. This case adds support to the association between a narrow IAC and aplasia or hypoplasia of the vestibulocochlear nerve. The normal facial nerve argues against the hypothesis that the narrow IAC is the result of a primary bony defect which inhibits the growth of the vestibulocochlear nerve. (orig.)

  4. Auditory hallucinations in nonverbal quadriplegics.

    Science.gov (United States)

    Hamilton, J

    1985-11-01

    When a system for communicating with nonverbal, quadriplegic, institutionalized residents was developed, it was discovered that many were experiencing auditory hallucinations. Nine cases are presented in this study. The "voices" described have many similar characteristics, the primary one being that they give authoritarian commands that tell the residents how to behave and to which the residents feel compelled to respond. Both the relationship of this phenomenon to the theoretical work of Julian Jaynes and its effect on the lives of the residents are discussed.

  5. Autosomal recessive hereditary auditory neuropathy

    Institute of Scientific and Technical Information of China (English)

    王秋菊; 顾瑞; 曹菊阳

    2003-01-01

    Objectives: Auditory neuropathy (AN) is a sensorineural hearing disorder characterized by absent or abnormal auditory brainstem responses (ABRs) and normal cochlear outer hair cell function as measured by otoacoustic emissions (OAEs). Many risk factors are thought to be involved in its etiology and pathophysiology. Three Chinese pedigrees with familial AN are presented herein to demonstrate involvement of genetic factors in AN etiology. Methods: Probands of the above - mentioned pedigrees, who had been diagnosed with AN, were evaluated and followed up in the Department of Otolaryngology Head and Neck Surgery, China PLA General Hospital. Their family members were studied and the pedigree diagrams were established. History of illness, physical examination,pure tone audiometry, acoustic reflex, ABRs and transient evoked and distortion- product otoacoustic emissions (TEOAEs and DPOAEs) were obtained from members of these families. DPOAE changes under the influence of contralateral sound stimuli were observed by presenting a set of continuous white noise to the non - recording ear to exam the function of auditory efferent system. Some subjects received vestibular caloric test, computed tomography (CT)scan of the temporal bone and electrocardiography (ECG) to exclude other possible neuropathy disorders. Results: In most affected subjects, hearing loss of various degrees and speech discrimination difficulties started at 10 to16 years of age. Their audiological evaluation showed absence of acoustic reflex and ABRs. As expected in AN, these subjects exhibited near normal cochlear outer hair cell function as shown in TEOAE & DPOAE recordings. Pure- tone audiometry revealed hearing loss ranging from mild to severe in these patients. Autosomal recessive inheritance patterns were observed in the three families. In Pedigree Ⅰ and Ⅱ, two affected brothers were found respectively, while in pedigree Ⅲ, 2 sisters were affected. All the patients were otherwise normal without

  6. Auditory training can improve working memory, attention, and communication in adverse conditions for adults with hearing loss

    OpenAIRE

    Ferguson, Melanie A.; Henshaw, Helen

    2015-01-01

    Auditory training (AT) helps compensate for degradation in the auditory signal. A series of three high-quality training studies are discussed, which include, (i) a randomized controlled trial (RCT) of phoneme discrimination in quiet that trained adults with mild hearing loss (n = 44), (ii) a repeated measures study that trained phoneme discrimination in noise in hearing aid (HA) users (n = 30), and (iii) a double-blind RCT that directly trained working memory (WM) in HA users (n = 57). AT res...

  7. Auditory training can improve working memory, attention and communication in adverse conditions for adults with hearing loss

    OpenAIRE

    Melanie Ann Ferguson; Helen eHenshaw

    2015-01-01

    Auditory training (AT) helps compensate for degradation in the auditory signal. A series of three high-quality training studies are discussed, (i) a randomized controlled trial (RCT) of phoneme discrimination in quiet that trained adults with mild hearing loss (n=44), (ii) a repeated measures study that trained phoneme discrimination in noise in hearing aid (HA) users (n=30), and (iii) a double-blind RCT that directly trained working memory (WM) in HA users (n=57). AT resulted in generalized ...

  8. Kif3a regulates planar polarization of auditory hair cells through both ciliary and non-ciliary mechanisms

    OpenAIRE

    Sipe, Conor W.; Lu, Xiaowei

    2011-01-01

    Auditory hair cells represent one of the most prominent examples of epithelial planar polarity. In the auditory sensory epithelium, planar polarity of individual hair cells is defined by their V-shaped hair bundle, the mechanotransduction organelle located on the apical surface. At the tissue level, all hair cells display uniform planar polarity across the epithelium. Although it is known that tissue planar polarity is controlled by non-canonical Wnt/planar cell polarity (PCP) signaling, the ...

  9. Heritability of non-speech auditory processing skills.

    Science.gov (United States)

    Brewer, Carmen C; Zalewski, Christopher K; King, Kelly A; Zobay, Oliver; Riley, Alison; Ferguson, Melanie A; Bird, Jonathan E; McCabe, Margaret M; Hood, Linda J; Drayna, Dennis; Griffith, Andrew J; Morell, Robert J; Friedman, Thomas B; Moore, David R

    2016-08-01

    Recent insight into the genetic bases for autism spectrum disorder, dyslexia, stuttering, and language disorders suggest that neurogenetic approaches may also reveal at least one etiology of auditory processing disorder (APD). A person with an APD typically has difficulty understanding speech in background noise despite having normal pure-tone hearing sensitivity. The estimated prevalence of APD may be as high as 10% in the pediatric population, yet the causes are unknown and have not been explored by molecular or genetic approaches. The aim of our study was to determine the heritability of frequency and temporal resolution for auditory signals and speech recognition in noise in 96 identical or fraternal twin pairs, aged 6-11 years. Measures of auditory processing (AP) of non-speech sounds included backward masking (temporal resolution), notched noise masking (spectral resolution), pure-tone frequency discrimination (temporal fine structure sensitivity), and nonsense syllable recognition in noise. We provide evidence of significant heritability, ranging from 0.32 to 0.74, for individual measures of these non-speech-based AP skills that are crucial for understanding spoken language. Identification of specific heritable AP traits such as these serve as a basis to pursue the genetic underpinnings of APD by identifying genetic variants associated with common AP disorders in children and adults. PMID:26883091

  10. Further Evidence of Auditory Extinction in Aphasia

    Science.gov (United States)

    Marshall, Rebecca Shisler; Basilakos, Alexandra; Love-Myers, Kim

    2013-01-01

    Purpose: Preliminary research ( Shisler, 2005) suggests that auditory extinction in individuals with aphasia (IWA) may be connected to binding and attention. In this study, the authors expanded on previous findings on auditory extinction to determine the source of extinction deficits in IWA. Method: Seventeen IWA (M[subscript age] = 53.19 years)…

  11. Mapping tonotopy in human auditory cortex

    NARCIS (Netherlands)

    van Dijk, Pim; Langers, Dave R M; Moore, BCJ; Patterson, RD; Winter, IM; Carlyon, RP; Gockel, HE

    2013-01-01

    Tonotopy is arguably the most prominent organizational principle in the auditory pathway. Nevertheless, the layout of tonotopic maps in humans is still debated. We present neuroimaging data that robustly identify multiple tonotopic maps in the bilateral auditory cortex. In contrast with some earlier

  12. Auditory Processing Disorder and Foreign Language Acquisition

    Science.gov (United States)

    Veselovska, Ganna

    2015-01-01

    This article aims at exploring various strategies for coping with the auditory processing disorder in the light of foreign language acquisition. The techniques relevant to dealing with the auditory processing disorder can be attributed to environmental and compensatory approaches. The environmental one involves actions directed at creating a…

  13. A corollary discharge mechanism modulates central auditory processing in singing crickets.

    Science.gov (United States)

    Poulet, J F A; Hedwig, B

    2003-03-01

    Crickets communicate using loud (100 dB SPL) sound signals that could adversely affect their own auditory system. To examine how they cope with this self-generated acoustic stimulation, intracellular recordings were made from auditory afferent neurons and an identified auditory interneuron-the Omega 1 neuron (ON1)-during pharmacologically elicited singing (stridulation). During sonorous stridulation, the auditory afferents and ON1 responded with bursts of spikes to the crickets' own song. When the crickets were stridulating silently, after one wing had been removed, only a few spikes were recorded in the afferents and ON1. Primary afferent depolarizations (PADs) occurred in the terminals of the auditory afferents, and inhibitory postsynaptic potentials (IPSPs) were apparent in ON1. The PADs and IPSPs were composed of many summed, small-amplitude potentials that occurred at a rate of about 230 Hz. The PADs and the IPSPs started during the closing wing movement and peaked in amplitude during the subsequent opening wing movement. As a consequence, during silent stridulation, ON1's response to acoustic stimuli was maximally inhibited during wing opening. Inhibition coincides with the time when ON1 would otherwise be most strongly excited by self-generated sounds in a sonorously stridulating cricket. The PADs and the IPSPs persisted in fictively stridulating crickets whose ventral nerve cord had been isolated from muscles and sense organs. This strongly suggests that the inhibition of the auditory pathway is the result of a corollary discharge from the stridulation motor network. The central inhibition was mimicked by hyperpolarizing current injection into ON1 while it was responding to a 100 dB SPL sound pulse. This suppressed its spiking response to the acoustic stimulus and maintained its response to subsequent, quieter stimuli. The corollary discharge therefore prevents auditory desensitization in stridulating crickets and allows the animals to respond to external

  14. Auditory Neural Prostheses – A Window to the Future

    Directory of Open Access Journals (Sweden)

    Mohan Kameshwaran

    2015-06-01

    Full Text Available Hearing loss is one of the commonest congenital anomalies to affect children world-over. The incidence of congenital hearing loss is more pronounced in developing countries like the Indian sub-continent, especially with the problems of consanguinity. Hearing loss is a double tragedy, as it leads to not only deafness but also language deprivation. However, hearing loss is the only truly remediable handicap, due to remarkable advances in biomedical engineering and surgical techniques. Auditory neural prostheses help to augment or restore hearing by integration of an external circuitry with the peripheral hearing apparatus and the central circuitry of the brain. A cochlear implant (CI is a surgically implantable device that helps restore hearing in patients with severe-profound hearing loss, unresponsive to amplification by conventional hearing aids. CIs are electronic devices designed to detect mechanical sound energy and convert it into electrical signals that can be delivered to the coch­lear nerve, bypassing the damaged hair cells of the coch­lea. The only true prerequisite is an intact auditory nerve. The emphasis is on implantation as early as possible to maximize speech understanding and perception. Bilateral CI has significant benefits which include improved speech perception in noisy environments and improved sound localization. Presently, the indications for CI have widened and these expanded indications for implantation are related to age, additional handicaps, residual hearing, and special etiologies of deafness. Combined electric and acoustic stimulation (EAS / hybrid device is designed for individuals with binaural low-frequency hearing and severe-to-profound high-frequency hearing loss. Auditory brainstem implantation (ABI is a safe and effective means of hearing rehabilitation in patients with retrocochlear disorders, such as neurofibromatosis type 2 (NF2 or congenital cochlear nerve aplasia, wherein the cochlear nerve is damaged

  15. LRP2 is an auxiliary SHH receptor required to condition the forebrain ventral midline for inductive signals.

    Science.gov (United States)

    Christ, Annabel; Christa, Anna; Kur, Esther; Lioubinski, Oleg; Bachmann, Sebastian; Willnow, Thomas E; Hammes, Annette

    2012-02-14

    Sonic hedgehog (SHH) is a regulator of forebrain development that acts through its receptor, patched 1. However, little is known about cellular mechanisms at neurulation, whereby SHH from the prechordal plate governs specification of the rostral diencephalon ventral midline (RDVM), a major forebrain organizer. We identified LRP2, a member of the LDL receptor gene family, as a component of the SHH signaling machinery in the RDVM. LRP2 acts as an apical SHH-binding protein that sequesters SHH in its target field and controls internalization and cellular trafficking of SHH/patched 1 complexes. Lack of LRP2 in mice and in cephalic explants results in failure to respond to SHH, despite functional expression of patched 1 and smoothened, whereas overexpression of LRP2 variants in cells increases SHH signaling capacity. Our data identify a critical role for LRP2 in SHH signaling and reveal the molecular mechanism underlying forebrain anomalies in mice and patients with Lrp2 defects.

  16. Speech perception as complex auditory categorization

    Science.gov (United States)

    Holt, Lori L.

    2002-05-01

    Despite a long and rich history of categorization research in cognitive psychology, very little work has addressed the issue of complex auditory category formation. This is especially unfortunate because the general underlying cognitive and perceptual mechanisms that guide auditory category formation are of great importance to understanding speech perception. I will discuss a new methodological approach to examining complex auditory category formation that specifically addresses issues relevant to speech perception. This approach utilizes novel nonspeech sound stimuli to gain full experimental control over listeners' history of experience. As such, the course of learning is readily measurable. Results from this methodology indicate that the structure and formation of auditory categories are a function of the statistical input distributions of sound that listeners hear, aspects of the operating characteristics of the auditory system, and characteristics of the perceptual categorization system. These results have important implications for phonetic acquisition and speech perception.

  17. Measuring the performance of visual to auditory information conversion.

    Directory of Open Access Journals (Sweden)

    Shern Shiou Tan

    Full Text Available BACKGROUND: Visual to auditory conversion systems have been in existence for several decades. Besides being among the front runners in providing visual capabilities to blind users, the auditory cues generated from image sonification systems are still easier to learn and adapt to compared to other similar techniques. Other advantages include low cost, easy customizability, and universality. However, every system developed so far has its own set of strengths and weaknesses. In order to improve these systems further, we propose an automated and quantitative method to measure the performance of such systems. With these quantitative measurements, it is possible to gauge the relative strengths and weaknesses of different systems and rank the systems accordingly. METHODOLOGY: Performance is measured by both the interpretability and also the information preservation of visual to auditory conversions. Interpretability is measured by computing the correlation of inter image distance (IID and inter sound distance (ISD whereas the information preservation is computed by applying Information Theory to measure the entropy of both visual and corresponding auditory signals. These measurements provide a basis and some insights on how the systems work. CONCLUSIONS: With an automated interpretability measure as a standard, more image sonification systems can be developed, compared, and then improved. Even though the measure does not test systems as thoroughly as carefully designed psychological experiments, a quantitative measurement like the one proposed here can compare systems to a certain degree without incurring much cost. Underlying this research is the hope that a major breakthrough in image sonification systems will allow blind users to cost effectively regain enough visual functions to allow them to lead secure and productive lives.

  18. Dynamic Vibrotactile Signals for Forward Collision Avoidance Warning Systems

    OpenAIRE

    Meng, Fanxing; Gray, Rob; Ho, Cristy.; Ahtamad, Mujthaba; Spence, Charles

    2015-01-01

    Objective: Four experiments were conducted in order to assess the effectiveness of dynamic vibrotactile collision-warning signals in potentially enhancing safe driving. Background: Auditory neuroscience research has demonstrated that auditory signals that move toward a person are more salient than those that move away. If this looming effect were found to extend to the tactile modality, then it could be utilized in the context of in-car warning signal design. Method: The effectiveness of vari...

  19. Developmental stress impairs performance on an association task in male and female songbirds, but impairs auditory learning in females only.

    Science.gov (United States)

    Farrell, Tara M; Morgan, Amanda; MacDougall-Shackleton, Scott A

    2016-01-01

    In songbirds, early-life environments critically shape song development. Many studies have demonstrated that developmental stress impairs song learning and the development of song-control regions of the brain in males. However, song has evolved through signaller-receiver networks and the effect stress has on the ability to receive auditory signals is equally important, especially for females who use song as an indicator of mate quality. Female song preferences have been the metric used to evaluate how developmental stress affects auditory learning, but preferences are shaped by many non-cognitive factors and preclude the evaluation of auditory learning abilities in males. To determine whether developmental stress specifically affects auditory learning in both sexes, we subjected juvenile European starlings, Sturnus vulgaris, to either an ad libitum or an unpredictable food supply treatment from 35 to 115 days of age. In adulthood, we assessed learning of both auditory and visual discrimination tasks. Females reared in the experimental group were slower than females in the control group to acquire a relative frequency auditory task, and slower than their male counterparts to acquire an absolute frequency auditory task. There was no difference in auditory performance between treatment groups for males. However, on the colour association task, birds from the experimental group committed more errors per trial than control birds. There was no correlation in performance across the cognitive tasks. Developmental stress did not affect all cognitive processes equally across the sexes. Our results suggest that the male auditory system may be more robust to developmental stress than that of females. PMID:26238792

  20. Auditory responses and stimulus-specific adaptation in rat auditory cortex are preserved across NREM and REM sleep.

    Science.gov (United States)

    Nir, Yuval; Vyazovskiy, Vladyslav V; Cirelli, Chiara; Banks, Matthew I; Tononi, Giulio

    2015-05-01

    Sleep entails a disconnection from the external environment. By and large, sensory stimuli do not trigger behavioral responses and are not consciously perceived as they usually are in wakefulness. Traditionally, sleep disconnection was ascribed to a thalamic "gate," which would prevent signal propagation along ascending sensory pathways to primary cortical areas. Here, we compared single-unit and LFP responses in core auditory cortex as freely moving rats spontaneously switched between wakefulness and sleep states. Despite robust differences in baseline neuronal activity, both the selectivity and the magnitude of auditory-evoked responses were comparable across wakefulness, Nonrapid eye movement (NREM) and rapid eye movement (REM) sleep (pairwise differences sleep and wakefulness using an oddball paradigm. Robust stimulus-specific adaptation (SSA) was observed following the onset of repetitive tones, and the strength of SSA effects (13-20%) was comparable across vigilance states. Thus, responses in core auditory cortex are preserved across sleep states, suggesting that evoked activity in primary sensory cortices is driven by external physical stimuli with little modulation by vigilance state. We suggest that sensory disconnection during sleep occurs at a stage later than primary sensory areas.

  1. Tactile feedback improves auditory spatial localization.

    Science.gov (United States)

    Gori, Monica; Vercillo, Tiziana; Sandini, Giulio; Burr, David

    2014-01-01

    Our recent studies suggest that congenitally blind adults have severely impaired thresholds in an auditory spatial bisection task, pointing to the importance of vision in constructing complex auditory spatial maps (Gori et al., 2014). To explore strategies that may improve the auditory spatial sense in visually impaired people, we investigated the impact of tactile feedback on spatial auditory localization in 48 blindfolded sighted subjects. We measured auditory spatial bisection thresholds before and after training, either with tactile feedback, verbal feedback, or no feedback. Audio thresholds were first measured with a spatial bisection task: subjects judged whether the second sound of a three sound sequence was spatially closer to the first or the third sound. The tactile feedback group underwent two audio-tactile feedback sessions of 100 trials, where each auditory trial was followed by the same spatial sequence played on the subject's forearm; auditory spatial bisection thresholds were evaluated after each session. In the verbal feedback condition, the positions of the sounds were verbally reported to the subject after each feedback trial. The no feedback group did the same sequence of trials, with no feedback. Performance improved significantly only after audio-tactile feedback. The results suggest that direct tactile feedback interacts with the auditory spatial localization system, possibly by a process of cross-sensory recalibration. Control tests with the subject rotated suggested that this effect occurs only when the tactile and acoustic sequences are spatially congruent. Our results suggest that the tactile system can be used to recalibrate the auditory sense of space. These results encourage the possibility of designing rehabilitation programs to help blind persons establish a robust auditory sense of space, through training with the tactile modality. PMID:25368587

  2. Tactile feedback improves auditory spatial localization

    Directory of Open Access Journals (Sweden)

    Monica eGori

    2014-10-01

    Full Text Available Our recent studies suggest that congenitally blind adults have severely impaired thresholds in an auditory spatial-bisection task, pointing to the importance of vision in constructing complex auditory spatial maps (Gori et al., 2014. To explore strategies that may improve the auditory spatial sense in visually impaired people, we investigated the impact of tactile feedback on spatial auditory localization in 48 blindfolded sighted subjects. We measured auditory spatial bisection thresholds before and after training, either with tactile feedback, verbal feedback or no feedback. Audio thresholds were first measured with a spatial bisection task: subjects judged whether the second sound of a three sound sequence was spatially closer to the first or the third sound. The tactile-feedback group underwent two audio-tactile feedback sessions of 100 trials, where each auditory trial was followed by the same spatial sequence played on the subject’s forearm; auditory spatial bisection thresholds were evaluated after each session. In the verbal-feedback condition, the positions of the sounds were verbally reported to the subject after each feedback trial. The no-feedback group did the same sequence of trials, with no feedback. Performance improved significantly only after audio-tactile feedback. The results suggest that direct tactile feedback interacts with the auditory spatial localization system, possibly by a process of cross-sensory recalibration. Control tests with the subject rotated suggested that this effect occurs only when the tactile and acoustic sequences are spatially coherent. Our results suggest that the tactile system can be used to recalibrate the auditory sense of space. These results encourage the possibility of designing rehabilitation programs to help blind persons establish a robust auditory sense of space, through training with the tactile modality.

  3. THE EFFECTS OF SALICYLATE ON AUDITORY EVOKED POTENTIAL AMPLITWDE FROM THE AUDITORY CORTEX AND AUDITORY BRAINSTEM

    Institute of Scientific and Technical Information of China (English)

    Brian Sawka; SUN Wei

    2014-01-01

    Tinnitus has often been studied using salicylate in animal models as they are capable of inducing tempo-rary hearing loss and tinnitus. Studies have recently observed enhancement of auditory evoked responses of the auditory cortex (AC) post salicylate treatment which is also shown to be related to tinnitus like behavior in rats. The aim of this study was to observe if enhancements of the AC post salicylate treatment are also present at structures in the brainstem. Four male Sprague Dawley rats with AC implanted electrodes were tested for both AC and auditory brainstem response (ABR) recordings pre and post 250 mg/kg intraperitone-al injections of salicylate. The responses were recorded as the peak to trough amplitudes of P1-N1 (AC), ABR wave V, and ABR waveⅡ. AC responses resulted in statistically significant enhancement of ampli-tude at 2 hours post salicylate with 90 dB stimuli tone bursts of 4, 8, 12, and 20 kHz. Wave V of ABR re-sponses at 90 dB resulted in a statistically significant reduction of amplitude 2 hours post salicylate and a mean decrease of amplitude of 31%for 16 kHz. WaveⅡamplitudes at 2 hours post treatment were signifi-cantly reduced for 4, 12, and 20 kHz stimuli at 90 dB SPL. Our results suggest that the enhancement chang-es of the AC related to salicylate induced tinnitus are generated superior to the level of the inferior colliculus and may originate in the AC.

  4. Temporal auditory processing in elders

    Directory of Open Access Journals (Sweden)

    Azzolini, Vanuza Conceição

    2010-03-01

    Full Text Available Introduction: In the trial of aging all the structures of the organism are modified, generating intercurrences in the quality of the hearing and of the comprehension. The hearing loss that occurs in consequence of this trial occasion a reduction of the communicative function, causing, also, a distance of the social relationship. Objective: Comparing the performance of the temporal auditory processing between elderly individuals with and without hearing loss. Method: The present study is characterized for to be a prospective, transversal and of diagnosis character field work. They were analyzed 21 elders (16 women and 5 men, with ages between 60 to 81 years divided in two groups, a group "without hearing loss"; (n = 13 with normal auditive thresholds or restricted hearing loss to the isolated frequencies and a group "with hearing loss" (n = 8 with neurosensory hearing loss of variable degree between light to moderately severe. Both the groups performed the tests of frequency (PPS and duration (DPS, for evaluate the ability of temporal sequencing, and the test Randon Gap Detection Test (RGDT, for evaluate the temporal resolution ability. Results: It had not difference statistically significant between the groups, evaluated by the tests DPS and RGDT. The ability of temporal sequencing was significantly major in the group without hearing loss, when evaluated by the test PPS in the condition "muttering". This result presented a growing one significant in parallel with the increase of the age group. Conclusion: It had not difference in the temporal auditory processing in the comparison between the groups.

  5. Assessment and Preservation of Auditory Nerve Integrity in the Deafened Guinea Pig

    NARCIS (Netherlands)

    Ramekers, D.

    2014-01-01

    Profound hearing loss is often caused by cochlear hair cell loss. Cochlear implants (CIs) essentially replace hair cells by encoding sound and conveying the signal by means of pulsatile electrical stimulation to the spiral ganglion cells (SGCs) which form the auditory nerve. SGCs progressively degen

  6. Auditory Imagery Shapes Movement Timing and Kinematics: Evidence from a Musical Task

    Science.gov (United States)

    Keller, Peter E.; Dalla Bella, Simone; Koch, Iring

    2010-01-01

    The role of anticipatory auditory imagery in music-like sequential action was investigated by examining timing accuracy and kinematics using a motion capture system. Musicians responded to metronomic pacing signals by producing three unpaced taps on three vertically aligned keys at the given tempo. Taps triggered tones in two out of three blocked…

  7. Activation of L-type calcium channels is required for gap junction-mediated intercellular calcium signaling in osteoblastic cells

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye; Teilmann, Stefan Cuoni; Henriksen, Zanne;

    2003-01-01

    in "slow" ICW. Human osteoblastic cells transmit intercellular calcium signals by both of these mechanisms. In the current studies we have examined the mechanism of slow gap junction-dependent ICW in osteoblastic cells. In ROS rat osteoblastic cells, gap junction-dependent ICW were inhibited by removal...

  8. Requirement of Dopamine Signaling in the Amygdala and Striatum for Learning and Maintenance of a Conditioned Avoidance Response

    Science.gov (United States)

    Darvas, Martin; Fadok, Jonathan P.; Palmiter, Richard D.

    2011-01-01

    Two-way active avoidance (2WAA) involves learning Pavlovian (association of a sound cue with a foot shock) and instrumental (shock avoidance) contingencies. To identify regions where dopamine (DA) is involved in mediating 2WAA, we restored DA signaling in specific brain areas of dopamine-deficient (DD) mice by local reactivation of conditionally…

  9. Euglycemia restoration by central leptin in type 1 diabetes requires STAT3 signaling but not fast-acting neurotransmitter release

    Science.gov (United States)

    Central leptin action is sufficient to restore euglycemia in insulinopenic type 1 diabetes (T1D); however, the underlying mechanism remains poorly understood. To examine the role of intracellular signal transducer and activator of transcription 3 (STAT3) pathways, we used LepRs/s mice with disrupted...

  10. MRI of unusual lesions in the internal auditory canal

    Energy Technology Data Exchange (ETDEWEB)

    Krainik, A.; Cyna-Gorse, F.; Vilgrain, V.; Denys, A.; Menu, Y. [Dept. of Radiology, Hopital Beaujon, Clichy (France); Bouccara, D.; Sterkers, O. [Dept. of Otorhinolaryngology, Hopital Beaujon, Clichy (France); Cazals-Hatem, D. [Dept. of Pathology, Hopital Beaujon, Clichy (France); Rey, A. [Dept. of Neurosurgery, Hopital Beaujon, Clichy (France)

    2001-01-01

    We report the MRI findings of six unusual lesions of the internal auditory canal: three haemangiomas, one lipoma, one metastasis and one traumatic neuroma. We compare the findings to those of 20 intracanalicular schwannomas. We noted the site and size of the tumour, its signal intensity, borders and the homogeneity of enhancement were studied on T1-weighted images before and after intravenous contrast medium and T2-weighted images. Most schwannomas were homogeneous lesions, isointense on T1- and T2-weighted images, and strongly enhancing. Spontaneous high signal on T1-weighted images, heterogeneous contrast enhancement and extranodular enhancement were helpful for recognising lesions other then schwannomas; site, size and signal on T2-weighted images were not. All the haemangiomas had a specific pattern of contrast enhancement, with an anterior core intensely enhancing portion and a posterior portion which enhanced moderately or not at all. (orig.)

  11. Agonist-Driven Development of CD4+CD25+Foxp3+Regulatory T Cells Requires a Second Signal Mediated by Stat6

    DEFF Research Database (Denmark)

    Sanchez-Guajardo, Vanesa Maria; Tanshot, C.; O'Malley, J.T.;

    2007-01-01

    The factors that induce Foxp3 expression and regulatory T (Treg) cell development remain unknown. In this study, we investigated the role of STAT4 and STAT6 in agonist-driven generation of Ag-specific Foxp3-expressing Treg cells. Our findings indicate that fully efficient induction of Foxp3...... expression and development of Ag-specific Treg cells requires the synergistic action of two signals: a TCR-mediated signal and a second signal mediated by STAT6. Indeed, by comparing the development of wild-type and STAT4- and STAT6-deficient hemagglutinin-specific T cells in the presence of hemagglutinin Ag...... a role for the STAT6 pathway in Treg cell development and maintenance....

  12. Relationship between Sympathetic Skin Responses and Auditory Hypersensitivity to Different Auditory Stimuli.

    Science.gov (United States)

    Kato, Fumi; Iwanaga, Ryoichiro; Chono, Mami; Fujihara, Saori; Tokunaga, Akiko; Murata, Jun; Tanaka, Koji; Nakane, Hideyuki; Tanaka, Goro

    2014-07-01

    [Purpose] Auditory hypersensitivity has been widely reported in patients with autism spectrum disorders. However, the neurological background of auditory hypersensitivity is currently not clear. The present study examined the relationship between sympathetic nervous system responses and auditory hypersensitivity induced by different types of auditory stimuli. [Methods] We exposed 20 healthy young adults to six different types of auditory stimuli. The amounts of palmar sweating resulting from the auditory stimuli were compared between groups with (hypersensitive) and without (non-hypersensitive) auditory hypersensitivity. [Results] Although no group × type of stimulus × first stimulus interaction was observed for the extent of reaction, significant type of stimulus × first stimulus interaction was noted for the extent of reaction. For an 80 dB-6,000 Hz stimulus, the trends for palmar sweating differed between the groups. For the first stimulus, the variance became larger in the hypersensitive group than in the non-hypersensitive group. [Conclusion] Subjects who regularly felt excessive reactions to auditory stimuli tended to have excessive sympathetic responses to repeated loud noises compared with subjects who did not feel excessive reactions. People with auditory hypersensitivity may be classified into several subtypes depending on their reaction patterns to auditory stimuli.

  13. TIF-IA-dependent regulation of ribosome synthesis in drosophila muscle is required to maintain systemic insulin signaling and larval growth.

    Science.gov (United States)

    Ghosh, Abhishek; Rideout, Elizabeth J; Grewal, Savraj S

    2014-10-01

    The conserved TOR kinase signaling network links nutrient availability to cell, tissue and body growth in animals. One important growth-regulatory target of TOR signaling is ribosome biogenesis. Studies in yeast and mammalian cell culture have described how TOR controls rRNA synthesis-a limiting step in ribosome biogenesis-via the RNA Polymerase I transcription factor TIF-IA. However, the contribution of TOR-dependent ribosome synthesis to tissue and body growth in animals is less clear. Here we show in Drosophila larvae that ribosome synthesis in muscle is required non-autonomously to maintain normal body growth and development. We find that amino acid starvation and TOR inhibition lead to reduced levels of TIF-IA, and decreased rRNA synthesis in larval muscle. When we mimic this decrease in muscle ribosome synthesis using RNAi-mediated knockdown of TIF-IA, we observe delayed larval development and reduced body growth. This reduction in growth is caused by lowered systemic insulin signaling via two endocrine responses: reduced expression of Drosophila insulin-like peptides (dILPs) from the brain and increased expression of Imp-L2-a secreted factor that binds and inhibits dILP activity-from muscle. We also observed that maintaining TIF-IA levels in muscle could partially reverse the starvation-mediated suppression of systemic insulin signaling. Finally, we show that activation of TOR specifically in muscle can increase overall body size and this effect requires TIF-IA function. These data suggest that muscle ribosome synthesis functions as a nutrient-dependent checkpoint for overall body growth: in nutrient rich conditions, TOR is required to maintain levels of TIF-IA and ribosome synthesis to promote high levels of systemic insulin, but under conditions of starvation stress, reduced muscle ribosome synthesis triggers an endocrine response that limits systemic insulin signaling to restrict growth and maintain homeostasis.

  14. TIF-IA-dependent regulation of ribosome synthesis in drosophila muscle is required to maintain systemic insulin signaling and larval growth.

    Directory of Open Access Journals (Sweden)

    Abhishek Ghosh

    2014-10-01

    Full Text Available The conserved TOR kinase signaling network links nutrient availability to cell, tissue and body growth in animals. One important growth-regulatory target of TOR signaling is ribosome biogenesis. Studies in yeast and mammalian cell culture have described how TOR controls rRNA synthesis-a limiting step in ribosome biogenesis-via the RNA Polymerase I transcription factor TIF-IA. However, the contribution of TOR-dependent ribosome synthesis to tissue and body growth in animals is less clear. Here we show in Drosophila larvae that ribosome synthesis in muscle is required non-autonomously to maintain normal body growth and development. We find that amino acid starvation and TOR inhibition lead to reduced levels of TIF-IA, and decreased rRNA synthesis in larval muscle. When we mimic this decrease in muscle ribosome synthesis using RNAi-mediated knockdown of TIF-IA, we observe delayed larval development and reduced body growth. This reduction in growth is caused by lowered systemic insulin signaling via two endocrine responses: reduced expression of Drosophila insulin-like peptides (dILPs from the brain and increased expression of Imp-L2-a secreted factor that binds and inhibits dILP activity-from muscle. We also observed that maintaining TIF-IA levels in muscle could partially reverse the starvation-mediated suppression of systemic insulin signaling. Finally, we show that activation of TOR specifically in muscle can increase overall body size and this effect requires TIF-IA function. These data suggest that muscle ribosome synthesis functions as a nutrient-dependent checkpoint for overall body growth: in nutrient rich conditions, TOR is required to maintain levels of TIF-IA and ribosome synthesis to promote high levels of systemic insulin, but under conditions of starvation stress, reduced muscle ribosome synthesis triggers an endocrine response that limits systemic insulin signaling to restrict growth and maintain homeostasis.

  15. The Experience of Patients with Schizophrenia Treated with Repetitive Transcranial Magnetic Stimulation for Auditory Hallucinations

    Directory of Open Access Journals (Sweden)

    Priya Subramanian

    2013-01-01

    Full Text Available Introduction. Auditory hallucinations are a common symptom experience of individuals with psychotic disorders and are often experienced as persistent, distressing, and disruptive. This case series examined the lived experiences of four individuals treated (successfully or unsuccessfully with low-frequency (1 Hz rTMS for auditory hallucinations. Methods. A phenomenological approach was used and modified to involve some predetermined data structuring to accommodate for expected cognitive impairments of participants and the impact of rTMS on auditory hallucinations. Data on thoughts and feelings in relation to the helpful, unhelpful, and other effects of rTMS on auditory hallucinations, on well-being, functioning, and the immediate environment were collected using semistructured interviews. Results. All four participants noted some improvements in their well-being following treatment and none reported a worsening of their symptoms. Only two participants noted an improvement in the auditory hallucinations and only one of them reported an improvement that was sustained after treatment completion. Conclusion. We suggest that there are useful findings in the study worth further exploration, specifically in relation to the role of an individual’s acceptance and ownership of the illness process in relation to this biomedical intervention. More mixed methods research is required to examine rTMS for auditory hallucinations.

  16. Norepinephrine is necessary for experience-dependent plasticity in the developing mouse auditory cortex.

    Science.gov (United States)

    Shepard, Kathryn N; Liles, L Cameron; Weinshenker, David; Liu, Robert C

    2015-02-11

    Critical periods are developmental windows during which the stimuli an animal encounters can reshape response properties in the affected system to a profound degree. Despite this window's importance, the neural mechanisms that regulate it are not completely understood. Pioneering studies in visual cortex initially indicated that norepinephrine (NE) permits ocular dominance column plasticity during the critical period, but later research has suggested otherwise. More recent work implicating NE in experience-dependent plasticity in the adult auditory cortex led us to re-examine the role of NE in critical period plasticity. Here, we exposed dopamine β-hydroxylase knock-out (Dbh(-/-)) mice, which lack NE completely from birth, to a biased acoustic environment during the auditory cortical critical period. This manipulation led to a redistribution of best frequencies (BFs) across auditory cortex in our control mice, consistent with prior work. By contrast, Dbh(-/-) mice failed to exhibit the expected redistribution of BFs, even though NE-deficient and NE-competent mice showed comparable auditory cortical organization when reared in a quiet colony environment. These data suggest that while intrinsic tonotopic patterning of auditory cortical circuitry occurs independently from NE, NE is required for critical period plasticity in auditory cortex. PMID:25673838

  17. Temporal coordination in joint music performance: effects of endogenous rhythms and auditory feedback.

    Science.gov (United States)

    Zamm, Anna; Pfordresher, Peter Q; Palmer, Caroline

    2015-02-01

    Many behaviors require that individuals coordinate the timing of their actions with others. The current study investigated the role of two factors in temporal coordination of joint music performance: differences in partners' spontaneous (uncued) rate and auditory feedback generated by oneself and one's partner. Pianists performed melodies independently (in a Solo condition), and with a partner (in a duet condition), either at the same time as a partner (Unison), or at a temporal offset (Round), such that pianists heard their partner produce a serially shifted copy of their own sequence. Access to self-produced auditory information during duet performance was manipulated as well: Performers heard either full auditory feedback (Full), or only feedback from their partner (Other). Larger differences in partners' spontaneous rates of Solo performances were associated with larger asynchronies (less effective synchronization) during duet performance. Auditory feedback also influenced temporal coordination of duet performance: Pianists were more coordinated (smaller tone onset asynchronies and more mutual adaptation) during duet performances when self-generated auditory feedback aligned with partner-generated feedback (Unison) than when it did not (Round). Removal of self-feedback disrupted coordination (larger tone onset asynchronies) during Round performances only. Together, findings suggest that differences in partners' spontaneous rates of Solo performances, as well as differences in self- and partner-generated auditory feedback, influence temporal coordination of joint sensorimotor behaviors.

  18. Polarity-specific transcranial direct current stimulation disrupts auditory pitch learning.

    Science.gov (United States)

    Matsushita, Reiko; Andoh, Jamila; Zatorre, Robert J

    2015-01-01

    Transcranial direct current stimulation (tDCS) is attracting increasing interest because of its potential for therapeutic use. While its effects have been investigated mainly with motor and visual tasks, less is known in the auditory domain. Past tDCS studies with auditory tasks demonstrated various behavioral outcomes, possibly due to differences in stimulation parameters, task-induced brain activity, or task measurements used in each study. Further research, using well-validated tasks is therefore required for clarification of behavioral effects of tDCS on the auditory system. Here, we took advantage of findings from a prior functional magnetic resonance imaging study, which demonstrated that the right auditory cortex is modulated during fine-grained pitch learning of microtonal melodic patterns. Targeting the right auditory cortex with tDCS using this same task thus allowed us to test the hypothesis that this region is causally involved in pitch learning. Participants in the current study were trained for 3 days while we measured pitch discrimination thresholds using microtonal melodies on each day using a psychophysical staircase procedure. We administered anodal, cathodal, or sham tDCS to three groups of participants over the right auditory cortex on the second day of training during performance of the task. Both the sham and the cathodal groups showed the expected significant learning effect (decreased pitch threshold) over the 3 days of training; in contrast we observed a blocking effect of anodal tDCS on auditory pitch learning, such that this group showed no significant change in thresholds over the 3 days. The results support a causal role for the right auditory cortex in pitch discrimination learning. PMID:26041982

  19. Polarity-Specific Transcranial Direct Current Stimulation Disrupts Auditory Pitch Learning

    Directory of Open Access Journals (Sweden)

    Reiko eMatsushita

    2015-05-01

    Full Text Available Transcranial direct current stimulation (tDCS is attracting increasing interest because of its potential for therapeutic use. While its effects have been investigated mainly with motor and visual tasks, less is known in the auditory domain. Past tDCS studies with auditory tasks demonstrated various behavioural outcomes, possibly due to differences in stimulation parameters or task measurements used in each study. Further research using well-validated tasks are therefore required for clarification of behavioural effects of tDCS on the auditory system. Here, we took advantage of findings from a prior functional magnetic resonance imaging study, which demonstrated that the right auditory cortex is modulated during fine-grained pitch learning of microtonal melodic patterns. Targeting the right auditory cortex with tDCS using this same task thus allowed us to test the hypothesis that this region is causally involved in pitch learning. Participants in the current study were trained for three days while we measured pitch discrimination thresholds using microtonal melodies on each day using a psychophysical staircase procedure. We administered anodal, cathodal, or sham tDCS to three groups of participants over the right auditory cortex on the second day of training during performance of the task. Both the sham and the cathodal groups showed the expected significant learning effect (decreased pitch threshold over the three days of training; in contrast we observed a blocking effect of anodal tDCS on auditory pitch learning, such that this group showed no significant change in thresholds over the three days. The results support a causal role for the right auditory cortex in pitch discrimination learning.

  20. Icaritin requires Phosphatidylinositol 3 kinase (PI3K)/Akt signaling to counteract skeletal muscle atrophy following mechanical unloading

    OpenAIRE

    ZHANG, Zong-Kang; Li, Jie; Liu, Jin; Baosheng GUO; Leung, Albert; Zhang, Ge; Zhang, Bao-Ting

    2016-01-01

    Counteracting muscle atrophy induced by mechanical unloading/inactivity is of great clinical need and challenge. A therapeutic agent that could counteract muscle atrophy following mechanical unloading in safety is desired. This study showed that natural product Icaritin (ICT) could increase the phosphorylation level of Phosphatidylinositol 3 kinase (PI3K) at p110 catalytic subunit and promote PI3K/Akt signaling markers in C2C12 cells. This study further showed that the high dose ICT treatment...

  1. Transiently Active Wnt/β-Catenin Signaling Is Not Required but Must Be Silenced for Stem Cell Function during Muscle Regeneration

    Directory of Open Access Journals (Sweden)

    Malea M. Murphy

    2014-09-01

    Full Text Available Adult muscle’s exceptional capacity for regeneration is mediated by muscle stem cells, termed satellite cells. As with many stem cells, Wnt/β-catenin signaling has been proposed to be critical in satellite cells during regeneration. Using new genetic reagents, we explicitly test in vivo whether Wnt/β-catenin signaling is necessary and sufficient within satellite cells and their derivatives for regeneration. We find that signaling is transiently active in transit-amplifying myoblasts, but is not required for regeneration or satellite cell self-renewal. Instead, downregulation of transiently activated β-catenin is important to limit the regenerative response, as continuous regeneration is deleterious. Wnt/β-catenin activation in adult satellite cells may simply be a vestige of their developmental lineage, in which β-catenin signaling is critical for fetal myogenesis. In the adult, surprisingly, we show that it is not activation but rather silencing of Wnt/β-catenin signaling that is important for muscle regeneration.

  2. FGF signaling via MAPK is required early and improves Activin A-induced definitive endoderm formation from human embryonic stem cells

    International Nuclear Information System (INIS)

    Highlights: ► Deep study the FGF signaling role during DE specification in the context of hESCs. ► DE differentiation from hESCs has an early dependence on FGF signaling. ► A serum-free DE protocol is developed based on the findings. ► The DE cells showed potential to differentiate into pancreatic progenitor cells. -- Abstract: Considering their unlimited proliferation and pluripotency properties, human embryonic stem cells (hESCs) constitute a promising resource applicable for cell replacement therapy. To facilitate this clinical translation, it is critical to study and understand the early stage of hESCs differentiation wherein germ layers are defined. In this study, we examined the role of FGF signaling in Activin A-induced definitive endoderm (DE) differentiation in the absence of supplemented animal serum. We found that activated FGF/MAPK signaling is required at the early time point of Activin A-induced DE formation. In addition, FGF activation increased the number of DE cells compared to Activin A alone. These DE cells could further differentiate into PDX1 and NKX6.1 positive pancreatic progenitors in vitro. We conclude that Activin A combined with FGF/MAPK signaling efficiently induce DE cells in the absence of serum. These findings improve our understanding of human endoderm formation, and constitute a step forward in the generation of clinical grade hESCs progenies for cell therapy.

  3. FGF signaling via MAPK is required early and improves Activin A-induced definitive endoderm formation from human embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Sui, Lina, E-mail: linasui@vub.ac.be [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium); Mfopou, Josue K. [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium); Geens, Mieke; Sermon, Karen [Department of Embryology and Genetics, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium); Bouwens, Luc [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium)

    2012-09-28

    Highlights: Black-Right-Pointing-Pointer Deep study the FGF signaling role during DE specification in the context of hESCs. Black-Right-Pointing-Pointer DE differentiation from hESCs has an early dependence on FGF signaling. Black-Right-Pointing-Pointer A serum-free DE protocol is developed based on the findings. Black-Right-Pointing-Pointer The DE cells showed potential to differentiate into pancreatic progenitor cells. -- Abstract: Considering their unlimited proliferation and pluripotency properties, human embryonic stem cells (hESCs) constitute a promising resource applicable for cell replacement therapy. To facilitate this clinical translation, it is critical to study and understand the early stage of hESCs differentiation wherein germ layers are defined. In this study, we examined the role of FGF signaling in Activin A-induced definitive endoderm (DE) differentiation in the absence of supplemented animal serum. We found that activated FGF/MAPK signaling is required at the early time point of Activin A-induced DE formation. In addition, FGF activation increased the number of DE cells compared to Activin A alone. These DE cells could further differentiate into PDX1 and NKX6.1 positive pancreatic progenitors in vitro. We conclude that Activin A combined with FGF/MAPK signaling efficiently induce DE cells in the absence of serum. These findings improve our understanding of human endoderm formation, and constitute a step forward in the generation of clinical grade hESCs progenies for cell therapy.

  4. Auditory Efferent System Modulates Mosquito Hearing.

    Science.gov (United States)

    Andrés, Marta; Seifert, Marvin; Spalthoff, Christian; Warren, Ben; Weiss, Lukas; Giraldo, Diego; Winkler, Margret; Pauls, Stephanie; Göpfert, Martin C

    2016-08-01

    The performance of vertebrate ears is controlled by auditory efferents that originate in the brain and innervate the ear, synapsing onto hair cell somata and auditory afferent fibers [1-3]. Efferent activity can provide protection from noise and facilitate the detection and discrimination of sound by modulating mechanical amplification by hair cells and transmitter release as well as auditory afferent action potential firing [1-3]. Insect auditory organs are thought to lack efferent control [4-7], but when we inspected mosquito ears, we obtained evidence for its existence. Antibodies against synaptic proteins recognized rows of bouton-like puncta running along the dendrites and axons of mosquito auditory sensory neurons. Electron microscopy identified synaptic and non-synaptic sites of vesicle release, and some of the innervating fibers co-labeled with somata in the CNS. Octopamine, GABA, and serotonin were identified as efferent neurotransmitters or neuromodulators that affect auditory frequency tuning, mechanical amplification, and sound-evoked potentials. Mosquito brains thus modulate mosquito ears, extending the use of auditory efferent systems from vertebrates to invertebrates and adding new levels of complexity to mosquito sound detection and communication. PMID:27476597

  5. Schizosaccharomyces pombe Git7p, a Member of the Saccharomyces cerevisiae Sgt1p Family, Is Required for Glucose and Cyclic AMP Signaling, Cell Wall Integrity, and Septation

    OpenAIRE

    Schadick, Kevin; Fourcade, H. Matthew; Boumenot, Peter; Seitz, Jeffrey J.; Morrell, Jennifer L.; Chang, Louise; Gould, Kathleen L.; Partridge, Janet F.; Allshire, Robin C.; Kitagawa, Katsumi; Hieter, Phil; Hoffman, Charles S.

    2002-01-01

    The Schizosaccharomyces pombe fbp1 gene, encoding fructose-1,6-bisphosphatase, is transcriptionally repressed by glucose. Mutations that confer constitutive fbp1 transcription identify git (glucose-insensitive transcription) genes that encode components of a cyclic AMP (cAMP) signaling pathway required for adenylate cyclase activation. Four of these genes encode the three subunits of a heterotrimeric G protein (gpa2, git5, and git11) and a G protein-coupled receptor (git3). Three additional g...

  6. Asymmetric transfer of auditory perceptual learning

    Directory of Open Access Journals (Sweden)

    Sygal eAmitay

    2012-11-01

    Full Text Available Perceptual skills can improve dramatically even with minimal practice. A major and practical benefit of learning, however, is in transferring the improvement on the trained task to untrained tasks or stimuli, yet the mechanisms underlying this process are still poorly understood. Reduction of internal noise has been proposed as a mechanism of perceptual learning, and while we have evidence that frequency discrimination (FD learning is due to a reduction of internal noise, the source of that noise was not determined. In this study, we examined whether reducing the noise associated with neural phase locking to tones can explain the observed improvement in behavioural thresholds. We compared FD training between two tone durations (15 and 100 ms that straddled the temporal integration window of auditory nerve fibers upon which computational modeling of phase locking noise was based. Training on short tones resulted in improved FD on probe tests of both the long and short tones. Training on long tones resulted in improvement only on the long tones. Simulations of FD learning, based on the computational model and on signal detection theory, were compared with the behavioral FD data. We found that improved fidelity of phase locking accurately predicted transfer of learning from short to long tones, but also predicted transfer from long to short tones. The observed lack of transfer from long to short tones suggests the involvement of a second mechanism. Training may have increased the temporal integration window which could not transfer because integration time for the short tone is limited by its duration. Current learning models assume complex relationships between neural populations that represent the trained stimuli. In contrast, we propose that training-induced enhancement of the signal-to-noise ratio offers a parsimonious explanation of learning and transfer that easily accounts for asymmetric transfer of learning.

  7. 2-O Heparan Sulfate Sulfation by Hs2st Is Required for Erk/Mapk Signalling Activation at the Mid-Gestational Mouse Telencephalic Midline.

    Directory of Open Access Journals (Sweden)

    Wai Kit Chan

    Full Text Available Heparan sulfate (HS is a linear carbohydrate composed of polymerized uronate-glucosamine disaccharide units that decorates cell surface and secreted glycoproteins in the extracellular matrix. In mammals HS is subjected to differential sulfation by fifteen different heparan sulfotransferase (HST enzymes of which Hs2st uniquely catalyzes the sulfation of the 2-O position of the uronate in HS. HS sulfation is postulated to be important for regulation of signaling pathways by facilitating the interaction of HS with signaling proteins including those of the Fibroblast Growth Factor (Fgf family which signal through phosphorylation of extracellular signal-regulated kinases Erk1/2. In the developing mouse telencephalon Fgf2 signaling regulates proliferation and neurogenesis. Loss of Hs2st function phenocopies the thinned cerebral cortex of mutant mice in which Fgf2 or Erk1/2 function are abrogated, suggesting the hypothesis that 2-O-sulfated HS structures play a specific role in Fgf2/Erk signaling pathway in this context in vivo. This study investigated the molecular role of 2-O sulfation in Fgf2/Erk signaling in the developing telencephalic midline midway through mouse embryogenesis at E12.5. We examined the expression of Hs2st, Fgf2, and Erk1/2 activity in wild-type and Hs2st-/- mice. We found that Hs2st is expressed at high levels at the midline correlating with high levels of Erk1/2 activation and Erk1/2 activation was drastically reduced in the Hs2st-/- mutant at the rostral telencephalic midline. We also found that 2-O sulfation is specifically required for the binding of Fgf2 protein to Fgfr1, its major cell-surface receptor at the rostral telencephalic midline. We conclude that 2-O sulfated HS structures generated by Hs2st are needed to form productive signaling complexes between HS, Fgf2 and Fgfr1 that activate Erk1/2 at the midline. Overall, our data suggest the interesting possibility that differential expression of Hs2st targets the rostral

  8. The Neurophysiology of Auditory Hallucinations – A Historic and Contemporary Review

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    Remko evan Lutterveld

    2011-05-01

    Full Text Available Electroencephalography (EEG and magnetoencephalography (MEG are two techniques that distinguish themselves from other neuroimaging methodologies through their ability to directly measure brain-related activity and their high temporal resolution. A large body of research has applied these techniques to study auditory hallucinations. Across a variety of approaches, the left superior temporal cortex is consistently reported to be involved in this symptom. Moreover, there is increasing evidence that a failure in corollary discharge, i.e. a neural signal originating in frontal speech areas that indicates to sensory areas that forthcoming thought is self-generated, may underlie the experience of auditory hallucinations

  9. Entropical Aspects in Auditory Processes and Psychoacoustical Law of Weber-Fechner

    Science.gov (United States)

    Cosma, I.; Popescu, D. I.

    For hearing sense, the mechanoreceptors fire action potentials when their membranes are physically stretched. Based on the statistical physics, we analyzed the entropical aspects in auditory processes of hearing. We develop a model that connects the logarithm of relative intensity of sound (loudness) to the level of energy disorder within the system of cellular sensory system. The increasing of entropy and disorder in the system is connected to the free energy available to signal the production of action potentials in inner hair cells of the vestibulocochlear auditory organ.

  10. Functional Neurochemistry of the Auditory System

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    Nourollah Agha Ebrahimi

    1993-03-01

    Full Text Available Functional Neurochemistry is one of the fields of studies in the auditory system which has had an outstanding development in the recent years. Many of the findings in the mentioned field had led not only the basic auditory researches but also the clinicians to new points of view in audiology.Here, we are aimed at discussing the latest investigations in the Functional Neurochemistry of the auditory system and have focused this review mainly on the researches which will arise flashes of hope for future clinical studies

  11. Auditory Neuropathy/Dyssynchrony in Biotinidase Deficiency

    Science.gov (United States)

    Yaghini, Omid

    2016-01-01

    Biotinidase deficiency is a disorder inherited autosomal recessively showing evidence of hearing loss and optic atrophy in addition to seizures, hypotonia, and ataxia. In the present study, a 2-year-old boy with Biotinidase deficiency is presented in which clinical symptoms have been reported with auditory neuropathy/auditory dyssynchrony (AN/AD). In this case, transient-evoked otoacoustic emissions showed bilaterally normal responses representing normal function of outer hair cells. In contrast, acoustic reflex test showed absent reflexes bilaterally, and visual reinforcement audiometry and auditory brainstem responses indicated severe to profound hearing loss in both ears. These results suggest AN/AD in patients with Biotinidase deficiency. PMID:27144235

  12. Functional Neurochemistry of the Auditory System

    OpenAIRE

    Nourollah Agha Ebrahimi

    1993-01-01

    Functional Neurochemistry is one of the fields of studies in the auditory system which has had an outstanding development in the recent years. Many of the findings in the mentioned field had led not only the basic auditory researches but also the clinicians to new points of view in audiology.Here, we are aimed at discussing the latest investigations in the Functional Neurochemistry of the auditory system and have focused this review mainly on the researches which will arise flashes of hope f...

  13. Assessing the aging effect on auditory-verbal memory by Persian version of dichotic auditory verbal memory test

    Directory of Open Access Journals (Sweden)

    Zahra Shahidipour

    2014-01-01

    Conclusion: Based on the obtained results, significant reduction in auditory memory was seen in aged group and the Persian version of dichotic auditory-verbal memory test, like many other auditory verbal memory tests, showed the aging effects on auditory verbal memory performance.

  14. Hand proximity facilitates spatial discrimination of auditory tones

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    Philip eTseng

    2014-06-01

    Full Text Available The effect of hand proximity on vision and visual attention has been well documented. In this study we tested whether such effect(s would also be present in the auditory modality. With hands placed either near or away from the audio sources, participants performed an auditory-spatial discrimination (Exp 1: left or right side, pitch discrimination (Exp 2: high, med, or low tone, and spatial-plus-pitch (Exp 3: left or right; high, med, or low discrimination task. In Exp 1, when hands were away from the audio source, participants consistently responded faster with their right hand regardless of stimulus location. This right hand advantage, however, disappeared in the hands-near condition because of a significant improvement in left hand’s reaction time. No effect of hand proximity was found in Exp 2 or 3, where a choice reaction time task requiring pitch discrimination was used. Together, these results suggest that the effect of hand proximity is not exclusive to vision alone, but is also present in audition, though in a much weaker form. Most important, these findings provide evidence from auditory attention that supports the multimodal account originally raised by Reed et al. in 2006.

  15. Test of a motor theory of long-term auditory memory.

    Science.gov (United States)

    Schulze, Katrin; Vargha-Khadem, Faraneh; Mishkin, Mortimer

    2012-05-01

    Monkeys can easily form lasting central representations of visual and tactile stimuli, yet they seem unable to do the same with sounds. Humans, by contrast, are highly proficient in auditory long-term memory (LTM). These mnemonic differences within and between species raise the question of whether the human ability is supported in some way by speech and language, e.g., through subvocal reproduction of speech sounds and by covert verbal labeling of environmental stimuli. If so, the explanation could be that storing rapidly fluctuating acoustic signals requires assistance from the motor system, which is uniquely organized to chain-link rapid sequences. To test this hypothesis, we compared the ability of normal participants to recognize lists of stimuli that can be easily reproduced, labeled, or both (pseudowords, nonverbal sounds, and words, respectively) versus their ability to recognize a list of stimuli that can be reproduced or labeled only with great difficulty (reversed words, i.e., words played backward). Recognition scores after 5-min delays filled with articulatory-suppression tasks were relatively high (75-80% correct) for all sound types except reversed words; the latter yielded scores that were not far above chance (58% correct), even though these stimuli were discriminated nearly perfectly when presented as reversed-word pairs at short intrapair intervals. The combined results provide preliminary support for the hypothesis that participation of the oromotor system may be essential for laying down the memory of speech sounds and, indeed, that speech and auditory memory may be so critically dependent on each other that they had to coevolve. PMID:22511719

  16. Jumpstarting auditory learning in children with cochlear implants through music experiences.

    Science.gov (United States)

    Barton, Christine; Robbins, Amy McConkey

    2015-09-01

    Musical experiences are a valuable part of the lives of children with cochlear implants (CIs). In addition to the pleasure, relationships and emotional outlet provided by music, it serves to enhance or 'jumpstart' other auditory and cognitive skills that are critical for development and learning throughout the lifespan. Musicians have been shown to be 'better listeners' than non-musicians with regard to how they perceive and process sound. A heuristic model of music therapy is reviewed, including six modulating factors that may account for the auditory advantages demonstrated by those who participate in music therapy. The integral approach to music therapy is described along with the hybrid approach to pediatric language intervention. These approaches share the characteristics of placing high value on ecologically valid therapy experiences, i.e., engaging in 'real' music and 'real' communication. Music and language intervention techniques used by the authors are presented. It has been documented that children with CIs consistently have lower music perception scores than do their peers with normal hearing (NH). On the one hand, this finding matters a great deal because it provides parameters for setting reasonable expectations and highlights the work still required to improve signal processing with the devices so that they more accurately transmit music to CI listeners. On the other hand, the finding might not matter much if we assume that music, even in its less-than-optimal state, functions for CI children, as for NH children, as a developmental jumpstarter, a language-learning tool, a cognitive enricher, a motivator, and an attention enhancer.

  17. Jumpstarting auditory learning in children with cochlear implants through music experiences.

    Science.gov (United States)

    Barton, Christine; Robbins, Amy McConkey

    2015-09-01

    Musical experiences are a valuable part of the lives of children with cochlear implants (CIs). In addition to the pleasure, relationships and emotional outlet provided by music, it serves to enhance or 'jumpstart' other auditory and cognitive skills that are critical for development and learning throughout the lifespan. Musicians have been shown to be 'better listeners' than non-musicians with regard to how they perceive and process sound. A heuristic model of music therapy is reviewed, including six modulating factors that may account for the auditory advantages demonstrated by those who participate in music therapy. The integral approach to music therapy is described along with the hybrid approach to pediatric language intervention. These approaches share the characteristics of placing high value on ecologically valid therapy experiences, i.e., engaging in 'real' music and 'real' communication. Music and language intervention techniques used by the authors are presented. It has been documented that children with CIs consistently have lower music perception scores than do their peers with normal hearing (NH). On the one hand, this finding matters a great deal because it provides parameters for setting reasonable expectations and highlights the work still required to improve signal processing with the devices so that they more accurately transmit music to CI listeners. On the other hand, the finding might not matter much if we assume that music, even in its less-than-optimal state, functions for CI children, as for NH children, as a developmental jumpstarter, a language-learning tool, a cognitive enricher, a motivator, and an attention enhancer. PMID:26561888

  18. AUDITORY CORTICAL PLASTICITY: DOES IT PROVIDE EVIDENCE FOR COGNITIVE PROCESSING IN THE AUDITORY CORTEX?

    OpenAIRE

    Irvine, Dexter R. F.

    2007-01-01

    The past 20 years have seen substantial changes in our view of the nature of the processing carried out in auditory cortex. Some processing of a cognitive nature, previously attributed to higher order “association” areas, is now considered to take place in auditory cortex itself. One argument adduced in support of this view is the evidence indicating a remarkable degree of plasticity in the auditory cortex of adult animals. Such plasticity has been demonstrated in a wide range of paradigms, i...

  19. Modulation of auditory cortex response to pitch variation following training with microtonal melodies.

    Science.gov (United States)

    Zatorre, Robert J; Delhommeau, Karine; Zarate, Jean Mary

    2012-01-01

    We tested changes in cortical functional response to auditory patterns in a configural learning paradigm. We trained 10 human listeners to discriminate micromelodies (consisting of smaller pitch intervals than normally used in Western music) and measured covariation in blood oxygenation signal to increasing pitch interval size in order to dissociate global changes in activity from those specifically associated with the stimulus feature that was trained. A psychophysical staircase procedure with feedback was used for training over a 2-week period. Behavioral tests of discrimination ability performed before and after training showed significant learning on the trained stimuli, and generalization to other frequencies and tasks; no learning occurred in an untrained control group. Before training the functional MRI data showed the expected systematic increase in activity in auditory cortices as a function of increasing micromelody pitch interval size. This function became shallower after training, with the maximal change observed in the right posterior auditory cortex. Global decreases in activity in auditory regions, along with global increases in frontal cortices also occurred after training. Individual variation in learning rate was related to the hemodynamic slope to pitch interval size, such that those who had a higher sensitivity to pitch interval variation prior to learning achieved the fastest learning. We conclude that configural auditory learning entails modulation in the response of auditory cortex to the trained stimulus feature. Reduction in blood oxygenation response to increasing pitch interval size suggests that fewer computational resources, and hence lower neural recruitment, is associated with learning, in accord with models of auditory cortex function, and with data from other modalities. PMID:23227019

  20. Modulation of auditory cortex response to pitch variation following training with microtonal melodies

    Directory of Open Access Journals (Sweden)

    Robert J Zatorre

    2012-12-01

    Full Text Available We tested changes in cortical functional response to auditory configural learning by training ten human listeners to discriminate micromelodies (consisting of smaller pitch intervals than normally used in Western music. We measured covariation in blood oxygenation signal to increasing pitch-interval size in order to dissociate global changes in activity from those specifically associated with the stimulus feature of interest. A psychophysical staircase procedure with feedback was used for training over a two-week period. Behavioral tests of discrimination ability performed before and after training showed significant learning on the trained stimuli, and generalization to other frequencies and tasks; no learning occurred in an untrained control group. Before training the functional MRI data showed the expected systematic increase in activity in auditory cortices as a function of increasing micromelody pitch-interval size. This function became shallower after training, with the maximal change observed in the right posterior auditory cortex. Global decreases in activity in auditory regions, along with global increases in frontal cortices also occurred after training. Individual variation in learning rate was related to the hemodynamic slope to pitch-interval size, such that those who had a higher sensitivity to pitch-interval variation prior to learning achieved the fastest learning. We conclude that configural auditory learning entails modulation in the response of auditory cortex specifically to the trained stimulus feature. Reduction in blood oxygenation response to increasing pitch-interval size suggests that fewer computational resources, and hence lower neural recruitment, is associated with learning, in accord with models of auditory cortex function, and with data from other modalities.

  1. Integrin α PAT-2/CDC-42 signaling is required for muscle-mediated clearance of apoptotic cells in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Hsiao-Han Hsieh

    Full Text Available Clearance of apoptotic cells by engulfment plays an important role in the homeostasis and development of multicellular organisms. Despite the fact that the recognition of apoptotic cells by engulfment receptors is critical in inducing the engulfment process, the molecular mechanisms are still poorly understood. Here, we characterize a novel cell corpse engulfment pathway mediated by the integrin α subunit PAT-2 in Caenorhabditis elegans and show that it specifically functions in muscle-mediated engulfment during embryogenesis. Inactivation of pat-2 results in a defect in apoptotic cell internalization. The PAT-2 extracellular region binds to the surface of apoptotic cells in vivo, and the intracellular region may mediate signaling for engulfment. We identify essential roles of small GTPase CDC-42 and its activator UIG-1, a guanine-nucleotide exchange factor, in PAT-2-mediated cell corpse removal. PAT-2 and CDC-42 both function in muscle cells for apoptotic cell removal and are co-localized in growing muscle pseudopods around apoptotic cells. Our data suggest that PAT-2 functions through UIG-1 for CDC-42 activation, which in turn leads to cytoskeletal rearrangement and apoptotic cell internalization by muscle cells. Moreover, in contrast to PAT-2, the other integrin α subunit INA-1 and the engulfment receptor CED-1, which signal through the conserved signaling molecules CED-5 (DOCK180/CED-12 (ELMO or CED-6 (GULP respectively, preferentially act in epithelial cells to mediate cell corpse removal during mid-embryogenesis. Our results show that different engulfing cells utilize distinct repertoires of receptors for engulfment at the whole organism level.

  2. Limiting hepatic Bmp-Smad signaling by matriptase-2 is required for erythropoietin-mediated hepcidin suppression in mice.

    Science.gov (United States)

    Nai, Antonella; Rubio, Aude; Campanella, Alessandro; Gourbeyre, Ophélie; Artuso, Irene; Bordini, Jessica; Gineste, Aurélie; Latour, Chloé; Besson-Fournier, Céline; Lin, Herbert Y; Coppin, Hélène; Roth, Marie-Paule; Camaschella, Clara; Silvestri, Laura; Meynard, Delphine

    2016-05-12

    Hepcidin, the main regulator of iron homeostasis, is repressed when erythropoiesis is acutely stimulated by erythropoietin (EPO) to favor iron supply to maturing erythroblasts. Erythroferrone (ERFE) has been identified as the erythroid regulator that inhibits hepcidin in stress erythropoiesis. A powerful hepcidin inhibitor is the serine protease matriptase-2, encoded by TMPRSS6, whose mutations cause iron refractory iron deficiency anemia. Because this condition has inappropriately elevated hepcidin in the presence of high EPO levels, a role is suggested for matriptase-2 in EPO-mediated hepcidin repression. To investigate the relationship between EPO/ERFE and matriptase-2, we show that EPO injection induces Erfe messenger RNA expression but does not suppress hepcidin in Tmprss6 knockout (KO) mice. Similarly, wild-type (WT) animals, in which the bone morphogenetic protein-mothers against decapentaplegic homolog (Bmp-Smad) pathway is upregulated by iron treatment, fail to suppress hepcidin in response to EPO. To further investigate whether the high level of Bmp-Smad signaling of Tmprss6 KO mice counteracts hepcidin suppression by EPO, we generated double KO Bmp6-Tmprss6 KO mice. Despite having Bmp-Smad signaling and hepcidin levels that are similar to WT mice under basal conditions, double KO mice do not suppress hepcidin in response to EPO. However, pharmacologic downstream inhibition of the Bmp-Smad pathway by dorsomorphin, which targets the BMP receptors, improves the hepcidin responsiveness to EPO in Tmprss6 KO mice. We concluded that the function of matriptase-2 is dominant over that of ERFE and is essential in facilitating hepcidin suppression by attenuating the BMP-SMAD signaling. PMID:26755707

  3. Erythropoietin activates two distinct signaling pathways required for the initiation and the elongation of c-myc

    Science.gov (United States)

    Chen, C.; Sytkowski, A. J.

    2001-01-01

    Erythropoietin (Epo) stimulation of erythroid cells results in the activation of several kinases and a rapid induction of c-myc expression. Protein kinase C is necessary for Epo up-regulation of c-myc by promoting elongation at the 3'-end of exon 1. PKCepsilon mediates this signal. We now show that Epo triggers two signaling pathways to c-myc. Epo rapidly up-regulated Myc protein in BaF3-EpoR cells. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 blocked Myc up-regulation in a concentration-dependent manner but had no effect on the Epo-induced phosphorylation of ERK1 and ERK2. LY294002 also had no effect on Epo up-regulation of c-fos. MEK1 inhibitor PD98059 blocked both the c-myc and the c-fos responses to Epo. PD98059 and the PKC inhibitor H7 also blocked the phosphorylation of ERK1 and ERK2. PD98059 but not LY294002 inhibited Epo induction of ERK1 and ERK2 phosphorylation in normal erythroid cells. LY294002 blocked transcription of c-myc at exon 1. PD98059 had no effect on transcription from exon 1 but, rather, blocked Epo-induced c-myc elongation at the 3'-end of exon 1. These results identify two Epo signaling pathways to c-myc, one of which is PI3K-dependent operating on transcriptional initiation, whereas the other is mitogen-activated protein kinase-dependent operating on elongation.

  4. Endogenous leptin signaling in the caudal nucleus tractus solitarius and area postrema is required for energy balance regulation

    OpenAIRE

    Hayes, Matthew R.; Skibicka, Karolina P; Leichner, Theresa M.; Guarnieri, Douglas J; DiLeone, Ralph J; Bence, Kendra K.; Grill, Harvey J.

    2010-01-01

    Medial nucleus tractus solitarius (mNTS) neurons express leptin receptors (LepR) and intramNTS delivery of leptin reduces food intake and body weight. Here, the contribution of endogenous LepR signaling in mNTS neurons to energy balance control was examined. Knockdown of LepR in mNTS and area postrema (AP) neurons of rats (LepRKD) via adeno-associated virus short hairpin RNA-interference (AAV-shRNAi) resulted in significant hyperphagia for chow, high-fat and sucrose diets, yielding increased ...

  5. Nitrogenase switch-off by ammonium ions in Azospirillum brasilense requires the GlnB nitrogen signal-transducing protein.

    Science.gov (United States)

    Klassen, Giseli; Souza, Emanuel M; Yates, M Geoffrey; Rigo, Liu Un; Costa, Roberta M; Inaba, Juliana; Pedrosa, Fábio O

    2005-09-01

    Nitrogenase activity in several diazotrophs is switched off by ammonium and reactivated after consumption. The signaling pathway to this system in Azospirillum brasilense is not understood. We show that ammonium-dependent switch-off through ADP-ribosylation of Fe protein was partial in a glnB mutant of A. brasilense but absent in a glnB glnZ double mutant. Triggering of inactivation by anaerobic conditions was not affected in either mutant. The results suggest that glnB is necessary for full ammonium-dependent nitrogenase switch-off in A. brasilense.

  6. Auditory evoked fields elicited by spectral, temporal, and spectral-temporal changes in human cerebral cortex

    Directory of Open Access Journals (Sweden)

    Hidehiko eOkamoto

    2012-05-01

    Full Text Available Natural sounds contain complex spectral components, which are temporally modulated as time-varying signals. Recent studies have suggested that the auditory system encodes spectral and temporal sound information differently. However, it remains unresolved how the human brain processes sounds containing both spectral and temporal changes. In the present study, we investigated human auditory evoked responses elicited by spectral, temporal, and spectral-temporal sound changes by means of magnetoencephalography (MEG. The auditory evoked responses elicited by the spectral-temporal change were very similar to those elicited by the spectral change, but those elicited by the temporal change were delayed by 30 – 50 ms and differed from the others in morphology. The results suggest that human brain responses corresponding to spectral sound changes precede those corresponding to temporal sound changes, even when the spectral and temporal changes occur simultaneously.

  7. The Wellcome Prize Lecture. A map of auditory space in the mammalian brain: neural computation and development.

    Science.gov (United States)

    King, A J

    1993-09-01

    The experiments described in this review have demonstrated that the SC contains a two-dimensional map of auditory space, which is synthesized within the brain using a combination of monaural and binaural localization cues. There is also an adaptive fusion of auditory and visual space in this midbrain nucleus, providing for a common access to the motor pathways that control orientation behaviour. This necessitates a highly plastic relationship between the visual and auditory systems, both during postnatal development and in adult life. Because of the independent mobility of difference sense organs, gating mechanisms are incorporated into the auditory representation to provide up-to-date information about the spatial orientation of the eyes and ears. The SC therefore provides a valuable model system for studying a number of important issues in brain function, including the neural coding of sound location, the co-ordination of spatial information between different sensory systems, and the integration of sensory signals with motor outputs. PMID:8240794

  8. Cytoplasmic vacuolation in cultured rat astrocytes induced by an organophosphorus agent requires extracellular signal-regulated kinase activation

    International Nuclear Information System (INIS)

    There are various toxic chemicals that cause cell death. However, in certain cases deleterious agents elicit various cellular responses prior to cell death. To determine the cellular mechanisms by which such cellular responses are induced is important, but sufficient attention has not been paid to this issue to date. In this study, we showed the characteristic effects of an organophosphorus (OP) agent, bis(pinacolyl methyl)phosphonate (BPMP), which we synthesized for the study of OP nerve agents, on cultured rat astrocytes. Morphologically, BPMP induced cytoplasmic vacuolation and stellation in the rat astrocytes. Cytoplasmic vacuolation is a cell pathological change observed, for example, in vacuolar degeneration, and stellation has been reported in astrocytic reactions against various stimuli. By pretreatment with cycloheximide, a protein synthesis inhibitor, stellation was inhibited, although vacuolation was not. Cell staining with a mitochondrion-selective dye indicated that the vacuolation probably occurs in the mitochondria that are swollen and vacuolatred in the center. Interestingly, the extracellular signal-regulated kinase (ERK) cascade inhibitor inhibited vacuolation and, to some extent, stellation. These results suggest that the ERK signaling cascade is important for the induction of mitochondrial vacuolation. We expect that a detailed study of these astrocytic reactions will provide us new perspectives regarding the variation and pathological significance of cell morphological changes, such as vacuolar degeneration, and also the mechanisms underlying various neurological disorders

  9. Requirement for SAPK-JNK signaling in the induction of apoptosis by ribosomal stress in REH lymphoid leukemia cells.

    Science.gov (United States)

    Johnson, C R; Jiffar, T; Fischer, U M; Ruvolo, P P; Jarvis, W D

    2003-11-01

    The present studies examined performance of SAPK cascades and apoptotic commitment following ribosomal trauma in REH lymphoid leukemia cells. Ribostatic insults included disruption of ribosomal activity by mechanistically dissimilar agents such as blasticidin-S (BCS) (which binds 28S-rRNA to block peptidyl bond formation), kasugamycin (KSM) (which binds 18S-rRNA to prevent translational initiation), and cycloheximide (CHX) (which blocks A-site to P-site translocation of peptidyl-tRNA). Exposure of REH cells to BCS elicited DNA degradation and apoptotic cytolysis. BCS stimulated JNK1/JNK2 and p38, and their shared targets c-Jun and ATF2. Inhibition of JNK1/JNK2 (but not of p38) antagonized blasticidin-induced apoptosis, whereas targeting alternative ribosomal sites with KSM or CHX limited translation, but failed to activate the SAPK cascade or initiate apoptosis. Our findings indicate that interference with 28S-rRNA by BCS initiates apoptosis in REH cells through recruitment of SAPK-JNK signaling. Disparities between the lethal actions of BCS, KSM, and CHX appear to reflect established differences in the subribosomal targets of these agents. We propose that the SAPK cascade comprises an essential mechanism for the transduction of specific lethal stress signals emanating from active ribosomes, and that interference with the 28S-rRNA, rather than the peptidyl transfer center of the large subunit, is critical to apoptotic commitment. PMID:12970763

  10. Antiapoptotic effects of erythropoietin in differentiated neuroblastoma SH-SY5Y cells require activation of both the STAT5 and AKT signaling pathways.

    Science.gov (United States)

    Um, Moonkyoung; Lodish, Harvey F

    2006-03-01

    The hematopoietic cytokine erythropoietin (Epo) prevents neuronal death during ischemic events in the brain and in neurodegenerative diseases, presumably through its antiapoptotic effects. To explore the role of different signaling pathways in Epo-mediated antiapoptotic effects in differentiated human neuroblastoma SH-SY5Y cells, we employed a prolactin receptor (PrlR)/erythropoietin receptor (EpoR) chimera system, in which binding of prolactin (Prl) to the extracellular domain activates EpoR signaling in the cytosol. On induction of apoptosis by staurosporine, Prl supports survival of the SH-SY5Y cells expressing the wild-type PrlR/EpoR chimera. In these cells Prl treatment strongly activates the STAT5, AKT, and MAPK signaling pathways and induces weak activation of the p65 NF-kappaB factor. Selective mutation of the eight tyrosine residues of the EpoR cytoplasmic domain results in impaired or absent activation of either STAT5 (mutation of Tyr(343)) or AKT (mutation of Tyr(479)) or both (mutation of all eight tyrosine residues). Most interestingly, Prl treatment does not prevent apoptosis in cells expressing mutant PrlR/EpoR chimeras in which either the STAT5 or the AKT signaling pathways are not activated. In contrast, ERK 1/2 is fully activated by all mutant PrlR/EpoR chimeras, comparable with the level seen with the wild-type PrlR/EpoR chimera, implying that activation of the MAPK signaling pathway per se is not sufficient for antiapoptotic activity. Therefore, the antiapoptotic effects of Epo in neuronal cells require the combinatorial activation of multiple signaling pathways, including STAT5, AKT, and potentially MAPK as well, in a manner similar to that observed in hematopoietic cells.

  11. Catecholaminergic innervation of central and peripheral auditory circuitry varies with reproductive state in female midshipman fish, Porichthys notatus.

    Directory of Open Access Journals (Sweden)

    Paul M Forlano

    Full Text Available In seasonal breeding vertebrates, hormone regulation of catecholamines, which include dopamine and noradrenaline, may function, in part, to modulate behavioral responses to conspecific vocalizations. However, natural seasonal changes in catecholamine innervation of auditory nuclei is largely unexplored, especially in the peripheral auditory system, where encoding of social acoustic stimuli is initiated. The plainfin midshipman fish, Porichthys notatus, has proven to be an excellent model to explore mechanisms underlying seasonal peripheral auditory plasticity related to reproductive social behavior. Recently, we demonstrated robust catecholaminergic (CA innervation throughout the auditory system in midshipman. Most notably, dopaminergic neurons in the diencephalon have widespread projections to auditory circuitry including direct innervation of the saccule, the main endorgan of hearing, and the cholinergic octavolateralis efferent nucleus (OE which also projects to the inner ear. Here, we tested the hypothesis that gravid, reproductive summer females show differential CA innervation of the auditory system compared to non-reproductive winter females. We utilized quantitative immunofluorescence to measure tyrosine hydroxylase immunoreactive (TH-ir fiber density throughout central auditory nuclei and the sensory epithelium of the saccule. Reproductive females exhibited greater density of TH-ir innervation in two forebrain areas including the auditory thalamus and greater density of TH-ir on somata and dendrites of the OE. In contrast, non-reproductive females had greater numbers of TH-ir terminals in the saccule and greater TH-ir fiber density in a region of the auditory hindbrain as well as greater numbers of TH-ir neurons in the preoptic area. These data provide evidence that catecholamines may function, in part, to seasonally modulate the sensitivity of the inner ear and, in turn, the appropriate behavioral response to reproductive acoustic

  12. Effect of omega-3 on auditory system

    Directory of Open Access Journals (Sweden)

    Vida Rahimi

    2014-01-01

    Full Text Available Background and Aim: Omega-3 fatty acid have structural and biological roles in the body 's various systems . Numerous studies have tried to research about it. Auditory system is affected a s well. The aim of this article was to review the researches about the effect of omega-3 on auditory system.Methods: We searched Medline , Google Scholar, PubMed, Cochrane Library and SID search engines with the "auditory" and "omega-3" keywords and read textbooks about this subject between 19 70 and 20 13.Conclusion: Both excess and deficient amounts of dietary omega-3 fatty acid can cause harmful effects on fetal and infant growth and development of brain and central nervous system esspesially auditory system. It is important to determine the adequate dosage of omega-3.

  13. Auditory perception modulated by word reading.

    Science.gov (United States)

    Cao, Liyu; Klepp, Anne; Schnitzler, Alfons; Gross, Joachim; Biermann-Ruben, Katja

    2016-10-01

    Theories of embodied cognition positing that sensorimotor areas are indispensable during language comprehension are supported by neuroimaging and behavioural studies. Among others, the auditory system has been suggested to be important for understanding sound-related words (visually presented) and the motor system for action-related words. In this behavioural study, using a sound detection task embedded in a lexical decision task, we show that in participants with high lexical decision performance sound verbs improve auditory perception. The amount of modulation was correlated with lexical decision performance. Our study provides convergent behavioural evidence of auditory cortex involvement in word processing, supporting the view of embodied language comprehension concerning the auditory domain. PMID:27324193

  14. [Approaches to therapy of auditory agnosia].

    Science.gov (United States)

    Fechtelpeter, A; Göddenhenrich, S; Huber, W; Springer, L

    1990-01-01

    In a 41-year-old stroke patient with bitemporal brain damage, we found severe signs of auditory agnosia 6 months after onset. Recognition of environmental sounds was extremely impaired when tested in a multiple choice sound-picture matching task, whereas auditory discrimination between sounds and picture identifications by written names was almost undisturbed. In a therapy experiment, we tried to enhance sound recognition via semantic categorization and association, imitation of sound and analysis of auditory features, respectively. The stimulation of conscious auditory analysis proved to be increasingly effective over a 4-week period of therapy. We were able to show that the patient's improvement was not only a simple effect of practicing, but it was stable and carried over to nontrained items.

  15. Auditory stimulation and cardiac autonomic regulation

    Directory of Open Access Journals (Sweden)

    Vitor E. Valenti

    2012-08-01

    Full Text Available Previous studies have already demonstrated that auditory stimulation with music influences the cardiovascular system. In this study, we described the relationship between musical auditory stimulation and heart rate variability. Searches were performed with the Medline, SciELO, Lilacs and Cochrane databases using the following keywords: "auditory stimulation", "autonomic nervous system", "music" and "heart rate variability". The selected studies indicated that there is a strong correlation between noise intensity and vagal-sympathetic balance. Additionally, it was reported that music therapy improved heart rate variability in anthracycline-treated breast cancer patients. It was hypothesized that dopamine release in the striatal system induced by pleasurable songs is involved in cardiac autonomic regulation. Musical auditory stimulation influences heart rate variability through a neural mechanism that is not well understood. Further studies are necessary to develop new therapies to treat cardiovascular disorders.

  16. Environment for Auditory Research Facility (EAR)

    Data.gov (United States)

    Federal Laboratory Consortium — EAR is an auditory perception and communication research center enabling state-of-the-art simulation of various indoor and outdoor acoustic environments. The heart...

  17. Improving Hearing Performance Using Natural Auditory Coding Strategies

    Science.gov (United States)

    Rattay, Frank

    Sound transfer from the human ear to the brain is based on three quite different neural coding principles when the continuous temporal auditory source signal is sent as binary code in excellent quality via 30,000 nerve fibers per ear. Cochlear implants are well-accepted neural prostheses for people with sensory hearing loss, but currently the devices are inspired only by the tonotopic principle. According to this principle, every sound frequency is mapped to a specific place along the cochlea. By electrical stimulation, the frequency content of the acoustic signal is distributed via few contacts of the prosthesis to corresponding places and generates spikes there. In contrast to the natural situation, the artificially evoked information content in the auditory nerve is quite poor, especially because the richness of the temporal fine structure of the neural pattern is replaced by a firing pattern that is strongly synchronized with an artificial cycle duration. Improvement in hearing performance is expected by involving more of the ingenious strategies developed during evolution.

  18. New perspectives on the auditory cortex: learning and memory.

    Science.gov (United States)

    Weinberger, Norman M

    2015-01-01

    Primary ("early") sensory cortices have been viewed as stimulus analyzers devoid of function in learning, memory, and cognition. However, studies combining sensory neurophysiology and learning protocols have revealed that associative learning systematically modifies the encoding of stimulus dimensions in the primary auditory cortex (A1) to accentuate behaviorally important sounds. This "representational plasticity" (RP) is manifest at different levels. The sensitivity and selectivity of signal tones increase near threshold, tuning above threshold shifts toward the frequency of acoustic signals, and their area of representation can increase within the tonotopic map of A1. The magnitude of area gain encodes the level of behavioral stimulus importance and serves as a substrate of memory strength. RP has the same characteristics as behavioral memory: it is associative, specific, develops rapidly, consolidates, and can last indefinitely. Pairing tone with stimulation of the cholinergic nucleus basalis induces RP and implants specific behavioral memory, while directly increasing the representational area of a tone in A1 produces matching behavioral memory. Thus, RP satisfies key criteria for serving as a substrate of auditory memory. The findings suggest a basis for posttraumatic stress disorder in abnormally augmented cortical representations and emphasize the need for a new model of the cerebral cortex.

  19. Auditory midbrain representation of a break in interaural correlation.

    Science.gov (United States)

    Wang, Qian; Li, Liang

    2015-10-01

    The auditory peripheral system filters broadband sounds into narrowband waves and decomposes narrowband waves into quickly varying temporal fine structures (TFSs) and slowly varying envelopes. When a noise is presented binaurally (with the interaural correlation being 1), human listeners can detect a transient break in interaural correlation (BIC), which does not alter monaural inputs substantially. The central correlates of BIC are unknown. This study examined whether phase locking-based frequency-following responses (FFRs) of neuron populations in the rat auditory midbrain [inferior colliculus (IC)] to interaurally correlated steady-state narrowband noises are modulated by introduction of a BIC. The results showed that the noise-induced FFR exhibited both a TFS component (FFRTFS) and an envelope component (FFREnv), signaling the center frequency and bandwidth, respectively. Introduction of either a BIC or an interaurally correlated amplitude gap (which had the summated amplitude matched to the BIC) significantly reduced both FFRTFS and FFREnv. However, the BIC-induced FFRTFS reduction and FFREnv reduction were not correlated with the amplitude gap-induced FFRTFS reduction and FFREnv reduction, respectively. Thus, although introduction of a BIC does not affect monaural inputs, it causes a temporary reduction in sustained responses of IC neuron populations to the noise. This BIC-induced FFR reduction is not based on a simple linear summation of noise signals.

  20. Hearing Mechanisms and Noise Metrics Related to Auditory Masking in Bottlenose Dolphins (Tursiops truncatus).

    Science.gov (United States)

    Branstetter, Brian K; Bakhtiari, Kimberly L; Trickey, Jennifer S; Finneran, James J

    2016-01-01

    Odontocete cetaceans are acoustic specialists that depend on sound to hunt, forage, navigate, detect predators, and communicate. Auditory masking from natural and anthropogenic sound sources may adversely affect these fitness-related capabilities. The ability to detect a tone in a broad range of natural, anthropogenic, and synthesized noise was tested with bottlenose dolphins using a psychophysical, band-widening procedure. Diverging masking patterns were found for noise bandwidths greater than the width of an auditory filter. Despite different noise types having equal-pressure spectral-density levels (95 dB re 1 μPa(2)/Hz), masked detection threshold differences were as large as 22 dB. Consecutive experiments indicated that noise types with increased levels of amplitude modulation resulted in comodulation masking release due to within-channel and across-channel auditory mechanisms. The degree to which noise types were comodulated (comodulation index) was assessed by calculating the magnitude-squared coherence between the temporal envelope from an auditory filter centered on the signal and temporal envelopes from flanking filters. Statistical models indicate that masked thresholds in a variety of noise types, at a variety of levels, can be explained with metrics related to the comodulation index in addition to the pressure spectral-density level of noise. This study suggests that predicting auditory masking from ocean noise sources depends on both spectral and temporal properties of the noise. PMID:26610950

  1. The effect of auditory memory load on intensity resolution in individuals with Parkinson's disease

    Science.gov (United States)

    Richardson, Kelly C.

    Purpose: The purpose of the current study was to investigate the effect of auditory memory load on intensity resolution in individuals with Parkinson's disease (PD) as compared to two groups of listeners without PD. Methods: Nineteen individuals with Parkinson's disease, ten healthy age- and hearing-matched adults, and ten healthy young adults were studied. All listeners participated in two intensity discrimination tasks differing in auditory memory load; a lower memory load, 4IAX task and a higher memory load, ABX task. Intensity discrimination performance was assessed using a bias-free measurement of signal detectability known as d' (d-prime). Listeners further participated in a continuous loudness scaling task where they were instructed to rate the loudness level of each signal intensity using a computerized 150mm visual analogue scale. Results: Group discrimination functions indicated significantly lower intensity discrimination sensitivity (d') across tasks for the individuals with PD, as compared to the older and younger controls. No significant effect of aging on intensity discrimination was observed for either task. All three listeners groups demonstrated significantly lower intensity discrimination sensitivity for the higher auditory memory load, ABX task, compared to the lower auditory memory load, 4IAX task. Furthermore, a significant effect of aging was identified for the loudness scaling condition. The younger controls were found to rate most stimuli along the continuum as significantly louder than the older controls and the individuals with PD. Conclusions: The persons with PD showed evidence of impaired auditory perception for intensity information, as compared to the older and younger controls. The significant effect of aging on loudness perception may indicate peripheral and/or central auditory involvement.

  2. Coding of communication calls in the subcortical and cortical structures of the auditory system.

    Science.gov (United States)

    Suta, D; Popelár, J; Syka, J

    2008-01-01

    The processing of species-specific communication signals in the auditory system represents an important aspect of animal behavior and is crucial for its social interactions, reproduction, and survival. In this article the neuronal mechanisms underlying the processing of communication signals in the higher centers of the auditory system--inferior colliculus (IC), medial geniculate body (MGB) and auditory cortex (AC)--are reviewed, with particular attention to the guinea pig. The selectivity of neuronal responses for individual calls in these auditory centers in the guinea pig is usually low--most neurons respond to calls as well as to artificial sounds; the coding of complex sounds in the central auditory nuclei is apparently based on the representation of temporal and spectral features of acoustical stimuli in neural networks. Neuronal response patterns in the IC reliably match the sound envelope for calls characterized by one or more short impulses, but do not exactly fit the envelope for long calls. Also, the main spectral peaks are represented by neuronal firing rates in the IC. In comparison to the IC, response patterns in the MGB and AC demonstrate a less precise representation of the sound envelope, especially in the case of longer calls. The spectral representation is worse in the case of low-frequency calls, but not in the case of broad-band calls. The emotional content of the call may influence neuronal responses in the auditory pathway, which can be demonstrated by stimulation with time-reversed calls or by measurements performed under different levels of anesthesia. The investigation of the principles of the neural coding of species-specific vocalizations offers some keys for understanding the neural mechanisms underlying human speech perception.

  3. An NB-LRR protein required for HR signalling mediated by both extra- and intracellular resistance proteins.

    NARCIS (Netherlands)

    S.H.E.J. Gabriels; J.H. Vossen; S.K. Ekengren; G. van Ooijen; A.M. Abd-El-Haliem; G.C.M. van den Berg; D.Y. Rainey; G.B. Martin; F.L.W. Takken; P.J.G.M. de Wit; M.H.A.J. Joosten

    2007-01-01

    Tomato (Solanum lycopersicum) Cf resistance genes confer hypersensitive response (HR)-associated resistance to strains of the pathogenic fungus Cladosporium fulvum that express the matching avirulence (Avr) gene. Previously, we identified an Avr4-responsive tomato (ART) gene that is required for Cf-

  4. An NB-LRR protein required for HR signalling mediated by both extra- and intracellular resistance proteins

    NARCIS (Netherlands)

    Gabriëls, S.H.E.J.; Vossen, J.H.; Ekengren, S.K.; Ooijen, van G.; Abd-El-Haliem, A.M.; Berg, van den G.C.M.; Rainey, D.Y.; Martin, G.B.; Takken, F.L.W.; Wit, de P.J.G.M.; Joosten, M.H.A.J.

    2007-01-01

    Tomato (Solanum lycopersicum) Cf resistance genes confer hypersensitive response (HR)-associated resistance to strains of the pathogenic fungus Cladosporium fulvum that express the matching avirulence (Avr) gene. Previously, we identified an Avr4-responsive tomato (ART) gene that is required for Cf-

  5. WNT/β-Catenin Signaling Is Required for Integration of CD24+ Renal Progenitor Cells into Glycerol-Damaged Adult Renal Tubules

    Directory of Open Access Journals (Sweden)

    Zhao Zhang

    2015-01-01

    Full Text Available During development, nephron progenitor cells (NPC are induced to differentiate by WNT9b signals from the ureteric bud. Although nephrogenesis ends in the perinatal period, acute kidney injury (AKI elicits repopulation of damaged nephrons. Interestingly, embryonic NPC infused into adult mice with AKI are incorporated into regenerating tubules. Since WNT/β-catenin signaling is crucial for primary nephrogenesis, we reasoned that it might also be needed for the endogenous repair mechanism and for integration of exogenous NPC. When we examined glycerol-induced AKI in adult mice bearing a β-catenin/TCF reporter transgene, endogenous tubular cells reexpressed the NPC marker, CD24, and showed widespread β-catenin/TCF signaling. We isolated CD24+ cells from E15 kidneys of mice with the canonical WNT signaling reporter. 40% of cells responded to WNT3a in vitro and when infused into glycerol-injured adult, the cells exhibited β-catenin/TCF reporter activity when integrated into damaged tubules. When embryonic CD24+ cells were treated with a β-catenin/TCF pathway inhibitor (IWR-1 prior to infusion into glycerol-injured mice, tubular integration of cells was sharply reduced. Thus, the endogenous canonical β-catenin/TCF pathway is reactivated during recovery from AKI and is required for integration of exogenous embryonic renal progenitor cells into damaged tubules. These events appear to recapitulate the WNT-dependent inductive process which drives primary nephrogenesis.

  6. Auditory sequence analysis and phonological skill

    OpenAIRE

    Grube, Manon; Kumar, Sukhbinder; Cooper, Freya E.; Turton, Stuart; Griffiths, Timothy D

    2012-01-01

    This work tests the relationship between auditory and phonological skill in a non-selected cohort of 238 school students (age 11) with the specific hypothesis that sound-sequence analysis would be more relevant to phonological skill than the analysis of basic, single sounds. Auditory processing was assessed across the domains of pitch, time and timbre; a combination of six standard tests of literacy and language ability was used to assess phonological skill. A significant correlation between ...

  7. Auditory memory function in expert chess players

    OpenAIRE

    Fattahi, Fariba; Geshani, Ahmad; Jafari, Zahra; Jalaie, Shohreh; Salman Mahini, Mona

    2015-01-01

    Background: Chess is a game that involves many aspects of high level cognition such as memory, attention, focus and problem solving. Long term practice of chess can improve cognition performances and behavioral skills. Auditory memory, as a kind of memory, can be influenced by strengthening processes following long term chess playing like other behavioral skills because of common processing pathways in the brain. The purpose of this study was to evaluate the auditory memory function of expert...

  8. Auditory brain-stem responses in syphilis.

    OpenAIRE

    Rosenhall, U; Roupe, G

    1981-01-01

    Analysis of auditory brain-stem electrical responses (BSER) provides an effective means of detecting lesions in the auditory pathways. In the present study the wave patterns were analysed in 11 patients with secondary or latent syphilis with no clinical symptoms referrable to the central nervous system and in two patients with congenital syphilis and general paralysis. Decreased amplitudes and prolonged latencies occurred frequently in patients with secondary and with advanced syphilis. This ...

  9. A specific sorting signal is not required for the polarized secretion of newly synthesized proteins from cultured intestinal epithelial cells.

    Science.gov (United States)

    Rindler, M J; Traber, M G

    1988-08-01

    Caco-2 cells, derived from human colon, have the morphological, functional, and biochemical properties of small intestinal epithelial cells. After infection with enveloped viruses, influenza virions assembled at the apical plasma membrane while vesicular stomatitis virus (VSV) particles appeared exclusively at the basolateral membrane, similar to the pattern observed in virus-infected Madin-Darby canine kidney (MDCK). When grown in Millicell filter chamber devices and labeled with [35S]methionine, Caco-2 monolayers released all of their radiolabeled secretory products preferentially into the basal chamber. Among the proteins identified were apolipoproteins AI and E, transferrin, and alpha-fetoprotein. No proteins were observed to be secreted preferentially from the apical cell surface. The lysosomal enzyme beta-hexosaminidase was also secreted primarily from the basolateral surface of the cells in the presence or absence of lysosomotropic drugs or tunicamycin, which inhibit the targetting of lysosomal enzymes to lysosomes. Neither of these drug treatments significantly affected the polarized secretion of other nonlysosomal proteins. In addition, growth hormone (GH), which is released in a nonpolar fashion from MDCK cells, was secreted exclusively from the basolateral membrane after transfection of Caco-2 cells with GH cDNA in a pSV2-based expression vector. Similar results were obtained in transient expression experiments and after selection of permanently transformed Caco-2 cells expressing GH. Since both beta-hexosaminidase and GH would be expected to lack sorting signals for polarized exocytosis in epithelial cells, these results indicate that in intestinal cells, proteins transported via the basolateral secretory pathway need not have specific sorting signals.

  10. Catalytic activity of nuclear PLC-beta(1) is required for its signalling function during C2C12 differentiation.

    Science.gov (United States)

    Ramazzotti, Giulia; Faenza, Irene; Gaboardi, Gian Carlo; Piazzi, Manuela; Bavelloni, Alberto; Fiume, Roberta; Manzoli, Lucia; Martelli, Alberto M; Cocco, Lucio

    2008-11-01

    Here we report that PLC-beta(1) catalytic activity plays a role in the increase of cyclin D3 levels and induces the differentiation of C2C12 skeletal muscle cells. PLC-beta(1) mutational analysis revealed the importance of His(331) and His(378) for the catalysis. The expression of PLC-beta(1) and cyclin D3 proteins is highly induced during the process of skeletal myoblast differentiation. We have previously shown that PLC-beta(1) activates cyclin D3 promoter during the differentiation of myoblasts to myotubes, indicating that PLC-beta(1) is a crucial regulator of the mouse cyclin D3 gene. We show that after insulin treatment cyclin D3 mRNA levels are lower in cells overexpressing the PLC-beta(1) catalytically inactive form in comparison to wild type cells. We describe a novel signalling pathway elicited by PLC-beta(1) that modulates AP-1 activity. Gel mobility shift assay and supershift performed with specific antibodies indicate that the c-jun binding site is located in a cyclin D3 promoter region specifically regulated by PLC-beta(1) and that c-Jun binding activity is significantly increased by insulin and PLC-beta(1) overexpression. Mutation of AP-1 site decreased the basal cyclin D3 promoter activity and eliminated its induction by insulin and PLC-beta(1). These results hint at the fact that PLC-beta(1) catalytic activity signals a c-jun/AP-1 target gene, i.e. cyclin D3, during myogenic differentiation.

  11. Anatomical pathways for auditory memory II: information from rostral superior temporal gyrus to dorsolateral temporal pole and medial temporal cortex.

    Science.gov (United States)

    Muñoz-López, M; Insausti, R; Mohedano-Moriano, A; Mishkin, M; Saunders, R C

    2015-01-01

    Auditory recognition memory in non-human primates differs from recognition memory in other sensory systems. Monkeys learn the rule for visual and tactile delayed matching-to-sample within a few sessions, and then show one-trial recognition memory lasting 10-20 min. In contrast, monkeys require hundreds of sessions to master the rule for auditory recognition, and then show retention lasting no longer than 30-40 s. Moreover, unlike the severe effects of rhinal lesions on visual memory, such lesions have no effect on the monkeys' auditory memory performance. The anatomical pathways for auditory memory may differ from those in vision. Long-term visual recognition memory requires anatomical connections from the visual association area TE with areas 35 and 36 of the perirhinal cortex (PRC). We examined whether there is a similar anatomical route for auditory processing, or that poor auditory recognition memory may reflect the lack of such a pathway. Our hypothesis is that an auditory pathway for recognition memory originates in the higher order processing areas of the rostral superior temporal gyrus (rSTG), and then connects via the dorsolateral temporal pole to access the rhinal cortex of the medial temporal lobe. To test this, we placed retrograde (3% FB and 2% DY) and anterograde (10% BDA 10,000 mW) tracer injections in rSTG and the dorsolateral area 38 DL of the temporal pole. Results showed that area 38DL receives dense projections from auditory association areas Ts1, TAa, TPO of the rSTG, from the rostral parabelt and, to a lesser extent, from areas Ts2-3 and PGa. In turn, area 38DL projects densely to area 35 of PRC, entorhinal cortex (EC), and to areas TH/TF of the posterior parahippocampal cortex. Significantly, this projection avoids most of area 36r/c of PRC. This anatomical arrangement may contribute to our understanding of the poor auditory memory of rhesus monkeys. PMID:26041980

  12. Carrier-dependent temporal processing in an auditory interneuron.

    Science.gov (United States)

    Sabourin, Patrick; Gottlieb, Heather; Pollack, Gerald S

    2008-05-01

    Signal processing in the auditory interneuron Omega Neuron 1 (ON1) of the cricket Teleogryllus oceanicus was compared at high- and low-carrier frequencies in three different experimental paradigms. First, integration time, which corresponds to the time it takes for a neuron to reach threshold when stimulated at the minimum effective intensity, was found to be significantly shorter at high-carrier frequency than at low-carrier frequency. Second, phase locking to sinusoidally amplitude modulated signals was more efficient at high frequency, especially at high modulation rates and low modulation depths. Finally, we examined the efficiency with which ON1 detects gaps in a constant tone. As reflected by the decrease in firing rate in the vicinity of the gap, ON1 is better at detecting gaps at low-carrier frequency. Following a gap, firing rate increases beyond the pre-gap level. This "rebound" phenomenon is similar for low- and high-carrier frequencies.

  13. A late requirement for Wnt and FGF signalling during activin-induced formation of foregut endoderm from mouse embryonic stem cells

    DEFF Research Database (Denmark)

    Hansson, Mattias; Petersen, Dorthe Rønn; Peterslund, Janny M.L.;

    2009-01-01

    requires FGF signaling in adherent but not aggregate culture. Lastly, we demonstrate that activin-induced definitive endoderm derived from mouse ES cells can incorporate into the developing foregut endoderm in vivo and adopt a mostly anterior foregut character after further culture in vitro.......Here we examine how BMP, Wnt, and FGF signaling modulate activin-induced mesendodermal differentiation of mouse ES cells grown under defined conditions in adherent monoculture. We monitor ES cells containing reporter genes for markers of primitive streak (PS) and its progeny and extend previous...... findings on the ability of increasing concentrations of activin to progressively induce more ES cell progeny to anterior PS and endodermal fates. We find that the number of Sox17- and Gsc-expressing cells increases with increasing activin concentration while the highest number of T-expressing cells...

  14. Effects of parietal TMS on visual and auditory processing at the primary cortical level -- a concurrent TMS-fMRI study.

    Science.gov (United States)

    Leitão, Joana; Thielscher, Axel; Werner, Sebastian; Pohmann, Rolf; Noppeney, Uta

    2013-04-01

    Accumulating evidence suggests that multisensory interactions emerge already at the primary cortical level. Specifically, auditory inputs were shown to suppress activations in visual cortices when presented alone but amplify the blood oxygen level-dependent (BOLD) responses to concurrent visual inputs (and vice versa). This concurrent transcranial magnetic stimulation-functional magnetic resonance imaging (TMS-fMRI) study applied repetitive TMS trains at no, low, and high intensity over right intraparietal sulcus (IPS) and vertex to investigate top-down influences on visual and auditory cortices under 3 sensory contexts: visual, auditory, and no stimulation. IPS-TMS increased activations in auditory cortices irrespective of sensory context as a result of direct and nonspecific auditory TMS side effects. In contrast, IPS-TMS modulated activations in the visual cortex in a state-dependent fashion: it deactivated the visual cortex under no and auditory stimulation but amplified the BOLD response to visual stimulation. However, only the response amplification to visual stimulation was selective for IPS-TMS, while the deactivations observed for IPS- and Vertex-TMS resulted from crossmodal deactivations induced by auditory activity to TMS sounds. TMS to IPS may increase the responses in visual (or auditory) cortices to visual (or auditory) stimulation via a gain control mechanism or crossmodal interactions. Collectively, our results demonstrate that understanding TMS effects on (uni)sensory processing requires a multisensory perspective.

  15. Xanthomonas campestris FabH is required for branched-chain fatty acid and DSF-family quorum sensing signal biosynthesis.

    Science.gov (United States)

    Yu, Yong-Hong; Hu, Zhe; Dong, Hui-Juan; Ma, Jin-Cheng; Wang, Hai-Hong

    2016-01-01

    Xanthomonas campestris pv. campestris (Xcc), a Gram-negative phytopathogenic bacterium, causes black rot disease of cruciferous vegetables. Although Xcc has a complex fatty acid profile comprised of straight-chain fatty acids and branched-chain fatty acids (BCFAs), and encodes a complete set of genes required for fatty acid synthesis, there is still little known about the mechanism of BCFA synthesis. We reported that expression of Xcc fabH restores the growth of Ralstonia solanacearum fabH mutant, and this allows the R. solanacearum fabH mutant to produce BCFAs. Using in vitro assays, we demonstrated that Xcc FabH is able to condense branched-chain acyl-CoAs with malonyl-ACP to initiate BCFA synthesis. Moreover, although the fabH gene is essential for growth of Xcc, it can be replaced with Escherichia coli fabH, and Xcc mutants failed to produce BCFAs. These results suggest that Xcc does not have an obligatory requirement for BCFAs. Furthermore, Xcc mutants lost the ability to produce cis-11-methyl-2-dodecenoic acid, a diffusible signal factor (DSF) required for quorum sensing of Xcc, which confirms that the fatty acid synthetic pathway supplies the intermediates for DSF signal biosynthesis. Our study also showed that replacing Xcc fabH with E. coli fabH affected Xcc pathogenesis in host plants. PMID:27595587

  16. Induction of Proinflammatory Responses in Macrophages by the Glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum: CELL SIGNALING RECEPTORS, GPI STRUCTURAL REQUIREMENT, AND REGULATION OF GPI ACTIVITY*

    Science.gov (United States)

    Krishnegowda, Gowdahalli; Hajjar, Adeline M.; Zhu, Jianzhong; Douglass, Erika J.; Uematsu, Satoshi; Akira, Shizuo; Woods, Amina S.; Gowda, D. Channe

    2016-01-01

    SUMMARY The proinflammatory cytokines produced by the innate immune system in response to pathogenic infection protect the host by controlling microbial growth. However, excessive proinflammatory responses could disrupt the host’s vital physiological functions, causing severe pathological conditions. In the case of Plasmodium falciparum, the protozoan parasite that causes fatal malaria in man, the glycosylphosphatidylinositol (GPI) anchors are thought to be the major factors that contribute to malaria pathogenesis through their ability to induce proinflammatory responses. In this study, we identified the receptors for P. falciparum GPI-induced cell signaling that leads to proinflammatory responses, and studied the GPI structure-activity relationship. The data show that GPI-signaling is mediated mainly through recognition by TLR2 and to a lesser extent by TLR4. The activity of sn-2 lyso GPIs is comparable to that of the intact GPIs, whereas the activity of Man3-GPIs is about 80% that of the intact GPIs. The GPIs with three (intact GPIs and Man3-GPIs) and two fatty acids (sn-2 lyso GPIs) appear to differ considerably in the requirement of the auxiliary receptor, TLR1 or TLR6, for recognition by TLR2. The former are preferentially recognized by TLR2/TLR1, whereas the latter are favored by TLR2/TLR6. However, the signaling pathways initiated by all three GPI types are similar, involving the MyD88-dependent activation of ERK, JNK and p38, and NF-κB signaling pathways. The signaling molecules of these pathways differentially contribute to the production of various cytokines and nitric oxide (Zhu, J., et al. (2004) J. Biol. Chem., accompanying manuscript). Our data also show that GPIs are degraded by the macrophage surface phospholipases, predominantly into inactive species, indicating that the host can regulate GPI activity, at least in part, by this mechanism. These results imply that macrophage surface phospholipases play important roles in the GPI-induced innate

  17. (U) Estimating the Photonics Budget, Resolution, and Signal Requirements for a Multi-Monochromatic X-ray Imager

    Energy Technology Data Exchange (ETDEWEB)

    Tregillis, Ian Lee [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-09-22

    This document examines the performance of a generic flat-mirror multimonochromatic imager (MMI), with special emphasis on existing instruments at NIF and Omega. We begin by deriving the standard equation for the mean number of photons detected per resolution element. The pinhole energy bandwidth is a contributing factor; this is dominated by the finite size of the source and may be considerable. The most common method for estimating the spatial resolution of such a system (quadrature addition) is, technically, mathematically invalid for this case. However, under the proper circumstances it may produce good estimates compared to a rigorous calculation based on the convolution of point-spread functions. Diffraction is an important contribution to the spatial resolution. Common approximations based on Fraunhofer (farfield) diffraction may be inappropriate and misleading, as the instrument may reside in multiple regimes depending upon its configuration or the energy of interest. It is crucial to identify the correct diffraction regime; Fraunhofer and Fresnel (near-field) diffraction profiles are substantially different, the latter being considerably wider. Finally, we combine the photonics and resolution analyses to derive an expression for the minimum signal level such that the resulting images are not dominated by photon statistics. This analysis is consistent with observed performance of the NIF MMI.

  18. Drosophila larval to pupal switch under nutrient stress requires IP3R/Ca2+ signalling in glutamatergic interneurons

    Science.gov (United States)

    Jayakumar, Siddharth; Richhariya, Shlesha; Reddy, O Venkateswara; Texada, Michael J; Hasan, Gaiti

    2016-01-01

    Neuronal circuits are known to integrate nutritional information, but the identity of the circuit components is not completely understood. Amino acids are a class of nutrients that are vital for the growth and function of an organism. Here, we report a neuronal circuit that allows Drosophila larvae to overcome amino acid deprivation and pupariate. We find that nutrient stress is sensed by the class IV multidendritic cholinergic neurons. Through live calcium imaging experiments, we show that these cholinergic stimuli are conveyed to glutamatergic neurons in the ventral ganglion through mAChR. We further show that IP3R-dependent calcium transients in the glutamatergic neurons convey this signal to downstream medial neurosecretory cells (mNSCs). The circuit ultimately converges at the ring gland and regulates expression of ecdysteroid biosynthetic genes. Activity in this circuit is thus likely to be an adaptation that provides a layer of regulation to help surpass nutritional stress during development. DOI: http://dx.doi.org/10.7554/eLife.17495.001 PMID:27494275

  19. Voluntary running depreciates the requirement of Ca2+-stimulated cAMP signaling in synaptic potentiation and memory formation.

    Science.gov (United States)

    Zheng, Fei; Zhang, Ming; Ding, Qi; Sethna, Ferzin; Yan, Lily; Moon, Changjong; Yang, Miyoung; Wang, Hongbing

    2016-08-01

    Mental health and cognitive functions are influenced by both genetic and environmental factors. Although having active lifestyle with physical exercise improves learning and memory, how it interacts with the specific key molecular regulators of synaptic plasticity is largely unknown. Here, we examined the effects of voluntary running on long-term potentiation (LTP) and memory formation in mice lacking type 1 adenylyl cyclase (AC1), a neurospecific synaptic enzyme that contributes to Ca(2+)-stimulated cAMP production. Following 1 mo of voluntary running-wheel exercise, the impaired LTP and object recognition memory in AC1 knockout (KO) mice were significantly attenuated. Running up-regulated exon II mRNA level of BDNF (brain-derived neurotrophic factor), though it failed to increase exon I and IV mRNAs in the hippocampus of AC1 KO mice. Intrahippocampal infusion of recombinant BDNF was sufficient to rescue LTP and object recognition memory defects in AC1 KO mice. Therefore, voluntary running and exogenous BDNF application overcome the defective Ca(2+)-stimulated cAMP signaling. Our results also demonstrate that alteration in Ca(2+)-stimulated cAMP can affect the molecular outcome of physical exercise. PMID:27421897

  20. Plasmin-induced migration requires signaling through protease-activated receptor 1 and integrin alpha(9)beta(1).

    Science.gov (United States)

    Majumdar, Mousumi; Tarui, Takehiko; Shi, Biao; Akakura, Nobuaki; Ruf, Wolfram; Takada, Yoshikazu

    2004-09-01

    Plasmin is a major extracellular protease that elicits intracellular signals to mediate platelet aggregation, chemotaxis of peripheral blood monocytes, and release of arachidonate and leukotriene from several cell types in a G protein-dependent manner. Angiostatin, a fragment of plasmin(ogen), is a ligand and an antagonist for integrin alpha(9)beta(1). Here we report that plasmin specifically interacts with alpha(9)beta(1) and that plasmin induces of cells expressing migration recombinant alpha(9)beta(1) (alpha(9)-Chinese hamster ovary (CHO) cells). Migration was dependent on an interaction of the kringle domains of plasmin with alpha(9)beta(1) as well as the catalytic activity of plasmin. Angiostatin, representing the kringle domains of plasmin, alone did not induce the migration of alpha(9)-CHO cells, but simultaneous activation of the G protein-coupled protease-activated receptor (PAR)-1 with an agonist peptide induced the migration on angiostatin, whereas PAR-2 or PAR-4 agonist peptides were without effect. Furthermore, a small chemical inhibitor of PAR-1 (RWJ 58259) and a palmitoylated PAR-1-blocking peptide inhibited plasmin-induced migration of alpha(9)-CHO cells. These results suggest that plasmin induces migration by kringle-mediated binding to alpha(9)beta(1) and simultaneous proteolytic activation of PAR-1. PMID:15247268

  1. Arabidopsis PROTEASOME REGULATOR1 is required for auxin-mediated suppression of proteasome activity and regulates auxin signalling.

    Science.gov (United States)

    Yang, Bao-Jun; Han, Xin-Xin; Yin, Lin-Lin; Xing, Mei-Qing; Xu, Zhi-Hong; Xue, Hong-Wei

    2016-01-01

    The plant hormone auxin is perceived by the nuclear F-box protein TIR1 receptor family and regulates gene expression through degradation of Aux/IAA transcriptional repressors. Several studies have revealed the importance of the proteasome in auxin signalling, but details on how the proteolytic machinery is regulated and how this relates to degradation of Aux/IAA proteins remains unclear. Here we show that an Arabidopsis homologue of the proteasome inhibitor PI31, which we name PROTEASOME REGULATOR1 (PTRE1), is a positive regulator of the 26S proteasome. Loss-of-function ptre1 mutants are insensitive to auxin-mediated suppression of proteasome activity, show diminished auxin-induced degradation of Aux/IAA proteins and display auxin-related phenotypes. We found that auxin alters the subcellular localization of PTRE1, suggesting this may be part of the mechanism by which it reduces proteasome activity. Based on these results, we propose that auxin regulates proteasome activity via PTRE1 to fine-tune the homoeostasis of Aux/IAA repressor proteins thus modifying auxin activity. PMID:27109828

  2. Requirement of catalytically active Tyk2 and accessory signals for the induction of TRAIL mRNA by IFN-beta.

    Science.gov (United States)

    Rani, M R Sandhya; Pandalai, Sudha; Shrock, Jennifer; Almasan, Alex; Ransohoff, Richard M

    2007-09-01

    Tumor necrosis factor (TNF)-related apoptosis-inducing ligand/Apo2 ligand (TRAIL/Apo2L) mRNA was induced preferentially by interferon (IFN)-beta but not IFN-alpha in human fibrosarcoma and primary fibroblast cells. To characterize the signaling components mediating the IFN subtype-specific induction of this gene, we used mutant cell lines lacking individual components involved in signaling by type I IFNs. TRAIL was not induced by IFN-beta in mutant cell lines U2A, U3A, U4A, U5A, and U6A, which lack, respectively, IFN regulatory factor-9 (IRF-9), Stat1, Jak1, IFNAR-2.2, and Stat2, indicating transcription factor IFN-stimulated gene factor 3 (ISGF3) was essential for the induction of this gene. TRAIL was not induced by IFN-beta in U1A (Tyk2 null) or U1A.R930 cells (that express a kinase-deficient point mutant of Tyk2) but was induced in U1A.wt-5 cells (U1A cells expressing wild-type Tyk2), indicating that Tyk2 protein and kinase activity were both required for induction of the gene. Biochemical and genetic analyses revealed the requirement of transcription factor NF-kappa B and phosphoinositide 3-kinase (PI3K) but not extracellular signal-regulated kinase (ERK) for the induction of TRAIL by IFN-beta. Furthermore, the antiproliferative but not antiviral effects of IFN-beta required catalytically active Tyk2, suggesting that expression of genes, such as TRAIL, may play an important role in mediating the biologic effects of IFNs.

  3. The maximal area of superconducting tunneling junction X-ray detectors determined by the required signal-to-noise ratio

    International Nuclear Information System (INIS)

    The intrinsically high energy resolution of superconducting tunneling junctions (STJ) requires a low noise charge sensitive amplifier circuit. The noise sources of such a junction + amplifier circuit are discussed. The dominant noise sources are the series noise and the 1/f flicker noise of the FET input stage, amplified by the large input capacitance of the STJ-detector. Means to reduce this capacitance are discussed. Reducing the preamplifier noise by a factor of two and the height of the potential barrier of the insulating layer by two orders of magnitude, by keeping the large conductance of the junction constant, would allow an increase in junction area by a factor of 15. (orig.)

  4. Rac1 signaling is required for insulin-stimulated glucose uptake and is dysregulated in insulin-resistant murine and human skeletal muscle

    DEFF Research Database (Denmark)

    Sylow, Lykke; Jensen, Thomas Elbenhardt; Kleinert, Maximilian;

    2013-01-01

    investigated. We hypothesized that Rac1 and its downstream target, p21-activated kinase (PAK), are regulators of insulin-stimulated glucose uptake in mouse and human skeletal muscle, and are dysregulated in insulin resistant states.Muscle specific inducible Rac1 knockout (KO) mice and pharmacological......The actin-cytoskeleton-regulating GTPase Rac1 is required for insulin-stimulated GLUT4 translocation in cultured muscle cells. However, involvement of Rac1 and its downstream signaling in glucose transport in insulin sensitive and insulin resistant mature skeletal muscle has not previously been...

  5. Lipid rafts are required for signal transduction by angiotensin II receptor type 1 in neonatal glomerular mesangial cells

    Energy Technology Data Exchange (ETDEWEB)

    Adebiyi, Adebowale, E-mail: aadebiyi@uthsc.edu; Soni, Hitesh; John, Theresa A.; Yang, Fen

    2014-05-15

    Angiotensin II (ANG-II) receptors (AGTRs) contribute to renal physiology and pathophysiology, but the underlying mechanisms that regulate AGTR function in glomerular mesangium are poorly understood. Here, we show that AGTR1 is the functional AGTR subtype expressed in neonatal pig glomerular mesangial cells (GMCs). Cyclodextrin (CDX)-mediated cholesterol depletion attenuated cell surface AGTR1 protein expression and ANG-II-induced intracellular Ca{sup 2+} ([Ca{sup 2+}]{sub i}) elevation in the cells. The COOH-terminus of porcine AGTR1 contains a caveolin (CAV)-binding motif. However, neonatal GMCs express CAV-1, but not CAV-2 and CAV-3. Colocalization and in situ proximity ligation assay detected an association between endogenous AGTR1 and CAV-1 in the cells. A synthetic peptide corresponding to the CAV-1 scaffolding domain (CSD) sequence also reduced ANG-II-induced [Ca{sup 2+}]{sub i} elevation in the cells. Real-time imaging of cell growth revealed that ANG-II stimulates neonatal GMC proliferation. ANG-II-induced GMC growth was attenuated by EMD 66684, an AGTR1 antagonist; BAPTA, a [Ca{sup 2+}]{sub i} chelator; KN-93, a Ca{sup 2+}/calmodulin-dependent protein kinase II inhibitor; CDX; and a CSD peptide, but not PD 123319, a selective AGTR2 antagonist. Collectively, our data demonstrate [Ca{sup 2+}]{sub i}-dependent proliferative effect of ANG-II and highlight a critical role for lipid raft microdomains in AGTR1-mediated signal transduction in neonatal GMCs. - Highlights: • AGTR1 is the functional AGTR subtype expressed in neonatal mesangial cells. • Endogenous AGTR1 associates with CAV-1 in neonatal mesangial cells. • Lipid raft disruption attenuates cell surface AGTR1 protein expression. • Lipid raft disruption reduces ANG-II-induced [Ca{sup 2+}]{sub i} elevation in neonatal mesangial cells. • Lipid raft disruption inhibits ANG-II-induced neonatal mesangial cell growth.

  6. Basal but not luminal mammary epithelial cells require PI3K/mTOR signaling for Ras-driven overgrowth.

    Science.gov (United States)

    Plichta, Kristin A; Mathers, Jessica L; Gestl, Shelley A; Glick, Adam B; Gunther, Edward J

    2012-11-15

    The mammary ducts of humans and mice are comprised of two main mammary epithelial cell (MEC) subtypes: a surrounding layer of basal MECs and an inner layer of luminal MECs. Breast cancer subtypes show divergent clinical behavior that may reflect properties inherent in their MEC compartment of origin. How the response to a cancer-initiating genetic event is shaped by MEC subtype remains largely unexplored. Using the mouse mammary gland, we designed organotypic three-dimensional culture models that permit challenge of discrete MEC compartments with the same oncogenic insult. Mammary organoids were prepared from mice engineered for compartment-restricted coexpression of oncogenic H-RAS(G12V) together with a nuclear fluorescent reporter. Monitoring of H-RAS(G12V)-expressing MECs during extended live cell imaging permitted visualization of Ras-driven phenotypes via video microscopy. Challenging either basal or luminal MECs with H-RAS(G12V) drove MEC proliferation and survival, culminating in aberrant organoid overgrowth. In each compartment, Ras activation triggered modes of collective MEC migration and invasion that contrasted with physiologic modes used during growth factor-initiated branching morphogenesis. Although basal and luminal Ras activation produced similar overgrowth phenotypes, inhibitor studies revealed divergent use of Ras effector pathways. Blocking either the phosphoinositide 3-kinase or the mammalian target of rapamycin pathway completely suppressed Ras-driven invasion and overgrowth of basal MECs, but only modestly attenuated Ras-driven phenotypes in luminal MECs. We show that MEC subtype defines signaling pathway dependencies downstream of Ras. Thus, cells-of-origin may critically determine the drug sensitivity profiles of mammary neoplasia. PMID:23010075

  7. Selective attention modulates human auditory brainstem responses: relative contributions of frequency and spatial cues.

    Directory of Open Access Journals (Sweden)

    Alexandre Lehmann

    Full Text Available Selective attention is the mechanism that allows focusing one's attention on a particular stimulus while filtering out a range of other stimuli, for instance, on a single conversation in a noisy room. Attending to one sound source rather than another changes activity in the human auditory cortex, but it is unclear whether attention to different acoustic features, such as voice pitch and speaker location, modulates subcortical activity. Studies using a dichotic listening paradigm indicated that auditory brainstem processing may be modulated by the direction of attention. We investigated whether endogenous selective attention to one of two speech signals affects amplitude and phase locking in auditory brainstem responses when the signals were either discriminable by frequency content alone, or by frequency content and spatial location. Frequency-following responses to the speech sounds were significantly modulated in both conditions. The modulation was specific to the task-relevant frequency band. The effect was stronger when both frequency and spatial information were available. Patterns of response were variable between participants, and were correlated with psychophysical discriminability of the stimuli, suggesting that the modulation was biologically relevant. Our results demonstrate that auditory brainstem responses are susceptible to efferent modulation related to behavioral goals. Furthermore they suggest that mechanisms of selective attention actively shape activity at early subcortical processing stages according to task relevance and based on frequency and spatial cues.

  8. Auditory sustained field responses to periodic noise

    Directory of Open Access Journals (Sweden)

    Keceli Sumru

    2012-01-01

    Full Text Available Abstract Background Auditory sustained responses have been recently suggested to reflect neural processing of speech sounds in the auditory cortex. As periodic fluctuations below the pitch range are important for speech perception, it is necessary to investigate how low frequency periodic sounds are processed in the human auditory cortex. Auditory sustained responses have been shown to be sensitive to temporal regularity but the relationship between the amplitudes of auditory evoked sustained responses and the repetitive rates of auditory inputs remains elusive. As the temporal and spectral features of sounds enhance different components of sustained responses, previous studies with click trains and vowel stimuli presented diverging results. In order to investigate the effect of repetition rate on cortical responses, we analyzed the auditory sustained fields evoked by periodic and aperiodic noises using magnetoencephalography. Results Sustained fields were elicited by white noise and repeating frozen noise stimuli with repetition rates of 5-, 10-, 50-, 200- and 500 Hz. The sustained field amplitudes were significantly larger for all the periodic stimuli than for white noise. Although the sustained field amplitudes showed a rising and falling pattern within the repetition rate range, the response amplitudes to 5 Hz repetition rate were significantly larger than to 500 Hz. Conclusions The enhanced sustained field responses to periodic noises show that cortical sensitivity to periodic sounds is maintained for a wide range of repetition rates. Persistence of periodicity sensitivity below the pitch range suggests that in addition to processing the fundamental frequency of voice, sustained field generators can also resolve low frequency temporal modulations in speech envelope.

  9. Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human natural killer cells.

    Directory of Open Access Journals (Sweden)

    Karsten Köhler

    Full Text Available It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK cell recognition, and suggest that optimal integration of activating and inhibitory receptor signals requires the receptor-ligand complexes to have similar dimensions.

  10. Loss of mitogen-activated protein kinase kinase kinase 4 (MAP3K4 reveals a requirement for MAPK signalling in mouse sex determination.

    Directory of Open Access Journals (Sweden)

    Debora Bogani

    2009-09-01

    Full Text Available Sex determination in mammals is controlled by the presence or absence of the Y-linked gene SRY. In the developing male (XY gonad, sex-determining region of the Y (SRY protein acts to up-regulate expression of the related gene, SOX9, a transcriptional regulator that in turn initiates a downstream pathway of testis development, whilst also suppressing ovary development. Despite the requirement for a number of transcription factors and secreted signalling molecules in sex determination, intracellular signalling components functioning in this process have not been defined. Here we report a role for the phylogenetically ancient mitogen-activated protein kinase (MAPK signalling pathway in mouse sex determination. Using a forward genetic screen, we identified the recessive boygirl (byg mutation. On the C57BL/6J background, embryos homozygous for byg exhibit consistent XY gonadal sex reversal. The byg mutation is an A to T transversion causing a premature stop codon in the gene encoding MAP3K4 (also known as MEKK4, a mitogen-activated protein kinase kinase kinase. Analysis of XY byg/byg gonads at 11.5 d post coitum reveals a growth deficit and a failure to support mesonephric cell migration, both early cellular processes normally associated with testis development. Expression analysis of mutant XY gonads at the same stage also reveals a dramatic reduction in Sox9 and, crucially, Sry at the transcript and protein levels. Moreover, we describe experiments showing the presence of activated MKK4, a direct target of MAP3K4, and activated p38 in the coelomic region of the XY gonad at 11.5 d post coitum, establishing a link between MAPK signalling in proliferating gonadal somatic cells and regulation of Sry expression. Finally, we provide evidence that haploinsufficiency for Map3k4 accounts for T-associated sex reversal (Tas. These data demonstrate that MAP3K4-dependent signalling events are required for normal expression of Sry during testis development, and

  11. Auditory and motor imagery modulate learning in music performance

    Science.gov (United States)

    Brown, Rachel M.; Palmer, Caroline

    2013-01-01

    Skilled performers such as athletes or musicians can improve their performance by imagining the actions or sensory outcomes associated with their skill. Performers vary widely in their auditory and motor imagery abilities, and these individual differences influence sensorimotor learning. It is unknown whether imagery abilities influence both memory encoding and retrieval. We examined how auditory and motor imagery abilities influence musicians' encoding (during Learning, as they practiced novel melodies), and retrieval (during Recall of those melodies). Pianists learned melodies by listening without performing (auditory learning) or performing without sound (motor learning); following Learning, pianists performed the melodies from memory with auditory feedback (Recall). During either Learning (Experiment 1) or Recall (Experiment 2), pianists experienced either auditory interference, motor interference, or no interference. Pitch accuracy (percentage of correct pitches produced) and temporal regularity (variability of quarter-note interonset intervals) were measured at Recall. Independent tests measured auditory and motor imagery skills. Pianists' pitch accuracy was higher following auditory learning than following motor learning and lower in motor interference conditions (Experiments 1 and 2). Both auditory and motor imagery skills improved pitch accuracy overall. Auditory imagery skills modulated pitch accuracy encoding (Experiment 1): Higher auditory imagery skill corresponded to higher pitch accuracy following auditory learning with auditory or motor interference, and following motor learning with motor or no interference. These findings suggest that auditory imagery abilities decrease vulnerability to interference and compensate for missing auditory feedback at encoding. Auditory imagery skills also influenced temporal regularity at retrieval (Experiment 2): Higher auditory imagery skill predicted greater temporal regularity during Recall in the presence of

  12. Auditory and motor imagery modulate learning in music performance.

    Science.gov (United States)

    Brown, Rachel M; Palmer, Caroline

    2013-01-01

    Skilled performers such as athletes or musicians can improve their performance by imagining the actions or sensory outcomes associated with their skill. Performers vary widely in their auditory and motor imagery abilities, and these individual differences influence sensorimotor learning. It is unknown whether imagery abilities influence both memory encoding and retrieval. We examined how auditory and motor imagery abilities influence musicians' encoding (during Learning, as they practiced novel melodies), and retrieval (during Recall of those melodies). Pianists learned melodies by listening without performing (auditory learning) or performing without sound (motor learning); following Learning, pianists performed the melodies from memory with auditory feedback (Recall). During either Learning (Experiment 1) or Recall (Experiment 2), pianists experienced either auditory interference, motor interference, or no interference. Pitch accuracy (percentage of correct pitches produced) and temporal regularity (variability of quarter-note interonset intervals) were measured at Recall. Independent tests measured auditory and motor imagery skills. Pianists' pitch accuracy was higher following auditory learning than following motor learning and lower in motor interference conditions (Experiments 1 and 2). Both auditory and motor imagery skills improved pitch accuracy overall. Auditory imagery skills modulated pitch accuracy encoding (Experiment 1): Higher auditory imagery skill corresponded to higher pitch accuracy following auditory learning with auditory or motor interference, and following motor learning with motor or no interference. These findings suggest that auditory imagery abilities decrease vulnerability to interference and compensate for missing auditory feedback at encoding. Auditory imagery skills also influenced temporal regularity at retrieval (Experiment 2): Higher auditory imagery skill predicted greater temporal regularity during Recall in the presence of

  13. The bifunctional abiotic stress signalling regulator and endogenous RNA silencing suppressor FIERY1 is required for lateral root formation

    KAUST Repository

    Chen, Hao

    2010-09-28

    The Arabidopsis FIERY1 (FRY1) locus was originally identified as a negative regulator of stress-responsive gene expression and later shown to be required for suppression of RNA silencing. In this study we discovered that the FRY1 locus also regulates lateral root formation. Compared with the wild type, fry1 mutant seedlings generated significantly fewer lateral roots under normal growth conditions and also exhibited a dramatically reduced sensitivity to auxin in inducing lateral root initiation. Using transgenic plants that overexpress a yeast homolog of FRY1 that possesses only the 3\\', 5\\'-bisphosphate nucleotidase activity but not the inositol 1-phosphatase activity, we demonstrated that the lateral root phenotypes in fry1 result from loss of the nucleotidase activity. Furthermore, a T-DNA insertion mutant of another RNA silencing suppressor, XRN4 (but not XRN2 or XRN3), which is an exoribonuclease that is inhibited by the substrate of the FRY1 3\\', 5\\'-bisphosphate nucleotidase, exhibits similar lateral root defects. Although fry1 and xrn4 exhibited reduced sensitivity to ethylene, our experiments demonstrated that restoration of ethylene sensitivity in the fry1 mutant is not sufficient to rescue the lateral root phenotypes of fry1. Our results indicate that RNA silencing modulated by FRY1 and XRN4 plays an important role in shaping root architecture. © 2010 Blackwell Publishing Ltd.

  14. Thyroid Hormone-Otx2 Signaling Is Required for Embryonic Ventral Midbrain Neural Stem Cells Differentiated into Dopamine Neurons.

    Science.gov (United States)

    Chen, Chunhai; Ma, Qinglong; Chen, Xiaowei; Zhong, Min; Deng, Ping; Zhu, Gang; Zhang, Yanwen; Zhang, Lei; Yang, Zhiqi; Zhang, Kuan; Guo, Lu; Wang, Liting; Yu, Zhengping; Zhou, Zhou

    2015-08-01

    Midbrain dopamine (DA) neurons are essential for maintaining multiple brain functions. These neurons have also been implicated in relation with diverse neurological disorders. However, how these neurons are developed from neuronal stem cells (NSCs) remains largely unknown. In this study, we provide both in vivo and in vitro evidence that the thyroid hormone, an important physiological factor for brain development, promotes DA neuron differentiation from embryonic ventral midbrain (VM) NSCs. We find that thyroid hormone deficiency during development reduces the midbrain DA neuron number, downregulates the expression of tyrosine hydroxylase (TH) and the dopamine transporter (DAT), and impairs the DA neuron-dependent motor behavior. In addition, thyroid hormone treatment during VM NSC differentiation in vitro increases the production of DA neurons and upregulates the expression of TH and DAT. We also found that the thyroid hormone enhances the expression of Otx2, an important determinant of DA neurogenesis, during DA neuron differentiation. Our in vitro gene silencing experiments indicate that Otx2 is required for thyroid hormone-dependent DA neuron differentiation from embryonic VM NSCs. Finally, we revealed both in vivo and in vitro that the thyroid hormone receptor alpha 1 is expressed in embryonic VM NSCs. Furthermore, it participates in the effects of thyroid hormone-induced Otx2 upregulation and DA neuron differentiation. These data demonstrate the role and molecular mechanisms of how the thyroid hormone regulates DA neuron differentiation from embryonic VM NSCs, particularly providing new mechanisms and a potential strategy for generating dopamine neurons from NSCs.

  15. Phonological working memory and auditory processing speed in children with specific language impairment

    Directory of Open Access Journals (Sweden)

    Fatemeh Haresabadi

    2015-02-01

    Full Text Available Background and Aim: Specific language impairment (SLI, one variety of developmental language disorder, has attracted much interest in recent decades. Much research has been conducted to discover why some children have a specific language impairment. So far, research has failed to identify a reason for this linguistic deficiency. Some researchers believe language disorder causes defects in phonological working memory and affects auditory processing speed. Therefore, this study reviews the results of research investigating these two factors in children with specific language impairment.Recent Findings: Studies have shown that children with specific language impairment face constraints in phonological working memory capacity. Memory deficit is one possible cause of linguistic disorder in children with specific language impairment. However, in these children, disorder in information processing speed is observed, especially regarding the auditory aspect.Conclusion: Much more research is required to adequately explain the relationship between phonological working memory and auditory processing speed with language. However, given the role of phonological working memory and auditory processing speed in language acquisition, a focus should be placed on phonological working memory capacity and auditory processing speed in the assessment and treatment of children with a specific language impairment.

  16. The effect of generation on long-term repetition priming in auditory and visual perceptual identification.

    Science.gov (United States)

    Mulligan, Neil W

    2011-05-01

    Perceptual implicit memory is typically most robust when the perceptual processing at encoding matches the perceptual processing required during retrieval. A consistent exception is the robust priming that semantic generation produces on the perceptual identification test (Masson & MacLeod, 2002), a finding which has been attributed to either (1) conceptual influences in this nominally perceptual task, or (2) covert orthographic processing during generative encoding. The present experiments assess these possibilities using both auditory and visual perceptual identification, tests in which participants identify auditory words in noise or rapidly-presented visual words. During the encoding phase of the experiments, participants generated some words and perceived others in an intermixed study list. The perceptual control condition was visual (reading) or auditory (hearing), and varied across participants. The reading and hearing conditions exhibited the expected modality-specificity, producing robust intra-modal priming and non-significant cross-modal priming. Priming in the generate condition depended on the perceptual control condition. With a read control condition, semantic generation produced robust visual priming but no auditory priming. With a hear control condition, the results were reversed: semantic generation produced robust auditory priming but not visual priming. This set of results is not consistent with a straightforward application of either the conceptual-influence or covert-orthography account, and implies that the nature of encoding in the generate condition is influenced by the broader list context. PMID:21388613

  17. Phosphoinositide-3-kinase/akt - dependent signaling is required for maintenance of [Ca2+]i,ICa, and Ca2+ transients in HL-1 cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Graves Bridget M

    2012-06-01

    Full Text Available Abstract The phosphoinositide 3-kinases (PI3K/Akt dependent signaling pathway plays an important role in cardiac function, specifically cardiac contractility. We have reported that sepsis decreases myocardial Akt activation, which correlates with cardiac dysfunction in sepsis. We also reported that preventing sepsis induced changes in myocardial Akt activation ameliorates cardiovascular dysfunction. In this study we investigated the role of PI3K/Akt on cardiomyocyte function by examining the role of PI3K/Akt-dependent signaling on [Ca2+]i, Ca2+ transients and membrane Ca2+ current, ICa, in cultured murine HL-1 cardiomyocytes. LY294002 (1–20 μM, a specific PI3K inhibitor, dramatically decreased HL-1 [Ca2+]i, Ca2+ transients and ICa. We also examined the effect of PI3K isoform specific inhibitors, i.e. α (PI3-kinase α inhibitor 2; 2–8 nM; β (TGX-221; 100 nM and γ (AS-252424; 100 nM, to determine the contribution of specific isoforms to HL-1 [Ca2+]i regulation. Pharmacologic inhibition of each of the individual PI3K isoforms significantly decreased [Ca2+]i, and inhibited Ca2+ transients. Triciribine (1–20 μM, which inhibits AKT downstream of the PI3K pathway, also inhibited [Ca2+]i, and Ca2+ transients and ICa. We conclude that the PI3K/Akt pathway is required for normal maintenance of [Ca2+]i in HL-1 cardiomyocytes. Thus, myocardial PI3K/Akt-PKB signaling sustains [Ca2+]i required for excitation-contraction coupling in cardiomyoctyes.

  18. Effects of Caffeine on Auditory Brainstem Response

    Directory of Open Access Journals (Sweden)

    Saleheh Soleimanian

    2008-06-01

    Full Text Available Background and Aim: Blocking of the adenosine receptor in central nervous system by caffeine can lead to increasing the level of neurotransmitters like glutamate. As the adenosine receptors are present in almost all brain areas like central auditory pathway, it seems caffeine can change conduction in this way. The purpose of this study was to evaluate the effects of caffeine on latency and amplitude of auditory brainstem response(ABR.Materials and Methods: In this clinical trial study 43 normal 18-25 years old male students were participated. The subjects consumed 0, 2 and 3 mg/kg BW caffeine in three different sessions. Auditory brainstem responses were recorded before and 30 minute after caffeine consumption. The results were analyzed by Friedman and Wilcoxone test to assess the effects of caffeine on auditory brainstem response.Results: Compared to control group the latencies of waves III,V and I-V interpeak interval of the cases decreased significantly after 2 and 3mg/kg BW caffeine consumption. Wave I latency significantly decreased after 3mg/kg BW caffeine consumption(p<0.01. Conclusion: Increasing of the glutamate level resulted from the adenosine receptor blocking brings about changes in conduction in the central auditory pathway.

  19. The harmonic organization of auditory cortex.

    Science.gov (United States)

    Wang, Xiaoqin

    2013-01-01

    A fundamental structure of sounds encountered in the natural environment is the harmonicity. Harmonicity is an essential component of music found in all cultures. It is also a unique feature of vocal communication sounds such as human speech and animal vocalizations. Harmonics in sounds are produced by a variety of acoustic generators and reflectors in the natural environment, including vocal apparatuses of humans and animal species as well as music instruments of many types. We live in an acoustic world full of harmonicity. Given the widespread existence of the harmonicity in many aspects of the hearing environment, it is natural to expect that it be reflected in the evolution and development of the auditory systems of both humans and animals, in particular the auditory cortex. Recent neuroimaging and neurophysiology experiments have identified regions of non-primary auditory cortex in humans and non-human primates that have selective responses to harmonic pitches. Accumulating evidence has also shown that neurons in many regions of the auditory cortex exhibit characteristic responses to harmonically related frequencies beyond the range of pitch. Together, these findings suggest that a fundamental organizational principle of auditory cortex is based on the harmonicity. Such an organization likely plays an important role in music processing by the brain. It may also form the basis of the preference for particular classes of music and voice sounds. PMID:24381544

  20. The role of the auditory brainstem in processing musically relevant pitch.

    Science.gov (United States)

    Bidelman, Gavin M

    2013-01-01

    Neuroimaging work has shed light on the cerebral architecture involved in processing the melodic and harmonic aspects of music. Here, recent evidence is reviewed illustrating that subcortical auditory structures contribute to the early formation and processing of musically relevant pitch. Electrophysiological recordings from the human brainstem and population responses from the auditory nerve reveal that nascent features of tonal music (e.g., consonance/dissonance, pitch salience, harmonic sonority) are evident at early, subcortical levels of the auditory pathway. The salience and harmonicity of brainstem activity is strongly correlated with listeners' perceptual preferences and perceived consonance for the tonal relationships of music. Moreover, the hierarchical ordering of pitch intervals/chords described by the Western music practice and their perceptual consonance is well-predicted by the salience with which pitch combinations are encoded in subcortical auditory structures. While the neural correlates of consonance can be tuned and exaggerated with musical training, they persist even in the absence of musicianship or long-term enculturation. As such, it is posited that the structural foundations of musical pitch might result from innate processing performed by the central auditory system. A neurobiological predisposition for consonant, pleasant sounding pitch relationships may be one reason why these pitch combinations have been favored by composers and listeners for centuries. It is suggested that important perceptual dimensions of music emerge well before the auditory signal reaches cerebral cortex and prior to attentional engagement. While cortical mechanisms are no doubt critical to the perception, production, and enjoyment of music, the contribution of subcortical structures implicates a more integrated, hierarchically organized network underlying music processing within the brain. PMID:23717294

  1. The role of the auditory brainstem in processing musically-relevant pitch

    Directory of Open Access Journals (Sweden)

    Gavin M. Bidelman

    2013-05-01

    Full Text Available Neuroimaging work has shed light on the cerebral architecture involved in processing the melodic and harmonic aspects of music. Here, recent evidence is reviewed illustrating that subcortical auditory structures contribute to the early formation and processing of musically-relevant pitch. Electrophysiological recordings from the human brainstem and population responses from the auditory nerve reveal that nascent features of tonal music (e.g., consonance/dissonance, pitch salience, harmonic sonority are evident at early, subcortical levels of the auditory pathway. The salience and harmonicity of brainstem activity is strongly correlated with listeners’ perceptual preferences and perceived consonance for the tonal relationships of music. Moreover, the hierarchical ordering of pitch intervals/chords described by the Western music practice and their perceptual consonance is well-predicted by the salience with which pitch combinations are encoded in subcortical auditory structures. While the neural correlates of consonance can be tuned and exaggerated with musical training, they persist even in the absence of musicianship or long-term enculturation. As such, it is posited that the structural foundations of musical pitch might result from innate processing performed by the central auditory system. A neurobiological predisposition for consonant, pleasant sounding pitch relationships may be one reason why these pitch combinations have been favored by composers and listeners for centuries. It is suggested that important perceptual dimensions of music emerge well before the auditory signal reaches cerebral cortex and prior to attentional engagement. While cortical mechanisms are no doubt critical to the perception, production, and enjoyment of music, the contribution of subcortical structures implicates a more integrated, hierarchically organized network underlying music processing within the brain.

  2. Contribution of auditory working memory to speech understanding in mandarin-speaking cochlear implant users.

    Directory of Open Access Journals (Sweden)

    Duoduo Tao

    Full Text Available To investigate how auditory working memory relates to speech perception performance by Mandarin-speaking cochlear implant (CI users.Auditory working memory and speech perception was measured in Mandarin-speaking CI and normal-hearing (NH participants. Working memory capacity was measured using forward digit span and backward digit span; working memory efficiency was measured using articulation rate. Speech perception was assessed with: (a word-in-sentence recognition in quiet, (b word-in-sentence recognition in speech-shaped steady noise at +5 dB signal-to-noise ratio, (c Chinese disyllable recognition in quiet, (d Chinese lexical tone recognition in quiet. Self-reported school rank was also collected regarding performance in schoolwork.There was large inter-subject variability in auditory working memory and speech performance for CI participants. Working memory and speech performance were significantly poorer for CI than for NH participants. All three working memory measures were strongly correlated with each other for both CI and NH participants. Partial correlation analyses were performed on the CI data while controlling for demographic variables. Working memory efficiency was significantly correlated only with sentence recognition in quiet when working memory capacity was partialled out. Working memory capacity was correlated with disyllable recognition and school rank when efficiency was partialled out. There was no correlation between working memory and lexical tone recognition in the present CI participants.Mandarin-speaking CI users experience significant deficits in auditory working memory and speech performance compared with NH listeners. The present data suggest that auditory working memory may contribute to CI users' difficulties in speech understanding. The present pattern of results with Mandarin-speaking CI users is consistent with previous auditory working memory studies with English-speaking CI users, suggesting that the lexical

  3. Different requirements for EDS1 and NDR1 by disease resistance genes define at least two R gene-mediated signaling pathways in Arabidopsis.

    Science.gov (United States)

    Aarts, N; Metz, M; Holub, E; Staskawicz, B J; Daniels, M J; Parker, J E

    1998-08-18

    The Arabidopsis genes EDS1 and NDR1 were shown previously by mutational analysis to encode essential components of race-specific disease resistance. Here, we examined the relative requirements for EDS1 and NDR1 by a broad spectrum of Resistance (R) genes present in three Arabidopsis accessions (Columbia, Landsberg-erecta, and Wassilewskija). We show that there is a strong requirement for EDS1 by a subset of R loci (RPP2, RPP4, RPP5, RPP21, and RPS4), conferring resistance to the biotrophic oomycete Peronospora parasitica, and to Pseudomonas bacteria expressing the avirulence gene avrRps4. The requirement for NDR1 by these EDS1-dependent R loci is either weak or not measurable. Conversely, three NDR1-dependent R loci, RPS2, RPM1, and RPS5, operate independently of EDS1. Another RPP locus, RPP8, exhibits no strong exclusive requirement for EDS1 or NDR1 in isolate-specific resistance to P. parasitica, although resistance is compromised weakly by eds1. Similarly, resistance conditioned by two EDS1-dependent RPP genes, RPP4 and RPP5, is impaired partially by ndr1, implicating a degree of pathway cross-talk. Our results provide compelling evidence for the preferential utilization of either signaling component by particular R genes and thus define at least two disease resistance pathways. The data also suggest that strong dependence on EDS1 or NDR1 is governed by R protein structural type rather than pathogen class.

  4. Estimating individual listeners’ auditory-filter bandwidth in simultaneous and non-simultaneous masking

    DEFF Research Database (Denmark)

    Buchholz, Jörg; Caminade, Sabine; Strelcyk, Olaf;

    2010-01-01

    Frequency selectivity in the human auditory system is often measured using simultaneous masking of tones presented in notched noise. Based on such masking data, the equivalent rectangular bandwidth (ERB) of the auditory filters can be derived by applying the power spectrum model of masking...... and assuming a rounded-exponential filter shape. If a forward masking paradigm is used instead of simultaneous masking, filter estimates typically show significantly sharper tuning. This difference in frequency selectivity has commonly been related to spectral suppression mechanisms observed in the cochlea...... the reliability of the individual estimates, a statistical resampling method is applied. It is demonstrated that a rather large set of experimental data is required to reliably estimate auditory filter bandwidth, particularly in the case of simultaneous masking. The poor overall reliability of the filter...

  5. EEG Responses to Auditory Stimuli for Automatic Affect Recognition

    Science.gov (United States)

    Hettich, Dirk T.; Bolinger, Elaina; Matuz, Tamara; Birbaumer, Niels; Rosenstiel, Wolfgang; Spüler, Martin

    2016-01-01

    Brain state classification for communication and control has been well established in the area of brain-computer interfaces over the last decades. Recently, the passive and automatic extraction of additional information regarding the psychological state of users from neurophysiological signals has gained increased attention in the interdisciplinary field of affective computing. We investigated how well specific emotional reactions, induced by auditory stimuli, can be detected in EEG recordings. We introduce an auditory emotion induction paradigm based on the International Affective Digitized Sounds 2nd Edition (IADS-2) database also suitable for disabled individuals. Stimuli are grouped in three valence categories: unpleasant, neutral, and pleasant. Significant differences in time domain domain event-related potentials are found in the electroencephalogram (EEG) between unpleasant and neutral, as well as pleasant and neutral conditions over midline electrodes. Time domain data were classified in three binary classification problems using a linear support vector machine (SVM) classifier. We discuss three classification performance measures in the context of affective computing and outline some strategies for conducting and reporting affect classification studies. PMID:27375410

  6. The effect of background music in auditory health persuasion

    NARCIS (Netherlands)

    Elbert, Sarah; Dijkstra, Arie

    2013-01-01

    In auditory health persuasion, threatening information regarding health is communicated by voice only. One relevant context of auditory persuasion is the addition of background music. There are different mechanisms through which background music might influence persuasion, for example through mood (

  7. Auditory Discrimination Development through Vestibulo-Cochlear Stimulation.

    Science.gov (United States)

    Palmer, Lyelle L.

    1980-01-01

    Three types of vestibular activities (active, adaptive, and passively imposed) to improve auditory discrimination development are described and results of a study using the vestibular stimulation techniques with 20 Ss (average age 9) having abnormal auditory discrimination. (PHR)

  8. Musical experience shapes top-down auditory mechanisms: evidence from masking and auditory attention performance.

    Science.gov (United States)

    Strait, Dana L; Kraus, Nina; Parbery-Clark, Alexandra; Ashley, Richard

    2010-03-01

    A growing body of research suggests that cognitive functions, such as attention and memory, drive perception by tuning sensory mechanisms to relevant acoustic features. Long-term musical experience also modulates lower-level auditory function, although the mechanisms by which this occurs remain uncertain. In order to tease apart the mechanisms that drive perceptual enhancements in musicians, we posed the question: do well-developed cognitive abilities fine-tune auditory perception in a top-down fashion? We administered a standardized battery of perceptual and cognitive tests to adult musicians and non-musicians, including tasks either more or less susceptible to cognitive control (e.g., backward versus simultaneous masking) and more or less dependent on auditory or visual processing (e.g., auditory versus visual attention). Outcomes indicate lower perceptual thresholds in musicians specifically for auditory tasks that relate with cognitive abilities, such as backward masking and auditory attention. These enhancements were observed in the absence of group differences for the simultaneous masking and visual attention tasks. Our results suggest that long-term musical practice strengthens cognitive functions and that these functions benefit auditory skills. Musical training bolsters higher-level mechanisms that, when impaired, relate to language and literacy deficits. Thus, musical training may serve to lessen the impact of these deficits by strengthening the corticofugal system for hearing. PMID:20018234

  9. DEVELOPING ‘STANDARD NOVEL ‘VAD’ TECHNIQUE’ AND ‘NOISE FREE SIGNALS’ FOR SPEECH AUDITORY BRAINSTEM RESPONSES FOR HUMAN SUBJECTS

    OpenAIRE

    Ranganadh Narayanam*

    2016-01-01

    In this research as a first step we have concentrated on collecting non-intra cortical EEG data of Brainstem Speech Evoked Potentials from human subjects in an Audiology Lab in University of Ottawa. The problems we have considered are the most advanced and most essential problems of interest in Auditory Neural Signal Processing area in the world: The first problem is the Voice Activity Detection (VAD) in Speech Auditory Brainstem Responses (ABR); The second problem is to identify the best De-...

  10. Cutaneous sensory nerve as a substitute for auditory nerve in solving deaf-mutes’ hearing problem: an innovation in multi-channel-array skin-hearing technology

    OpenAIRE

    Li, Jianwen; Li, Yan; Zhang, Ming; Ma, Weifang; Ma, Xuezong

    2014-01-01

    The current use of hearing aids and artificial cochleas for deaf-mute individuals depends on their auditory nerve. Skin-hearing technology, a patented system developed by our group, uses a cutaneous sensory nerve to substitute for the auditory nerve to help deaf-mutes to hear sound. This paper introduces a new solution, multi-channel-array skin-hearing technology, to solve the problem of speech discrimination. Based on the filtering principle of hair cells, external voice signals at different...

  11. Are auditory percepts determined by experience?

    Science.gov (United States)

    Monson, Brian B; Han, Shui'Er; Purves, Dale

    2013-01-01

    Audition--what listeners hear--is generally studied in terms of the physical properties of sound stimuli and physiological properties of the auditory system. Based on recent work in vision, we here consider an alternative perspective that sensory percepts are based on past experience. In this framework, basic auditory qualities (e.g., loudness and pitch) are based on the frequency of occurrence of stimulus patterns in natural acoustic stimuli. To explore this concept of audition, we examined five well-documented psychophysical functions. The frequency of occurrence of acoustic patterns in a database of natural sound stimuli (speech) predicts some qualitative aspects of these functions, but with substantial quantitative discrepancies. This approach may offer a rationale for auditory phenomena that are difficult to explain in terms of the physical attributes of the stimuli as such.

  12. Are auditory percepts determined by experience?

    Directory of Open Access Journals (Sweden)

    Brian B Monson

    Full Text Available Audition--what listeners hear--is generally studied in terms of the physical properties of sound stimuli and physiological properties of the auditory system. Based on recent work in vision, we here consider an alternative perspective that sensory percepts are based on past experience. In this framework, basic auditory qualities (e.g., loudness and pitch are based on the frequency of occurrence of stimulus patterns in natural acoustic stimuli. To explore this concept of audition, we examined five well-documented psychophysical functions. The frequency of occurrence of acoustic patterns in a database of natural sound stimuli (speech predicts some qualitative aspects of these functions, but with substantial quantitative discrepancies. This approach may offer a rationale for auditory phenomena that are difficult to explain in terms of the physical attributes of the stimuli as such.

  13. Phonetic categorization in auditory word perception.

    Science.gov (United States)

    Ganong, W F

    1980-02-01

    To investigate the interaction in speech perception of auditory information and lexical knowledge (in particular, knowledge of which phonetic sequences are words), acoustic continua varying in voice onset time were constructed so that for each acoustic continuum, one of the two possible phonetic categorizations made a word and the other did not. For example, one continuum ranged between the word dash and the nonword tash; another used the nonword dask and the word task. In two experiments, subjects showed a significant lexical effect--that is, a tendency to make phonetic categorizations that make words. This lexical effect was greater at the phoneme boundary (where auditory information is ambiguous) than at the ends of the condinua. Hence the lexical effect must arise at a stage of processing sensitive to both lexical knowledge and auditory information.

  14. Auditory temporal processes in the elderly

    Directory of Open Access Journals (Sweden)

    E. Ben-Artzi

    2011-03-01

    Full Text Available Several studies have reported age-related decline in auditory temporal resolution and in working memory. However, earlier studies did not provide evidence as to whether these declines reflect overall changes in the same mechanisms, or reflect age-related changes in two independent mechanisms. In the current study we examined whether the age-related decline in auditory temporal resolution and in working memory would remain significant even after controlling for their shared variance. Eighty-two participants, aged 21-82 performed the dichotic temporal order judgment task and the backward digit span task. The findings indicate that age-related decline in auditory temporal resolution and in working memory are two independent processes.

  15. What determines auditory distraction? On the roles of local auditory changes and expectation violations.

    Directory of Open Access Journals (Sweden)

    Jan P Röer

    Full Text Available Both the acoustic variability of a distractor sequence and the degree to which it violates expectations are important determinants of auditory distraction. In four experiments we examined the relative contribution of local auditory changes on the one hand and expectation violations on the other hand in the disruption of serial recall by irrelevant sound. We present evidence for a greater disruption by auditory sequences ending in unexpected steady state distractor repetitions compared to auditory sequences with expected changing state endings even though the former contained fewer local changes. This effect was demonstrated with piano melodies (Experiment 1 and speech distractors (Experiment 2. Furthermore, it was replicated when the expectation violation occurred after the encoding of the target items (Experiment 3, indicating that the items' maintenance in short-term memory was disrupted by attentional capture and not their encoding. This seems to be primarily due to the violation of a model of the specific auditory distractor sequences because the effect vanishes and even reverses when the experiment provides no opportunity to build up a specific neural model about the distractor sequence (Experiment 4. Nevertheless, the violation of abstract long-term knowledge about auditory regularities seems to cause a small and transient capture effect: Disruption decreased markedly over the course of the experiments indicating that participants habituated to the unexpected distractor repetitions across trials. The overall pattern of results adds to the growing literature that the degree to which auditory distractors violate situation-specific expectations is a more important determinant of auditory distraction than the degree to which a distractor sequence contains local auditory changes.

  16. Auditory Neuropathy Spectrum Disorder Masquerading as Social Anxiety

    OpenAIRE

    Behere, Rishikesh V.; Rao, Mukund G.; Mishra, Shree; Varambally, Shivarama; Nagarajarao, Shivashankar; Bangalore N Gangadhar

    2015-01-01

    The authors report a case of a 47-year-old man who presented with treatment-resistant anxiety disorder. Behavioral observation raised clinical suspicion of auditory neuropathy spectrum disorder. The presence of auditory neuropathy spectrum disorder was confirmed on audiological investigations. The patient was experiencing extreme symptoms of anxiety, which initially masked the underlying diagnosis of auditory neuropathy spectrum disorder. Challenges in diagnosis and treatment of auditory neur...

  17. ABR and auditory P300 findings inchildren with ADHD

    OpenAIRE

    Schochat Eliane; Scheuer Claudia Ines; Andrade Ênio Roberto de

    2002-01-01

    Auditory processing disorders (APD), also referred as central auditory processing disorders (CAPD) and attention deficit hyperactivity disorders (ADHD) have become popular diagnostic entities for school age children. It has been demonstrated a high incidence of comorbid ADHD with communication disorders and auditory processing disorder. The aim of this study was to investigate ABR and P300 auditory evoked potentials in children with ADHD, in a double-blind study. Twenty-one children, ages bet...

  18. Functional neuroanatomy of auditory scene analysis in Alzheimer's disease

    OpenAIRE

    Golden, Hannah L.; Jennifer L. Agustus; Johanna C. Goll; Downey, Laura E; Mummery, Catherine J.; Jonathan M Schott; Crutch, Sebastian J.; Jason D Warren

    2015-01-01

    Auditory scene analysis is a demanding computational process that is performed automatically and efficiently by the healthy brain but vulnerable to the neurodegenerative pathology of Alzheimer's disease. Here we assessed the functional neuroanatomy of auditory scene analysis in Alzheimer's disease using the well-known ‘cocktail party effect’ as a model paradigm whereby stored templates for auditory objects (e.g., hearing one's spoken name) are used to segregate auditory ‘foreground’ and ‘back...

  19. Auditory and motor imagery modulate learning in music performance

    Directory of Open Access Journals (Sweden)

    Rachel M. Brown

    2013-07-01

    Full Text Available Skilled performers such as athletes or musicians can improve their performance by imagining the actions or sensory outcomes associated with their skill. Performers vary widely in their auditory and motor imagery abilities, and these individual differences influence sensorimotor learning. It is unknown whether imagery abilities influence both memory encoding and retrieval. We examined how auditory and motor imagery abilities influence musicians’ encoding (during Learning, as they practiced novel melodies, and retrieval (during Recall of those melodies. Pianists learned melodies by listening without performing (auditory learning or performing without sound (motor learning; following Learning, pianists performed the melodies from memory with auditory feedback (Recall. During either Learning (Experiment 1 or Recall (Experiment 2, pianists experienced either auditory interference, motor interference, or no interference. Pitch accuracy (percentage of correct pitches produced and temporal regularity (variability of quarter-note interonset intervals were measured at Recall. Independent tests measured auditory and motor imagery skills. Pianists’ pitch accuracy was higher following auditory learning than following motor learning and lower in motor interference conditions (Experiments 1 and 2. Both auditory and motor imagery skills improved pitch accuracy overall. Auditory imagery skills modulated pitch accuracy encoding (Experiment 1: Higher auditory imagery skill corresponded to higher pitch accuracy following auditory learning with auditory or motor interference, and following motor learning with motor or no interference. These findings suggest that auditory imagery abilities decrease vulnerability to interference and compensate for missing auditory feedback at encoding. Auditory imagery skills also influenced temporal regularity at retrieval (Experiment 2: Higher auditory imagery skill predicted greater temporal regularity during Recall in the

  20. Auditory Brainstem Response Improvements in Hyperbillirubinemic Infants

    Science.gov (United States)

    Abdollahi, Farzaneh Zamiri; Manchaiah, Vinaya; Lotfi, Yones

    2016-01-01

    Background and Objectives Hyperbillirubinemia in infants have been associated with neuronal damage including in the auditory system. Some researchers have suggested that the bilirubin-induced auditory neuronal damages may be temporary and reversible. This study was aimed at investigating the auditory neuropathy and reversibility of auditory abnormalities in hyperbillirubinemic infants. Subjects and Methods The study participants included 41 full term hyperbilirubinemic infants (mean age 39.24 days) with normal birth weight (3,200-3,700 grams) that admitted in hospital for hyperbillirubinemia and 39 normal infants (mean age 35.54 days) without any hyperbillirubinemia or other hearing loss risk factors for ruling out maturational changes. All infants in hyperbilirubinemic group had serum bilirubin level more than 20 milligram per deciliter and undergone one blood exchange transfusion. Hearing evaluation for each infant was conducted twice: the first one after hyperbilirubinemia treatment and before leaving hospital and the second one three months after the first hearing evaluation. Hearing evaluations included transient evoked otoacoustic emission (TEOAE) screening and auditory brainstem response (ABR) threshold tracing. Results The TEOAE and ABR results of control group and TEOAE results of the hyperbilirubinemic group did not change significantly from the first to the second evaluation. However, the ABR results of the hyperbilirubinemic group improved significantly from the first to the second assessment (p=0.025). Conclusions The results suggest that the bilirubin induced auditory neuronal damage can be reversible over time so we suggest that infants with hyperbilirubinemia who fail the first hearing tests should be reevaluated after 3 months of treatment. PMID:27144228